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European CF Society Neonatal Screening Working Group (ECFS NSWG): Sabine Renner , Max Zeyda , Elke de Wachter , Luc Regal , Felix Votava, Andrea Holubova, Marianne Skov , Tessa Morgan, Paul Bregeaut , Loretta O'Grady, Ines Bucci , Stefano Pantano , Simonetta Simonetti, Domenica De Venuto, Donatello Salvatore, Nicola Perrotti, Mimma Caloiero, Giuseppe Castaldo, Antonella Tosco, Francesca Righetti, Giovanna Pisi, Fiorella Battistini, Antonio Angeloni, Giuseppe Cimino, Giovanni Fiocchi, Antonella Angiolillo, Michela Cassanello, Luisella Alberti, Laura E Claut, Raffaele Badolato, Enza Pavanello, Benedetta Fabrizzi, Elisabetta Bignamini, Anna Cardillo, Mariangela Lombardo, Letizia Cocciadiferro, Lisa Termini, Daniela Dolce, Vito Terlizzi, Anna Tamanini, Francesca Pauro, Giancarlo la Marca, Elina Aleksejeva, Dita Gaidule-Logina, Stoika Fustik, Violeta Anastasovska, Marelle Bouva, Alastair Reid, Jennifer Cundick, Emma Lundman, Egil Bakkeheim, Katarzyna Zybert, Mariusz Oltarzewski, Laura Vilarinho, Victoria Sherman, Elena Kondratyeva, Sarah Smith, Gordana Vilotijevic Dautovic, Maria Knapkova, Zuzana Mydlova, Rosa Mª López, Valle Velasco, Felicitas Díaz Flores, Cristóbal Colón Mejeras, Eva Sl Pedersen, Ugur Ozcelik, Bulent Karadag, Halyna Makukh, Moat Stuart. European CF Society Neonatal Screening Working Group (ECFS NSWG): INSA - Laura Vilarinho Background: The aim of this study was to record the current status of newborn bloodspot screening (NBS) for CF across Europe and assess performance. Methods: Survey of representatives of NBS for CF programmes across Europe. Performance was assessed through a framework developed in a previous exercise. Results: In 2022, we identified 22 national and 34 regional programmes in Europe. Barriers to establishing NBS included cost and political inertia. Performance was assessed from 2019 data reported by 21 national and 21 regional programmes. All programmes employed different protocols, with IRT-DNA the most common strategy. Six national and 11 regional programmes did not use DNA analysis. Conclusions: Integrating DNA analysis into the NBS protocol improves PPV, but at the expense of increased carrier and CFSPID recognition. Some programmes employ strategies to mitigate these outcomes. Programmes should constantly strive to improve performance but large datasets are needed to assess outcomes reliably. Highlights: In 2022, newborn bloodspot screening (NBS) for CF is undertaken in 30 European countries, 26 of them are national programmes; Some programmes are still not achieving ECFS standards. Compared to 2014, there is an improvement in sensitivity but a deterioration in achieving a sufficient PPV; There continues to be a wide variety of approaches, but the majority of national programmes are now using DNA analysis as a 2nd tier; This survey demonstrates areas of good practice, but there is considerable scope for improvement in the quality of NBS for CF across Europe; The framework of the 20 parameters to calculate the 8 key outcomes should be part of any annual report of a CF NBS programme, and thus improve future surveys. The survey was funded by the European CF Society info:eu-repo/semantics/publishedVersion

Purpose: To develop a conceptual framework of the factors likely to influence clinicians' use of a new participation-focused outcome measurement protocol in a large paediatric speech-language pathology program.Method: A convenience sample of 27 end users (clinicians, managers) were recruited from Ontario, Canada's Preschool Speech and Language Program. Participants engaged in one virtual concept mapping session in groups of five to six during which they learned about the new protocol, and generated statements in response to a prompt asking them to identify factors that would influence their use of the protocol. Following all sessions, participants asynchronously sorted and rated all statements, and data were analysed using multidimensional scaling and hierarchical cluster analyses.Result: Six themes were identified: (1) response from families; (2) use of resources; (3) feasibility and clinical utility; (4) relevance and value-added for clinicians; (5) streamlining policies and guidelines; and (6) delivery, administration, and modification of tool. Response from families, feasibility and clinical utility, and use of resources received the highest importance ratings.Conclusion: Concept mapping methodology was used to engage clinicians and managers to identify the barriers to a new implementation protocol for outcome measurement. Results will support future research and implementation efforts.

Background Early identification of dysphagia aims to mitigate the risk of health consequences in adults poststroke; however, the evidence from experimental trials alone is inconclusive. This meta‐analysis assessed dysphagia screening benefit from both trial and observational data. Methods and Results Seven electronic databases were searched to December 2019. Unique abstracts and full articles were screened for eligibility by 2 independent blinded raters using a priori criteria and discrepancies resolved by consensus. Included studies were summarized descriptively and assessed for methodological quality using Cochrane Risk of Bias Tool. Across studies, pooled estimates of health benefit were derived for homogeneous data using Review Manger 5.3. From the yield of 8860 citations, 30 unique articles were selected: 24 observational and 6 randomized trials. Across studies, comparisons varied: no screening versus screening, late versus earlier screening, informal versus formal screening, pre‐ versus postscreening, and pre‐ versus poststroke guidelines that included screening. Pooled estimates across comparisons favored experimental groups for pneumonia odds ratio (OR), 0.57 (95% CI, 0.45–0.72), mortality OR, 0.52 (95% CI, 0.35–0.77), dependency OR, 0.54 (95% CI, 0.35–0.85), and length of stay standardized mean difference, −0.62 (95% CI, −1.05 to −0.20). Conclusions Combining evidence from experimental and observational studies derived a significant protective health benefit of dysphagia screening following adult acute stroke for pneumonia, mortality, dependency, and length of stay.

Background and Purpose: Following adult stroke, dysphagia, dysarthria, and aphasia are common sequelae. Little is known about these impairments in pediatric stroke. We assessed frequencies, co-occurrence and associations of dysphagia, oral motor, motor speech, language impairment, and caregiver burden in pediatric stroke. Methods: Consecutive acute patients from term birth-18 years, hospitalized for arterial ischemic stroke (AIS), and cerebral sinovenous thrombosis, from January 2013 to November 2018 were included. Two raters reviewed patient charts to detect documentation of in-hospital dysphagia, oral motor dysfunction, motor speech and language impairment, and caregiver burden, using a priori operational definitions for notation and assessment findings. Other variables abstracted included demographics, preexisting conditions, stroke characteristics, and discharge disposition. Impairment frequencies were obtained by univariate and bivariate analysis and associations by simple logistic regression. Results: A total of 173 patients were stratified into neonates (N=67, mean age 2.9 days, 54 AIS, 15 cerebral sinovenous thrombosis) and children (N=106, mean age 6.5 years, 73 AIS, 35 cerebral sinovenous thrombosis). Derived frequencies of impairments included dysphagia (39% neonates, 41% children); oral motor (6% neonates, 41% children); motor speech (37% children); and language (31% children). Common overlapping impairments included oral motor and motor speech (24%) and dysphagia and motor speech (23%) in children. Associations were found only in children between stroke type (AIS over cerebral sinovenous thrombosis) and AIS severity (more severe deficit at presentation) for all impairments except feeding impairment alone. Caregiver burden was present in 58% patients. Conclusions: For the first time, we systematically report the frequencies and associations of dysphagia, oral motor, motor speech, and language impairment during acute presentation of pediatric stroke, ranging from 30% to 40% for each impairment. Further research is needed to determine long-term effects of these impairments and to design standardized age-specific assessment protocols for early recognition following stroke.

Bedside dysphagia assessment protocols are not well developed in acute pediatric stroke unlike adults. The objective of this study was to identify items deemed relevant and feasible by expert consensus to inform the development of a bedside dysphagia screening tool for acute pediatric stroke. A two-phase study was conducted: (1) literature review and expert consultation generated a comprehensive list of dysphagia assessment items; (2) items were formatted in an online survey asking respondents opinion of relevance to acute pediatric stroke and feasibility for bedside administration by a trained health professional. The Dillman Tailored Design approach optimized response rate. Respondents were identified using the snowball method. Speech-language pathologists with 2 years in pediatric dysphagia were invited to complete the survey. Demographic and practice variables were compared using univariate statistics. Item relevance and feasibility were made using binary or ordinal responses, combined to derive item-content validity indices (I-CVI) to guide item reduction. Items with I-CVI 0.78 (excellent content validity) were moved forward to tool development. Of the 71 invited respondents, 57(80.3%) responded, of which 34(59.6%) were from North America. Sixty-one items were generated of which 4(6.6%) items were rated 'to keep'. These were face symmetry (I-CVI:0.89), salivary control (I-CVI:0.95), alertness (I-CVI:0.89) and choking (I-CVI:0.84). Of all respondents, 31(54.4%) endorsed swallowing trials, of which 25(80.6%) endorsed thin liquid by teaspoon (n = 17, 68%) or open cup (n = 20, 80%). We identified candidate items for bedside dysphagia screening with excellent content validity for acute pediatric stroke patients. Next steps include assessment of the psychometric value of each item in identifying dysphagia in children in the acute stage of recovery from stroke.

Background: The problem of vitamin D deficiency is particularly relevant for the entire territory of Russia, since most parts of the country are located above the 42nd geographical latitude and the residents are therefore at risk of vitamin D deficiency. Despite the urgency of the problem, a comprehensive study of the molecular and genetic mechanisms and exogenous factors of vitamin D deficiency in children living in various geographical areas of the Russian Federation has not been conducted. Different variants in the loci of the genes responsible for the synthesis, hydroxylation, and transport of vitamin D (such as DHCR7, CYP2R1, CYP24A1, and GC), as well as VDR gene polymorphisms may also be associated with the risk of vitamin D deficiency. The aim of this study was to analyze the influence of exogenous factors on the blood levels of 25-hydroxyvitamin D (25(OH)D) in children of three regions of the Russian Federation, as well as the relationship of blood 25(OH)D levels with polymorphic variants of cytochrome P450 genes and VDR gene.Methods: We conducted blood 25(OH)D level analysis in 333 healthy children and adolescents in three regions located in different geographical zones of the Russian Federation. We studied the polymorphic variants c.1075A>C (I359L, rs1057910, CYP2C9*3) and c.430C>T (R144C, rs1799853, CYP2C9*2) in the CYP2C9 gene, c.1334T>C (M445T, rs4986910, CYP3A4*3), and CYP3A4*1B (c.-392C>T, rs2740574) in the CYP3A4 gene, 1846G>A, (rs3892097, CYP2D6*4) in the CYP2D6gene, TaqI (NM_000376.2: c.1056T>C; rs731236), FokI (NM_000376.2:c.2T>C; (rs2228570), and BsmI (NM_000376.2: c.1024+283G>A; rs1544410) in the VDR gene. We also analyzed the influence of exogenous factors on the level of 25(OH)D in children of the three study regions, as well as the relationship of the level of 25(OH)D with variants CYP2C9*2 (c.430C>T; R144C), CYP2C9*3 (c,1075A>C; I359L), CYP2D6*4 (1846G>A), CYP3A4*3 (c.1334T>C), and CYP3A4*1B (c.-392C>T) and rs731236, rs2228570 and rs1544410 in the VDR gene.Results: We found that the blood level of 25(OH)D depended on the geographical location and the number of sunny days per year. The average blood level of 25(OH)D in adolescent boys was statistically significantly lower than in girls of this age group. The level of 25(OH)D also significantly depended on the prophylactic dose of cholecalciferol administered to the subjects. In the study, it was shown that a dose of cholecalciferol ≥1,000 IU per day can achieve a normal level of 25(OH)D in healthy children. We found no statistically significant association between single-nucleotide polymorphic variants of cytochrome P450 genes (CYP2C9*3, CYP3A4*3, CYP2C9*2, CYP2D6*4, and CYP3A4*1B) and blood level of 25(OH)D in the subjects. We also did not find a relationship between the TaqI, FokI, and BsmI polymorphisms of the VDR gene and serum 25(OH)D concentration.Conclusion: Exogenous factors (time of year, place of residence, and prophylactic administration of cholecalciferol), as well as endogenous factors (age and sex), play a determining role in the development of vitamin D deficiency and insufficiency; in contrast to genetic factors—polymorphic variants of the genes of xenobiotic phase 1 enzymes (CYP2C9, CYP2C19, CYP2D6, and CYP3A4) and the VDR gene—which do not play such role. This study shows the need to create a diagnostic algorithm for Vitamin D deficiency based on the age, season of the year, and prophylactic dose of cholecalciferol.

The goal was to study the phenotypic manifestations of c.3844T>C (p.Trp1282Arg, W1282R) variant, a CF-causing mutation, in patients from the Russian Federation. Clinical manifestations and complications (the age at CF diagnosis, sweat test, pancreatic status, lung function, microbial infection, body mass index (BMI), the presence of meconium ileus (MI), diabetes, and severe liver disease) were compared in four groups: group 1—patients carrying c.3844T>C and severe class I or II variant in trans; group 2—3849+10kbC>T/F508del patients; group 3—F508del/F508del patients; and group 4—patients with W1282R and “mild” variant in trans. Based on the analyses, W1282R with class I or II variant in trans appears to cause at least as severe CF symptoms as F508del homozygotes as reflected in the early age of diagnosis, high sweat chloride concentration, insufficient pancreatic function, and low lung function, in contrast to 3849+10kbC-T/F508del compound heterozygotes having milder clinical phenotypes. The W1282R pathogenic variant is seemed to lead to severe disease phenotype with pancreatic insufficiency similarly to the F508del homozygous genotype.

This systematic review targeted frequency estimates of dysphagia (feeding and swallowing problems), related health outcomes, and caregiver burden in children with stroke or unilateral cerebral palsy (CP).Six electronic databases were searched from their inception to November 2017 along with a manual search of eight relevant journals. Two blinded raters assessed abstracts and full articles for eligibility. Discrepancies were resolved by consensus. Accepted articles were evaluated for quality. Data were extracted and analysed descriptively.Of 1660 abstracts, five met inclusion criteria, of which three focused on stroke and two unilateral CP. Across studies, operational definitions of feeding and swallowing varied. Insufficient details were provided on assessment methods and timing. Reported frequencies of dysphagia ranged from 24.2% to 88.6%. One study reported dysphagia-related health outcomes and none reported caregiver burden.These results suggest that dysphagia is common in children with stroke and unilateral CP; however, its frequency is yet unknown as is its impact on health and caregiver burden. Availability of a standardized tool to identify dysphagia in these children accurately is a recommended first step to address this evidence gap.There is limited data on the incidence of dysphagia after childhood stroke and unilateral cerebral palsy. Available evidence shows reported dysphagia frequencies from 24.2% to 88.6%. Only one study reported on dysphagia-related health outcomes. No study reported on caregiver burden.DEFICIENCIA DE LA ALIMENTACIÓN Y DEGLUCIÓN EN NIÑOS CON ACCIDENTE CEREBROVASCULAR Y PARÁLISIS CEREBRAL UNILATERAL: UNA REVISIÓN SISTEMÁTICA: OBJETIVO: Esta revisión sistemática se centró en las estimaciones de frecuencia de disfagia (problemas de alimentación y deglución), resultados de salud relacionados y carga del cuidador en niños con accidente cerebrovascular o parálisis cerebral unilateral (PC).Se realizaron búsquedas en seis bases de datos electrónicas desde su inicio hasta noviembre de 2017, junto con una búsqueda manual de ocho revistas relevantes. Dos evaluadores, en forma ciega, evaluaron los resúmenes y los artículos completos para determinar su elegibilidad. Las discrepancias se resolvieron por consenso. Los artículos aceptados fueron evaluados por su calidad. Los datos fueron extraídos y analizados descriptivamente.De los 1.660 resúmenes, cinco cumplieron con los criterios de inclusión, de los cuales tres se centraron en el accidente cerebrovascular y dos en PC unilaterales. Entre los estudios, las definiciones operativas de alimentación y deglución variaban. No se proporcionaron detalles suficientes sobre los métodos de evaluación y el timing de ellas. Las frecuencias reportadas de disfagia variaron de 24,2% a 88,6%. Un estudio informó los resultados de salud relacionados con la disfagia y ninguno informó la carga del cuidador.Estos resultados sugieren que la disfagia es común en niños con accidente cerebrovascular y PC unilateral; sin embargo, aún se desconoce su frecuencia y su impacto en la salud, y en la carga del cuidador. La disponibilidad de una herramienta estandarizada para identificar con precisión la disfagia en estos niños es un primer paso recomendado para abordar esta brecha en la evidencia.DEFICIÊNCIA NA ALIMENTAÇÃO E DEGLUTIÇÃO DE CRIANÇAS COM ACIDENTE VASCULAR ENCEFÁLICO E PARALISIA CEREBRAL UNILATERAL: REVISÃO SISTEMÁTICA: OBJETIVO: Esta revisão sistemática selecionou estimativas de frequência de disfagia (problemas de alimentação e deglutição), desfechos desfavoráveis relacionados e sobrecarga do cuidador em crianças com acidente vascular cerebral ou paralisia cerebral unilateral (PC). MÉTODO: Seis bancos de dados eletrônicos foram pesquisados desde o início até novembro de 2017, juntamente com uma busca manual de oito periódicos relevantes. Dois avaliadores cegos avaliaram resumos e artigos completos para elegibilidade. As discrepâncias foram resolvidas por consenso. Os artigos aceitos foram avaliados quanto à qualidade. Os dados foram extraídos e analisados descritivamente. RESULTADOS: De 1660 resumos, cinco preencheram os critérios de inclusão, dos quais três se concentraram em acidente vascular cerebral e dois CP unilateral. Nos estudos, as definições operacionais de alimentação e deglutição variaram. Foram fornecidos detalhes insuficientes sobre métodos de avaliação e tempo. As frequências relatadas de disfagia variaram de 24,2% a 88,6%. Um estudo relatou desfechos de saúde relacionados à disfagia e nenhum relatou sobrecarga do cuidador. INTERPRETAÇÃO: Esses resultados sugerem que a disfagia é comum em crianças com acidente vascular cerebral e PC unilateral; entretanto, sua frequência ainda é desconhecida, assim como seu impacto na saúde e na sobrecarga do cuidador. A disponibilidade de uma ferramenta padronizada para identificar com precisão a disfagia nessas crianças é um primeiro passo recomendado para abordar essa lacuna de evidência.

Early identification of dysphagia by screening is recommended best practice for patients admitted to hospital with acute stroke. Screening can reduce the risk of pneumonia and promote stroke recovery, yet some institutions do not utilize a formal screening protocol. This study assessed the accuracy of informal dysphagia detection prior to implementation of a formal screening protocol. We conducted a secondary analysis of data captured between 2003 and 2008 from a sample of 250 adult stroke survivors admitted to a tertiary care centre. Using a priori criteria, patient medical records were reviewed for notation about dysphagia; if present, the date/time of notation, writer's profession, and suggestion of dysphagia presence. To assess accuracy of notations indicating dysphagia presence, we used speech language pathology (SLP) assessments as the criterion reference. There were 221 patient medical records available for review. Patients were male (56%), averaged 68 years (SD = 15.0), with a mean Canadian Neurological Scale score of 8.1 (SD = 3.0). First notations of swallowing by SLP were excluded. Of the remaining 170 patients, 147 (87%) had first notations (104 by nurses; 40 by physicians) within a median of 24.3 h from admission. Accuracy of detecting dysphagia from informal notations was low, with a sensitivity of 36.7% [95% CI, 24.9, 50.1], but specificity was high (94.2% [95% CI, 86.5, 97.9]). Informal identification methods, although timely, are suboptimal in their accuracy to detect dysphagia and leave patients with stroke at risk for poor health outcomes. Given these findings, we encourage the use of psychometrically validated formal screening protocols to identify dysphagia.

Introduction: Amoxicillin preparations and ciprofloxacin are widely used to treat infections in children with cystic fibrosis (CF). Objective: to study of factors affecting the pharmacokinetics of these drugs to select an effective dosing regimen. Materials and methods: Аmoxicillin / clavulanate and ciprofloxacin were administered as a single per os dose in children with CF between 2 and 16 years of age. Blood samples were obtained every 1.5 hours post dose for 7.5 hours. The concentration of amoxicillin and ciprofloxacin in serum was analyzed by high performance liquid chromatography. PK data were available in 35 children. Pharmacokinetic (PK) parameters were assessed using the non-compartmental method. Results: The PK profile of amoxicillin and ciprofloxacin varied widely among children with cystic fibrosis. The smallest values of the median maximum plasma concentration Cmax (µg / ml), Cmax norm (µg / ml) / (mg / kg), area under the time-concentration curve AUC0-t, µg * h / ml and area under the time-concentration curve (AUC) after normalization of doses to body weight AUC0-t norm, (µg * h / ml) / (mg / kg) were obtained in the subgroup of children ages 2-3 years old. The highest values of the median Cmax (µg / ml), Cmax norm (µg / ml) / (mg / kg), AUC0-t, µg * h / ml and AUC0-t norm, (µg * h / ml) / (mg / kg) were obtained in the subgroup of adolescents 12-16 years old. Conclusion: The data obtained indicate a relatively higher apparent total body clearance of amoxicillin and ciprofloxacin in the age subgroup of 2-3 years. The results require further study to identify factors affecting the pharmacokinetics of amoxicillin and ciprofloxacin in children with CF.

Background Cystic fibrosis (CF; OMIM #219700) is a common autosomal recessive disease caused by pathogenic variants (henceforward mutations) in the cystic fibrosis transmembrane conductance regulator gene (CFTR). The spectrum and frequencies of CFTR mutations vary among different populations. Characterization of the specific distribution of CFTR mutations can be used to optimize genetic counseling, foster reproductive choices, and facilitate the introduction of mutation-specific therapies. Chechens are a distinct Caucasian ethnic group of the Nakh peoples that originated from the North Caucasus. Chechens are one of the oldest ethnic groups in the Caucasus, the sixth largest ethnic group in the Russian Federation (RF), and constitute the majority population of the Chechen Republic (Chechnya). The spectrum of CFTR mutations in a representative cohort of Chechen CF patients and healthy individuals was analyzed. Methods Molecular genetic analysis of 34 CFTR mutations (representing approx. 80–85% of mutations in multiethnic CF populations of the RF) was performed in 32 CF patients from 31 unrelated Chechen families living in Chechnya. One hundred randomly chosen healthy Chechens were analyzed for the 15 most common “Russian” mutations. The clinical symptoms in Chechen CF patients with different CFTR genotypes were investigated. Results High frequencies of c.1545_1546delTA (p.Tyr515X; 1677delTA) (52 out of 64 CFTR alleles tested; 81.3%) and c.274G > A (p.Glu92Lys, E92K) (8/64, 12.5%) mutations were found. Twenty patients were homozygous for the c.1545_1546delTA mutation, and eight were compound heterozygous for the c.1545_1546delTA and c.274G > A mutations. Three carriers of the c.1545_1546delTA mutation were also found in the cohort of 100 apparently healthy Chechens (frequency – 0.015). The c.1545_1546delTA and c.274G > A mutations are linked to the same haplotype (22–7–16–13) of intragenic Short Tandem Repeat markers, i.e., IVS1CA, IVS6aGATT, IVS8CA, and IVS17bCA. Conclusions The distribution of CFTR mutations in the Chechen CF population is unique regarding the high frequency of mutations c.1545_1546delTA and c.274G > A (more than 90% of the mutant alleles). The c.274G > A mutation is associated with a less severe course of CF than that observed in c.1545_1546delTA homozygotes. Testing for these two variants can be proposed as the first step of CF DNA diagnosis in the Chechen population.

The distribution and frequency of the CFTR gene mutations vary considerably between countries and ethnic groups. Russians are an East Slavic ethnic groups are native to Eastern Europe. Russians, the most numerous people of the Russian Federation (RF), make about 80% of the population. The aim is to reveal the molecular causes of CF in ethnic Russian patients as comprehensively as possible. The analysis of most common CFTR mutations utilized for CF diagnosis in multiethnic RF population accounts for about 83% of all CF-causing mutations in 1384 ethnic Russian patients. Variants c.1521_1523delCTT (F508del), c.54-5940_273+10250del21kb (CFTRdele2,3), c.2012delT (2143delT), c.2052_2053insA (2184insA), and c.3691delT (3821delT) are most typical for CF patients of Russian origin. DNA of 154 CF patients, Russian by origin, in whom at least one mutant allele was not previously identified (164 CF alleles), was analyzed by Sanger sequencing followed by the multiplex ligase-dependent probe amplification (MLPA) method. In addition to the 29 variants identified during the previous test for common mutations, 91 pathogenic CFTR variants were also revealed: 29 missense, 19 nonsense, 14 frame shift in/del, 17 splicing, 1 in frame ins, and 11 copy number variations (CNV). Each of the 61 variants was revealed once, and 17 twice. Each of the variants c.1209G&gt, C (E403D), c.2128A&gt, T (K710X), c.3883delA (4015delA), and c.3884_3885insT (4016insT) were detected for three, c.1766+1G&gt, A (1898+1G&gt, A) and c.2834C&gt, T (S945L) for four, c.1766+1G&gt, C (1898+1G&gt, C) and c.(743+1_744-1)_(1584+1_1585-1)dup (CFTRdup6b-10) for five, c.2353C&gt, T (R785X) and c.4004T&gt, C (L1335P) for six, c.3929G&gt, A (W1310X) for seven, c.580-1G&gt, T (712-1G&gt, T for eight, and c.1240_1244delCAAAA (1365del5) for 11 unrelated patients. A comprehensive analysis of CFTR mutant alleles with sequencing followed by MLPA, allowed not only the identification of 163 of 164 unknown alleles in our patient sample, but also expansion of the mutation spectrum with novel and additional frequent variants for ethnic Russians.

Significant progress has been made in cystic fibrosis (CF) treatment using new antibiotic (AB) therapy options. However, the spectrum of bacterial pathogens and their susceptibility to AB have changed as well. Study objective: to investigate microflora prevailing in CF subjects’ respiratory tract (RT) change over 15 years. CF subjects’ sputum culture test results collected from 2000 till 2015 were analyzed. There were 9774 samples reviewed, 16703 strains identified. “MYCROB” system of microbiological monitoring was used for entry, statistical processing and analysis of data. Study results: S. aur. identification dropped from 42% (2000-03) to 32% (2012-15). P. aerug. from 24% (2000-03) to 11% (2011-15), P. aerug. muc. from 17% (2000-03) to 9% (2012-15). Incidence of chronic P. aerug. infection in CF children decreased from 57% in 1999 to 26% in 2011 and even 14% in 2014. MRSA identification growth from 6% (2000-03) to 9,5% (2008-11) and further to 12% (2012-15) is worrisome. B. cepacia comp. identification grew from 1% (2000-03) to 11% (2008-11) and 7% (2012-15). S. maltophilia identification dropped from 6% (2000-03) to 3% (2012-15). A. xylosoxidans identification grew from 3% (2000-03) to 5% (2012-15). The data presented demonstrate significant change in the distribution of the species identified. In parallel with P. aerug, and P. aerug. muc. identification frequency drop and reduction of chronic P. aerug. infection cases, there is a tendency to higher incidence of B.cepacia complex, A. xylosoxidans and MRSA identification which is quite challenging for further CF subjects care.