A comparative study between children and adults with bacterial neuroinfections

Abstract Introduction: Bacterial meningitis is an acute purulent infection of the meninges. There are significant differences in the etiological spectrum, clinical course and outcome of bacterial meningitis in the age groups, and their recognition is important for early diagnosis and adequate therapy. Aim: The study aims to determine the differences in the etiology and clinical presentation of bacterial meningitis between children and adults. Materials and methods: The study included 90 patients (25 children and 65 adults) with bacterial neuroinfection admitted to St George University Hospital, Plovdiv between January 1, 2016 and September 31, 2019. We applied epidemiological and clinical analysis, microbiological and statistical methods. Results: In adults, the most common etiological agent was Streptococcus pneumoniae (20%), followed by Staphylococcus spp. (18.5%), Listeria monocytogenes (12.3%), Streptococcus spp. (3.1%), Haemophilus influenzae (3.1%), Klebsiella pneumoniae (1.5%), and Mycobacterium tuberculosis (1.5%). The etiological structure in children was different: Neisseria meningitidis (20%), Streptococcus pneumoniae (16%), Klebsiella pneumoniae (8%), Enterococcus faecium (8%), Streptococcus salivarius (4%), and Mycobacterium tuberculosis (4%). In 40% of the cases, both children and adults, the causative agent was not identified. Conclusions: Regarding the clinical presentation, a statistical significance between the age groups was found with headache and alterations in consciousness, more commonly seen in adults, while vomiting, ear pain was more common in children (p<0.05). Concomitant otitis, sinusitis, pneumonia, and sepsis were often observed. The mortality rate was much higher in adults (43%) when compared with children (8%)

Care of patients with inborn errors of immunity in thirty J Project countries between 2004 and 2021

IntroductionThe 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.ResultsIn 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).Conclusions1) 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

Два Нови Безсерумни И Без Протеинни Щама, Получени От Клетъчна Линия Hep-2: Културални Условия И Пролиферативна Активност

Two new cell strains – HEp-2-Plovdiv E and HEp-2-Plovdiv F were derived from the HEp-2 cell line. They could be cultivated indefinitely in vitro in DMEM/Ham’s F12 1:1 medium. These are serum-free and protein-free cultures because they grown only in medium that is chemically defined. Serum-free cultures could be distinguished by morphological characteristics, growth dynamics, sensitivity to trypsinization, prolife-ration activity and doubling time. The number of cell population’s doublings of the initial carcinoma cell line and the two serum-free cultures was calculated. The dynamics of cell proliferation was investigated and doubling time for HEp-2 cell line (22.6 h), HEp-2-Plovdiv F strain (25.8 h) and HEp-2-Plovdiv E strain (28.4 h) was calculated. DMSO of 7 % was added in the growth medium for storage in liquid nitrogen. Optimized parameters for cultivation and subcultivation of the cell cultures are suggested. Possible ways of application of the new serum free cell cultures, based on preliminary studies for viral cultivation and detection of serum autoantibodies are discussed.От клетъчна линия HEp-2 са получени два нови клетъчни щама HEp-2-Plovdiv E и HEp-2-Plovdiv F, които могат да се култивират неограничено вре-е в условия ин витро в среда DMEM/Ham’s F-12 (1:1). Те са безсерумни и без протеинни култури, защото се отглеждат само в среда, която е хими-чески дефинирана. Безсерумните култури се различават по морфологични характеристики, динамика на развитие на културата, чувствителност при трипсинизиране, пролиферативна активност и време на удвояване. Изчис-лени са броят удвоявания на клетъчната популация за изходната серумна карциномна клетъчна линия и двете нови безсерумни култури, заложени в шест различни начални посевни гъстоти. Проследена е динамиката на про-лиферативната активност и е изчислено времето на удвояване на клетъч-ната култура HEp-2 (22,6 часа), щам HEp-2-Plovdiv F (25,8 часа) и щам HEp-2-Plovdiv E (28,4 часа). Съхраняването в течен азот на безсерумните клетки от двата щама се осъществява в растежна среда, допълнена с 7 % DMSO. Препоръчват се оптимизирани параметри при процедурите на култивиране и субкултивиране на клетъчните култури. Дискутират се някои възможни направления за приложение на новите безсерумни клетки, базирани на пред-варителни изследвания за култивиране на вируси и детекция на серумни автоантитела

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Two new cell strains \u2013 HEp-2-Plovdiv E and HEp-2-Plovdiv F were derived from the HEp-2 cell line. They could be cultivated indefinitely in vitro in DMEM/Ham\u2019s F12 1:1 medium. These are serum-free and protein-free cultures because they grown only in medium that is chemically defined. Serum-free cultures could be distinguished by morphological characteristics, growth dynamics, sensitivity to trypsinization, prolife-ration activity and doubling time. The number of cell population\u2019s doublings of the initial carcinoma cell line and the two serum-free cultures was calculated. The dynamics of cell proliferation was investigated and doubling time for HEp-2 cell line (22.6 h), HEp-2-Plovdiv F strain (25.8 h) and HEp-2-Plovdiv E strain (28.4 h) was calculated. DMSO of 7 % was added in the growth medium for storage in liquid nitrogen. Optimized parameters for cultivation and subcultivation of the cell cultures are suggested. Possible ways of application of the new serum free cell cultures, based on preliminary studies for viral cultivation and detection of serum autoantibodies are discussed.\u41e\u442 \u43a\u43b\u435\u442\u44a\u447\u43d\u430 \u43b\u438\u43d\u438\u44f HEp-2 \u441\u430 \u43f\u43e\u43b\u443\u447\u435\u43d\u438 \u434\u432\u430 \u43d\u43e\u432\u438 \u43a\u43b\u435\u442\u44a\u447\u43d\u438 \u449\u430\u43c\u430 HEp-2-Plovdiv E \u438 HEp-2-Plovdiv F, \u43a\u43e\u438\u442\u43e \u43c\u43e\u433\u430\u442 \u434\u430 \u441\u435 \u43a\u443\u43b\u442\u438\u432\u438\u440\u430\u442 \u43d\u435\u43e\u433\u440\u430\u43d\u438\u447\u435\u43d\u43e \u432\u440\u435-\u435 \u432 \u443\u441\u43b\u43e\u432\u438\u44f \u438\u43d \u432\u438\u442\u440\u43e \u432 \u441\u440\u435\u434\u430 DMEM/Ham\u2019s F-12 (1:1). \u422\u435 \u441\u430 \u431\u435\u437\u441\u435\u440\u443\u43c\u43d\u438 \u438 \u431\u435\u437 \u43f\u440\u43e\u442\u435\u438\u43d\u43d\u438 \u43a\u443\u43b\u442\u443\u440\u438, \u437\u430\u449\u43e\u442\u43e \u441\u435 \u43e\u442\u433\u43b\u435\u436\u434\u430\u442 \u441\u430\u43c\u43e \u432 \u441\u440\u435\u434\u430, \u43a\u43e\u44f\u442\u43e \u435 \u445\u438\u43c\u438-\u447\u435\u441\u43a\u438 \u434\u435\u444\u438\u43d\u438\u440\u430\u43d\u430. \u411\u435\u437\u441\u435\u440\u443\u43c\u43d\u438\u442\u435 \u43a\u443\u43b\u442\u443\u440\u438 \u441\u435 \u440\u430\u437\u43b\u438\u447\u430\u432\u430\u442 \u43f\u43e \u43c\u43e\u440\u444\u43e\u43b\u43e\u433\u438\u447\u43d\u438 \u445\u430\u440\u430\u43a\u442\u435\u440\u438\u441\u442\u438\u43a\u438, \u434\u438\u43d\u430\u43c\u438\u43a\u430 \u43d\u430 \u440\u430\u437\u432\u438\u442\u438\u435 \u43d\u430 \u43a\u443\u43b\u442\u443\u440\u430\u442\u430, \u447\u443\u432\u441\u442\u432\u438\u442\u435\u43b\u43d\u43e\u441\u442 \u43f\u440\u438 \u442\u440\u438\u43f\u441\u438\u43d\u438\u437\u438\u440\u430\u43d\u435, \u43f\u440\u43e\u43b\u438\u444\u435\u440\u430\u442\u438\u432\u43d\u430 \u430\u43a\u442\u438\u432\u43d\u43e\u441\u442 \u438 \u432\u440\u435\u43c\u435 \u43d\u430 \u443\u434\u432\u43e\u44f\u432\u430\u43d\u435. \u418\u437\u447\u438\u441-\u43b\u435\u43d\u438 \u441\u430 \u431\u440\u43e\u44f\u442 \u443\u434\u432\u43e\u44f\u432\u430\u43d\u438\u44f \u43d\u430 \u43a\u43b\u435\u442\u44a\u447\u43d\u430\u442\u430 \u43f\u43e\u43f\u443\u43b\u430\u446\u438\u44f \u437\u430 \u438\u437\u445\u43e\u434\u43d\u430\u442\u430 \u441\u435\u440\u443\u43c\u43d\u430 \u43a\u430\u440\u446\u438\u43d\u43e\u43c\u43d\u430 \u43a\u43b\u435\u442\u44a\u447\u43d\u430 \u43b\u438\u43d\u438\u44f \u438 \u434\u432\u435\u442\u435 \u43d\u43e\u432\u438 \u431\u435\u437\u441\u435\u440\u443\u43c\u43d\u438 \u43a\u443\u43b\u442\u443\u440\u438, \u437\u430\u43b\u43e\u436\u435\u43d\u438 \u432 \u448\u435\u441\u442 \u440\u430\u437\u43b\u438\u447\u43d\u438 \u43d\u430\u447\u430\u43b\u43d\u438 \u43f\u43e\u441\u435\u432\u43d\u438 \u433\u44a\u441\u442\u43e\u442\u438. \u41f\u440\u43e\u441\u43b\u435\u434\u435\u43d\u430 \u435 \u434\u438\u43d\u430\u43c\u438\u43a\u430\u442\u430 \u43d\u430 \u43f\u440\u43e-\u43b\u438\u444\u435\u440\u430\u442\u438\u432\u43d\u430\u442\u430 \u430\u43a\u442\u438\u432\u43d\u43e\u441\u442 \u438 \u435 \u438\u437\u447\u438\u441\u43b\u435\u43d\u43e \u432\u440\u435\u43c\u435\u442\u43e \u43d\u430 \u443\u434\u432\u43e\u44f\u432\u430\u43d\u435 \u43d\u430 \u43a\u43b\u435\u442\u44a\u447-\u43d\u430\u442\u430 \u43a\u443\u43b\u442\u443\u440\u430 HEp-2 (22,6 \u447\u430\u441\u430), \u449\u430\u43c HEp-2-Plovdiv F (25,8 \u447\u430\u441\u430) \u438 \u449\u430\u43c HEp-2-Plovdiv E (28,4 \u447\u430\u441\u430). \u421\u44a\u445\u440\u430\u43d\u44f\u432\u430\u43d\u435\u442\u43e \u432 \u442\u435\u447\u435\u43d \u430\u437\u43e\u442 \u43d\u430 \u431\u435\u437\u441\u435\u440\u443\u43c\u43d\u438\u442\u435 \u43a\u43b\u435\u442\u43a\u438 \u43e\u442 \u434\u432\u430\u442\u430 \u449\u430\u43c\u430 \u441\u435 \u43e\u441\u44a\u449\u435\u441\u442\u432\u44f\u432\u430 \u432 \u440\u430\u441\u442\u435\u436\u43d\u430 \u441\u440\u435\u434\u430, \u434\u43e\u43f\u44a\u43b\u43d\u435\u43d\u430 \u441 7 % DMSO. \u41f\u440\u435\u43f\u43e\u440\u44a\u447\u432\u430\u442 \u441\u435 \u43e\u43f\u442\u438\u43c\u438\u437\u438\u440\u430\u43d\u438 \u43f\u430\u440\u430\u43c\u435\u442\u440\u438 \u43f\u440\u438 \u43f\u440\u43e\u446\u435\u434\u443\u440\u438\u442\u435 \u43d\u430 \u43a\u443\u43b\u442\u438\u432\u438\u440\u430\u43d\u435 \u438 \u441\u443\u431\u43a\u443\u43b\u442\u438\u432\u438\u440\u430\u43d\u435 \u43d\u430 \u43a\u43b\u435\u442\u44a\u447\u43d\u438\u442\u435 \u43a\u443\u43b\u442\u443\u440\u438. \u414\u438\u441\u43a\u443\u442\u438\u440\u430\u442 \u441\u435 \u43d\u44f\u43a\u43e\u438 \u432\u44a\u437\u43c\u43e\u436\u43d\u438 \u43d\u430\u43f\u440\u430\u432\u43b\u435\u43d\u438\u44f \u437\u430 \u43f\u440\u438\u43b\u43e\u436\u435\u43d\u438\u435 \u43d\u430 \u43d\u43e\u432\u438\u442\u435 \u431\u435\u437\u441\u435\u440\u443\u43c\u43d\u438 \u43a\u43b\u435\u442\u43a\u438, \u431\u430\u437\u438\u440\u430\u43d\u438 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Image_1_Care of patients with inborn errors of immunity in thirty J Project countries between 2004 and 2021.jpeg

IntroductionThe 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.ResultsIn 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).Conclusions1) 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.</p

Table_1_Care of patients with inborn errors of immunity in thirty J Project countries between 2004 and 2021.docx

IntroductionThe 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.ResultsIn 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).Conclusions1) 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.</p

DataSheet_2_Care of patients with inborn errors of immunity in thirty J Project countries between 2004 and 2021.docx

IntroductionThe 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.ResultsIn 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).Conclusions1) 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.</p