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BACKGROUND: Early oral feeding is currently considered the optimal routine feeding strategy after pancreatoduodenectomy (PD). Some have suggested that patients with preoperative symptoms of gastric outlet obstruction (GOO) who undergo PD have such a high risk of developing delayed gastric emptying that these patients should rather receive routine postoperative tube feeding. The aim of this study was to determine whether clinical outcomes after PD in these patients differ between postoperative early oral feeding and routine tube feeding. METHODS: We analyzed a consecutive multicenter cohort of patients with preoperative symptoms of GOO undergoing PD (2010-2013). Patients were categorized into two groups based on the applied postoperative feeding strategy (dependent on their center's routine strategy): early oral feeding or routine nasojejunal tube feeding. RESULTS: Of 497 patients undergoing PD, 83 (17%) suffered from preoperative symptoms of GOO. 49 patients received early oral feeding and 29 patients received routine tube feeding. Time to resumption of adequate oral intake (primary outcome; 14 vs. 12 days, p = 0.61) did not differ between these two feeding strategies. Furthermore, overall complications and length of stay were similar in both groups. Of the patients receiving early oral feeding, 24 (49%) ultimately required postoperative tube feeding. In patients with an uncomplicated postoperative course, early oral feeding was associated with shorter time to adequate oral intake (8 vs. 12 days, p = 0.008) and shorter hospital stay (9 vs. 13 days, p < 0.001). CONCLUSION: Also in patients with preoperative symptoms of GOO, early oral feeding can be considered the routine feeding strategy after PD.
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Nutrição Enteral/métodos , Obstrução da Saída Gástrica/terapia , Pancreaticoduodenectomia , Cuidados Pós-Operatórios/métodos , Adulto , Idoso , Nutrição Enteral/instrumentação , Feminino , Obstrução da Saída Gástrica/diagnóstico , Gastroparesia/etiologia , Gastroparesia/prevenção & controle , Humanos , Intubação Gastrointestinal , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Período Pré-Operatório , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVE: The aim of this study was to evaluate whether a change in the routine feeding strategy applied after pancreatoduodenectomy (PD) from nasojejunal tube (NJT) feeding to early oral feeding improved clinical outcomes. METHODS: An observational cohort study was performed in 102 consecutive patients undergoing PD. In period 1 (n = 51, historical controls), the routine postoperative feeding strategy was NJT feeding. This was changed to a protocol of early oral feeding with on-demand NJT feeding in period 2 (n = 51, consecutive prospective cohort). The primary outcome was time to resumption of adequate oral intake. RESULTS: The baseline characteristics of study subjects in both periods were comparable. In period 1, 98% (n = 50) of patients received NJT feeding, whereas in period 2, 53% (n = 27) of patients did so [for delayed gastric empting (DGE) (n = 20) or preoperative malnutrition (n = 7)]. The time to resumption of adequate oral intake significantly decreased from 12 days in period 1 to 9 days in period 2 (P = 0.015), and the length of hospital stay shortened from 18 days in period 1 to 13 days in period 2 (P = 0.015). Overall, there were no differences in the incidences of complications of Clavien-Dindo Grade III or higher, DGE, pancreatic fistula, postoperative haemorrhage and mortality between the two periods. CONCLUSIONS: The introduction of an early oral feeding strategy after PD reduced the time to resumption of adequate oral intake and length of hospital stay without negatively impacting postoperative morbidity.
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Nutrição Enteral/métodos , Idoso , Estudos de Casos e Controles , Ingestão de Alimentos , Nutrição Enteral/efeitos adversos , Feminino , Humanos , Tempo de Internação , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Pancreaticoduodenectomia/efeitos adversos , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Recuperação de Função Fisiológica , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Immunogenicity to meningococcal serogroup ACWY (MenACWY) conjugate vaccine has not been studied in immunocompromised minors with juvenile idiopathic arthritis (JIA) or inflammatory bowel disease (IBD). We determined immunogenicity of a MenACWY-TT vaccine in JIA and IBD patients at adolescent age and compared results to data from aged-matched healthy controls (HCs). METHODS: We performed a prospective observational cohort study in JIA and IBD patients (14-18 years old), who received a MenACWY vaccination during a nationwide catch-up campaign (2018-2019) in the Netherlands. Primary aim was to compare MenACWY polysaccharide-specific serum IgG geometric mean concentrations (GMCs) in patients with HCs and secondary between patients with or without anti-TNF therapy. GMCs were determined before and 3-6, 12, and 24 months postvaccination and compared with data from HCs at baseline and 12 months postvaccination. Serum bactericidal antibody (SBA) titers were determined in a subset of patients at 12 months postvaccination. RESULTS: We included 226 JIA and IBD patients (66 % and 34 % respectively). GMCs were lower for MenA and MenW (GMC ratio 0·24 [0·17-0·34] and 0·16 [0·10-0·26] respectively, p < 0·01) in patients compared to HCs at 12 months postvaccination. Anti-TNF users had lower MenACWY GMCs postvaccination compared with those without anti-TNF (p < 0·01). The proportion protected (SBA ≥ 8) for MenW was reduced in anti-TNF users (76 % versus 92 % in non-anti-TNF and 100 % in HCs, p < 0.01). CONCLUSION: The MenACWY conjugate vaccine was immunogenic in the vast majority of JIA and IBD patients at adolescent age, but seroprotection was lower in patients using anti-TNF agents. Therefore, an extra booster MenACWY vaccination should be considered.
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Artrite Juvenil , Infecções Meningocócicas , Vacinas Meningocócicas , Adolescente , Humanos , Anticorpos Antibacterianos , Artrite Juvenil/tratamento farmacológico , Imunogenicidade da Vacina , Infecções Meningocócicas/prevenção & controle , Vacinas Meningocócicas/efeitos adversos , Estudos Prospectivos , Vacinas Conjugadas/efeitos adversosRESUMO
PURPOSE: The purpose of the study was to analyse the development of ocular complications and visual prognosis in juvenile idiopathic arthritis associated uveitis (JIA-uveitis) compared to the previous decade in the light of new treatment guidelines. METHODS: In this retrospective cohort, 143 patients with JIA-uveitis were stratified into two cohorts based on the year of diagnosis of uveitis, <2010 (n = 61) and ≥2010 (n = 82). Development of ocular complications and visual outcomes were analysed by univariate and multivariate methods. Treatment with systemic corticosteroids and immunomodifying medication (IMT) were documented. RESULTS: In total, 109 and 133 affected eyes, respectively, for cohort 1 (<2010) and cohort 2 (≥2010) were included for analysis. In the multivariate analysis with correction for paired eyes, patients in cohort 1 were at higher risk for cataract surgery (p = 0.03) and secondary glaucoma (p = 5.15 × 10-3 ). Also, the number of eyes that were legally blind and visually impaired at 5 years of follow-up was significantly higher in cohort 1 (7% versus 2% and 8% versus 0%, p = 0.01 respectively). The number of patients that started IMT was significantly higher in cohort 2 (57% versus 98%, p = 2.17 × 10-6 ). In cohort 2, both methotrexate and anti-TNF-α therapy were prescribed earlier in the disease course (1.41 versus 0.05 years, p = 8.31 × 10-6 and 6.07 versus 1.84 years, p = 5.14 × 10-5 respectively). CONCLUSIONS: The prognosis of JIA-uveitis has improved during the last decade. There is a reduction in the number of cataract surgeries and secondary glaucoma and fewer patients lose their vision parallel with earlier access to tertiary care and earlier introduction of IMT.
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Artrite Juvenil , Catarata , Glaucoma , Uveíte , Corticosteroides/uso terapêutico , Artrite Juvenil/complicações , Artrite Juvenil/diagnóstico , Artrite Juvenil/tratamento farmacológico , Catarata/complicações , Glaucoma/complicações , Humanos , Metotrexato/uso terapêutico , Estudos Retrospectivos , Inibidores do Fator de Necrose Tumoral , Uveíte/diagnóstico , Uveíte/tratamento farmacológico , Uveíte/epidemiologiaRESUMO
PURPOSE: To identify a serum biomarker signature that can help predict response to conventional synthetic disease-modifying antirheumatic drug (csDMARD) therapy in pediatric noninfectious uveitis. METHODS: In this case-control cohort study, we performed a 368-plex proteomic analysis of serum samples of 72 treatment-free patients with active uveitis (new onset or relapse) and 15 healthy controls. Among these, 37 patients were sampled at diagnosis before commencing csDMARD therapy. After 6 months, csDMARD response was evaluated and cases were categorized as "responder" or "nonresponder." Patients were considered "nonresponders" if remission was not achieved under csDMARD therapy. Serum protein profiles were used to train random forest models to predict csDMARD failure and compared to a model based on eight clinical parameters at diagnosis (e.g., maximum cell grade). RESULTS: In total, 19 of 37 (51%) cases were categorized as csDMARD nonresponders. We identified a 10-protein signature that could predict csDMARD failure with an overall accuracy of 84%, which was higher compared to a model based on eight clinical parameters (73% accuracy). Adjusting for age, sex, anatomic location of uveitis, and cell grade, cases stratified by the 10-protein signature at diagnosis showed a large difference in risk for csDMARD failure (hazard ratio, 12.8; 95% confidence interval, 2.5-64.6; P = 0.002). CONCLUSIONS: Machine learning models based on the serum proteome can stratify pediatric patients with uveitis at high risk for csDMARD failure. TRANSLATIONAL RELEVANCE: The identified protein signature has implications for the development of clinical decision tools that integrate clinical parameters with biological data to better predict the best treatment option.
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Antirreumáticos , Uveíte , Antirreumáticos/uso terapêutico , Proteínas Sanguíneas , Estudos de Casos e Controles , Criança , Humanos , Proteômica , Resultado do Tratamento , Uveíte/diagnóstico , Uveíte/tratamento farmacológicoRESUMO
PURPOSE: To examine the clinical course and outcome in children with idiopathic chronic anterior uveitis (iCAU), and to compare the results with those of age-matched children with juvenile idiopathic arthritis-associated uveitis (JIA-U). DESIGN: Retrospective cohort study. METHODS: Data regarding ocular complications, visual acuity, and systemic treatment were retrospectively collected for 2 patient groups that were matched regarding age and year of uveitis diagnosis. Outcome was evaluated using survival analysis. RESULTS: The iCAU and JIA-U groups included 48 patients with 83 affected eyes and 48 patients with 73 affected eyes, respectively. Multivariate analyses showed that iCAU was associated with a higher prevalence of posterior synechiae (adjusted hazard rate [aHR] = 3.63; P < .001) and cataract surgery (aHR = 2.90; P = .006). Baseline visual acuity was worse in the iCAU group compared to the JIA-U group (20/25 vs 20/20, respectively; P < .001), but improved in the iCAU group after 5 years (20/20 vs 20/20, respectively; P = .052). At the 5-year follow-up, the younger children with iCAU (≤8 years of age at diagnosis) had a higher prevalence of posterior synechiae (aHR = 2.56; P = .007), secondary glaucoma (aHR = 16.0; P = .020), and cataract surgery (aHR = 4.79; P = .004) compared to older children with iCAU (≥9 years at diagnosis). CONCLUSIONS: Vision-threatening ocular complications are more common in children with iCAU compared to children with JIA-U, particularly in cases in which the onset of uveitis occurred at ≤8 years of age. However, the long-term vision of these children can be improved with adequate treatment.
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Artrite Juvenil , Catarata , Doenças da Íris , Uveíte Anterior , Uveíte , Adolescente , Artrite Juvenil/complicações , Artrite Juvenil/diagnóstico , Catarata/complicações , Criança , Humanos , Estudos Retrospectivos , Fatores de Risco , Uveíte/complicações , Uveíte Anterior/complicações , Uveíte Anterior/diagnóstico , Uveíte Anterior/epidemiologiaRESUMO
Purpose: Early identification of patients with noninfectious uveitis requiring steroid-sparing immunomodulatory therapy (IMT) is currently lacking in objective molecular biomarkers. We evaluated the proteomic signature of patients at the onset of disease and associated proteomic clusters with the need for IMT during the course of the disease. Design: Multicenter cohort study. Participants: Two hundred thirty treatment-free patients with active noninfectious uveitis. Methods: We used aptamer-based proteomics (n = 1305 proteins) and a bioinformatic pipeline as a molecular stratification tool to define the serum protein network of a Dutch discovery cohort (n = 78) of patients and healthy control participants and independently validated our results in another Dutch cohort (n = 111) and a United States cohort (n = 67). Multivariate Cox analysis was used to assess the relationship between the protein network and IMT use. Main Outcome Measures: Serum protein levels and use of IMT. Results: Network-based analyses revealed a tightly coexpressed serum cluster (n = 85 proteins) whose concentration was consistently low in healthy control participants (n = 26), but varied among patients with noninfectious uveitis (n = 52). Patients with high levels of the serum cluster at disease onset showed a significantly increased need for IMT during follow-up, independent of anatomic location of uveitis (hazard ratio, 3.42; 95% confidence interval, 1.22-9.5; P = 0.019). The enrichment of neutrophil-associated proteins in the protein cluster led to our finding that the neutrophil count could serve as a clinical proxy for this proteomic signature (correlation: r = 0.57, P = 0.006). In an independent Dutch cohort (n = 111), we confirmed that patients with relatively high neutrophil count at diagnosis (> 5.2 × 109/L) had a significantly increased chance of requiring IMT during follow-up (hazard ratio, 3.2; 95% confidence interval, 1.5-6.8; P = 0.002). We validated these findings in a third cohort of 67 United States patients. Conclusions: A serum protein signature correlating with neutrophil levels was highly predictive for IMT use in noninfectious uveitis. We developed a routinely available tool that may serve as a novel objective biomarker to aid in clinical decision-making for noninfectious uveitis.
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Purpose: To describe the results of tocilizumab treatment in children with refractory non-anterior uveitis.Methods: A case series of seven children with refractory non-anterior uveitis (onset ≤16 years) with leakage on fluorescein angiogram (FA) were treated with tocilizumab intravenously every 4 weeks (eight mg/kg). Minimum follow-up was 6 months. Reported outcomes are changes in BCVA, central macular thickness (CMT) on OCT image, FA scores, dose of systemic steroids, complications and side effects.Results: In all patients, there was an improvement of macular edema and capillary leakage on FA. The median FA score decreased from 14 (10-18) at baseline to 8 (2-9) after 6 months of treatment (p = .018). The CMT decreased from 321 (314-384) to 295 (255-312) (p = .043). BCVA improved in five eyes and worsened in one eye due to cataract. No systemic or ocular complications were reported.Conclusion: Tocilizumab is an effective therapeutic option for reducing disease activity in children with refractory non-anterior uveitis.
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Anticorpos Monoclonais Humanizados/administração & dosagem , Pan-Uveíte/tratamento farmacológico , Acuidade Visual , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Feminino , Angiofluoresceinografia/métodos , Seguimentos , Fundo de Olho , Humanos , Infusões Intravenosas , Masculino , Pan-Uveíte/diagnóstico , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Purpose: Classical alleles of the human leukocyte antigen (HLA) complex have been linked to specific entities of pediatric noninfectious uveitis, yet genetic predisposition encoded by the HLA super-locus across the patient population remains understudied. Methods: We performed next-generation full-length sequencing of HLA-A, HLA-B, HLA-C, HLA-DPB1, HLA-DQB1, and HLA-DRB1 in 280 cases. Dense genotype data from 499 Dutch controls from Genome of the Netherlands were imputed using an HLA-specific reference panel (n = 5225 samples from European ancestry). Cases and controls were compared using logistic regression models adjusting for sex. Results: In total, 179 common and rare alleles were detected. Considering all cases and controls, HLA-DQB1*04:02 and HLA-DRB1*08:01 were identified as the principal HLA association, which was mainly driven by 92 cases with juvenile idiopathic arthritis-associated uveitis (JIA-U). The HLA-DQB1*04:02-HLA-DRB1*08:01 haplotype was also the primary association for the phenotypically similar idiopathic chronic anterior uveitis without arthritis (CAU). Also, HLA-DQB1*05:03 was an independent risk allele for CAU, but not in JIA-U. Analysis of 185 cases with other forms of uveitis revealed HLA-wide associations (P < 2.79 × 10-4) for HLA-DRB1*01:02, HLA-DRB1*04:03, and HLA-DQB1*05:03, which could be primarily attributed to cases with panuveitis. Finally, amino acid substitution modeling revealed that aspartic acid at position 57 that distinguishes the risk allele HLA-DQB1*05:03 (for CAU and panuveitis) from nonrisk alleles, significantly increased the binding capacity of naturally presented ligands to HLA-DQ. Conclusions: These results uncovered novel shared HLA associations among clinically distinct phenotypes of pediatric uveitis and highlight genetic predisposition affecting the antigen presentation pathway.
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Predisposição Genética para Doença , Antígenos HLA/genética , Uveíte/genética , Adolescente , Alelos , Criança , Feminino , Frequência do Gene , Genótipo , Antígenos HLA/metabolismo , Haplótipos , Humanos , Masculino , Fenótipo , Análise de Sequência , Uveíte/metabolismoRESUMO
Purpose: Patients with juvenile idiopathic arthritis (JIA) are prone to developing chronic anterior uveitis (JIA-U+). Although several risk factors for JIA-U+ have been identified, the underlying etiology is poorly understood. Histopathological studies demonstrate B cell infiltrates in eye tissues of patients with JIA-U+. Methods: We performed transcriptome profiling of peripheral blood CD19-positive B cells taken from 14 cases with JIA-U+, 13 JIA cases without uveitis (JIA-U-), and five healthy controls. Deconvolution-based estimation was used to determine the immune cell fractions for each sample. Results: Deconvolution results revealed that naive B cells made up on average 71% of the CD19-positive cell fractions analyzed. Differential expression analysis identified 614 differentially expressed genes (DEGs) between the groups at nominal significance and six genes at a false discovery rate of 5% (FDR < 0.05). Head-to-head comparison of all JIA-U- versus JIA-U+ revealed no DEGs in the CD19+ B cell pool (FDR < 0.05). However, principal component analysis based on a panel of key genes for B cell subsets revealed that JIA-U+ cases bifurcate into distinct clusters, characterized by markedly disparate expression for genes associated with specific memory B cell populations. CIBERSORT analysis of the overall transcriptome of the new uveitis cluster identified an increased proportion of memory B cells. Conclusion: These data show that JIA-U- and JIA-U+ have a globally similar transcriptome considering the global peripheral CD19-positive B cell pool. However, heterogeneity in B cell memory genes among cases with uveitis suggests a role for specific memory B cell subsets in the etiology of JIA-U+.
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Artrite Juvenil/genética , Subpopulações de Linfócitos B/imunologia , Linfócitos B/imunologia , Olho/patologia , Uveíte/genética , Adolescente , Adulto , Antígenos CD19/metabolismo , Artrite Juvenil/complicações , Células Cultivadas , Criança , Feminino , Humanos , Memória Imunológica , Masculino , Uveíte/complicações , Adulto JovemRESUMO
Brain compression of precisely defined degree and duration was produced by means of expansion of a supratentorial epidural balloon in anaesthetized and mechanically ventilated dogs. After deflation of the balloon there was a rebound of the intracranial pressure (ICP) to values in the range 30-89 mm Hg when critical thresholds of time and compression had been exceeded during the period of compression. A time versus cerebral perfusion pressure (CPP) graph indicated a CPP threshold of about 50 mm Hg and time threshold of about 6 min. Within these limits the critical CPP varied as a function of time. The ICP rebound had an approximately exponential time course with an initial rapid rise levelling off towards a final plateau in about 30 min. The final value was dependent on the time of compression but independent of the CPP. A transtentorial pressure gradient was induced during the compression phase and reestablished after the decompression when a rebound of ICP developed. Hydrostatic compression by means of infusion of fluid into the subarachnoid space was followed by a rebound of ICP in only 2/21 of the experiments in spite of time and CPP parameters which crossed the critical thresholds defined in the balloon compression experiments. These results support the hypothesis that the rebound phenomenon is related to an ischaemic mechanism. The difference in incidence of rebound in balloon compression and hydrostatic compression can probably be accounted for by a greater depth of ischaemia in the former case because of a direct compressive effect on the vascular bed by the balloon.