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1.
Med Princ Pract ; 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38569485

RESUMO

INTRODUCTION: The robotic platform compared to laparoscopy has proven to have similar postoperative outcomes, however its adoption in the Middle East has been slow and there is limited data regarding outcomes with its use in small newly established robotic colorectal programs. Our aim was to report our experience and outcomes of robotic colorectal surgery performed by fellowship-trained robotic colorectal surgeons and compare them to larger, more experienced centers. METHODS: This is retrospective review of data collected between November 2021 and March 2023 from a tertiary health care referral center. The series included 51 patients who had elective or urgent robotic colorectal surgery. Patients who had emergency surgery were excluded. The outcomes were overall morbidity, serious morbidity, mortality, conversion to open, length of hospital stay, and quality of oncological specimen. RESULTS: The overall morbidity was 31.4% (n = 16 patients). Only 9.8% (n = 5) had serious morbidity of which three required interventions under general anesthesia. The median length of hospital stay was 6 days (IQR = 4), and there was no mortality. Of 17 rectal cancer resections, 88% had complete mesorectal excision, 15 of them were R0 resections, median lymph node harvested was 14 (IQR = 7) and two cases were converted to open. All the colon cancer resections had R0 resection, median lymph nodes harvested was 21 (IQR = 4) and none were converted to open. CONCLUSIONS: The implementation and integration of robotic colorectal surgery at a newly established center in a small country, when led by fellowship trained robotic colorectal surgeons, is safe and effective in terms of morbidity, mortality, conversion to open and specimen pathological quality.

2.
J Fluoresc ; 32(3): 949-960, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35166972

RESUMO

Nanomedicine and fluorescent optical imaging are effective in early cancer detection. The current study synthesized biocompatible nanocomposites from natural biomaterials towards inexpensive and safe cancer theragnostic. Two forms of nanocomposites were synthesized using the ionic gelation method: 1. Chitosan/ Withania Somnifera /tripolyphosphate nanocomposites, 2. Withania Somnifera/Chitosan nanocomposites. The nanocomposites were characterized by dynamic light scattering, zeta potential, and the transmission electron microscope. Fourier transform infrared spectroscopy analyzed the Withania Somnifera root water extract, Chitosan, and the synthesized nanocomposites. The cytotoxicity of the nanocomposites was investigated against the colon cancer cells (Caco2 cells) in the absence and the presence of laser (665 nm, 5 mW) irradiation. MTT assay evaluated the cytotoxicity, and Trypan blue assay assessed the cell viability. Cancerous cells were photographed under the inverted microscope in the presence and the absence of laser irradiation. Results were analyzed statistically using one-way variance (ANOVA) analysis with Bonferroni post-Hoc multiple two-group comparisons. The characterization results ensured the successful synthesis of Withania Somnifera/Chitosan nanocomposites. The results showed an increase in the cytotoxicity against colon carcinoma and a decrease in cell viability in the presence and absence of Near-infrared laser irradiation under the action of nanocomposites. The cytotoxicity of the synthesized nanocomposites increased by exposing the cells to the laser. The shining light of the nanocomposites appeared on the cells photographed under the inverted microscope. The synthesized natural nanocomposites promise systemic cytotoxicity will be efficient in molecular imaging in vivo applications.


Assuntos
Quitosana , Nanocompostos , Neoplasias , Withania , Células CACO-2 , Quitosana/química , Meios de Contraste , Humanos , Nanocompostos/química , Extratos Vegetais , Withania/química
3.
Clin Exp Immunol ; 203(1): 3-12, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32939755

RESUMO

Variations in the immune response could explain resistance to hepatitis C virus (HCV) infection. Toll-like receptor gene (TLR)-3 is an innate detector of dsRNA viruses, and the TLR-9 gene recognizes bacterial and viral unmethylated cytosine-phosphate-guanosine (CpG) motifs. We previously reported that the TLR-3.rs3775290 CC genotype was associated with HCV chronicity and that the TLR-9 gene played no major role in this infection. This study identified the role of TLR-3.rs3775290 (c.1377C/T), TLR-9.rs5743836 (-1237T→C) and TLR-9.rs352140 (G2848A) gene polymorphisms in predicting the outcome of HCV-specific cell-mediated immunity (CMI) among Egyptian health-care workers (HCWs). We enrolled 265 HCWs in this study and divided them into four groups. Group 1: 140 seronegative-aviraemic HCWs; group 2: 20 seronegative-viraemic HCWs; group 3: 35 subjects with spontaneously resolved HCV infection; and group 4: 70 chronic HCV HCWs (patients). All subjects were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis for the TLR-3.rs3775290, TLR-9.rs5743836 and TLR-9.rs352140 single nucleotide polymorphisms (SNPs). We also quantified HCV-specific CMI in the four groups using an interferon (IFN)-γ enzyme-linked immunospot (ELISPOT) assay in response to nine HCV genotype 4a, overlapping 15mer peptide pools covering the whole viral genome. No statistically significant difference was found between CMI-responding subjects with different HCV states and TLR-3.rs3775290 or TLR-9.rs352140 genotypes. However, there was a significant relationship between the outcome of the HCV-specific CMI and the TLR-9.rs5743836 genotype among the responding subjects (P = 0·005) and the chronic HCV patients (P = 0·044). In conclusion, TLR-9.rs5743836 SNP, but not TLR-3.rs3775290 or TLR-9.rs352140 genotypes, could predict the outcome of HCV-specific CMI responses among Egyptians infected with genotype-4.


Assuntos
Pessoal de Saúde , Hepacivirus , Hepatite C Crônica , Imunidade Celular , Polimorfismo de Nucleotídeo Único , Receptor 3 Toll-Like , Adulto , Feminino , Hepacivirus/genética , Hepacivirus/imunologia , Hepatite C Crônica/genética , Hepatite C Crônica/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Receptor 3 Toll-Like/genética , Receptor 3 Toll-Like/imunologia , Receptor Toll-Like 9/genética , Receptor Toll-Like 9/imunologia
4.
Br J Surg ; 108(4): 441-447, 2021 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-33615351

RESUMO

BACKGROUND: Complicated intra-abdominal infections (cIAIs) are associated with significant morbidity and mortality. The aim of this study was to describe the clinical characteristics of patients with cIAI in a multicentre study and to develop clinical prediction models (CPMs) to help identify patients at risk of mortality or relapse. METHODS: A multicentre observational study was conducted from August 2016 to February 2017 in the UK. Adult patients diagnosed with cIAI were included. Multivariable logistic regression was performed to develop CPMs for mortality and cIAI relapse. The c-statistic was used to test model discrimination. Model calibration was tested using calibration slopes and calibration in the large (CITL). The CPMs were then presented as point scoring systems and validated further. RESULTS: Overall, 417 patients from 31 surgical centres were included in the analysis. At 90 days after diagnosis, 17.3 per cent had a cIAI relapse and the mortality rate was 11.3 per cent. Predictors in the mortality model were age, cIAI aetiology, presence of a perforated viscus and source control procedure. Predictors of cIAI relapse included the presence of collections, outcome of initial management, and duration of antibiotic treatment. The c-statistic adjusted for model optimism was 0.79 (95 per cent c.i. 0.75 to 0.87) and 0.74 (0.73 to 0.85) for mortality and cIAI relapse CPMs. Adjusted calibration slopes were 0.88 (95 per cent c.i. 0.76 to 0.90) for the mortality model and 0.91 (0.88 to 0.94) for the relapse model; CITL was -0.19 (95 per cent c.i. -0.39 to -0.12) and - 0.01 (- 0.17 to -0.03) respectively. CONCLUSION: Relapse of infection and death after complicated intra-abdominal infections are common. Clinical prediction models were developed to identify patients at increased risk of relapse or death after treatment, these now require external validation.


Assuntos
Regras de Decisão Clínica , Infecções Intra-Abdominais/etiologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Feminino , Humanos , Infecções Intra-Abdominais/diagnóstico , Infecções Intra-Abdominais/tratamento farmacológico , Infecções Intra-Abdominais/mortalidade , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Recidiva , Fatores de Risco
5.
J Contemp Dent Pract ; 22(1): 93-100, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34002717

RESUMO

AIM: The present review aimed to summarize and evaluate the available literature regarding the survival rate and outcomes of dental implants in patients with Papillon-Lefèvre syndrome (PLS). MATERIALS AND METHODS: An extensive search of the literature was conducted on PubMed, Scopus and Web of Science databases for all data published from January 1996 till April 2020 using a combination of the following keywords: 'Papillon Lefévre Syndrome', 'prosthodontic rehabilitation' and 'dental implant' according to the PRISMA guidelines for the focused research question constructed using the PICO criteria. Clinical trials and observational studies on implant placement in PLS patients reported in English language were included in the study. RESULTS: A total of 10 studies (nine case reports and one case series) comprising 124 dental implants placed in 13 PLS patients were included. The follow-up period ranged from 4 months to 9 years. With regard to implant loading, 9 studies reported delayed loading, while one study did not provide any information regarding the nature of implant loading. The design of prosthodontic superstructure was either a removable or fixed prosthesis. Out of the 124 inserted implants, 20 (16%) were reported as failed. The overall survival rate was 84%. CONCLUSION: The limited available evidence suggests that the survival rate of dental implants in patients with PLS is lower than that among healthy individuals. Nevertheless, no strict contraindication for implant-supported prosthesis seems to be justified in this group of patients. Further longitudinal studies with adequate follow-up periods are highly warranted. CLINICAL SIGNIFICANCE: The prognosis of implant treatment for PLS patients has not yet been established. Dental practitioners should follow a careful approach in planning the dental implant treatment for this cohort of patients.


Assuntos
Implantes Dentários , Doença de Papillon-Lefevre , Implantação Dentária Endóssea , Prótese Dentária Fixada por Implante , Falha de Restauração Dentária , Odontólogos , Seguimentos , Humanos , Papel Profissional , Taxa de Sobrevida
6.
Int J Dent Hyg ; 18(1): 44-51, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30829440

RESUMO

OBJECTIVES: The present systematic review assessed the efficacy of aloe vera mouthrinse on plaque and gingival inflammation. METHODS: A comprehensive search of PubMed, EMBASE, Scopus and Web of Science was conducted in February 2018 to identify all relevant studies using the following keywords: aloe vera, gingivitis, gingival inflammation, plaque-induced gingivitis, periodontal health and plaque control. The eligibility criteria were all randomized clinical trials that assessed the efficacy of aloe vera mouthrinse in comparison to chlorhexidine on plaque and gingivitis. The risk of bias of the included studies was assessed using the Cochrane risk of bias assessment tool. RESULTS: Six randomized clinical trials comprising 1358 subjects were included in this systematic review. All included studies showed that aloe vera was effective in reducing plaque and gingival inflammation. Four studies found aloe vera as effective as chlorhexidine in reducing plaque scores, while two studies found chlorhexidine significantly more effective than aloe vera. With regard to gingival inflammation, three studies showed comparable results between aloe vera and chlorhexidine, while one study showed better results with chlorhexidine. Moreover, the results showed that aloe vera had no or very minimal side effects compared to chlorhexidine, which showed significant side effects including stains and altered taste sensation. CONCLUSION: The available evidence remains inconclusive but suggests that aloe vera mouthwash is comparable to chlorhexidine in reducing gingival inflammation but inferior to chlorhexidine in reducing plaque. These findings are preliminary and further high-quality studies with adequate sample sizes are highly recommended.


Assuntos
Aloe , Placa Dentária , Gengivite , Clorexidina , Humanos , Antissépticos Bucais
7.
Lupus ; 28(8): 995-1002, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31184250

RESUMO

BACKGROUND: Pediatric-onset SLE (pSLE) is a multisystem autoimmune disease. Recently, the ficolin-2 (FCN2) gene has emerged as a potential candidate gene for susceptibility to SLE. OBJECTIVES: The objective of this study was to evaluate the association of the FCN2 gene polymorphisms at positions -986 (G/A), -602 (G/A), -4 (A/G) and SNP C/T (rs3124954) located in intron 1, with susceptibility to pSLE in Egyptian children and adolescents. METHODS: This was a multicenter study of 280 patients diagnosed with pSLE, and 280 well-matched healthy controls. The FCN2 promoter polymorphisms at -986 G/A (rs3124952), -602 G/A (rs3124953), -4 A/G (rs17514136) and SNP C/T (rs3124954) located in intron 1 were genotyped by polymerase chain reaction, while serum ficolin-2 levels were assessed using enzyme-linked immunosorbent assay. RESULTS: The frequencies of the FCN2 GG genotype and G allele at -986 and -602 positions were significantly more represented in patients with pSLE than in controls (p < 0.001). Conversely, the FCN2 AA genotype and A allele at position -4 were more common in patients than in controls (p < 0.001). Moreover, patients carrying the FCN2 GG genotype in -986 position were more likely to develop lupus nephritis (odds ratio: 2.6 (95% confidence interval: 1.4-4.78); p = 0.006). The FCN2 AA genotype at position -4 was also identified as a possible risk factor for lupus nephritis (odds ratio: 3.12 (95% confidence interval: 1.25-7.84); p = 0.024). CONCLUSION: The FCN2 promoter polymorphisms may contribute to susceptibility to pSLE in Egyptian children and adolescents. Moreover, the FCN2 GG genotype at position -986 and AA genotype at position -4 were associated with low serum ficolin-2 levels and may constitute risk factors for lupus nephritis in pSLE.


Assuntos
Predisposição Genética para Doença , Lectinas/genética , Lúpus Eritematoso Sistêmico/genética , Nefrite Lúpica/genética , Adolescente , Alelos , Estudos de Casos e Controles , Criança , Egito , Feminino , Humanos , Modelos Logísticos , Masculino , Polimorfismo de Nucleotídeo Único , Estudos Prospectivos , Fatores de Risco , Ficolinas
8.
Public Health ; 175: 148-155, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31494336

RESUMO

OBJECTIVES: In this article, we present death and myocardial infarction (MI) incidences over 22 years in relation to possible risk factors and their explanatory value. STUDY DESIGN: In 1993, 980 middle-aged Swedish men in an automotive industry were surveyed at a health checkup as part of the Renault-Volvo Coeur project. The Swedish cohort was revisited in 2015. METHODS: In 2015, incident MIs were identified using postal questionnaires, hospital records, and the Swedish national MI and death registers. The statistical results were given as odds ratios (ORs) and pseudo-R2 (PR2), showing the proportion of variation in risk explained by logistic models. RESULTS: One hundred and four deaths (4.6 per 1000 person-years) and 89 first MIs (4.2 per 1000 person-years) were identified. The Framingham risk index showed the strongest association with MI (OR = 23; 95% confidence interval [CI] = 5.42, 96.9), comparing the fifth quintile with the first. The all-cause death showed an OR of 3.2 (95% CI = 1.65, 6.08), with a suggested U-shape over quintiles. The percentages of PR2 for MI and death were 8.8% and 6.6%, respectively. All risk factors together explained 22% of the variation in risk of MI. Comparing mortality in men living alone with those married yielded an OR of 3.78, which was found to be statistically significant. The corresponding OR for MI was not significant. CONCLUSIONS: Traditional risk factors were confirmed but explained a modest proportion of the risk variation.


Assuntos
Mortalidade/tendências , Infarto do Miocárdio/epidemiologia , Estudos de Coortes , Emprego/estatística & dados numéricos , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Suécia/epidemiologia
9.
Sensors (Basel) ; 19(3)2019 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-30700041

RESUMO

. Over the past ten years, diabetes has rapidly become more prevalent in all age demographics and especially in children. Improved dietary assessment techniques are necessary for epidemiological studies that investigate the relationship between diet and disease. Current nutritional research is hindered by the low accuracy of traditional dietary intake estimation methods used for portion size assessment. This paper presents the development and validation of a novel instrumentation system for measuring accurate dietary intake for diabetic patients. This instrument uses a mobile Structured Light System (SLS), which measures the food volume and portion size of a patient's diet in daily living conditions. The SLS allows for the accurate determination of the volume and portion size of a scanned food item. Once the volume of a food item is calculated, the nutritional content of the item can be estimated using existing nutritional databases. The system design includes a volume estimation algorithm and a hardware add-on that consists of a laser module and a diffraction lens. The experimental results demonstrate an improvement of around 40% in the accuracy of the volume or portion size measurement when compared to manual calculation. The limitations and shortcomings of the system are discussed in this manuscript.

10.
Clin Genet ; 93(2): 360-364, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28503735

RESUMO

The advancement in genomic sequencing has greatly improved the diagnostic yield for neurodevelopmental disorders and led to the discovery of large number of novel genes associated with these disorders. WDR45B has been identified as a potential intellectual disability gene through genomic sequencing of 2 large cohorts of affected individuals. In this report we present 6 individuals from 3 unrelated families with homozygous pathogenic variants in WDR45B: c.799C>T (p.Q267*) in 1 family and c.673C>T (p.R225*) in 2 families. These individuals shared a similar phenotype including profound development delay, early-onset refractory epilepsy, progressive spastic quadriplegia and contractures, and brain malformations. Neuroimaging showed ventriculomegaly, reduced cerebral white matter volume, and thinning of cerebral gray matter. The consistency in the phenotype strongly supports that WDR45B is associated with this disease.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Predisposição Genética para Doença , Deficiência Intelectual/genética , Transtornos do Neurodesenvolvimento/genética , Adolescente , Criança , Pré-Escolar , Epilepsia/genética , Epilepsia/patologia , Feminino , Homozigoto , Humanos , Lactente , Deficiência Intelectual/patologia , Masculino , Mutação , Transtornos do Neurodesenvolvimento/patologia , Quadriplegia/genética , Quadriplegia/patologia
11.
Clin Genet ; 94(6): 554-563, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30054919

RESUMO

Retinal dystrophies (RDs) are hereditary blinding eye conditions that are highly variable in their clinical presentation. The remarkable genetic heterogeneity that characterizes RD was a major challenge in establishing the molecular diagnosis in these patients until the recent advent of next-generation sequencing. It remains unclear, however, what percentage of autosomal recessive RD remain undiagnosed when all established RD genes are sequenced. We enrolled 75 families in which RD segregates in an apparently autosomal recessive manner. We show that the yield of a multigene panel that contains known RD genes is 67.5%. The higher yield (82.3%) when whole exome sequencing was implemented instead was often due to hits in genes that were not included in the original design of the panel. We also show the value of homozygosity mapping even during the era of exome sequencing in uncovering cryptic mutations. In total, we describe 45 unique likely deleterious variants (of which 18 are novel including one deep intronic and one genomic deletion mutation). Our study suggests that the genetic heterogeneity of autosomal recessive RD is approaching saturation and that any new RD genes will probably account for only a minor role in the mutation burden.


Assuntos
Genes Recessivos , Estudos de Associação Genética , Predisposição Genética para Doença , Mutação , Distrofias Retinianas/diagnóstico , Distrofias Retinianas/genética , Alelos , Substituição de Aminoácidos , Consanguinidade , Genótipo , Humanos , Fenótipo , Polimorfismo de Nucleotídeo Único , Sequenciamento do Exoma , Fluxo de Trabalho
12.
Clin Genet ; 93(6): 1210-1222, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29450879

RESUMO

Microphthalmia is a developmental eye defect that is highly variable in severity and in its potential for systemic association. Despite the discovery of many disease genes in microphthalmia, at least 50% of patients remain undiagnosed genetically. Here, we describe a cohort of 147 patients (93 families) from our highly consanguineous population with various forms of microphthalmia (including the distinct entity of posterior microphthalmos) that were investigated using a next-generation sequencing multi-gene panel (i-panel) as well as whole exome sequencing and molecular karyotyping. A potentially causal mutation was identified in the majority of the cohort with microphthalmia (61%) and posterior microphthalmos (82%). The identified mutations (55 point mutations, 15 of which are novel) spanned 24 known disease genes, some of which have not or only very rarely been linked to microphthalmia (PAX6, SLC18A2, DSC3 and CNKSR1). Our study has also identified interesting candidate variants in 2 genes that have not been linked to human diseases (MYO10 and ZNF219), which we present here as novel candidates for microphthalmia. In addition to revealing novel phenotypic aspects of microphthalmia, this study expands its allelic and locus heterogeneity and highlights the need for expanded testing of patients with this condition.


Assuntos
Microftalmia/genética , Família , Humanos , Microftalmia/diagnóstico por imagem , Mutação Puntual/genética
13.
Mol Psychiatry ; 22(4): 615-624, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27431290

RESUMO

Intellectual disability (ID) is a measurable phenotypic consequence of genetic and environmental factors. In this study, we prospectively assessed the diagnostic yield of genomic tools (molecular karyotyping, multi-gene panel and exome sequencing) in a cohort of 337 ID subjects as a first-tier test and compared it with a standard clinical evaluation performed in parallel. Standard clinical evaluation suggested a diagnosis in 16% of cases (54/337) but only 70% of these (38/54) were subsequently confirmed. On the other hand, the genomic approach revealed a likely diagnosis in 58% (n=196). These included copy number variants in 14% (n=54, 15% are novel), and point mutations revealed by multi-gene panel and exome sequencing in the remaining 43% (1% were found to have Fragile-X). The identified point mutations were mostly recessive (n=117, 81%), consistent with the high consanguinity of the study cohort, but also X-linked (n=8, 6%) and de novo dominant (n=19, 13%). When applied directly on all cases with negative molecular karyotyping, the diagnostic yield of exome sequencing was 60% (77/129). Exome sequencing also identified likely pathogenic variants in three novel candidate genes (DENND5A, NEMF and DNHD1) each of which harbored independent homozygous mutations in patients with overlapping phenotypes. In addition, exome sequencing revealed de novo and recessive variants in 32 genes (MAMDC2, TUBAL3, CPNE6, KLHL24, USP2, PIP5K1A, UBE4A, TP53TG5, ATOH1, C16ORF90, SLC39A14, TRERF1, RGL1, CDH11, SYDE2, HIRA, FEZF2, PROCA1, PIANP, PLK2, QRFPR, AP3B2, NUDT2, UFC1, BTN3A2, TADA1, ARFGEF3, FAM160B1, ZMYM5, SLC45A1, ARHGAP33 and CAPS2), which we highlight as potential candidates on the basis of several lines of evidence, and one of these genes (SLC39A14) was biallelically inactivated in a potentially treatable form of hypermanganesemia and neurodegeneration. Finally, likely causal variants in previously published candidate genes were identified (ASTN1, HELZ, THOC6, WDR45B, ADRA2B and CLIP1), thus supporting their involvement in ID pathogenesis. Our results expand the morbid genome of ID and support the adoption of genomics as a first-tier test for individuals with ID.


Assuntos
Deficiência Intelectual/diagnóstico , Deficiência Intelectual/genética , Adulto , Criança , Pré-Escolar , Estudos de Coortes , Variações do Número de Cópias de DNA , Exoma/genética , Feminino , Genômica , Humanos , Deficiência Intelectual/metabolismo , Cariotipagem/métodos , Masculino , Mutação , Estudos Prospectivos , Sensibilidade e Especificidade , Análise de Sequência de DNA/métodos , Adulto Jovem
14.
Clin Genet ; 92(3): 327-331, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28218389

RESUMO

Dominant SCN1B mutations are known to cause several epilepsy syndromes in humans. Only 2 epilepsy patients to date have been reported to have recessive mutations in SCN1B as the likely cause of their phenotype. Here, we confirm the recessive inheritance of 2 novel SCN1B mutations in 5 children from 3 families with developmental epileptic encephalopathy. The recessive inheritance and early death in these patients is consistent with the Dravet-like phenotype observed in Scn1b-/- mice. The 'negative' clinical exome in one of these families highlights the need to consider recessive mutations in the interpretation of variants in typically dominant genes.


Assuntos
Epilepsia/diagnóstico , Epilepsia/genética , Genes Recessivos , Mutação , Fenótipo , Subunidade beta-1 do Canal de Sódio Disparado por Voltagem/genética , Animais , Biomarcadores , Encéfalo/patologia , Criança , Consanguinidade , Análise Mutacional de DNA , Eletroencefalografia , Fácies , Evolução Fatal , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Camundongos , Camundongos Knockout , Linhagem
15.
Ann Surg ; 264(1): 47-53, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-26756766

RESUMO

OBJECTIVE: The aim of the study was to assess the impact of a preoperative medically supervised exercise program on outcomes after elective abdominal aortic aneurysm (AAA) repair. BACKGROUND: Functional capacity is an important predictor of postoperative outcomes after elective AAA repair. Improving patients' preoperative fitness with exercise has the potential to positively influence recovery. METHODS: A randomized controlled trial was performed at a tertiary vascular unit. Patients scheduled for open or endovascular AAA repair were randomized to either 6 weeks of preoperative supervised exercise or standard treatment using sealed envelopes. The primary outcome measure was a composite endpoint of cardiac, pulmonary, and renal complications. Secondary outcome measures were 30-day mortality, lengths of hospital and critical care stay, Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, reoperation, and postoperative bleeding. RESULTS: One hundred twenty-four patients were randomized (111 men, mean [SD] age 73 [7] y). Fourteen patients sustained postoperative complications in the exercise group (22.6%), compared with 26 in the nonexercise group (41.9%; P = 0.021). Four patients (2 in each group) died within the first 30 postoperative days. Duration of hospital stay was significantly shorter in the exercise group (median 7 [interquartile range 5-9] vs 8 [interquartile range 6-12.3] d; P = 0.025). There were no significant differences between the groups in the length of critical care stay (P = 0.845), APACHE II scores (P = 0.256), incidence of reoperations (P = 1.000), or postoperative bleeding (P = 0.343). CONCLUSIONS: A period of preoperative supervised exercise training reduces postoperative cardiac, respiratory, renal complications, and length of hospital stay in patients undergoing elective AAA repair.


Assuntos
Aneurisma da Aorta Abdominal/cirurgia , Procedimentos Cirúrgicos Eletivos , Exercício Físico , Tempo de Internação , Cuidados Pré-Operatórios , Idoso , Idoso de 80 Anos ou mais , Aneurisma da Aorta Abdominal/mortalidade , Procedimentos Cirúrgicos Eletivos/métodos , Feminino , Hemorragia , Hospitais Universitários , Humanos , Masculino , Cuidados Pré-Operatórios/métodos , Estudos Prospectivos , Reoperação , Fatores de Risco , Resultado do Tratamento
16.
BMC Med Genet ; 16: 50, 2015 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-26188928

RESUMO

BACKGROUND: Offspring of consanguineous couples are at increased risk of congenital disorders. The risk increases as parents are more closely related. Individuals that have the same degree of relatedness according to their pedigree, show variable genomic kinship coefficients. To investigate whether we can differentiate between couples with high- and low risk for offspring with congenital disorders, we have compared the genomic kinship coefficient of consanguineous parents with a child affected with an autosomal recessive disorder with that of consanguineous parents with only healthy children, corrected for the degree of pedigree relatedness. METHODS: 151 consanguineous couples (73 cases and 78 controls) from 10 different ethnic backgrounds were genotyped on the Affymetrix platform and passed quality control checks. After pruning SNPs in linkage disequilibrium, 57,358 SNPs remained. Kinship coefficients were calculated using three different toolsets: PLINK, King and IBDelphi, yielding five different estimates (IBDelphi, PLINK (all), PLINK (by population), King robust (all) and King homo (by population)). We performed a one-sided Mann Whitney test to investigate whether the median relative difference regarding observed and expected kinship coefficients is bigger for cases than for controls. Furthermore, we fitted a mixed effects linear model to correct for a possible population effect. RESULTS: Although the estimated degrees of genomic relatedness with the different toolsets show substantial variability, correlation measures between the different estimators demonstrated moderate to strong correlations. Controls have higher point estimates for genomic kinship coefficients. The one-sided Mann Whitney test did not show any evidence for a higher median relative difference for cases compared to controls. Neither did the regression analysis exhibit a positive association between case-control status and genomic kinship coefficient. CONCLUSIONS: In this case-control setting, in which we compared consanguineous couples corrected for degree of pedigree relatedness, a higher degree of genomic relatedness was not significantly associated with a higher likelihood of having an affected child. Further translational research should focus on which parts of the genome and which pathogenic mutations couples are sharing. Looking at relatedness coefficients by determining genome-wide SNPs does not seem to be an effective measure for prospective risk assessment in consanguineous parents.


Assuntos
Anormalidades Congênitas/genética , Consanguinidade , Genes Recessivos , Genoma Humano/genética , Sequência de Bases , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Masculino , Linhagem , Polimorfismo de Nucleotídeo Único , Análise de Sequência de DNA , Estatísticas não Paramétricas
17.
Paediatr Anaesth ; 25(9): 883-90, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26033312

RESUMO

BACKGROUND: Data are still insufficient about the effects of different concentrations of caudal dexmedetomidine when used to prolong postoperative analgesia in children. The aim of this study was to assess the analgesic efficacy and side effects of two doses of caudal dexmedetomidine (1 and 2 µg·kg(-1)) co-administered with bupivacaine in terms of postoperative pain scores and requirement of postoperative analgesia over 24 h in children undergoing infra-umbilical surgery. METHODS: Ninety-one children, aged 1-6 years, undergoing infra-umbilical surgery were included and randomly allocated into three groups of caudal block. Group B received 0.25% bupivacaine 2 mg·kg(-1) (0.8 ml·kg(-1)). Groups BD1 and BD2 received dexmedetomidine 1 and 2 µg·kg(-1), respectively along with bupivacaine 2 mg·kg(-1) in a total volume of 0.8 ml·kg(-1). Anesthesia was induced and maintained with sevoflurane in 100% oxygen. Hemodynamic and other routine intraoperative monitoring was carried out in addition to endtidal sevoflurane concentration. Time to spontaneous eye opening and postoperative pain and sedation scores were recorded in addition to time to first analgesia, paracetamol analgesic requirements, and any side effects during the first 24 postoperative hours. RESULTS: Time to first analgesia requirement was significantly longer in BD1 and BD2 groups compared to B group with mean values (95% CI) of 809 min (652-965), 880 (733-1026), and 396 (343-448), respectively, P < 0.001. Postoperative paracetamol analgesic requirements over 24 h were higher in group B compared to BD1 and BD2 groups (Mean (95% CI): 3.2 (2.9-3.5) doses, 1.9 (1.5-2.3), and 1.6 (1.3-1.9), respectively), P < 0.001. The dexmedetomidine groups had significantly higher postoperative sedation scores compared to plain bupivacaine group that were dose dependent and for longer time in BD2 group. Two patients in BD2 group developed bradycardia and hypotension, and one developed urine retention compared to none in other groups. CONCLUSION: A 1 µg·kg(-1) dose of caudal dexmedetomidine achieved comparable prolongation of postoperative analgesia to 2 µg·kg(-1) dose, with shorter duration of postoperative sedation and lower incidence of other side effects.


Assuntos
Abdome/cirurgia , Analgesia/métodos , Anestesia Caudal/métodos , Bupivacaína , Dexmedetomidina , Dor Pós-Operatória/tratamento farmacológico , Anestésicos Locais , Criança , Pré-Escolar , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Hipnóticos e Sedativos , Lactente , Masculino , Períneo/cirurgia , Estudos Prospectivos
18.
Mycopathologia ; 179(3-4): 195-204, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25515243

RESUMO

Candida albicans is a major agent of fungaemias and frequently causes systemic disease through seeded, blood stream dissemination. These infections, particularly common in hospitalized patients with central venous catheters (CVCs), appear to persevere due to biofilm reservoirs of the yeast that tend to develop on the device. Although it is known that candidal biofilms are intrinsically resistant to antifungals compared with their planktonic counterparts, there is a paucity of data on the expression of antifungal drug resistance genes (DRGs) in candidal biofilms in CVC reservoirs. Furthermore, notwithstanding the fact that CVCs are constantly bathed in human serum, there are no studies on the effect of the latter on the DRG expression in candidal biofilms. Hence, we developed in vitro biofilms of three different C. albicans strains on silicone CVC discs immersed in human serum and evaluated the temporal expression of nine antifungal DRGs. In an attempt to evaluate the effect of hyphal elements on DRG expression, we incorporated a hyphal mutant (HM) and its wild-type (WT) counterpart, as well as a fresh clinical isolate in the studies. Human serum significantly up-regulated DRG transcripts in Candida biofilms on CVCs, at different stages of biofilm growth, while the WT strain over-expressed more DRGs than the HM strain. Here, we report, for the first time, that both human serum and the hyphal elements of the yeast have a profound modulatory effect on DRG expression in C. albicans biofilms on CVCs.


Assuntos
Biofilmes/efeitos dos fármacos , Candida albicans/genética , Cateteres Venosos Centrais/microbiologia , Farmacorresistência Fúngica , Soro/química , Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Candida albicans/crescimento & desenvolvimento , Cateteres Venosos Centrais/efeitos adversos , Contaminação de Equipamentos , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Regulação Fúngica da Expressão Gênica , Humanos , Hifas/efeitos dos fármacos , Hifas/genética , Hifas/crescimento & desenvolvimento , Masculino , Regulação para Cima
19.
Ann Vasc Surg ; 28(1): 80-6, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24200132

RESUMO

BACKGROUND: The purpose of this study was to evaluate morbidity, mortality, and survival in octogenarians undergoing open repair of ruptured abdominal aortic aneurysms (RAAAs) in comparison to younger patients. METHODS: This investigation was a retrospective analysis of a prospectively maintained database from a tertiary referral center. We included all consecutive RAAA patients who underwent open repair from 1990 to 2011. Univariate and multivariate analyses were used to identify predictors of inferior short- and long-term outcomes. RESULTS: Overall, 463 patients were identified, of whom 138 (30%) were octogenarians (group 2), with a mean age of 84 ± 0.47 years. There were 96 (69%) men and 42 women (31%). There were more women in group 2 (31%) compared with the <80-year-old patients of group 1 (14%) (P < 0.001). The 30-day mortality for group 2 was 43.5% compared with 28.0% for group 1 (P < 0.001). Preoperatively, 63% of group 1 patients presented with shock compared with 65% of those in group 2 (P = 0.751). There was no difference between the two groups in terms of preoperative systolic blood pressure (SBP), duration of operation, and intraoperative blood loss (P > 0.05). Median preoperative hemoglobin (P < 0.001) and creatinine (P = 0.031) levels were significantly different between the groups. There was no significant difference between the two groups in terms of postoperative complications and length of hospital stay. Median long-term survival for octogenarians (group 2) was 5.4 years compared with 12.4 years for the younger patient group (group 1) (P < 0.001). Multivariate analysis identified age as an independent predictor of 30-day mortality (odds ratio [OR] = 1.154, 95% confidence interval [CI] 1.037-1.285) and inferior long-term survival (OR = 1.074, 95% CI 1.011-1.141). History of cigarette smoking also predicted worse long-term outcomes (OR = 3.044, 95% CI 1.318-7.032) as did multiorgan failure in the postoperative course (OR = 1.363, 95% CI 1.080-14.130). CONCLUSIONS: Advanced age is associated with high surgical mortality; however, for octogenarians surviving surgical repair, long-term outcome is acceptable. Therefore, with responsible decision-making, surgical intervention is justifiable in the elderly. Smoking and multiorgan failure were both predictive of worse survival.


Assuntos
Aneurisma da Aorta Abdominal/cirurgia , Ruptura Aórtica/cirurgia , Procedimentos Cirúrgicos Vasculares , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Aneurisma da Aorta Abdominal/diagnóstico , Aneurisma da Aorta Abdominal/mortalidade , Ruptura Aórtica/diagnóstico , Ruptura Aórtica/mortalidade , Distribuição de Qui-Quadrado , Inglaterra , Feminino , Humanos , Estimativa de Kaplan-Meier , Tempo de Internação , Modelos Logísticos , Masculino , Insuficiência de Múltiplos Órgãos/etiologia , Insuficiência de Múltiplos Órgãos/mortalidade , Análise Multivariada , Razão de Chances , Complicações Pós-Operatórias/etiologia , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Fumar/efeitos adversos , Fumar/mortalidade , Fatores de Tempo , Resultado do Tratamento , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Procedimentos Cirúrgicos Vasculares/mortalidade
20.
Ann Vasc Surg ; 28(1): 74-9, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24332259

RESUMO

BACKGROUND: Aerobic fitness is an important predictor of postoperative outcome in major surgery. In this study, we assess the effects of a period of preoperative exercise on aerobic fitness as measured by cardiopulmonary exercise testing (CPET) in patients scheduled for abdominal aortic aneurysm (AAA) repair. METHODS: As part of a randomized trial, the first patients recruited in the intervention group were enrolled in a supervised exercise program of six week duration. Treadmill CPET parameters were measured before and after exercise preoperatively for these patients. These parameters were as follows: peak oxygen uptake (VO2 peak), anaerobic threshold (AT), and ventilator equivalents for oxygen and carbon dioxide (VE/VO2 and VE/VCO2, respectively). Total exercise time and the time at which AT was achieved were also recorded. A comparison between pre- and postexercise parameters was made to detect for a possible improvement in aerobic fitness. RESULTS: Twenty patients with AAA (17 men; mean age: 74.9 ± 5.9 years) were included in this study. Thirty-five percent of patients had a history of ischemic heart disease, 25% of obstructive airway disease, and 15% of cerebral vascular events. Seventy percent were previous smokers, and 15% were current smokers. Fifty-five percent of patients were taking aspirin and 75% were undergoing statin therapy. The median (interquartile range) VO2 peak at baseline was 18.2 (15.4-19.9) mL/kg/min, and after exercise was 19.9 (17.1-21.1; P = 0.048). Median AT at baseline was 12.2 (10.5-14.9), and 14.4 (12.3-15.4) after exercise (P = 0.023). Time of exercise tolerated also improved from a median of 379 to 604 sec (P = 0.001). No significant changes were seen in VE/VO2, VE/VCO2, or the time at which AT was achieved. CONCLUSION: This study shows that cardiopulmonary aerobic fitness improves after a period of supervised exercise in patients scheduled for AAA repair. This is justification for a randomized trial to assess whether this affects morbidity and mortality after AAA repair.


Assuntos
Aneurisma da Aorta Abdominal/cirurgia , Procedimentos Endovasculares , Terapia por Exercício , Aptidão Física , Procedimentos Cirúrgicos Vasculares , Listas de Espera , Idoso , Idoso de 80 Anos ou mais , Limiar Anaeróbio , Aneurisma da Aorta Abdominal/diagnóstico , Aneurisma da Aorta Abdominal/fisiopatologia , Procedimentos Cirúrgicos Eletivos , Inglaterra , Teste de Esforço , Feminino , Humanos , Masculino , Consumo de Oxigênio , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
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