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BACKGROUND: Inflammatory bowel disease (IBD) is a chronic inflammatory immune-mediated condition that affects the gastrointestinal system and alters bone growth and bone mineral density (BMD). Here we aimed to study the prevalence and predictors of a low BMD in pediatric patients with IBD. METHODS: This retrospective cross-sectional analytical study included pediatric patients with IBD in whom BMD was evaluated using dual energy X-ray absorptiometry of the total body and lumbar spine. Osteoporosis was defined as a BMD Z-score ≤-2, osteopenia as -2 to -1, and normal as >-1. Clinical and laboratory findings were compared between patients with and without osteoporosis. RESULTS: Of the 48 patients, 30 (62.5%) were males, 35 (72.9%) had Crohn's disease, and 13 (27.1%) had ulcerative colitis. The mean age at diagnosis was 9.9±2.8 years. The median age at the time of the BMD scans was 11.9 (interquartile range, 9.9-14.3) years. Total body BMD scans identified 13 (27.1%) and 16 (33.3%) patients with osteoporosis and osteopenia, respectively. Spinal BMD scans revealed that 17 (39.5%) and 14 (32.6%) patients had osteoporosis and osteopenia, respectively. A low body mass index (BMI) Z-score (p=0.038), ileocolonic disease location (p=0.008), and a low calcium level (p=0.008) were significant predictors of osteoporosis on the total body BMD scans. A low BMI Z-score (p=0.039), decreased hemoglobin level (p=0.018), low calcium level (p=0.033), and infliximab use (p=0.019) were significant predictors of osteoporosis on the spinal BMD scans. CONCLUSIONS: This study showed a high prevalence of low BMD among pediatric patients with IBD. A low BMI, ileocolonic disease location, low hemoglobin and calcium levels, and infliximab use were significantly associated with osteoporosis.
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Background@#Inflammatory bowel disease (IBD) is a chronic inflammatory immune-mediated condition that affects the gastrointestinal system and alters bone growth and bone mineral density (BMD). Here we aimed to study the prevalence and predictors of a low BMD in pediatric patients with IBD. @*Methods@#This retrospective cross-sectional analytical study included pediatric patients with IBD in whom BMD was evaluated using dual energy X-ray absorptiometry of the total body and lumbar spine. Osteoporosis was defined as a BMD Z-score ≤-2, osteopenia as -2 to -1, and normal as >-1. Clinical and laboratory findings were compared between patients with and without osteoporosis. @*Results@#Of the 48 patients, 30 (62.5%) were males, 35 (72.9%) had Crohn’s disease, and 13 (27.1%) had ulcerative colitis. The mean age at diagnosis was 9.9±2.8 years. The median age at the time of the BMD scans was 11.9 (interquartile range, 9.9–14.3) years. Total body BMD scans identified 13 (27.1%) and 16 (33.3%) patients with osteoporosis and osteopenia, respectively. Spinal BMD scans revealed that 17 (39.5%) and 14 (32.6%) patients had osteoporosis and osteopenia, respectively. A low body mass index (BMI) Z-score (p=0.038), ileocolonic disease location (p=0.008), and a low calcium level (p=0.008) were significant predictors of osteoporosis on the total body BMD scans. A low BMI Z-score (p=0.039), decreased hemoglobin level (p=0.018), low calcium level (p=0.033), and infliximab use (p=0.019) were significant predictors of osteoporosis on the spinal BMD scans. @*Conclusions@#This study showed a high prevalence of low BMD among pediatric patients with IBD. A low BMI, ileocolonic disease location, low hemoglobin and calcium levels, and infliximab use were significantly associated with osteoporosis.
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The purpose of the study was to characterize the resistome, virulome, mobilome and Clustered Regularly Interspaced Short Palindromic Repeats-associated (CRISPR-Cas) system of extended-spectrum ß-lactamase producing Klebsiella pneumoniae (ESBL-KP) clinical isolates and to determine their phylogenetic relatedness. The isolates were from Algeria, isolated at the University Hospital Establishment of Oran, between 2011 and 2012. ESBL-KP isolates (n = 193) were screened for several antibiotic resistance genes (ARGs) using qPCR followed by Pulsed-Field Gel Electrophoresis (PFGE). Representative isolates were selected from PFGE clusters and subjected to whole-genome sequencing (WGS). Genomic characterization of the WGS data by studying prophages, CRISPR-Cas systems, Multi-Locus Sequence Typing (MLST), serotype, ARGs, virulence genes, plasmid replicons, and their pMLST. Phylogenetic and comparative genomic were done using core genome MLST and SNP-Based analysis. Generally, the ESBL-KP isolates were polyclonal. The whole genome sequences of nineteen isolates were taken of main PFGE clusters. Sixteen sequence types (ST) were found including high-risk clones ST14, ST23, ST37, and ST147. Serotypes K1 (n = 1), K2 (n = 2), K3 (n = 1), K31 (n = 1), K62 (n = 1), and K151 (n = 1) are associated with hyper-virulence. CRISPR-Cas system was found in 47.4%, typed I-E and I-E*. About ARGs, from 193 ESBL-KP, the majority of strains were multidrug-resistant, the CTX-M-1 enzyme was predominant (99%) and the prevalence of plasmid-mediated quinolone resistance (PMQR) genes was high with aac(6')-lb-cr (72.5%) and qnr's (65.8%). From 19 sequenced isolates we identified ESBL, AmpC, and carbapenemase genes: blaCTX-M-15 (n = 19), blaOXA-48 (n = 1), blaCMY-2 (n = 2), and blaCMY-16 (n = 2), as well as non-ESBL genes: qnrB1 (n = 12), qnrS1 (n = 1) and armA (n = 2). We found IncF, IncN, IncL/M, IncA/C2, and Col replicon types, at least once per isolate. This study is the first to report qnrS in ESBL-KP in Algeria. Our analysis shows the concerning co-existence of virulence and resistance genes and would support that genomic surveillance should be a high priority in the hospital environment.
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Proteínas Bacterianas/genética , Infecciones por Klebsiella/tratamiento farmacológico , Klebsiella pneumoniae/enzimología , beta-Lactamasas/genética , Argelia , Antibacterianos/efectos adversos , Antibacterianos/farmacología , Proteínas Bacterianas/metabolismo , Células Clonales/citología , Células Clonales/efectos de los fármacos , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Farmacorresistencia Bacteriana Múltiple/genética , Genoma Bacteriano/genética , Hospitales Universitarios , Humanos , Infecciones por Klebsiella/enzimología , Infecciones por Klebsiella/microbiología , Infecciones por Klebsiella/patología , Klebsiella pneumoniae/patogenicidad , Pruebas de Sensibilidad Microbiana , Tipificación de Secuencias Multilocus , Filogenia , Plásmidos/efectos de los fármacos , Secuenciación Completa del Genoma , beta-Lactamasas/metabolismoRESUMEN
The prevalence of carbapenem-resistant Enterobacterales (CRE) in the Arabian Peninsula is predicted to be high, as suggested from published case reports. Of particular concern, is carbapenem-resistant E. coli (CR-EC), due to the importance of this species as a community pathogen. Herein, we conducted a comprehensive molecular characterization of putative CR-EC strains from Oman. We aim to establish a baseline for future molecular monitoring. We performed whole-genome sequencing (WGS) for 35 putative CR-EC. Isolates were obtained from patients at multiple centers in 2015. Genetic relatedness was investigated using several typing approaches such as MLST, SNP calling, phylogroup and CRISPR typing. Maxiuium likelihood SNP-tree was performed by RAxML after variant calling and removal of recombination regions with Snippy and Gubbins, respectively. Resistance genes, plasmid replicon types, virulence genes, and prophage were also characterised. The online databases CGE, CRISPRcasFinder, Phaster and EnteroBase were used for the in silico analyses. Screening for mutations in genes regulating the expression of porins and efflux pump as well as mutations lead to fluoroquinolones resistance were performed with CLC Genomics Workbench. The genetic diversity suggests a polyclonal population structure with 21 sequence types (ST), of which ST38 being the most prevalent (11%). SNPs analysis revealed possible transmission episodes. Whereas, CRISPR typing helped to spot outlier strains belonged to phylogroups other than B2 which was CRISPR-free. The virulent phylogroups B2 and D were detected in 4 and 9 isolates, respectively. In some strains bacteriophages acted as vectors for virulence genes. Regarding resistance to ß-lactam, 22 were carbapenemase producers, 3 carbapenem non-susceptible but carbapenemase-negative, 9 resistant to expanded-spectrum cephalosporins, and one isolate with susceptibility to cephalosporins and carbapenems. Thirteen out of the 22 (59%) carbapenemase-producing isolates were NDM and 7 (23%) were OXA-48-like which mirrors the situation in Indian subcontinent. Two isolates co-produced NDM and OXA-48-like enzymes. In total, 80% (28/35) were CTX-M-15 producers and 23% (8/35) featured AmpC. The high-risk subclones ST131-H30Rx/C2, ST410-H24RxC and ST1193-H64RxC were detected, the latter associated with NDM. To our knowledge, this is the first report of ST1193-H64Rx subclone with NDM. In conclusion, strains showed polyclonal population structure with OXA-48 and NDM as the only carbapenemases in CR-EC from Oman. We detected the high-risk subclone ST131-H30Rx/C2, ST410-H24RxC and ST1193-H64RxC. The latter was reported with carbapenemase gene for the first time here.
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Carbapenémicos/farmacología , Infecciones por Escherichia coli , Proteínas de Escherichia coli/genética , Escherichia coli , Resistencia betalactámica/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Bases de Datos Genéticas , Escherichia coli/clasificación , Escherichia coli/efectos de los fármacos , Escherichia coli/aislamiento & purificación , Infecciones por Escherichia coli/epidemiología , Infecciones por Escherichia coli/microbiología , Femenino , Genes Bacterianos , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Omán , Plásmidos , Factores de Virulencia/genética , Adulto JovenRESUMEN
BACKGROUND: Colistin is a polypeptide antibiotic drug that targets lipopolysaccharides in the outer membrane of Gram-negative bacteria. Inactivation of the mgrB-gene is a common mechanism behind colistin-resistance in Klebsiella pneumoniae (Kpn). Since colistin is a cyclic polypeptide, it may exhibit cross-resistance with the antimicrobial peptide LL-37, and with other innate effector mechanisms, but previous results are inconclusive. OBJECTIVE: To study potential cross-resistance between colistin and LL-37, as well as with other innate effector mechanisms, and to compare virulence of colistin-resistant and susceptible Kpn strains. MATERIALS/METHODS: Carbapenemase-producing Kpn from Oman (n = 17) were subjected to antimicrobial susceptibility testing and whole genome sequencing. Susceptibility to colistin and LL-37 was studied. The surface charge was determined by zeta-potential measurements and the morphology of treated bacteria was analyzed with electron microscopy. Bacterial survival was assessed in human whole blood and serum, as well as in a zebrafish infection-model. RESULTS: Genome-analysis revealed insertion-sequences in the mgrB gene, as a cause of colistin resistance in 8/17 isolates. Colistin-resistant (Col-R) isolates were found to be more resistant to LL-37 compared to colistin-susceptible (Col-S) isolates, but only at concentrations ≥50 µg/ml. There was no significant difference in surface charge between the isolates. The morphological changes were similar in both Col-R and Col-S isolates after exposure to LL-37. Finally, no survival difference between the Col-R and Col-S isolates was observed in whole blood or serum, or in zebrafish embryos. CONCLUSION: Cross-resistance between colistin and LL-37 was observed at elevated concentrations of LL-37. However, Col-R and Col-S isolates exhibited similar survival in serum and whole blood, and in a zebrafish infection-model, suggesting that cross-resistance most likely play a limited role during physiological conditions. However, it cannot be ruled out that the observed cross-resistance could be relevant in conditions where LL-37 levels reach high concentrations, such as during infection or inflammation.
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AIMS: To evaluate the safety of saxagliptin ± metformin over 4 years in patients with Type 2 diabetes mellitus. METHODS: Drug-naive (n = 401; study 11) or metformin-treated (n = 743; study 14) adults with HbA(1c) of 53-86 mmol/mol (7.0-10%) were enrolled in two randomized, placebo-controlled, double-blind trials of saxagliptin 2.5, 5 or 10 mg/day. Patients rescued during or completing 24 weeks of treatment could continue in a 42-month long-term blinded phase, for which the primary goal was assessment of safety and tolerability. Between-group efficacy was not evaluated in the long-term phase of study 11. Time to rescue or discontinuation because of inadequate glycaemic control, change from baseline in HbA(1c) and percentages of patients achieving HbA(1c) < 53 mmol/mol (< 7.0%) were assessed in study 14. RESULTS: No new safety findings were noted during the long-term phase. Most adverse events were mild or moderate, with slightly greater frequency of upper respiratory infections with saxagliptin. Hypoglycaemic event rates were similar with saxagliptin and placebo. In study 14, time to rescue or discontinuation because of inadequate glycaemic control was longer with saxagliptin plus metformin than for placebo plus metformin. From baseline to week 154, HbA(1c) decreased with saxagliptin but increased with placebo. CONCLUSION: Saxagliptin monotherapy or add-on to metformin is generally safe and well tolerated, with no increased risk of hypoglycaemia, for up to 4 years.
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Adamantano/análogos & derivados , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Dipéptidos/uso terapéutico , Hipoglucemiantes/uso terapéutico , Metformina/uso terapéutico , Adamantano/uso terapéutico , Glucemia/metabolismo , Diabetes Mellitus Tipo 2/sangre , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Método Doble Ciego , Quimioterapia Combinada , Femenino , Hemoglobina Glucada/metabolismo , Humanos , Hipoglucemia/inducido químicamente , Hipoglucemia/prevención & control , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Tiempo , Resultado del TratamientoRESUMEN
A major challenge to the success of malaria control program in Saudi Arabia is the high influx of expatriates and holy visitors from malaria endemic countries. In the present study we examined whether drug resistant parasite genotypes reported in Jazan region, southwest of Saudi Arabia are imported or developed locally. We examined 178 Plasmodium falciparum isolates for alleles of dihydropteroate synthase (dhps) and dihydrofolate reductase (dhfr), associated with Sulfadoxine-Pyrimethamine (SP) resistance, and three microsatellites flanking each gene. In addition, we examined a neutral polymorphic gene (Pfg377). We compared the dhfr and dhps haplotypes in Jazan, using network analysis, to an existing similar data set of 94 P. falciparum isolates from eastern Sudan. In Jazan, double mutant dhfr allele (51I, 108N) occurred with a prevalence of 33%. The vast majority (99%) of dhps were wild-type alleles. The mean expected heterozygosity (H(e)) of microsatellites around mutant dhfr alleles (H(e)=0.312; n=60) was lower (P ≤ 0.05) than that around the wild-type allele (H(e)=0.834; n=116). Also, the mutant dhfr isolates showed high H(e) for dhps (H(e)=0.80) and the non-drug resistance locus Pfg377 (H(e)=0.63) indicative of selection for mutant dhfr only. The predominant double mutant dhfr haplotype in Jazan (73%), was prevalent among P. falciparum in east Africa. Network analysis suggests the mutant haplotype of dhfr gene was possibly introduced into Jazan from East Africa. The absence of mutations in dhps as well as triple mutant dhfr haplotype associated with SP failure support the current use of SP as a partner with artesunate as a first line therapy in Saudi Arabia. However, the close relationship between the major mutant dhfr haplotype in Sudan and Saudi Arabia, favour the hypothesis of recent migration as a source of the major resistant dhfr lineage. Thus, regular monitoring of the dhfr and dhps haplotypes is of high priority to guard possible importation of high level SP resistant lineages.
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Antimaláricos/farmacología , Malaria Falciparum/parasitología , Plasmodium falciparum/genética , ADN Protozoario/análisis , ADN Protozoario/genética , Dihidropteroato Sintasa/genética , Combinación de Medicamentos , Resistencia a Medicamentos , Haplotipos , Humanos , Malaria Falciparum/prevención & control , Malaria Falciparum/transmisión , Repeticiones de Microsatélite , Modelos Genéticos , Mutación , Plasmodium falciparum/efectos de los fármacos , Plasmodium falciparum/enzimología , Pirimetamina/farmacología , Arabia Saudita , Sulfadoxina/farmacología , Tetrahidrofolato Deshidrogenasa/genéticaRESUMEN
Two hundred and three Plasmodium falciparum isolates from Jazan area, southwest Saudi Arabia, were typed for Pfcrt, Pfmdr1, dhps, and dhfr mutations associated with resistance to chloroquine, mefloquine, halofantrine, artemisinin, sulfadoxine-pyrimethamine, and the neutral polymorphic gene Pfg377. A large proportion (33%) of isolates harbored double mutant dhfr genotype (51I,59C,108N). However, only one isolate contained mutation dhps-437G. For Pfcrt, almost all examined isolates (163; 99%) harbored the mutant genotype (72C,73V,74I,75E,76T), whereas only 49 (31%) contained the mutant Pfmdr1 genotype (86Y,184F,1034S,1042N), 109 (66%) harbored the single mutant genotype (86N,184F,1034S,1042N), and no mutations were seen in codons 1034, 1042, and 1246. Nonetheless, three new single-nucleotide polymorphisms were detected at codons 182, 192, and 102. No differences were seen in distribution of drug resistance genes among Saudis and expatriates. There was a limited multiplicity (5%), mean number of clones (1.05), and two dominant multilocus genotypes among infected individuals in Jazan. A pattern consistent with limited cross-mating and recombination among local parasite was apparent.
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Genotipo , Plasmodium falciparum/efectos de los fármacos , Plasmodium falciparum/genética , Plasmodium falciparum/aislamiento & purificación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antimaláricos/farmacología , Artemisininas/uso terapéutico , Niño , Preescolar , Cloroquina/uso terapéutico , Combinación de Medicamentos , Resistencia a Medicamentos/genética , Femenino , Humanos , Lactante , Masculino , Mefloquina/uso terapéutico , Proteínas de Transporte de Membrana/genética , Proteínas de Transporte de Membrana/metabolismo , Persona de Mediana Edad , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/genética , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/metabolismo , Mutación , Fenantrenos/uso terapéutico , Plasmodium falciparum/patogenicidad , Polimorfismo de Nucleótido Simple , Proteínas Protozoarias/genética , Proteínas Protozoarias/metabolismo , Pirimetamina/uso terapéutico , Arabia Saudita/epidemiología , Sulfadoxina/uso terapéutico , Tetrahidrofolato Deshidrogenasa/genética , Tetrahidrofolato Deshidrogenasa/aislamiento & purificación , Adulto JovenRESUMEN
Os autores apresentam um caso unico na literatura medica de galactorreia e hiperprolactinemia devido a presenca de metastase de carcinoma folicular da tiroide para sela turcica. Comentam a localizacao incomum desta metastase e os provaveis aspectos fisiopatologicos envolvidos na producao excessiva de prolactina. Analisam, finalmente, outros sintomas como proptose, amaurose e epistaxe decorrentes da evolucao da metastase
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Persona de Mediana Edad , Humanos , Femenino , Metástasis de la Neoplasia , Neoplasias Hipofisarias , Prolactina , Neoplasias de la Tiroides , Silla TurcaAsunto(s)
Humanos , Masculino , Femenino , Galactorrea , Hormona Luteinizante , Trastornos de la Menstruación , Neoplasias Hipofisarias , ProlactinaRESUMEN
Os autores relatam um caso de hipertireoidismo infantil, dando enfase a pouca frequencia desta patologia tireoidiana na faixa etaria infantil. Sao discutidos os aspectos etiopatogenicos, clinicos e terapeuticos