182 results on '"Pasic S"'
Search Results
52. Epstein-Barr virus-associated haemophagocytic lymphohistiocytosis in Wiskott-Aldrich syndrome
- Author
-
Pasic, S, primary, Micic, D, additional, and Kuzmanovic, M, additional
- Published
- 2007
- Full Text
- View/download PDF
53. Local bacillus Calmette-Guérin infection in hyperimmunoglobulin-E syndrome
- Author
-
Pasic, S, primary
- Published
- 2007
- Full Text
- View/download PDF
54. Impaired thymic output and restricted T-cell repertoire in two infants with immunodeficiency and early-onset generalized dermatitis
- Author
-
Pirovano, S, primary, Mazzolari, E, additional, Pasic, S, additional, Albertini, A, additional, Notarangelo, Luigi D, additional, and Imberti, L, additional
- Published
- 2003
- Full Text
- View/download PDF
55. Pneumocystis carinii pneumonitis in haemophagocytic lymphohistiocytosis
- Author
-
Pasic, S, primary, Jankovic, I, additional, Rosic, R, additional, and Ognjanovic, M, additional
- Published
- 2001
- Full Text
- View/download PDF
56. Severe combined immunodeficiency in Yugoslavia
- Author
-
PASIC, S, primary
- Published
- 1998
- Full Text
- View/download PDF
57. Disseminated Bacillus Calmette‐Guérin infection in a girl with hyperimmunoglobulin E syndrome
- Author
-
Pasic, S, primary, Lilic, D, additional, Pejnovic, N, additional, Vojvodic, D, additional, Simic, R, additional, and Abinun, M, additional
- Published
- 1998
- Full Text
- View/download PDF
58. Immunodeficiency with Hyper-Immunoglobulin M in an Infant Who Had Cryptosporidiosis Associated with Interferon Deficiency
- Author
-
Pasic, S., primary
- Published
- 1996
- Full Text
- View/download PDF
59. Treatment of the X-linked lymphoproliferative, Griscelli and Chédiak-Higashi syndromes by HLH directed therapy.
- Author
-
Trottestam H, Beutel K, Meeths M, Carlsen N, Heilmann C, Pasic S, Webb D, Hasle H, and Henter JI
- Published
- 2009
- Full Text
- View/download PDF
60. The Pediatric Rheumatology International Trials Organization/American College of Rheumatology provisional criteria for the evaluation of response to therapy in juvenile systemic lupus erythematosus: prospective validation of the definition of improvement.
- Author
-
Ruperto N, Ravelli A, Oliveira S, Alessio M, Mihaylova D, Pasic S, Cortis E, Apaz M, Burgos-Vargas R, Kanakoudi-Tsakalidou F, Norambuena X, Corona F, Gerloni V, Hagelberg S, Aggarwal A, Dolezalova P, Saad CM, Bae SC, Vesely R, and Avcin T
- Published
- 2006
61. Prenatal diagnosis of RAG-deficient Omenn syndrome.
- Author
-
Villa, Anna, Bozzi, Fabio, Sobacchi, Cristina, Strina, Dario, Fasth, Andres, Pasic, Srdjan, Notarangelo, Luigi D., Vezzoni, Paolo, Villa, A, Bozzi, F, Sobacchi, C, Strina, D, Fasth, A, Pasic, S, Notarangelo, L D, and Vezzoni, P
- Published
- 2000
- Full Text
- View/download PDF
62. Measurement of the component of the Ge-detector response function due to escape of secondary radiation
- Author
-
Pasic, S. and Ilakovac, K.
- Published
- 1998
- Full Text
- View/download PDF
63. Performance of the birmingham vasculitis activity score and disease extent index in childhood vasculitides
- Author
-
Demirkaya, E., Ozen, S., Pistorio, A., Galasso, R., Ravelli, A., Hasija, R., Baskin, E., Dressler, F., Fischbach, M., Consuegra, J. G., Iagaru, N., Pasic, S., Scarpato, S., Rossum, M. A. J., Apaz, M. T., Barash, J., Calcagno, G., Gonzalez, B., Hoppenreijs, E., Ioseliani, M., Mazur-Zielinska, H., Vougiouka, O., Wulffraat, N., Luqmani, R., Martini, A., NICOLINO RUPERTO, Dolezalova, P., Amsterdam institute for Infection and Immunity, and Paediatric Infectious Diseases / Rheumatology / Immunology
- Abstract
Objectives. To evaluate the performance of the Birmingham Vasculitis Activity Score (BVAS) v3 and the Disease Extent Index (DEI) for the assessment of disease activity in 4 primary childhood (c-) systemic vasculitides. Methods. Patients fulfilling the EU-LAR/PRINTO/PRES (Ankara) c-vasculitis classification criteria for Henoch-Schonlein purpura (HSP), childhood (c) polyarteritis nodosa (c-PAN), c-Wegener's granulomatosis (c-WG) and c-Takayasu arteritis (c-TA) with disease duration at the time of diagnosis 1.5) for both tools. The performance characteristics of the BVAS and DEI with the unweighted methods were comparable. Conclusion. This study demonstrates that both the BVAS and DEI are valid tools for the assessment of the level of disease activity in a large cohort of childhood acute and chronic vasculitides
64. Necrobiotic cutaneous granulomas in Nijmegen breakage syndrome
- Author
-
Pasic, S., Lidija Kandolf-Sekulovic, Djuricic, S., Zolotarevski, L., Simic, R., and Abinun, M.
- Subjects
Granuloma ,Necrobiotic Disorders ,Humans ,Female ,Child ,Nijmegen Breakage Syndrome ,Skin
65. Expansion of immunoglobulin-secreting cells and defects in B cell tolerance in Rag-dependent immunodeficiency
- Author
-
Walter, J E, Rucci, F, Patrizi, L, Recher, M, Regenass, S, Paganini, T, Keszei, M, Pessach, I, Lang, P A, Poliani, P L, Giliani, S, Al-Herz, W, Cowan, M J, Puck, J M, Bleesing, J, Niehues, T, Schuetz, C, Malech, H, DeRavin, S S, Facchetti, F, Gennery, A R, Andersson, E, Kamani, N R, Sekiguchi, J, Alenezi, H M, Chinen, J, Dbaibo, G, ElGhazali, G, Fontana, A, Pasic, S, Detre, C, Terhorst, C, Alt, F W, and Notarangelo, L D
- Subjects
3. Good health
66. Anti-vaccinationists
- Author
-
Pašić Srđan
- Subjects
nema ,Medicine - Abstract
nema
- Published
- 2017
- Full Text
- View/download PDF
67. Local bacillus Calmette-Guérin infection in hyperimmunoglobulin-E syndrome.
- Author
-
Pasic, S.
- Subjects
- *
JUVENILE diseases , *IMMUNOGLOBULIN E , *BCG vaccines - Abstract
Reports on a 14-month-old male infant with hyperimmunoglobulin-E syndrome (HIES) who developed persistent/local infection after bacillus Calmette-Guerin (BCG) immunization in infancy. Characteristics of HIES; Complications of BCG immunization; Spontaneous resolution of the persistent/local BCG infection.
- Published
- 2002
- Full Text
- View/download PDF
68. Periodic fever syndromes in Eastern and Central European countries: results of a pediatric multinational survey
- Author
-
Stefan Mariana, Harjaček Miroslav, Wolska-Kuśnierz Beata, Čižnar Peter, Pašić Srdjan, Sedivà Anna, Constantin Tamas, Dolezalovà Pavla, Toplak Nataša, Ruperto Nicolino, Gattorno Marco, and Avčin Tadej
- Subjects
Pediatrics ,RJ1-570 ,Diseases of the musculoskeletal system ,RC925-935 - Abstract
Abstract Objective To analyze the prevalence of diagnosed and suspected autoinflammatory diseases in Eastern and Central European (ECE) countries, with a particular interest on the diagnostic facilities in these countries. Methods Two different strategies were used to collect data on patients with periodic fever syndromes from ECE countries- the Eurofever survey and collection of data with the structured questionnaire. Results Data from 35 centers in 14 ECE countries were collected. All together there were 11 patients reported with genetically confirmed familial Mediterranean fever (FMF), 14 with mevalonate-kinase deficiency (MKD), 11 with tumor necrosis factor receptor associated periodic syndrome (TRAPS) and 4 with chronic infantile neurological cutaneous and articular syndrome (CINCA). Significantly higher numbers were reported for suspected cases which were not genetically tested. All together there were 49 suspected FMF patients reported, 24 MKD, 16 TRAPS, 7 CINCA and 2 suspected Muckle-Wells syndrome (MWS) patients. Conclusions The number of genetically confirmed patients with periodic fever syndromes in ECE countries is very low. In order to identify more patients in the future, it is important to organize educational programs for increasing the knowledge on these diseases and to establish a network for genetic testing of periodic fever syndromes in ECE countries.
- Published
- 2010
- Full Text
- View/download PDF
69. Pancreatitis and atypical Kawasaki disease
- Author
-
Paunovic Zoran, Ristic Goran, Prokic Dragan, and Pasic Srdjan
- Subjects
Pediatrics ,RJ1-570 ,Diseases of the musculoskeletal system ,RC925-935 - Abstract
Abstract We report on pediatric patient with clinical and laboratory evidence of pancreatitis at onset of atypical Kawasaki disease (KD). In KD pancreatic inflammation was described previously, but clinical pancreatitis was rarely reported and its true incidence is unknown. In febrile pediatric patients suspected to have KD, but not fulfilling classical diagnostic criteria, signs of pancreatic inflammation may help in making correct diagnosis. Further analysis of cases with atypical KD developing pancreatitis may reveal if signs of pancreatic inflammation can be used as supportive diagnostic finding.
- Published
- 2010
- Full Text
- View/download PDF
70. An accurate absolute-scale measurement of bremsstrahlung following absorption of incident X- and g-rays
- Author
-
Pasic, S. and Ilakovac, K.
- Published
- 2001
- Full Text
- View/download PDF
71. Therapeutic approaches for the treatment of new onset and flared juvenile systemic lupus erythematosus with active renal disease: an international multicenter PRINTO study.
- Author
-
Miettunen, P, Pistorio, A, Ravelli, A, Oliveira, S, Alessio, M, Cuttica, R, Mihaylova, D, Espada, G, Pasic, S, Cortis, E, Ozen, S, Porras, O, Sztajnbok, F, Palmisani, E, Martini, A, and Ruperto, N
- Subjects
SYSTEMIC lupus erythematosus - Abstract
An abstract of the conference paper "Therapeutic approaches for the treatment of new onset and flared juvenile systemic lupus erythematosus with active renal disease: an international multicenter PRINTO study," by S. Pasic, and colleagues, is presented.
- Published
- 2011
- Full Text
- View/download PDF
72. Clinical heterogeneity and diagnostic delay of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome
- Author
-
Alberto Vitali, Federica Ortolani, Roberto Rusconi, Srdjan Pasic, Rosa Bacchetta, Fabio Buzi, Donatella Capalbo, Annarosa Soresina, Andrea Taddio, Vassilios Lougaris, Claudio Pignata, Lucia Dora Notarangelo, Mariacarolina Salerno, Małgorzata Pac, Giorgio Radetti, Monique de Vroede, Giuseppe Maggiore, Silvana Martino, Sanal Ozden, Raffaele Badolato, Nella Augusta Greggio, Giovanna Weber, Cinzia Mazza, Alessandro Plebani, Sara Sebnem Kilic, Luigi D. Notarangelo, Mazza, C., Buzi, Paola, Ortolani, F., Karabchuk, Vitali, Notarangelo, L. D., Weber, G., Bacchetta, R., Soresina, A., Lougaris, V., Greggio, N., Taddio, A., Pasic, S., de Vroede, M., Pac, M., Kilic, S. S., Ozden, S., Rusconi, R., Martino, S., Capalbo, D., Salerno, M., Pignata, C., Radetti, G., Maggiore, G., Plebani, A., Notarangelo, Ld., Badolato, R., Çocuk Sağlığı ve Hastalıkları, Buzi, F., Vitali, A., Greggio, N. A., Taddio, Andrea, Uludağ Üniversitesi/Tıp Fakültesi/Pediatri Anabilim Dalı., Kılıç, Sara Şebnem, AAH-1658-2021, Mazza, C, Buzi, F, Ortolani, F, Vitali, A, Notarangelo, Ld, Weber, Giovanna, Bacchetta, R, Soresina, A, Lougaris, V, Greggio, Na, Taddio, A, Pasic, S, de Vroede, M, Pac, M, Kilic, S, Ozden, S, Rusconi, R, Martino, S, Capalbo, D, Salerno, M, Pignata, C, Radetti, G, Maggiore, G, and Plebani, A
- Subjects
Time Factors ,Autoimmunity ,Endocrinopathy ,Disease ,Type-1 ,medicine.disease_cause ,Mucocutaneous Candidiasis ,Homozygosity ,Genetic heterogeneity ,0302 clinical medicine ,Immunology and Allergy ,Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy ,Chronic mucocutaneous candidiasis ,Child ,Polyendocrinopathies, Autoimmune ,Priority journal ,0303 health sciences ,Heterozygosity ,Candidiasis ,Genetic analysis ,Homozygote ,Autoimmune polyendocrinopathy ,Middle Aged ,Autoimmune regulator ,Common ,3. Good health ,Child, Preschool ,APECED, diagnostic tool, children ,Mutations ,diagnostic tool ,Human ,Adult ,Heterozygote ,animal structures ,Adolescent ,Clinical article ,Immunology ,Socio-culturale ,030209 endocrinology & metabolism ,APECED, DIAGNOSIS ,DIAGNOSIS ,Article ,03 medical and health sciences ,Young Adult ,children ,medicine ,Humans ,Gene mutation ,Preschool ,Autoantibodies ,030304 developmental biology ,Gene amplification ,Hepatitis ,business.industry ,Protein ,Dystrophy ,Disease type-ı ,medicine.disease ,Polyendocrinopathies ,Autoimmune regulator protein ,Preschool child ,Regulator aire gene ,Type 1 Autoimmune Polyendocrinopathy Syndrome ,Regulator ,Central Tolerance ,Mutation ,Genetic association ,School child ,business ,Autoimmune ,APECED - Abstract
Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare autosomal recessive organ-specific autoimmune disorder that is characterized by a variable combination of (i) chronic mucocutaneous candidiasis, (ii) polyendocrinopathy and/or hepatitis and (iii) dystrophy of the dental enamel and nails. We analyzed the AIRE (autoimmune regulator) gene in subjects who presented any symptom that has been associated with APECED, including candidiasis and autoimmune endocrinopathy. We observed that 83.3% of patients presented at least two of the three typical manifestations of APECED, while the remaining 16.7% of patients showed other signs of the disease. Analysis of the genetic diagnosis of these subjects revealed that a considerable delay occurs in the majority of patients between the appearance of symptoms and the diagnosis. Overall, the mean diagnostic delay in our patients was 10.2 years. These results suggest that molecular analysis of AIRE should be performed in patients with relapsing mucocutaneous candidiasis for early identification of APECED. Fondazione Cariplo Fondazione Telethon European Commission (FP7 HLH-cure) (201461) Ministry of Education, Universities and Research (MIUR) Research Projects of National Relevance (PRIN) (2007ACZMMZ_005) Seventh Framework Programme (201461)
- Published
- 2011
73. X-linked lymphoproliferative disease due to SAP/SH2D1A deficiency: a multicenter study on the manifestations, management and outcome of the disease
- Author
-
Claire, Booth, Kimberly C, Gilmour, Paul, Veys, Andrew R, Gennery, Mary A, Slatter, Helen, Chapel, Paul T, Heath, Colin G, Steward, Owen, Smith, Anna, O'Meara, Hilary, Kerrigan, Nizar, Mahlaoui, Marina, Cavazzana-Calvo, Alain, Fischer, Despina, Moshous, Stephane, Blanche, Jana, Pachlopnik Schmid, Jana, Pachlopnick-Schmid, Sylvain, Latour, Genevieve, de Saint-Basile, Michael, Albert, Gundula, Notheis, Nikolaus, Rieber, Brigitte, Strahm, Henrike, Ritterbusch, Arjan, Lankester, Nico G, Hartwig, Isabelle, Meyts, Alessandro, Plebani, Annarosa, Soresina, Andrea, Finocchi, Claudio, Pignata, Emilia, Cirillo, Sonia, Bonanomi, Christina, Peters, Krzysztof, Kalwak, Srdjan, Pasic, Petr, Sedlacek, Janez, Jazbec, Hirokazu, Kanegane, Kim E, Nichols, I Celine, Hanson, Neena, Kapoor, Elie, Haddad, Morton, Cowan, Sharon, Choo, Joanne, Smart, Peter D, Arkwright, Hubert B, Gaspar, Pediatrics, Booth, C., Gilmour, K. C., Veys, P., Gennery, A. R., Slatter, M. A., Chapel, H., Heath, P. T., Steward, C. G., Smith, O., O'Meara, A., Kerrigan, H., Mahlaoui, N., Cavazzana Calvo, M., Fischer, A., Moshous, D., Blanche, S., Pachlopnik Schmid, J., Latour, S., de Saint Basile, G., Albert, M., Notheis, G., Rieber, N., Strahm, B., Ritterbusch, H., Lankester, A., Hartwig, N. G., Meyts, I., Plebani, A., Soresina, A., Finocchi, A., Pignata, Claudio, Cirillo, E., Bonanomi, S., Peters, C., Kalwak, K., Pasic, S., Sedlacek, P., Jazbec, J., Kanegane, H., Nichols, K. E., Hanson, I. C., Kapoor, N., Haddad, E., Cowan, M., Choo, S., Smart, J., Arkwright, P. D., and Gaspar, H. B.
- Subjects
Male ,Pediatrics ,Epstein-Barr Virus Infections ,Herpesvirus 4, Human ,Clinical Trials and Observations ,medicine.medical_treatment ,Hematopoietic stem cell transplantation ,medicine.disease_cause ,Biochemistry ,0302 clinical medicine ,Signaling Lymphocytic Activation Molecule Family Member 1 ,hemic and lymphatic diseases ,Antineoplastic Combined Chemotherapy Protocols ,Medicine ,X-Linked Lymphoproliferative Syndrome ,Signaling Lymphocytic Activation Molecule Associated Protein ,Child ,Immunodeficiency ,0303 health sciences ,Hematopoietic Stem Cell Transplantation ,Intracellular Signaling Peptides and Proteins ,Hematology ,Middle Aged ,3. Good health ,Survival Rate ,Child, Preschool ,Female ,SAP ,Adult ,medicine.medical_specialty ,Adolescent ,Immunology ,Lymphoproliferative disorders ,Receptors, Cell Surface ,XLP, SAP ,Lymphohistiocytosis, Hemophagocytic ,03 medical and health sciences ,Young Adult ,Antigens, CD ,XLP ,Humans ,Survival rate ,030304 developmental biology ,Settore MED/38 - Pediatria Generale e Specialistica ,Hemophagocytic lymphohistiocytosis ,business.industry ,Infant, Newborn ,X-linked lymphoproliferative disease ,Infant ,Cell Biology ,Immune dysregulation ,medicine.disease ,stem-cell transplantation barr-virus infection hemophagocytic lymphohistiocytosis cutting edge t-cells lymphocytic vasculitis encoding gene sap activation mononucleosis ,Lymphoproliferative Disorders ,Mutation ,business ,030215 immunology - Abstract
X-linked lymphoproliferative disease (XLP1) is a rare immunodeficiency characterized by severe immune dysregulation and caused by mutations in the SH2D1A/SAP gene. Clinical manifestations are varied and include hemophagocytic lymphohistiocytosis (HLH), lymphoma and dysgammaglobulinemia, often triggered by Epstein-Barr virus infection. Historical data published before improved treatment regimens shows very poor outcome. We describe a large cohort of 91 genetically defined XLP1 patients collected from centers worldwide and report characteristics and outcome data for 43 patients receiving hematopoietic stem cell transplant (HSCT) and 48 untransplanted patients. The advent of better treatment strategies for HLH and malignancy has greatly reduced mortality for these patients, but HLH still remains the most severe feature of XLP1. Survival after allogeneic HSCT is 81.4% with good immune reconstitution in the large majority of patients and little evidence of posttransplant lymphoproliferative disease. However, survival falls to 50% in patients with HLH as a feature of disease. Untransplanted patients have an overall survival of 62.5% with the majority on immunoglobulin replacement therapy, but the outcome for those untransplanted after HLH is extremely poor (18.8%). HSCT should be undertaken in all patients with HLH, because outcome without transplant is extremely poor. The outcome of HSCT for other manifestations of XLP1 is very good, and if HSCT is not undertaken immediately, patients must be monitored closely for evidence of disease progression.
- Published
- 2011
74. Wiskott-Aldrich syndrome: a study of 577 patients defines the genotype as a biomarker for disease severity and survival.
- Author
-
Vallée TC, Glasmacher JS, Buchner H, Arkwright PD, Behrends U, Bondarenko A, Browning MJ, Buchbinder D, Cattoni A, Chernyshova L, Ciznar P, Cole T, Czogała W, Dueckers G, Edgar JDM, Erbey F, Fasth A, Ferrua F, Formankova R, Gambineri E, Gennery AR, Goldman FD, Gonzalez-Granado LI, Heilmann C, Heiskanen-Kosma T, Juntti H, Kainulainen L, Kanegane H, Karaca NE, Kilic SS, Klein C, Kołtan S, Kondratenko I, Meyts I, Nasrullayeva GM, Notarangelo LD, Pasic S, Pellier I, Pignata C, Misbah S, Schulz A, Segundo GR, Shcherbina A, Slatter M, Sokolic R, Soler-Palacin P, Stepensky P, van Montfrans JM, Ryhänen S, Wolska-Kuśnierz B, Ziegler JB, Zhao X, Aiuti A, Ochs HD, and Albert MH
- Subjects
- Humans, Adolescent, Child, Male, Female, Child, Preschool, Adult, Retrospective Studies, Infant, Young Adult, Biomarkers, Hematopoietic Stem Cell Transplantation, Severity of Illness Index, Wiskott-Aldrich Syndrome Protein genetics, Follow-Up Studies, Middle Aged, Prognosis, Survival Rate, Wiskott-Aldrich Syndrome genetics, Wiskott-Aldrich Syndrome diagnosis, Wiskott-Aldrich Syndrome therapy, Genotype
- Abstract
Abstract: Wiskott-Aldrich syndrome (WAS) is a multifaceted monogenic disorder with a broad disease spectrum and variable disease severity and a variety of treatment options including allogeneic hematopoietic stem cell transplantation (HSCT) and gene therapy (GT). No reliable biomarker exists to predict disease course and outcome for individual patients. A total of 577 patients with a WAS variant from 26 countries and a median follow-up of 8.9 years (range, 0.3-71.1), totaling 6118 patient-years, were included in this international retrospective study. Overall survival (OS) of the cohort (censored at HSCT or GT) was 82% (95% confidence interval, 78-87) at age 15 years and 70% (61-80) at 30 years. The type of variant was predictive of outcome: patients with a missense variant in exons 1 or 2 or with the intronic hot spot variant c.559+5G>A (class I variants) had a 15-year OS of 93% (89-98) and a 30-year OS of 91% (86-97), compared with 71% (62-81) and 48% (34-68) in patients with any other variant (class II; P < .0001). The cumulative incidence rates of disease-related complications such as severe bleeding (P = .007), life-threatening infection (P < .0001), and autoimmunity (P = .004) occurred significantly later in patients with a class I variant. The cumulative incidence of malignancy (P = .6) was not different between classes I and II. It confirms the spectrum of disease severity and quantifies the risk for specific disease-related complications. The class of the variant is a biomarker to predict the outcome for patients with WAS.
- Published
- 2024
- Full Text
- View/download PDF
75. Exploratory genetic analysis in children with autism spectrum disorder and other developmental disorders using whole exome sequencing.
- Author
-
Hamzic E, Spahic L, Pistoljevic N, Dzanko E, Pasic S, Kadric L, Serdarevic F, and Hajdarpasic A
- Subjects
- Humans, Male, Female, Child, Preschool, Child, Developmental Disabilities genetics, Developmental Disabilities diagnosis, Genetic Predisposition to Disease, Autism Spectrum Disorder genetics, Autism Spectrum Disorder diagnosis, Exome Sequencing methods
- Abstract
Developmental disorders (DDs), such as autism spectrum disorder (ASD), incorporate various conditions; once identified, further diagnostics are necessary to specify their type and severity. The aim of this exploratory study was to identify genetic variants that can help differentiate ASD early from other DDs. We selected 36 children (mean age 60.1 months) with DDs using Developmental Behavioral Scales (DBS) through "EDUS-Education for All", an organization providing services for children with developmental disorders in Bosnia and Herzegovina. We further rated children's autistic traits with the preschool version of the Childhood Autism Rating Scale, second edition (CARS-II). We defined ASD if scores were >25.5 and other DDs if scores were <25.5. Diagnosis of ASD and DD were independently confirmed by child psychiatrists. Whole exome sequencing (WES) was performed by Veritas Genetics, USA, using Illumina NovaSeq 6000 (Illumina Inc., San Diego, CA, USA) next-generation sequencing (NGS) apparatus. We tested genetic association by applying SKAT-O, which optimally combines the standard Sequence Kernel Association Test (SKAT) and burden tests to identify rare variants associated with complex traits in samples of limited power. The analysis yielded seven genes (DSE, COL10A1, DLK2, CSMD1, FAM47E, PPIA, PYDC2) to potentially differentiate observed phenotypic characteristics between our cohort participants with ASD and other DDs. Our exploratory study in a small sample of participants with ASD and other DDs contributed to gene discovery in differentiating ASD from DDs. A replication study is needed in a larger sample to confirm our results.
- Published
- 2024
- Full Text
- View/download PDF
76. Mechanisms of redox balance and inflammatory response after the use of methylprednisolone in children with multisystem inflammatory syndrome associated with COVID-19.
- Author
-
Krasic S, Vukomanovic V, Ninic S, Pasic S, Samardzija G, Mitrovic N, Cehic M, Nesic D, and Bajcetic M
- Subjects
- Male, Female, Humans, Antioxidants, Methylprednisolone therapeutic use, Prospective Studies, SARS-CoV-2, Oxidation-Reduction, Superoxide Dismutase, COVID-19 complications, Connective Tissue Diseases
- Abstract
Background: Multisystem inflammatory syndrome in children (MIS-C) associated with being infected with coronavirus-19 (COVID-19) is a life-threatening condition resulting from cytokine storm, increased synthesis of reactive oxygen species (ROSs), and hyperinflammation occurring in genetically predisposed children following an infection with SARS-CoV-2., Aim: The primary aims of our study were to identify changes in the activity of antioxidant enzymes in erythrocytes and total oxidative status in plasma after being treated with methylprednisolone (MP)., Methods: A prospective cohort study of 67 children (56.7% male) under 18 with MIS-C being treated with MP was conducted at the Mother and Child Health Institute from January 2021 to April 2022. The impact of the therapy was assessed on the basis of the clinical condition, haematological and biochemical blood parameters, and echocardiographic findings., Results: 59.7% of patients presented cardiovascular (CV) manifestations, while myocardial dysfunction was observed in half of all patients (50.7%). A severe clinical course was observed in 22/67 patients. Children with CV involvement had a significantly higher relative concentration of B lymphocytes and lower relative concentration of NK cells than patients without CV issues (p < 0.001 and p = 0.004, respectively). Patients with severe MIS-C had a lower relative count of NK cells than those with moderate MIS-C (p = 0.015). Patients with myocardial dysfunction had a higher total oxidative plasma status (TOPS) than children without (p = 0.05), which implicates pronounced oxidative stress in the former cohort. In patients with shock, lower erythrocytes superoxide dismutase (SOD) activity was observed on admission compared to patients without shock (p = 0.04). After MP was administered, TOPS was significantly reduced, while catalase (CAT) and SOD activity increased significantly. Treatment failure (TF) was observed in 6 patients, only females (p=0.005). These patients were younger (p=0.05) and had lower CAT activity on admission (p=0.04) than patients with favorable treatment responses. In the group of patients with TF, TOPS increased after treatment (before 176.2 ± 10.3 mV, after 199.0 ± 36.7 mV)., Conclusion: MP leads to rapid modulation of TOPS and increases the activity of antioxidant enzymes in erythrocytes resulting in clinical and echocardiographic improvement. Based on the observed changes in the activity of the antioxidant enzymes, we can conclude that s hydrogen peroxide is the dominant ROS in patients with MIS-C. Patients with TF showed reduced CAT activity, whereas the treatment with MP led to pronounced oxidation. This implies that low CAT activity may be a contraindication for using MP., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Krasic, Vukomanovic, Ninic, Pasic, Samardzija, Mitrovic, Cehic, Nesic and Bajcetic.)
- Published
- 2023
- Full Text
- View/download PDF
77. Analysis of cardiac manifestation and treatment of multisystem inflammatory syndrome in children related to SARS-CoV-2.
- Author
-
Krasic S, Ninic S, Prijic S, Popovic S, Pasic S, Petrovic G, Zec B, Ristic S, Nesic D, Nikolic L, and Vukomanovic V
- Subjects
- Child, Humans, Immunoglobulins, Intravenous therapeutic use, Retrospective Studies, Stroke Volume, Ventricular Function, Left, Child, Preschool, COVID-19 complications, SARS-CoV-2
- Abstract
Cardiovascular manifestations are common (35-100%) in the multisystem inflammatory syndrome in children. Our study aimed to analyze treatment impact and cardiovascular involvement in patients with multisystem inflammatory syndrome in children. The retrospective cohort included 81 patients treated between April 2020 and December 2021 (9.3±4.6 years). Elevated cardiac troponin I and pro-B-type natriuretic peptide were observed in 34.2% and 88.5% of patients, respectively. Myocardial dysfunction was observed in 50.6%. Children older than 10 years had a 4-fold increased risk of myocardial dysfunction (odds ratio [OR] 3.6, 95% confidence interval [CI] 1.4-8.9; p=0.006). A moderate negative correlation was proved between left ventricle ejection fraction and C-reactive protein (rr = - 0.48; p < 0.001). More than one-fifth of the patients presented with shock. Coronary artery dilatation was observed in 6.2% of patients. Mild pericardial effusion was detected in 27.1% of children. On standard electrocardiogram, 52.6% of children had negative T waves in the inferior and/or precordial leads; transient QTc prolongation was registered in 43% of patients. Treatment failure was observed in 19 patients. Patients initially treated with intravenous immunoglobulins had 10-fold higher chances for treatment failure than patients treated with corticosteroids (OR 10.6, 95% CI 3,18 - 35.35; p < 0.001). Cardiovascular manifestations were observed in more than half of the patients, with acute myocardial dysfunction being the most common, especially in children older than 10 years. We established a negative association between the degree of elevation of inflammatory markers and left ventricular ejection fraction. Patients treated with intravenous immunoglobulins who had cardiovascular manifestations had treatment failures more frequently than patients treated with corticosteroids.
- Published
- 2023
- Full Text
- View/download PDF
78. Association of Antiphospholipid Antibodies with Clinical Manifestations in Children with Systemic Lupus Erythematosus.
- Author
-
Petrovic G, Pasic S, and Soldatovic I
- Abstract
Background: The aim of the study is to evaluate the effect of the presence of antiphospholipid antibodies on the clinical and laboratory manifestations, disease activity and outcomes of the disease in patients with childhood-onset systemic lupus erythematosus (cSLE)., Methods: We conducted a 10-year cross-sectional study with a retrospective analysis of clinical and laboratory parameters and outcome of the disease (kidney, nervous system involvement, thrombosis). For the purpose of the study, patients were divided into cohort groups based on the presence of antiphospholipid antibodies (aPLA), named the aPLA positive group, or their absence, named the aPLA negative group. Values of aPLA were defined in reference laboratories. The disease activity was measured by the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score, whereas tissue damage degree was measured by Systemic Lupus International Collaborating Clinics/American College of Rheumatology-Damage Index (SLICC/ACR DI; SDI; DI)., Results: Research in our center showed that patients with cSLE often had hematological, cutaneous, and non-thrombotic neurological manifestations. Antiphospholipid antibodies may be present transiently or permanently. A significant change in the titer value was observed in the IgG isotype of aCLA. The presence of higher values of IgM β2GP1 at the beginning indicates that higher disease activity can be expected. Higher disease activity correlates with greater tissue damage. Additionally, it has been shown that aPLA positive patients have two and a half times higher risk of tissue damage than aPLA negative ones., Conclusion: Our study shows that the presence of antiphospholipid antibodies in patients with childhood onset systemic lupus erythematosus may indicate a higher risk of tissue damage, but since it is a rare disease in childhood, prospective and multicenter studies are necessary to assess the importance of the presence of these antibodies.
- Published
- 2023
- Full Text
- View/download PDF
79. Care of patients with inborn errors of immunity in thirty J Project countries between 2004 and 2021.
- Author
-
Abolhassani H, Avcin T, Bahceciler N, Balashov D, Bata Z, Bataneant M, Belevtsev M, Bernatowska E, Bidló J, Blazsó P, Boisson B, Bolkov M, Bondarenko A, Boyarchuk O, Bundschu A, Casanova JL, Chernishova L, Ciznar P, Csürke I, Erdős M, Farkas H, Fomina DS, Galal N, Goda V, Guner SN, Hauser P, Ilyina NI, Iremadze T, Iritsyan S, Ismaili-Jaha V, Jesenak M, Kelecic J, Keles S, Kindle G, Kondratenko IV, Kostyuchenko L, Kovzel E, Kriván G, Kuli-Lito G, Kumánovics G, Kurjane N, Latysheva EA, Latysheva TV, Lázár I, Markelj G, Markovic M, Maródi L, Mammadova V, Medvecz M, Miltner N, Mironska K, Modell F, Modell V, Mosdósi B, Mukhina AA, Murdjeva M, Műzes G, Nabieva U, Nasrullayeva G, Naumova E, Nagy K, Onozó B, Orozbekova B, Pac M, Pagava K, Pampura AN, Pasic S, Petrosyan M, Petrovic G, Pocek L, Prodeus AP, Reisli I, Ress K, Rezaei N, Rodina YA, Rumyantsev AG, Sciuca S, Sediva A, Serban M, Sharapova S, Shcherbina A, Sitkauskiene B, Snimshchikova I, Spahiu-Konjusha S, Szolnoky M, Szűcs G, Toplak N, Tóth B, Tsyvkina G, Tuzankina I, Vlasova E, and Volokha A
- Subjects
- Infant, Newborn, Humans, Administration, Intravenous, Educational Status, Egypt, Europe, Immunoglobulin G
- Abstract
Introduction: The J Project (JP) physician education and clinical research collaboration program was started in 2004 and includes by now 32 countries mostly in Eastern and Central Europe (ECE). Until the end of 2021, 344 inborn errors of immunity (IEI)-focused meetings were organized by the JP to raise awareness and facilitate the diagnosis and treatment of patients with IEI., Results: In this study, meeting profiles and major diagnostic and treatment parameters were studied. JP center leaders reported patients' data from 30 countries representing a total population of 506 567 565. Two countries reported patients from JP centers (Konya, Turkey and Cairo University, Egypt). Diagnostic criteria were based on the 2020 update of classification by the IUIS Expert Committee on IEI. The number of JP meetings increased from 6 per year in 2004 and 2005 to 44 and 63 in 2020 and 2021, respectively. The cumulative number of meetings per country varied from 1 to 59 in various countries reflecting partly but not entirely the population of the respective countries. Altogether, 24,879 patients were reported giving an average prevalence of 4.9. Most of the patients had predominantly antibody deficiency (46,32%) followed by patients with combined immunodeficiencies (14.3%). The percentages of patients with bone marrow failure and phenocopies of IEI were less than 1 each. The number of patients was remarkably higher that those reported to the ESID Registry in 13 countries. Immunoglobulin (IgG) substitution was provided to 7,572 patients (5,693 intravenously) and 1,480 patients received hematopoietic stem cell therapy (HSCT). Searching for basic diagnostic parameters revealed the availability of immunochemistry and flow cytometry in 27 and 28 countries, respectively, and targeted gene sequencing and new generation sequencing was available in 21 and 18 countries. The number of IEI centers and experts in the field were 260 and 690, respectively. We found high correlation between the number of IEI centers and patients treated with intravenous IgG (IVIG) (correlation coefficient, cc, 0,916) and with those who were treated with HSCT (cc, 0,905). Similar correlation was found when the number of experts was compared with those treated with HSCT. However, the number of patients treated with subcutaneous Ig (SCIG) only slightly correlated with the number of experts (cc, 0,489) and no correlation was found between the number of centers and patients on SCIG (cc, 0,174)., Conclusions: 1) this is the first study describing major diagnostic and treatment parameters of IEI care in countries of the JP; 2) the data suggest that the JP had tremendous impact on the development of IEI care in ECE; 3) our data help to define major future targets of JP activity in various countries; 4) we suggest that the number of IEI centers and IEI experts closely correlate to the most important treatment parameters; 5) we propose that specialist education among medical professionals plays pivotal role in increasing levels of diagnostics and adequate care of this vulnerable and still highly neglected patient population; 6) this study also provides the basis for further analysis of more specific aspects of IEI care including genetic diagnostics, disease specific prevalence, newborn screening and professional collaboration in JP countries., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Abolhassani, Avcin, Bahceciler, Balashov, Bata, Bataneant, Belevtsev, Bernatowska, Bidló, Blazsó, Boisson, Bolkov, Bondarenko, Boyarchuk, Bundschu, Casanova, Chernishova, Ciznar, Csürke, Erdős, Farkas, Fomina, Galal, Goda, Guner, Hauser, Ilyina, Iremadze, Iritsyan, Ismaili-Jaha, Jesenak, Kelecic, Keles, Kindle, Kondratenko, Kostyuchenko, Kovzel, Kriván, Kuli-Lito, Kumánovics, Kurjane, Latysheva, Latysheva, Lázár, Markelj, Markovic, Maródi, Mammadova, Medvecz, Miltner, Mironska, Modell, Modell, Mosdósi, Mukhina, Murdjeva, Műzes, Nabieva, Nasrullayeva, Naumova, Nagy, Onozó, Orozbekova, Pac, Pagava, Pampura, Pasic, Petrosyan, Petrovic, Pocek, Prodeus, Reisli, Ress, Rezaei, Rodina, Rumyantsev, Sciuca, Sediva, Serban, Sharapova, Shcherbina, Sitkauskiene, Snimshchikova, Spahiu-Konjusha, Szolnoky, Szűcs, Toplak, Tóth, Tsyvkina, Tuzankina, Vlasova and Volokha.)
- Published
- 2022
- Full Text
- View/download PDF
80. Case Report: Early Onset Systemic Lupus Erythematosus Due to Hereditary C1q Deficiency Treated With Fresh Frozen Plasma.
- Author
-
Zecevic M, Minic A, Pasic S, Perovic V, and Prohászka Z
- Abstract
Background: Hereditary C1q deficiency is associated with early-onset autoimmunity causing SLE or SLE-like disease as well as increased risk for infections with encapsulated bacteria. It is a rare genetic condition inherited in an autosomal recessive manner, caused by mutations in C1q genes. Treatment and management of this rare disease are very complex and include prophylactic vaccination, antibiotics, and immunosuppressive drugs. There are two possible modalities for the replacement of the missing protein: regular fresh frozen plasma (FFP) administration and allogeneic hematopoietic stem cell transplant because the protein is derived from monocytes. Replacing C1q with FFP is being attempted in some patients with success in controlling the disease and in avoiding flare. Case Report: We report a case of sixteen-month-old girl with ulcerations in her mouth, skin erythema, and elevated liver enzymes. ANAs were positive, antibodies against dsDNA were negative, but she had positive anti-Smith antibodies. Complement complements C3 and C4 levels were normal. Total complement activity, classical pathway (hemolytic test) was deficient and C1q antigen was below the detection limit supporting the presence of C1q deficiency. The girl has pathogenic homozygous nonsense mutation in C1qC gene, Arg69Ter (c205>T). The initial response to corticosteroid therapy was good. Regular fresh frozen plasma infusions keep her disease under control, and we were able to reduce the dose of corticosteroids. Conclusion: Young patients with cutaneous lesions resembling SLE, early onset of autoimmunity, with normal C3, C4, elevated ANAs, and negative anti-dsDNA, C1q deficiency should be suspected and complement screening tests should be done. It is important to exclude secondary C1q deficiency. FFP in our patient seems to be well tolerated, without any side effects, able to control the disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zecevic, Minic, Pasic, Perovic and Prohászka.)
- Published
- 2021
- Full Text
- View/download PDF
81. Previous liver regeneration induces fibro-protective mechanisms during thioacetamide-induced chronic liver injury.
- Author
-
Gratte FD, Pasic S, Abu Bakar NDB, Gogoi-Tiwari J, Liu X, Carlessi R, Kisseleva T, Brenner DA, Ramm GA, Olynyk JK, and Tirnitz-Parker JEE
- Subjects
- Animals, Cells, Cultured, Chemical and Drug Induced Liver Injury etiology, Chemical and Drug Induced Liver Injury metabolism, Coculture Techniques, Disease Models, Animal, Hepatic Stellate Cells metabolism, Liver metabolism, Liver Cirrhosis etiology, Liver Cirrhosis metabolism, Male, Mice, Mice, Inbred C57BL, Stem Cells metabolism, Chemical and Drug Induced Liver Injury pathology, Hepatic Stellate Cells cytology, Liver cytology, Liver Cirrhosis pathology, Liver Regeneration physiology, Stem Cells cytology, Thioacetamide toxicity
- Abstract
Chronic liver injury is characterised by continuous or repeated epithelial cell loss and inflammation. Hepatic wound healing involves matrix deposition through activated hepatic stellate cells (HSCs) and the expansion of closely associated Ductular Reactions and liver progenitor cells (LPCs), which are thought to give rise to new epithelial cells. In this study, we used the murine thioacetamide (TAA) model to reliably mimic these injury and regeneration dynamics and assess the impact of a recovery phase on subsequent liver injury and fibrosis. Age-matched naïve or 6-week TAA-treated/4-week recovered mice (C57BL/6 J, n = 5-9) were administered TAA for six weeks (C57BL/6 J, n = 5-9). Sera and liver tissues were harvested at key time points to assess liver injury biochemically, by real-time PCR for fibrotic mediators, Sirius Red staining and hydroxyproline assessment for collagen deposition as well as immunofluorescence for inflammatory, HSC and LPC markers. In addition, primary HSCs and the HSC cell line LX-2 were co-cultured with the well-characterised LPC line BMOL and analysed for potential changes in expression of fibrogenic mediators. Our data demonstrate that recovery from a previous TAA insult, with LPCs still present on day 0 of the second treatment, led to a reduced TAA-induced disease progression with less severe fibrosis than in naïve TAA-treated animals. Importantly, primary activated HSCs significantly reduced pro-fibrogenic gene expression when co-cultured with LPCs. Taken together, previous TAA injury established a fibro-protective molecular and cellular microenvironment. Our proof-of principle HSC/LPC co-culture data demonstrate that LPCs communicate with HSCs to regulate fibrogenesis, highlighting a key role for LPCs as regulatory cells during chronic liver disease., (Copyright © 2021 Elsevier Ltd. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
82. The Clinical and Genetic Spectrum of 82 Patients With RAG Deficiency Including a c.256_257delAA Founder Variant in Slavic Countries.
- Author
-
Sharapova SO, Skomska-Pawliszak M, Rodina YA, Wolska-Kuśnierz B, Dabrowska-Leonik N, Mikołuć B, Pashchenko OE, Pasic S, Freiberger T, Milota T, Formánková R, Szaflarska A, Siedlar M, Avčin T, Markelj G, Ciznar P, Kalwak K, Kołtan S, Jackowska T, Drabko K, Gagro A, Pac M, Naumova E, Kandilarova S, Babol-Pokora K, Varabyou DS, Barendregt BH, Raykina EV, Varlamova TV, Pavlova AV, Grombirikova H, Debeljak M, Mersiyanova IV, Bondarenko AV, Chernyshova LI, Kostyuchenko LV, Guseva MN, Rascon J, Muleviciene A, Preiksaitiene E, Geier CB, Leiss-Piller A, Yamazaki Y, Kawai T, Walter JE, Kondratenko IV, Šedivá A, van der Burg M, Kuzmenko NB, Notarangelo LD, Bernatowska E, and Aleinikova OV
- Subjects
- Adolescent, Child, Child, Preschool, Female, Gene Frequency, Humans, Incidence, Infant, Infant, Newborn, Male, Phenotype, Polymorphism, Genetic, Retrospective Studies, Treatment Outcome, Young Adult, DNA-Binding Proteins genetics, Genotype, Homeodomain Proteins genetics, Immunologic Deficiency Syndromes genetics, Nuclear Proteins genetics, Sequence Deletion genetics, White People
- Abstract
Background: Variants in recombination-activating genes ( RAG ) are common genetic causes of autosomal recessive forms of combined immunodeficiencies (CID) ranging from severe combined immunodeficiency (SCID), Omenn syndrome (OS), leaky SCID, and CID with granulomas and/or autoimmunity (CID-G/AI), and even milder presentation with antibody deficiency. Objective: We aim to estimate the incidence, clinical presentation, genetic variability, and treatment outcome with geographic distribution of patients with the RAG defects in populations inhabiting South, West, and East Slavic countries. Methods: Demographic, clinical, and laboratory data were collected from RAG -deficient patients of Slavic origin via chart review, retrospectively. Recombinase activity was determined in vitro by flow cytometry-based assay. Results: Based on the clinical and immunologic phenotype, our cohort of 82 patients from 68 families represented a wide spectrum of RAG deficiencies, including SCID ( n = 20), OS ( n = 37), and LS/CID ( n = 25) phenotypes. Sixty-seven (81.7%) patients carried RAG1 and 15 patients (18.3%) carried RAG2 biallelic variants. We estimate that the minimal annual incidence of RAG deficiency in Slavic countries varies between 1 in 180,000 and 1 in 300,000 live births, and it may vary secondary to health care disparities in these regions. In our cohort, 70% ( n = 47) of patients with RAG1 variants carried p.K86Vfs
* 33 (c.256_257delAA) allele, either in homozygous ( n = 18, 27%) or in compound heterozygous ( n = 29, 43%) form. The majority (77%) of patients with homozygous RAG1 p.K86Vfs* 33 variant originated from Vistula watershed area in Central and Eastern Poland, and compound heterozygote cases were distributed among all Slavic countries except Bulgaria. Clinical and immunological presentation of homozygous RAG1 p.K86Vfs* 33 cases was highly diverse (SCID, OS, and AS/CID) suggestive of strong influence of additional genetic and/or epigenetic factors in shaping the final phenotype. Conclusion: We propose that RAG1 p.K86Vfs* 33 is a founder variant originating from the Vistula watershed region in Poland, which may explain a high proportion of homozygous cases from Central and Eastern Poland and the presence of the variant in all Slavs. Our studies in this cohort of RAG1 founder variants confirm that clinical and immunological phenotypes only partially depend on the underlying genetic defect. As access to HSCT is improving among RAG-deficient patients in Eastern Europe, we anticipate improvements in survival., (Copyright © 2020 Sharapova, Skomska-Pawliszak, Rodina, Wolska-Kuśnierz, Dabrowska-Leonik, Mikołuć, Pashchenko, Pasic, Freiberger, Milota, Formánková, Szaflarska, Siedlar, Avčin, Markelj, Ciznar, Kalwak, Kołtan, Jackowska, Drabko, Gagro, Pac, Naumova, Kandilarova, Babol-Pokora, Varabyou, Barendregt, Raykina, Varlamova, Pavlova, Grombirikova, Debeljak, Mersiyanova, Bondarenko, Chernyshova, Kostyuchenko, Guseva, Rascon, Muleviciene, Preiksaitiene, Geier, Leiss-Piller, Yamazaki, Kawai, Walter, Kondratenko, Šedivá, van der Burg, Kuzmenko, Notarangelo, Bernatowska and Aleinikova.)- Published
- 2020
- Full Text
- View/download PDF
83. Impact of genotype on neutropenia in a large cohort of Serbian patients with glycogen storage disease type Ib.
- Author
-
Sarajlija A, Djordjevic M, Kecman B, Skakic A, Pavlovic S, Pasic S, and Stojiljkovic M
- Subjects
- Adolescent, Adult, Child, Child, Preschool, Cohort Studies, Female, Genetic Association Studies, Genotype, Glycogen Storage Disease Type I complications, Humans, Incidence, Inflammatory Bowel Diseases genetics, Male, Mutation, Neutropenia blood, Neutropenia cerebrospinal fluid, Neutropenia physiopathology, Neutrophils cytology, Phenotype, Serbia, Antiporters genetics, Glycogen Storage Disease Type I genetics, Inflammatory Bowel Diseases complications, Monosaccharide Transport Proteins genetics, Neutropenia genetics
- Abstract
Background: Glycogen storage disease type Ib (GSD-Ib) is an inherited metabolic disorder caused by autosomal recessive mutations in SLC37A4 coding for the glucose-6-phosphate transporter. Neutropenia represents major feature of GSD-Ib along with metabolic disturbances. Previous research in GSD-Ib patients did not reveal significant genotype-phenotype correlation. Our objective was to explore the frequency and severity of neutropenia and it's complications in relation to genotype of GSD-Ib patients., Methods: We estimated cumulative incidence of neutropenia and severe neutropenia, relation of genotype to absolute neutrophil count (ANC), and dynamics of ANC during serious bacterial infections (SBI) in a cohort of Serbian GSD Ib patients. Impact of genotype on GSD Ib-related inflammatory bowel disease (IBD) was also assessed., Results: Absolute neutrophil count (ANC) < 1500/mm
3 was present in all 33 patients, with severe neutropenia (ANC<500/mm3 ) occurring in 60.6% of patients. The median age at neutropenia onset was 24 months, while severe neutropenia developed at median of 4.5 years. The ANC was elevated during 90.5% episodes of SBI. Genotypes c.81T>A/c.785G>A and c.81T>A/c.1042_1043delCT are associated with earlier onset of neutropenia. Patients carrying c.785G>A mutation express a higher capacity for ANC increase during SBI. Inflammatory bowel disease was diagnosed in 8 patients (24.2% of total) with median age of onset at 7 years. Risk for IBD occurrence was not significantly affected by gender, genotype and severity of neutropenia., Conclusions: We may conclude that certain mutations in SLC37A4 influence the risk for severe neutropenia occurrence but also affect the capacity to increase ANC during SBI., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)- Published
- 2020
- Full Text
- View/download PDF
84. Transdifferentiation of pancreatic progenitor cells to hepatocyte-like cells is not serum-dependent when facilitated by extracellular matrix proteins.
- Author
-
Gratte FD, Pasic S, Olynyk JK, Yeoh GCT, Tosh D, Coombe DR, and Tirnitz-Parker JEE
- Subjects
- Biomarkers analysis, Cell Culture Techniques methods, Cell Line, Fibronectins metabolism, Humans, Laminin metabolism, Liver Diseases therapy, Microscopy, Electron, Serum, Stem Cells cytology, Cell Transdifferentiation, Extracellular Matrix Proteins pharmacology, Hepatocytes cytology, Pancreas cytology
- Abstract
The rising prevalence of chronic liver disease, coupled with a permanent shortage of organs for liver transplantation, has sparked enormous interest in alternative treatment strategies. Previous protocols to generate hepatocyte-like cells (HLCs) via pancreas-to-liver transdifferentiation have utilised fetal bovine serum, introducing unknown variables and severely limiting study reproducibility. Therefore, the main goal of this study was to develop a protocol for transdifferentiation of pancreatic progenitor cells to HLCs in a chemically defined, serum-free culture medium. The clonal pancreatic progenitor cell line AR42J-B13 was cultured in basal growth medium on uncoated plastic culture dishes in the absence or presence of Dexamethasone on uncoated, laminin- or fibronectin-coated culture substrata, with or without serum supplementation. The hepatocytic differentiation potential was evaluated: (i) morphologically through bright-field and scanning electron microscopy, (ii) by assessing pancreatic and hepatic marker expression and (iii) by determining the function of HLCs through their ability to synthesise glycogen or take up and release indocyanine green. Here we demonstrate for the first time that transdifferentiation of pancreatic cells to HLCs is not dependent on serum. These results will assist in converting current differentiation protocols into procedures that are compliant with clinical use in future cell-based therapies to treat liver-related metabolic disorders.
- Published
- 2018
- Full Text
- View/download PDF
85. Secondary hemophagocytic lymphohistiocytosis in a child with Leptospira infection: A case report.
- Author
-
Jevtic D, Djokic D, Redzic D, Aleksic D, Parezanovic M, and Pasic S
- Abstract
Jevtic D, Djokic D, Redzic D, Aleksic D, Parezanovic M, Pasic S. Secondary hemophagocytic lymphohistiocytosis in a child with Leptospira infection: A case report. Turk J Pediatr 2018; 60: 735-738. Leptospirosis caused by spirochetes of the genus Leptospira in most patients result in very mild illness without jaundice. However, a small portion of patients develop various complications due to the involvement of multiple organ systems. Hemophagocytic lymphohistiocytosis is characterized by prolonged fever, hepatosplenomegaly and cytopenias, hyperferritinemia and hypertriglyceridemias, hyperfibrinogenemia, and hemophagocytosis in bone marrow, lymph nodes, spleen, or liver. Hemophagocytic lymphohistiocytosis associated with leptospirosis is a very rare condition and it should be considered in patients with multiple organ dysfunctions, together with adequate laboratory findings. It can delay the correct diagnosis of leptospirosis and contribute to an adverse outcome. We present a 13-year-old girl with secondary hemophagocytic lymphohistiocytosis caused by leptospira infection and favorable outcome with appropriate antibiotics and corticosteroid therapy.
- Published
- 2018
- Full Text
- View/download PDF
86. Outcome of hematopoietic cell transplantation for DNA double-strand break repair disorders.
- Author
-
Slack J, Albert MH, Balashov D, Belohradsky BH, Bertaina A, Bleesing J, Booth C, Buechner J, Buckley RH, Ouachée-Chardin M, Deripapa E, Drabko K, Eapen M, Feuchtinger T, Finocchi A, Gaspar HB, Ghosh S, Gillio A, Gonzalez-Granado LI, Grunebaum E, Güngör T, Heilmann C, Helminen M, Higuchi K, Imai K, Kalwak K, Kanazawa N, Karasu G, Kucuk ZY, Laberko A, Lange A, Mahlaoui N, Meisel R, Moshous D, Muramatsu H, Parikh S, Pasic S, Schmid I, Schuetz C, Schulz A, Schultz KR, Shaw PJ, Slatter MA, Sykora KW, Tamura S, Taskinen M, Wawer A, Wolska-Kuśnierz B, Cowan MJ, Fischer A, and Gennery AR
- Subjects
- Adolescent, Alleles, Child, Child, Preschool, DNA Repair-Deficiency Disorders diagnosis, DNA Repair-Deficiency Disorders mortality, Female, Follow-Up Studies, Graft vs Host Disease diagnosis, Graft vs Host Disease etiology, Humans, Infant, Kaplan-Meier Estimate, Male, Mutation, Prognosis, Treatment Outcome, Virus Diseases, Young Adult, DNA Breaks, Double-Stranded, DNA Repair, DNA Repair-Deficiency Disorders genetics, DNA Repair-Deficiency Disorders therapy, Hematopoietic Stem Cell Transplantation adverse effects, Hematopoietic Stem Cell Transplantation methods
- Abstract
Background: Rare DNA breakage repair disorders predispose to infection and lymphoreticular malignancies. Hematopoietic cell transplantation (HCT) is curative, but coadministered chemotherapy or radiotherapy is damaging because of systemic radiosensitivity. We collected HCT outcome data for Nijmegen breakage syndrome, DNA ligase IV deficiency, Cernunnos-XRCC4-like factor (Cernunnos-XLF) deficiency, and ataxia-telangiectasia (AT)., Methods: Data from 38 centers worldwide, including indication, donor, conditioning regimen, graft-versus-host disease, and outcome, were analyzed. Conditioning was classified as myeloablative conditioning (MAC) if it contained radiotherapy or alkylators and reduced-intensity conditioning (RIC) if no alkylators and/or 150 mg/m
2 fludarabine or less and 40 mg/kg cyclophosphamide or less were used., Results: Fifty-five new, 14 updated, and 18 previously published patients were analyzed. Median age at HCT was 48 months (range, 1.5-552 months). Twenty-nine patients underwent transplantation for infection, 21 had malignancy, 13 had bone marrow failure, 13 received pre-emptive transplantation, 5 had multiple indications, and 6 had no information. Twenty-two received MAC, 59 received RIC, and 4 were infused; information was unavailable for 2 patients. Seventy-three of 77 patients with DNA ligase IV deficiency, Cernunnos-XLF deficiency, or Nijmegen breakage syndrome received conditioning. Survival was 53 (69%) of 77 and was worse for those receiving MAC than for those receiving RIC (P = .006). Most deaths occurred early after transplantation, suggesting poor tolerance of conditioning. Survival in patients with AT was 25%. Forty-one (49%) of 83 patients experienced acute GvHD, which was less frequent in those receiving RIC compared with those receiving MAC (26/56 [46%] vs 12/21 [57%], P = .45). Median follow-up was 35 months (range, 2-168 months). No secondary malignancies were reported during 15 years of follow-up. Growth and developmental delay remained after HCT; immune-mediated complications resolved., Conclusion: RIC HCT resolves DNA repair disorder-associated immunodeficiency. Long-term follow-up is required for secondary malignancy surveillance. Routine HCT for AT is not recommended., (Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)- Published
- 2018
- Full Text
- View/download PDF
87. Long-term outcomes of 176 patients with X-linked hyper-IgM syndrome treated with or without hematopoietic cell transplantation.
- Author
-
de la Morena MT, Leonard D, Torgerson TR, Cabral-Marques O, Slatter M, Aghamohammadi A, Chandra S, Murguia-Favela L, Bonilla FA, Kanariou M, Damrongwatanasuk R, Kuo CY, Dvorak CC, Meyts I, Chen K, Kobrynski L, Kapoor N, Richter D, DiGiovanni D, Dhalla F, Farmaki E, Speckmann C, Español T, Shcherbina A, Hanson IC, Litzman J, Routes JM, Wong M, Fuleihan R, Seneviratne SL, Small TN, Janda A, Bezrodnik L, Seger R, Raccio AG, Edgar JD, Chou J, Abbott JK, van Montfrans J, González-Granado LI, Bunin N, Kutukculer N, Gray P, Seminario G, Pasic S, Aquino V, Wysocki C, Abolhassani H, Dorsey M, Cunningham-Rundles C, Knutsen AP, Sleasman J, Costa Carvalho BT, Condino-Neto A, Grunebaum E, Chapel H, Ochs HD, Filipovich A, Cowan M, Gennery A, Cant A, Notarangelo LD, and Roifman CM
- Subjects
- Adolescent, Adult, Child, Child, Preschool, Cohort Studies, Female, Follow-Up Studies, Humans, Infant, Kaplan-Meier Estimate, Male, Middle Aged, Proportional Hazards Models, Retrospective Studies, Time, Young Adult, Hematopoietic Stem Cell Transplantation mortality, Hyper-IgM Immunodeficiency Syndrome mortality, Hyper-IgM Immunodeficiency Syndrome therapy
- Abstract
Background: X-linked hyper-IgM syndrome (XHIGM) is a primary immunodeficiency with high morbidity and mortality compared with those seen in healthy subjects. Hematopoietic cell transplantation (HCT) has been considered a curative therapy, but the procedure has inherent complications and might not be available for all patients., Objectives: We sought to collect data on the clinical presentation, treatment, and follow-up of a large sample of patients with XHIGM to (1) compare long-term overall survival and general well-being of patients treated with or without HCT along with clinical factors associated with mortality and (2) summarize clinical practice and risk factors in the subgroup of patients treated with HCT., Methods: Physicians caring for patients with primary immunodeficiency diseases were identified through the Jeffrey Modell Foundation, United States Immunodeficiency Network, Latin American Society for Immunodeficiency, and Primary Immune Deficiency Treatment Consortium. Data were collected with a Research Electronic Data Capture Web application. Survival from time of diagnosis or transplantation was estimated by using the Kaplan-Meier method compared with log-rank tests and modeled by using proportional hazards regression., Results: Twenty-eight clinical sites provided data on 189 patients given a diagnosis of XHIGM between 1964 and 2013; 176 had valid follow-up and vital status information. Sixty-seven (38%) patients received HCT. The average follow-up time was 8.5 ± 7.2 years (range, 0.1-36.2 years). No difference in overall survival was observed between patients treated with or without HCT (P = .671). However, risk associated with HCT decreased for diagnosis years 1987-1995; the hazard ratio was significantly less than 1 for diagnosis years 1995-1999. Liver disease was a significant predictor of overall survival (hazard ratio, 4.9; 95% confidence limits, 2.2-10.8; P < .001). Among survivors, those treated with HCT had higher median Karnofsky/Lansky scores than those treated without HCT (P < .001). Among patients receiving HCT, 27 (40%) had graft-versus-host disease, and most deaths occurred within 1 year of transplantation., Conclusion: No difference in survival was observed between patients treated with or without HCT across all diagnosis years (1964-2013). However, survivors treated with HCT experienced somewhat greater well-being, and hazards associated with HCT decreased, reaching levels of significantly less risk in the late 1990s. Among patients treated with HCT, treatment at an early age is associated with improved survival. Optimism remains guarded as additional evidence accumulates., (Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2017
- Full Text
- View/download PDF
88. Distribution of Clostridium difficile PCR ribotypes and high proportion of 027 and 176 in some hospitals in four South Eastern European countries.
- Author
-
Rupnik M, Tambic Andrasevic A, Trajkovska Dokic E, Matas I, Jovanovic M, Pasic S, Kocuvan A, and Janezic S
- Subjects
- Clostridioides difficile genetics, Enterocolitis, Pseudomembranous diagnosis, Enterocolitis, Pseudomembranous microbiology, Europe, Eastern epidemiology, Hospitals, Humans, Polymerase Chain Reaction, Ribotyping, Clostridioides difficile classification, Clostridioides difficile isolation & purification, Disease Outbreaks, Enterocolitis, Pseudomembranous epidemiology
- Abstract
While Clostridium difficile epidemiology is well documented in many European countries, data are largely missing for South Eastern European region. Here we report the PCR ribotype distribution of 249 C. difficile isolates received for typing from six hospital settings from Croatia, Bosnia and Herzegovina, Republic of Macedonia and Serbia in time period from 2008 to 2015. Twenty-four PCR ribotypes were detected. The majority of strains from Bosnia and Herzegovina and Serbia belonged to PCR ribotype 027 (65.8%). Other three dominating PCR ribotypes were 176 (18 strains; Croatia), 001/072 (15 strains; all countries) and 014/020 (15 strains; all countries)., (Copyright © 2016 Elsevier Ltd. All rights reserved.)
- Published
- 2016
- Full Text
- View/download PDF
89. Nijmegen Breakage Syndrome: Clinical and Immunological Features, Long-Term Outcome and Treatment Options - a Retrospective Analysis.
- Author
-
Wolska-Kuśnierz B, Gregorek H, Chrzanowska K, Piątosa B, Pietrucha B, Heropolitańska-Pliszka E, Pac M, Klaudel-Dreszler M, Kostyuchenko L, Pasic S, Marodi L, Belohradsky BH, Čižnár P, Shcherbina A, Kilic SS, Baumann U, Seidel MG, Gennery AR, Syczewska M, Mikołuć B, Kałwak K, Styczyński J, Pieczonka A, Drabko K, Wakulińska A, Gathmann B, Albert MH, Skarżyńska U, and Bernatowska E
- Subjects
- Adolescent, Adult, Child, Child, Preschool, Chromosomal Instability, Female, Humans, Immunologic Deficiency Syndromes, Infant, Lymphoma, Non-Hodgkin, Male, Microcephaly, Nijmegen Breakage Syndrome genetics, Nijmegen Breakage Syndrome therapy, Prognosis, Retrospective Studies, Young Adult, Hematopoietic Stem Cell Transplantation, Nijmegen Breakage Syndrome diagnosis, Time Factors
- Abstract
Purpose: Nijmegen Breakage Syndrome (NBS) is a rare inherited condition, characterized by microcephaly, chromosomal instability, immunodeficiency, and predisposition to malignancy. This retrospective study, characterizing the clinical and immunological status of patients with NBS at time of diagnosis, was designed to assess whether any parameters were useful in disease prognosis, and could help determine patients qualified for hematopoietic stem cell transplantation., Methods: The clinical and immunological characteristics of 149 NBS patients registered in the online database of the European Society for Immune Deficiencies were analyzed., Results: Of the 149 NBS patients, 91 (61%), of median age 14.3 years, remained alive at the time of analysis. These patients were clinically heterogeneous, with variable immune defects, ranging from negligible to severe dysfunction. Humoral deficiencies predisposed NBS patients to recurrent/chronic respiratory tract infections and worsened long-term clinical prognosis. Eighty malignancies, most of lymphoid origin (especially non-Hodgkin's lymphomas), were diagnosed in 42% of patients, with malignancy being the leading cause of death in this cohort. Survival probabilities at 5, 10, 20 and 30 years of age were 95, 85, 50 and 35%, respectively, and were significantly lower in patients with than without malignancies., Conclusions: The extremely high incidence of malignancies, mostly non-Hodgkin's lymphomas, was the main risk factor affecting survival probability in NBS patients. Because treatment of NBS is very difficult and frequently unsuccessful, the search for an alternative medical intervention such as hematopoietic stem cell transplantation is of great clinical importance.
- Published
- 2015
- Full Text
- View/download PDF
90. Rubinstein-Taybi syndrome associated with humoral immunodeficiency.
- Author
-
Pasic S
- Subjects
- Child, Female, Humans, Immunoglobulins, Intravenous administration & dosage, Immunologic Deficiency Syndromes diagnosis, Immunologic Factors administration & dosage, Immunologic Tests, Predictive Value of Tests, Recurrence, Respiratory Tract Infections diagnosis, Respiratory Tract Infections drug therapy, Rubinstein-Taybi Syndrome diagnosis, Treatment Outcome, Immunity, Humoral, Immunologic Deficiency Syndromes immunology, Respiratory Tract Infections immunology, Rubinstein-Taybi Syndrome immunology
- Published
- 2015
91. Recurrent BCG Infection in a Boy With X-Linked Chronic Granulomatous Disease.
- Author
-
Pasic S
- Subjects
- Axilla, Child, Humans, Male, Recurrence, Tuberculosis, Lymph Node microbiology, Granulomatous Disease, Chronic immunology, Mycobacterium bovis, Tuberculosis, Lymph Node immunology
- Published
- 2015
92. International Nosocomial Infection Control Consortium (INICC) report, data summary of 43 countries for 2007-2012. Device-associated module.
- Author
-
Rosenthal VD, Maki DG, Mehta Y, Leblebicioglu H, Memish ZA, Al-Mousa HH, Balkhy H, Hu B, Alvarez-Moreno C, Medeiros EA, Apisarnthanarak A, Raka L, Cuellar LE, Ahmed A, Navoa-Ng JA, El-Kholy AA, Kanj SS, Bat-Erdene I, Duszynska W, Van Truong N, Pazmino LN, See-Lum LC, Fernández-Hidalgo R, Di-Silvestre G, Zand F, Hlinkova S, Belskiy V, Al-Rahma H, Luque-Torres MT, Bayraktar N, Mitrev Z, Gurskis V, Fisher D, Abu-Khader IB, Berechid K, Rodríguez-Sánchez A, Horhat FG, Requejo-Pino O, Hadjieva N, Ben-Jaballah N, García-Mayorca E, Kushner-Dávalos L, Pasic S, Pedrozo-Ortiz LE, Apostolopoulou E, Mejía N, Gamar-Elanbya MO, Jayatilleke K, de Lourdes-Dueñas M, and Aguirre-Avalos G
- Subjects
- Africa epidemiology, Asia epidemiology, Centers for Disease Control and Prevention, U.S., Europe epidemiology, Humans, Infection Control methods, Intensive Care Units, Latin America epidemiology, Prospective Studies, United States epidemiology, Cross Infection epidemiology, Cross Infection prevention & control, Infection Control statistics & numerical data
- Abstract
We report the results of an International Nosocomial Infection Control Consortium (INICC) surveillance study from January 2007-December 2012 in 503 intensive care units (ICUs) in Latin America, Asia, Africa, and Europe. During the 6-year study using the Centers for Disease Control and Prevention's (CDC) U.S. National Healthcare Safety Network (NHSN) definitions for device-associated health care-associated infection (DA-HAI), we collected prospective data from 605,310 patients hospitalized in the INICC's ICUs for an aggregate of 3,338,396 days. Although device utilization in the INICC's ICUs was similar to that reported from ICUs in the U.S. in the CDC's NHSN, rates of device-associated nosocomial infection were higher in the ICUs of the INICC hospitals: the pooled rate of central line-associated bloodstream infection in the INICC's ICUs, 4.9 per 1,000 central line days, is nearly 5-fold higher than the 0.9 per 1,000 central line days reported from comparable U.S. ICUs. The overall rate of ventilator-associated pneumonia was also higher (16.8 vs 1.1 per 1,000 ventilator days) as was the rate of catheter-associated urinary tract infection (5.5 vs 1.3 per 1,000 catheter days). Frequencies of resistance of Pseudomonas isolates to amikacin (42.8% vs 10%) and imipenem (42.4% vs 26.1%) and Klebsiella pneumoniae isolates to ceftazidime (71.2% vs 28.8%) and imipenem (19.6% vs 12.8%) were also higher in the INICC's ICUs compared with the ICUs of the CDC's NHSN., (Copyright © 2014 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.)
- Published
- 2014
- Full Text
- View/download PDF
93. The role of D-dimer in prediction of the course and outcome in pediatric acute pancreatitis.
- Author
-
Boskovic A, Pasic S, Soldatovic I, Milinic N, and Stankovic I
- Subjects
- Acute Disease, Adolescent, Area Under Curve, Biomarkers blood, Child, Child, Preschool, Female, Humans, Infant, Male, Multiple Organ Failure etiology, Pancreatitis blood, Pancreatitis complications, Pancreatitis, Acute Necrotizing blood, Pancreatitis, Acute Necrotizing complications, Pancreatitis, Acute Necrotizing diagnosis, Prognosis, Retrospective Studies, Sensitivity and Specificity, Decision Support Techniques, Fibrin Fibrinogen Degradation Products metabolism, Pancreatitis diagnosis, Severity of Illness Index
- Abstract
Background: Current predictive severity scores for pediatric acute pancreatitis are either extrapolated from adult studies or difficult to use in practice. The aim of this study was to assess the value of the plasma D-dimer level as a marker of severity and outcome in pediatric AP., Methods: 36 patients (aged 1-17 yrs) with AP were included in the study. Levels of D-dimer and other routine laboratory parameters for AP were determined on admission. The Pediatric Acute Pancreatitis Severity Score was used to assess disease severity. The development of systemic and local complications was also recorded., Results: D-dimer level was significantly higher in a group of patients with complications, median 1189.5 (271-4800) vs 172.5 (105-1086) in a group of patients without complications (p < 0.001). D-dimer showed high precision in the prediction of acute necrotic collection, with the optimal cut-off values of 442.5 μg/L, Sensitivity (Sn) 100%, Specificity (Sp) 62.1% and in the prediction of multiple organ failure with optimal cut-off value 1189 μg/L, Sn 100% and Sp 87.5%. According to the areas under the curve (AUCs) of each parameter, D-dimer seemed to have predictive power similar to PAPS score and higher than C-reactive protein and Lactate dehydrogenase level., Conclusion: D-dimer level may be a simple clinical predictor of severity in pediatric acute pancreatitis., (Published by Elsevier B.V.)
- Published
- 2014
- Full Text
- View/download PDF
94. Severe combined immunodeficiency in Serbia and Montenegro between years 1986 and 2010: a single-center experience.
- Author
-
Pasic S, Vujic D, Veljković D, Slavkovic B, Mostarica-Stojkovic M, Minic P, Minic A, Ristic G, Giliani S, Villa A, Sobacchi C, Lilić D, and Abinun M
- Subjects
- Age of Onset, Delayed Diagnosis, Hematopoietic Stem Cell Transplantation, Humans, Infant, Infant, Newborn, Montenegro epidemiology, Neonatal Screening, Prenatal Diagnosis, Retrospective Studies, Serbia epidemiology, Severe Combined Immunodeficiency diagnosis, Severe Combined Immunodeficiency therapy, Treatment Outcome, Severe Combined Immunodeficiency epidemiology
- Abstract
Severe combined immunodeficiency (SCID), including the 'variant' Omenn syndrome (OS), represent a heterogeneous group of monogenic disorders characterized by defect in differentiation of T- and/or B lymphocytes and susceptibility to infections since birth. In the period of 25 years, between January 1986 and December 2010, a total of 21 patients (15 SCID, 6 OS) were diagnosed in Mother & Child Health Institute of Serbia, a tertiary-care teaching University hospital and a national referral center for patients affected with primary immunodeficiency (PID). The diagnoses were based on anamnestic data, clinical findings, and immunological and genetic analysis. The median age at the onset of the first infection was the 2nd month of life. Seven (33 %) patients had positive family history for SCID. Out of five male infants with T-B+NK- SCID phenotype, mutation analysis revealed interleukin-2 (common) gamma-chain receptor (IL2RG) mutations in 3 with positive X-linked family history, and Janus-kinase (JAK)-3 gene defects in the other two. Six patients had T-B-NK+ SCID phenotype and further 6 features of OS, 11 of which had recombinase-activating gene (RAG1or RAG2) and 1 Artemis gene mutations. One child with T+B+NK+ SCID phenotype as well had proven RAG mutation. One child each with T-B+NK+ SCID phenotype, CD8 lymphopenia and unknown phenotype remained without known underlying genetic defect. Of the eight patients who underwent hematopoetic stem cell transplant (HSCT) 5 survived, the other 13 died between 2 days and 12 months after diagnosis was made. Early diagnosis of SCID, before onset of severe infections, offers possibility for HSCT and cure. Education of primary-care pediatricians, in particular including awareness of the risk of using live vaccines and non-irradiated blood products, should improve prognosis of SCID in our setting.
- Published
- 2014
- Full Text
- View/download PDF
95. Central nervous system involvement in hemophagocytic lymphohistiocytosis: a single-center experience.
- Author
-
Jovanovic A, Kuzmanovic M, Kravljanac R, Micic D, Jovic M, Gazikalovic S, and Pasic S
- Subjects
- Adolescent, Child, Preschool, Female, Humans, Infant, Lymphohistiocytosis, Hemophagocytic cerebrospinal fluid, Lymphohistiocytosis, Hemophagocytic diagnosis, Magnetic Resonance Imaging, Male, Prognosis, ROC Curve, Survival Analysis, Tomography, X-Ray Computed, Brain pathology, Brain physiopathology, Lymphohistiocytosis, Hemophagocytic pathology, Lymphohistiocytosis, Hemophagocytic physiopathology
- Abstract
Background: Hemophagocytic lymphohistiocytosis is a rare multisystem disorder characterized by proliferation and diffuse infiltration multiple organs with histiocytes, including the central nervous system., Patients and Methods: Thirty children diagnosed with hemophagocytic lymphohistiocytosis between 1997 and 2010 were reviewed and analyzed. Central nervous system disease involvement was defined as the presence of neurological symptoms and signs or elevated values of cerebrospinal fluid cells and/or proteins., Results: Among the 30 patients, 17 (56%) had central nervous system involvement. Fourteen patients (46%) presented with neurological symptoms including seizures, irritability, bulging fontanelle, cranial nerve palsy, or disturbance of consciousness, whereas the remaining three patients developed central nervous system symptoms during the course of the disease. Seventeen patients (56%) had cerebrospinal fluid abnormalities. Neuroradiological studies were performed in nine patients. The most common findings were edema, atrophy, subcortical necrosis, and high signal intensity on T2-weighted magnetic resonance imaging. All patients were treated according to the Hemophagocytic Lymphohistiocytosis-94 and Hemophagocytic Lymphohistiocytosis-2004 protocols. Patients with central nervous system involvement had greater mortality. In prediction of the outcome, the cutoff value for cerebrospinal fluid protein was 470 mg/L. The most common neurological sequela was psychomotor delay., Conclusion: Central nervous system involvement in hemophagocytic lymphohistiocytosis is common and is associated with poor outcome., (Copyright © 2014 Elsevier Inc. All rights reserved.)
- Published
- 2014
- Full Text
- View/download PDF
96. Celiac-like sprue in Nijmegen breakage syndrome: successful treatment with budesonide.
- Author
-
Pasic S, Ristic G, Djuricic S, Prokic D, and Zdravkovic S
- Subjects
- Adult, Humans, Male, Budesonide therapeutic use, Celiac Disease drug therapy, Nijmegen Breakage Syndrome complications
- Published
- 2014
97. Bilateral giant coronary aneurysms in Kawasaki disease: how difficult can it be?
- Author
-
Prijic S, Ristic G, Pasic S, Minic A, Vukomanovic V, Adjic O, Ninic S, and Kosutic J
- Subjects
- Acute Disease, Child, Preschool, Echocardiography, Humans, Magnetic Resonance Imaging, Male, Coronary Aneurysm diagnostic imaging, Coronary Aneurysm etiology, Coronary Aneurysm pathology, Mucocutaneous Lymph Node Syndrome complications, Multimodal Imaging, Severity of Illness Index
- Published
- 2013
- Full Text
- View/download PDF
98. Nijmegen breakage syndrome and chronic polyarthritis.
- Author
-
Pasic S, Cupic M, Jovanovic T, Djukic S, Kavaric M, and Lazarevic I
- Subjects
- Anti-Inflammatory Agents, Non-Steroidal therapeutic use, Antibodies, Monoclonal, Murine-Derived therapeutic use, Antirheumatic Agents therapeutic use, Arthritis diagnostic imaging, Arthritis genetics, Child, Chronic Disease, Drug Therapy, Combination, Female, Follow-Up Studies, Humans, Nijmegen Breakage Syndrome genetics, Nijmegen Breakage Syndrome physiopathology, Radiography, Rare Diseases, Risk Assessment, Rituximab, Severity of Illness Index, Treatment Outcome, Arthritis drug therapy, Arthritis etiology, Nijmegen Breakage Syndrome complications
- Abstract
We report on pediatric patient with Nijmegen breakage syndrome (NBS), a rare DNA repair disorder characterized by microcephaly, immunodeficiency and predisposition to malignant lymphomas, who developed juvenile idiopathic arthritis (JIA)-like polyarthritis. In patients with primary immunodeficiencies (PID), septic arthritis due to pyogenic bacteria or mycoplasmal arthritis are the most common osteoarticular manifestations. In certain PID, chronic, non-infectious arthritis resembling rheumatoid arthritis may occur. In our patient microbiologic cultures of synovial fluid including Mycoplasma spp. were negative. At first, because of suspected mycoplasmal arthritis we used macrolides and doxycycline combined with hydroxychloroquine but without therapeutic response. However, the use of rituximab led to remission of her polyarthritis lasting for 9 months. Autoimmune features were rarely reported in NBS. An occurrence of JIA-like, chronic polyarthritis in NBS, a DNA repair disorder characterized by decreased tolerance of immunosuppressive drugs such as methotrexate and a high natural risk for lymphomas, makes therapeutic approach even more complex.
- Published
- 2013
- Full Text
- View/download PDF
99. Common variable immunodeficiency classification by quantifying T-cell receptor and immunoglobulin κ-deleting recombination excision circles.
- Author
-
Kamae C, Nakagawa N, Sato H, Honma K, Mitsuiki N, Ohara O, Kanegane H, Pasic S, Pan-Hammarström Q, van Zelm MC, Morio T, Imai K, and Nonoyama S
- Subjects
- Adolescent, Adult, Child, Child, Preschool, Common Variable Immunodeficiency classification, Humans, Male, Middle Aged, Young Adult, Common Variable Immunodeficiency genetics, Common Variable Immunodeficiency immunology, Genes, Immunoglobulin Light Chain, Genes, T-Cell Receptor, Immunoglobulin kappa-Chains genetics, Receptors, Antigen, T-Cell genetics, Recombination, Genetic immunology
- Published
- 2013
- Full Text
- View/download PDF
100. Comparison of double disk synergy test, VITEK 2 and Check-MDR CT102 for detection of ESBL producing isolates.
- Author
-
Numanovic F, Hukic M, Delibegovic Z, Tihic N, Pasic S, and Gegic M
- Subjects
- beta-Lactamases biosynthesis, Enterobacteriaceae metabolism, Klebsiella oxytoca metabolism, Klebsiella pneumoniae metabolism, Microbial Sensitivity Tests methods, Proteus mirabilis metabolism, beta-Lactamases isolation & purification
- Abstract
Objective: This study is to define the statistical significance for detection of ESBL producers by the double disk synergy test and molecular test (Check-MDR CT102), microdilution test (VITEK 2 with AES) and double disk synergy test (DDST), as well as the microdilution test and molecular test., Materials and Methods: Phenotypic testing of 55 isolates Enterobacteriaceae (Escherichia coli (14/55), Klebsiella pneumoniae (34/55), Klebsiella oxytoca (3/55) and Proteus mirabilis (4/55) was performed by VITEK 2 Compact/AES. When this test showed positive results for the ESBL phenotype, then DDST with amoxicillin/clavulanate, ceftazidime, cefpodoxime, aztreonam, ceftriaxone and cefoxitin disks was performed along with Check-MDR CT102 which identified CTX-M, TEM and SHV β-lactamases., Results: Applying the McNemar test, we determined that there was a statistically significant difference in the results of detection of ESBLs bacteria using DDST compared to molecular methods (95% CI=41.92 to 54.55; p<0.0001), as well as a DDST and VITEK 2/AES (95% CI=40.13 to 52.73; p<0.0001). We did not find any statistically significant difference in the results of detection of ESBL producers using molecular techniques and VITEK 2/AES (CI=-4,43 to 5,36; p=1). Also we did not find any statistical.. difference between the resistance to cefpodoxime and ceftriaxone (50/50) compared to the results of molecular tests., Conclusion: In routine daily testing, good detection of ESBLs bacteria, especially CTX-M can be obtained with phenotypic methods with VITEK 2/AES and by DDST with cefpodoxime, and ceftriaksone disks., (Copyright © 2013 by Academy of Sciences and Arts of Bosnia and Herzegovina.)
- Published
- 2013
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.