95 results on '"Launay EA"'
Search Results
2. Eculizumab for Shiga‐toxin‐induced hemolytic uremic syndrome in adults with neurological involvement.
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Lee, Benjamin J., Arter, Zhaohui, Doh, Jean, Griffin, Shawn P., Vittayawacharin, Pongthep, Atallah, Steven, Shieh, Kevin R., Tran, Minh‐Ha, Jodele, Sonata, Kongtim, Piyanuch, and Ciurea, Stefan O.
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- 2024
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3. Complement inhibitors in pediatric kidney diseases: new therapeutic opportunities.
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Antonucci, Luca, Thurman, Joshua M., and Vivarelli, Marina
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PROTEINURIA ,IMMUNOSUPPRESSIVE agents ,LUPUS nephritis ,ANTINEUTROPHIL cytoplasmic antibodies ,COMPLEMENT (Immunology) ,HEMOLYTIC-uremic syndrome ,MONOCLONAL antibodies ,PEDIATRICS ,DRUG efficacy ,QUALITY of life ,KIDNEY diseases ,GENETIC mutation ,IMMUNITY ,CHILDREN - Abstract
Historically, the complement system (classical, lectin, alternative, and terminal pathways) is known to play a crucial role in the etiopathogenesis of many kidney diseases. Direct or indirect activation in these settings is revealed by consumption of complement proteins at the serum level and kidney tissue deposition seen by immunofluorescence and electron microscopy. The advent of eculizumab has shown that complement inhibitors may improve the natural history of certain kidney diseases. Since then, the number of available therapeutic molecules and experimental studies on complement inhibition has increased exponentially. In our narrative review, we give a summary of the main complement inhibitors that have completed phase II and phase III studies or are currently used in adult and pediatric nephrology. The relevant full-text works, abstracts, and ongoing trials (clinicaltrials.gov site) are discussed. Data and key clinical features are reported for eculizumab, ravulizumab, crovalimab, avacopan, danicopan, iptacopan, pegcetacoplan, and narsoplimab. Many of these molecules have been shown to be effective in reducing proteinuria and stabilizing kidney function in different complement-mediated kidney diseases. Thanks to their efficacy and target specificity, these novel drugs may radically improve the outcome of complement-mediated kidney diseases, contributing to an improvement in our understanding of their underlying pathophysiology. [ABSTRACT FROM AUTHOR]
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- 2024
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4. Constipation and hemolytic uremic syndrome.
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Crawford, Brendan, Strebeck, Paige, and Saccente, Suzanne
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DIAGNOSIS of diarrhea ,DIAGNOSIS of escherichia coli diseases ,HEMOLYTIC-uremic syndrome diagnosis ,HEMOLYTIC-uremic syndrome treatment ,ESCHERICHIA coli ,CLINICAL pathology ,DIARRHEA ,CONSTIPATION ,ESCHERICHIA coli diseases ,CHILD psychopathology ,ABDOMINAL pain ,HEMOLYTIC-uremic syndrome ,DISEASE complications - Abstract
Background: Shiga toxin-producing Escherichia coli (STEC) hemolytic uremic syndrome (HUS) classically presents with diarrhea. Absence of diarrheal prodrome increases suspicion for atypical HUS (aHUS). Inability to obtain a fecal specimen for culture or culture-independent testing limits the ability to differentiate STEC-HUS and aHUS. Case-diagnosis/treatment: Our patient presented with abdominal pain and constipation, and evaluation of pallor led to a diagnosis of HUS. There was a complete absence of diarrhea during the disease course. Lack of fecal specimen for several days delayed testing for STEC. Treatment for atypical HUS was initiated with complement-blockade therapy. PCR-testing for Shiga toxin from fecal specimen later returned positive. Alternative complement-pathway testing did not identify a causative genetic variant or anti-Factor H antibody. A diagnosis of STEC-HUS was assigned, and complement-blockade therapy was stopped. Conclusion: Diagnosis of aHUS remains a diagnosis of exclusion, whereby other causes of HUS are eliminated with reasonable certainty. Exclusion of STEC is necessary and relies on testing availability and recognition of testing limitations. Diarrhea-negative STEC-HUS remains a minority of cases, and future research is needed to explore the clinical characteristics of these patients. [ABSTRACT FROM AUTHOR]
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- 2024
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5. Duration of prodromal phase and severity of hemolytic uremic syndrome.
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Balestracci, Alejandro, Meni Battaglia, Luciana, Toledo, Ismael, Martin, Sandra Mariel, and Beaudoin, Laura
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ESCHERICHIA coli ,C-reactive protein ,STATISTICS ,ALBUMINS ,HEMOGLOBINS ,CONFIDENCE intervals ,UREA ,TIME ,MULTIVARIATE analysis ,SODIUM ,MANN Whitney U Test ,SEVERITY of illness index ,COMPARATIVE studies ,LEUKOCYTE count ,DESCRIPTIVE statistics ,CHI-squared test ,HEMOLYTIC-uremic syndrome ,BACTERIAL toxins ,RECEIVER operating characteristic curves ,OXIDOREDUCTASES ,STATISTICAL models ,LOGISTIC regression analysis ,LONGITUDINAL method ,CREATININE ,DISEASE risk factors ,SYMPTOMS ,EVALUATION ,CHILDREN - Abstract
Background: Some data have recognized an association between shorter prodromal phase and severe episode of Shiga toxin-producing Escherichia coli-related hemolytic uremic syndrome (STEC-HUS). Our aims were to confirm such association and analyze characteristics of STEC-HUS patients according to duration of the prodromal phase. Methods: Patients treated from 2000 to 2022 were compared according to the presence of severe (> 10 days of dialysis and/or extra-renal complications) or non-severe disease. Association between prodromal phase duration and disease severity was assessed by ROC curve and by classifying the cohort in 3 groups according to time to diagnosis. Results: Non-severe (n = 145) and severe (n = 71) cases were compared. The latter had shorter prodromal phase, higher leukocyte count, hemoglobin, lactic dehydrogenase, liver enzymes, C-reactive protein, urea and creatinine, and lower albumin and sodium; only prodromal phase duration (p = 0.02) and leukocyte count (p = 0.02) remained significant in multivariate analysis. By ROC curve analysis, time to diagnosis resulted in a poor predictor of outcomes (AUC = 0.27). Since prodromal phase duration was 5 days (IQR 3–7), we divided the cohort into Groups A (1–2 days), B (3–7 days), and C (≥ 8 days). Rates of severe disease were 75.8%, 29.6%, and 11.4%, respectively. Taking Group B as reference, Group A patients had higher risk of complications (p = 0.00001; OR 7.4, 95% CI: 2.98–18.7) while Group C ones had significantly less risk (p = 0.02; OR 0.3, 95% CI: 0.1–0.91). Conclusions: This study found that duration of prodromal phase is an independent predictor of complicated STEC-HUS and confirms that shorter prodromal phase is associated with worse prognosis. [ABSTRACT FROM AUTHOR]
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- 2024
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6. Cerebral microstructural changes in children suffering from hemolytic uremic syndrome.
- Author
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Bültmann, Eva, Zapf, Antonia, Mussgnug, Hans Joachim, Kanzelmeyer, Nele, and Hartmann, Hans
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HEMOLYTIC-uremic syndrome ,DIFFUSION magnetic resonance imaging ,MAGNETIC resonance imaging ,BASAL ganglia ,SIGNAL detection ,THROMBOTIC thrombocytopenic purpura - Abstract
To evaluate microstructural cerebral changes in children suffering from typical hemolytic uremic syndrome (HUS) based on apparent diffusion coefficient (ADC) maps. For 12 pediatric HUS patients (0.8 - 14.6 years of age) conventional magnetic resonance imaging (cMRI) at 1.5 T was retrospectively analyzed. ADC values were measured in 35 different brain regions and compared with age-related, previously published ADC reference values from a healthy pediatric control group. The HUS cohort was divided into 2 subgroups depending on clinical outcome. Subgroup A showed poor neurological outcome whereas subgroup B demonstrated improvement without lasting neurological deficits. Qualitative analysis revealed lesions by diffusion-weighted imaging (DWI) with hypointense correlate on the ADC map in basal ganglia and/or thalami and corresponding T2 hyperintensities in the majority of patients in Subgroup A (80%). Those in Subgroup B did not show qualitative DWI alterations with ADC correlate even when T2 hyperintense lesions were detected in basal ganglia and/or thalami. Quantitative analysis demonstrated abnormal ADC values in all HUS patients with a trend to a greater number of affected regions in Subgroup A compared to Subgroup B (16 versus 11 median number of regions respectively, p = 0.56). Conclusion: Using DWI qualitative and quantitative differences were found between HUS patients showing poor neurological outcome and those without neurological deficits at discharge. While ADC values indicated more extensive cerebral changes than conventional qualitative findings, both may provide early prognostic indicators for neurological outcome in pediatric HUS patients. What is Known: • In patients with STEC-HUS and neurological symptoms, MRI may show hyperintense signals on T2 and altered diffusivity mostly affecting basal ganglia, thalami and periventricular white matter. What is New: • In such patients, early MRI including quantitative ADC measurements over different brain regions may allow for detection of signal alterations possibly reflecting microstructural changes in such patients. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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7. Hemolytic Uremic Syndrome-Induced Acute Kidney Injury Treated via Immunomodulation with the Selective Cytopheretic Device.
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Hambrick, H. Rhodes, Short, Kara, Askenazi, David, Krallman, Kelli, Pino, Christopher, Yessayan, Lenar, Westover, Angela, Humes, H. David, and Goldstein, Stuart L.
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ACUTE kidney failure ,VASCULAR endothelial cells ,MULTIPLE organ failure ,CHILD patients ,IMMUNOREGULATION ,THROMBOTIC thrombocytopenic purpura - Abstract
Introduction: Shiga-toxin associated-hemolytic uremic syndrome (STEC-HUS) is a severe cause of acute kidney injury (AKI) in children. Although most children recover, about 5% die and 30% develop chronic renal morbidity. HUS pathophysiology includes activated neutrophils damaging vascular endothelial cells. Therapeutic immunomodulation of activated neutrophils may alter the progression of disease. We present 3 pediatric patients treated with the selective cytopheretic device (SCD). Methods: We describe a 12 y.o. (patient 1) and two 2 y.o. twins (patients 2 and 3) with STEC-HUS requiring continuous renal replacement therapy (CRRT) who were enrolled in two separate studies of the SCD. Results: Patient 1 presented with STEC-HUS causing AKI and multisystem organ failure and received 7 days of SCD and CRRT treatment. After SCD initiation, the patient had gradual recovery of multi-organ dysfunction, with normal kidney and hematologic parameters at 60-day follow-up. Patients 2 and 3 presented with STEC-HUS with AKI requiring dialysis. Each received 24 h of SCD therapy. Thereafter, both gradually improved, with normalization (patient 2) and near-normalization (patient 3) of kidney function at 60-day follow-up. Conclusion: Immunomodulatory treatment with the SCD was associated with improvements in multisystem stigmata of STEC-HUS-induced AKI and was well-tolerated without any device-related adverse events. [ABSTRACT FROM AUTHOR]
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- 2023
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8. Factors affecting dialysis duration in children with Shiga toxin–producing Escherichia coli–associated hemolytic uremic syndrome.
- Author
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Khalid, Myda, Miller, Chloe, Gebregziabher, Netsanet, Guckien, Zoe, Goswami, Shrea, Perkins, Anthony, and Andreoli, Sharon Phillips
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ESCHERICHIA coli ,CHRONIC kidney failure ,ANTIHYPERTENSIVE agents ,HEMATOCRIT ,NONSTEROIDAL anti-inflammatory agents ,BLOOD platelets ,LEUCOCYTES ,RETROSPECTIVE studies ,SEVERITY of illness index ,RISK assessment ,RESEARCH funding ,PREDICTION models ,HEMOLYTIC-uremic syndrome ,HEMODIALYSIS ,ELECTRONIC health records ,DATA analysis software ,LONGITUDINAL method ,DISEASE risk factors ,CHILDREN - Abstract
Background: Predicting disease severity can be informative for management of HUS. Dialysis requirement, volume depletion, elevated white blood cell counts, very young age, and use of antimotility agents are known factors associated with severe HUS. Methods: A retrospective cohort analysis was performed to identify factors associated with dialysis duration using electronic medical record and chart review of 76 children ≤ 18 years of age at presentation with STEC-HUS identified through billing data from July 2008 to April 2020 at James Whitcomb Riley Hospital for Children, Indiana University, Indiana. Results: Novel findings associated with prolonged dialysis duration were age ≥ 6 years old at presentation (p = 0.041) and lack of drop in platelets below 60,000/mm
3 anytime during the illness (p = 0.015). In addition, children with NSAID exposure trended longer on dialysis: 15 days with vs. 10 days without (p = 0.117). Known risk factors for severe disease including elevated peak white blood cell (WBC) count and higher hematocrit at presentation were also associated with longer dialysis duration: children with peak WBC > 20,000/mm3 were on dialysis for 15 vs. 9.5 days (p = 0.002) and in children on dialysis ≥ 14 days hematocrit at presentation was 29.6% vs. 24.2% (p = 0.03). Children requiring dialysis for 20 days or longer were more likely to be on anti-hypertensive medications (p = 0.025) and have chronic kidney disease at 12-month follow up (p = 0.044). Conclusions: Age ≥ 6, elevated WBC count > 20,000/mm3 , higher hematocrit at presentation, lack of drop in platelets to < 60,000/mm3 , and possibly NSAID exposure during illness are associated with longer dialysis duration in STEC-HUS. [ABSTRACT FROM AUTHOR]- Published
- 2023
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9. Haemolytic Uremic Syndrome: A Study Cohort over 10-Year Period in a Paediatric Tertiary Centre Hospital.
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Alletto, Alessio, Attaianese, Federica, Montemaggi, Alessandra, Becherucci, Francesca, Romagnani, Paola, and Trapani, Sandra
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- 2023
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10. Hyperuricemia: an unrecognized risk factor for kidney-related sequelae in children with hemolytic uremic syndrome.
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Balestracci, Alejandro, Meni Battaglia, Luciana, Toledo, Ismael, Beaudoin, Laura, Martin, Sandra Mariel, Grisolía, Nicolás Ariel, and Hogg, Ronald J.
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CHRONIC kidney failure complications ,HYPERURICEMIA ,STATISTICS ,CONFIDENCE intervals ,MULTIVARIATE analysis ,RETROSPECTIVE studies ,ACQUISITION of data ,CASE-control method ,RISK assessment ,MEDICAL records ,HEMOLYTIC-uremic syndrome ,HEMODIALYSIS ,ODDS ratio ,URIC acid ,DISEASE risk factors - Abstract
Background: Chronic kidney-related sequelae after STEC-HUS occur in 20–40% of patients. Hyperuricemia (HU) may cause acute and chronic toxicity involving the kidneys. We retrospectively assessed if there was an association between the presence of HU during the acute illness and that of kidney-related sequelae in children with STEC-HUS. Methods: Children with STEC-HUS who had clinical and laboratory data at 2 years of follow-up were included in this case–control study. Univariate and multivariate analyses were performed between patients with (cases) or without (controls) kidney-related sequelae to identify factors associated with outcomes, including different measures of serum uric acid (sUA) (baseline level, peak, and duration of HU). HU was defined as sUA > 8 mg/dL. Results: Of 86 patients included, 77.9% had HU. Patients with sequelae (n = 41) had a higher prevalence of HU (41/41 vs. 26/45, p < 0.01), higher baseline leukocyte count, serum creatinine (sCr), and sUA levels as well as lower sodium than controls. During hospitalization, cases also had higher sCr peak, sUA peak and duration of HU, requirement and duration of dialysis, extrarenal complications, and hypertension. By multivariate analysis, after adjusting for length of dialysis, only duration of HU (p = 0.0005; OR 1.7, 95% CI 1.27–2.36) remained as an independent predictor of sequelae, with a best cutoff of 5.5 days (AUC 0.95, specificity 80%, sensitivity 100%). Conclusions: The presence of HU is a common finding in children with STEC-HUS and its duration during the acute stage was associated with kidney-related sequelae, regardless of the duration of dialysis. [ABSTRACT FROM AUTHOR]
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- 2023
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11. The treatment of atypical hemolytic uremic syndrome with eculizumab in pediatric patients: a systematic review.
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de Souza, Raquel Medeiros, Correa, Bernardo Henrique Mendes, Melo, Paulo Henrique Moreira, Pousa, Pedro Antunes, de Mendonça, Tamires Sara Campos, Rodrigues, Lucas Gustavo Castelar, and Simões e Silva, Ana Cristina
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THERAPEUTIC use of monoclonal antibodies ,ONLINE information services ,MEDICAL databases ,SYSTEMATIC reviews ,MONOCLONAL antibodies ,DESCRIPTIVE statistics ,HEMOLYTIC-uremic syndrome ,MEDLINE ,CHILDREN ,ADOLESCENCE - Abstract
Background: The atypical hemolytic uremic syndrome (aHUS) is a rare form of thrombotic microangiopathy associated with high morbidity and high mortality. Eculizumab, a humanized anti-C5 monoclonal antibody, was the first medication approved for treating aHUS in 2011. Objective: The objective of this study is to evaluate the efficacy and safety of eculizumab treatment in pediatric patients with aHUS. Data sources: We consulted PubMed, Scopus, SciELO, and Cochrane Library databases in July 2021. The descriptors were as follows: "Atypical Hemolytic Uremic Syndrome," "aHUS," "eculizumab," "Pediatrics," "Pediatric," "Child," "Children," "Adolescent." Study eligibility criteria: The study eligibility criteria are as follows: clinical trials and observational studies that included pediatric patients with aHUS diagnosis and who were treated with eculizumab. Participants and interventions: The participants are pediatric patients, up to 18 years old, with aHUS. The intervention was eculizumab treatment. Study appraisal: For quality assessment, we used the Newcastle–Ottawa Scale, the National Institutes of Health (NIH) quality assessment tool for case series studies, and the Risk of Bias In Non-Randomized Studies of Interventions (ROBINS-I) tool. Results: The initial search retrieved 433 studies, from which 15 were selected after complete assessment: 9 cohorts, 4 case series, and 1 clinical trial. The publication date ranged from 2015 to 2021. In total, 940 pediatric patients were included, and 682 received eculizumab. All studies reported improvements in renal and hematological parameters in most of the patients treated with eculizumab. The mortality rate was 1.6% for all patients treated with eculizumab. Limitations: The number of studies is limited, and the included studies were methodologically heterogeneous. The studies were mostly observational and many had small sample sizes. Conclusions: Eculizumab appears to be safe and effective for the treatment of aHUS in pediatric patients. More research is necessary to establish long-term efficacy, safety, and time of discontinuation. Systematic review registration number: CRD42021266255. [ABSTRACT FROM AUTHOR]
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- 2023
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12. Erythropoietin in children with hemolytic uremic syndrome: a pilot randomized controlled trial.
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Balestracci, Alejandro, Capone, Marina Andrea, Meni Battaglia, Luciana, Toledo, Ismael, Martin, Sandra Mariel, Beaudoin, Laura, Balbaryski, Jeanette, and Gómez, Lorena
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PILOT projects ,DRUG efficacy ,HEMOGLOBINS ,BLOOD transfusion ,RANDOMIZED controlled trials ,DESCRIPTIVE statistics ,ANEMIA ,HOSPITAL care ,HEMOLYTIC-uremic syndrome ,STATISTICAL sampling ,HEMODYNAMICS ,OXIDOREDUCTASES ,ERYTHROPOIETIN ,RECOMBINANT proteins ,CREATININE ,TOXINS ,CHILDREN - Abstract
Background: The efficacy of recombinant human erythropoietin (rHuEPO) in sparing red blood cell (RBC) transfusions in children with hemolytic uremic syndrome related to Shiga toxin–producing Escherichia coli (STEC-HUS) is uncertain. Methods: We conducted a pilot randomized controlled open trial between December 2018 and January 2021. Children were randomized to the intervention (subcutaneous rHuEPO 50 U/kg three times weekly until discharge + RBC transfusion if hemoglobin ≤ 7 g/dL and/or hemodynamic instability) or to the control arm (RBC transfusion if hemoglobin ≤ 7 g/dL and/or hemodynamic instability). Primary outcome was the number of RBC transfusions received during hospitalization. Secondary outcomes were to explore whether baseline EPO levels were adequate to the degree of anemia, to correlate selected acute phase parameters with the number of RBC transfusions, and to assess possible adverse events. Results: Twelve patients per arm were included; they were comparable at recruitment and throughout the disease course. Median number of RBC transfusions was similar between groups (1.5, p = 0.76). Most patients had baseline EPO levels adequate to the degree of anemia, which did not correlate with the number of transfusions (r = 0.19, p = 0.44). Conversely, baseline (r = 0.73, p = 0.032) and maximum lactic dehydrogenase levels (r = 0.78, p = 0.003), creatinine peak (r = 0.71, p = 0.03) and dialysis duration (r = 0.7, p = 0.04) correlated significantly with RBC requirements. No side effects were recorded. Conclusion: In children with STEC-HUS, the administration of rHuEPO did not reduce the number of RBC transfusions. Larger studies addressing higher doses and similar severity of kidney failure at rHuEPO initiation (e.g. at start of dialysis) are warranted. Trial registration: ClinicalTrials.gov identifier: NCT03776851. A higher resolution version of the Graphical abstract is available as Supplementary information. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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13. Evaluation of Clinical Features and Renal Replacement Therapy in Children with Typical Hemolytic Uremic Syndrome.
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GUNGOR, Tulin, KARAKAYA, Deniz, KARGIN CAKICI, Evrim, YAZILITAS, Fatma, UYSAL YAZICI, Mutlu, CELIKKAYA, Evra, AZAPAGASI, Ebru, and BULBUL, Mehmet
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RENAL replacement therapy ,HEMOLYTIC-uremic syndrome ,ARTIFICIAL respiration - Abstract
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- 2022
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14. Utility of high b‐value diffusion‐weighted imaging in hemolytic uremic syndrome.
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Tonosono, Kohei, Fujii, Katsunori, Hasunuma, Ryuji, Konda, Yutaka, Kobayashi, Hironobu, Kitazawa, Katsuhiko, and Honda, Akihito
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DIAGNOSIS of brain diseases ,CEREBROSPINAL fluid examination ,HEMOLYTIC-uremic syndrome diagnosis ,DIAGNOSIS of fever ,GASTROENTERITIS ,BRAIN ,DIARRHEA ,HEMOGLOBINS ,ELECTROENCEPHALOGRAPHY ,STATUS epilepticus ,DIFFUSION ,MAGNETIC resonance imaging ,VOMITING ,FECES ,SEIZURES (Medicine) ,COMPUTED tomography ,NEURORADIOLOGY ,MICROBIAL sensitivity tests ,SYMPTOMS - Abstract
The article presents a case study of a pediatric patient with hemolytic uremic syndrome (HUS) encephalopathy, where high b-value diffusion-weighted imaging (DWI) was crucial in identifying subtle thalamic lesions. Topics discussed include the utility of high b-value DWI in diagnosing HUS encephalopathy, the advantages and disadvantages of high b-value imaging, and the potential prognostic value of lesions detected only on high b-value DWI in pediatric encephalopathy.
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- 2023
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15. Severely ill pediatric patients with Shiga toxin-associated hemolytic uremic syndrome (STEC-HUS) who suffered from multiple organ involvement in the early stage.
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Luna, Mariana, Kamariski, Mariana, Principi, Iliana, Bocanegra, Victoria, and Vallés, Patricia G.
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THERAPEUTICS ,LEFT heart ventricle ,HYPERTENSION ,METHYLPREDNISOLONE ,NEUROLOGICAL disorders ,CRITICALLY ill ,CARDIOMYOPATHIES ,PLASMA exchange (Therapeutics) ,PATIENTS ,MULTIPLE organ failure ,PEDIATRICS ,RETROSPECTIVE studies ,RENAL replacement therapy ,ARTIFICIAL respiration ,ADULT respiratory distress syndrome ,ESCHERICHIA coli diseases ,BACTERIAL toxins ,HEMOLYTIC-uremic syndrome ,HEART ventricle diseases ,ACUTE kidney failure ,SEPTIC shock ,HEMORRHAGE ,DISEASE risk factors ,CHILDREN - Abstract
Background: Shiga toxin-producing Escherichia coli-associated hemolytic uremic syndrome (STEC-HUS) is the main cause of pediatric acute kidney injury (AKI) in Argentina. Endothelial injury is the trigger event in the microangiopathic process. The host inflammatory response to toxin and E. coli lipopolysaccharide (LPS) is involved in disease pathophysiology. Methods: This retrospective study describes pediatric STEC-HUS patients with multiorgan involvement at the initial phase of disease. A retrospective study of critically ill HUS patients with evidence of E. coli infection was conducted through a period of 15 years. Results: Forty-four patients 35.4 ± 4.1 months were admitted to the intensive care unit for 21 ± 2 days. Mechanical ventilation was required in 41 patients, early inotropic support in 37, and 28 developed septic shock. Forty-one patients required kidney replacement therapy for 12 ± 1 days. Forty-one patients showed neurological dysfunction. Dilated cardiomyopathy was demonstrated in 3 patients, left ventricular systolic dysfunction in 4, and hypertension in 17. Four patients had pulmonary hemorrhage, and acute respiratory distress syndrome in 2. Colectomy for transmural colonic necrosis was performed in 3 patients. Thirty-seven patients were treated with therapeutic plasma exchange, and 28 patients received methylprednisolone (10 mg/kg for 3 days). Of the surviving 32 patients, neurological sequelae were seen in 11 and chronic kidney failure in 5. Conclusions: Severe clinical outcome at onset suggests an amplified inflammatory response after exposure to Shiga toxin and/or E. coli LPS. STEC-HUS associated with severe neurological involvement, hemodynamic instability, and AKI requires intensive care and focused therapy. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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16. Neurological manifestations of thrombotic microangiopathy syndromes in adult patients.
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Weil, Erika L. and Rabinstein, Alejandro A.
- Abstract
The objective of this study was to compare the frequency and severity of neurologic manifestations in adult patients diagnosed with thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS) and atypical HUS (aHUS). This is a retrospective cohort study of adult patients diagnosed with TTP, HUS and atypical HUS hospitalized at a tertiary center between January 2004 and October 2016. A total of 42 TTP, 16 HUS and 20 aHUS episodes were reviewed to collect clinical, laboratory and radiographic data, as well as information regarding long-term functional outcome. Neurologic symptoms are more common in patients with TTP and HUS as compared to aHUS (p < 0.001 and p = 0.002, respectively). Encephalopathy occurred in 29 TTP (69%) and 11 HUS (68%) episodes. Focal deficits were only observed in patients with TTP (n = 8 [19%]). Seizures were most commonly seen in HUS patients (n = 8 [50%]). Posterior reversible encephalopathy syndrome (PRES) was the most common neuroimaging finding in these syndromes; ischemic infarcts and hemorrhages occurred uncommonly. There was no correlation between presence of neurologic symptoms or neuroimaging abnormalities and poor outcome. Patients with TTP and HUS appear to have a similar spectrum of neurologic manifestations, whereas neurologic involvement is less common in aHUS. PRES is the most common imaging abnormality, and may present atypically. Despite presence of neurologic symptoms or neuroimaging abnormalities, patients with thrombotic microangiopathy (TMA) tend to have favorable long-term outcomes. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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17. Cerebrovascular disease in patients with COVID-19: neuroimaging, histological and clinical description.
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Hernández-Fernández, Francisco, Valencia, Hernán Sandoval, Barbella-Aponte, Rosa Angélica, Collado-Jiménez, Rosa, Ayo-Martín, Óscar, Barrena, Cristina, Molina-Nuevo, Juan David, García-García, Jorge, Lozano-Setién, Elena, Alcahut-Rodriguez, Cristian, Martínez-Martín, Álvaro, Sánchez-López, Antonio, Segura, Tomás, and Sandoval Valencia, Hernán
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COVID-19 ,NEUROLOGICAL disorders ,CEREBRAL hemorrhage ,CEREBROVASCULAR disease ,SYMPTOMS ,THROMBOTIC thrombocytopenic purpura ,LEUKOENCEPHALOPATHIES ,VIRAL pneumonia ,BRAIN ,BRAIN diseases ,FERRITIN ,AGE distribution ,MAGNETIC resonance imaging ,DISEASE incidence ,EPIDEMICS ,COMPUTED tomography ,CEREBRAL ischemia ,COMORBIDITY ,NEURORADIOLOGY - Abstract
Since the appearance of the first case of coronavirus disease 2019 (COVID-19) a pandemic has emerged affecting millions of individuals worldwide. Although the main clinical manifestations are respiratory, an increase in neurological conditions, specifically acute cerebrovascular disease, has been detected. We present cerebrovascular disease case incidence in hospitalized patients with SARS-CoV-2 infection. Patients were confirmed by microbiological/serological testing, or on chest CT semiology. Available data on co-morbidity, laboratory parameters, treatment administered, neuroimaging, neuropathological studies and clinical evolution during hospitalization, measured by the modified Rankin scale, were analysed. A bivariate study was also designed to identify differences between ischaemic and haemorrhagic subtypes. A statistical model of binary logistic regression and sensitivity analysis was designed to study the influence of independent variables over prognosis. In our centre, there were 1683 admissions of patients with COVID-19 over 50 days, of which 23 (1.4%) developed cerebrovascular disease. Within this group of patients, cerebral and chest CT scans were performed in all cases, and MRI in six (26.1%). Histological samples were obtained in 6/23 cases (two brain biopsies, and four arterial thrombi). Seventeen patients were classified as cerebral ischaemia (73.9%, with two arterial dissections), five as intracerebral haemorrhage (21.7%), and one leukoencephalopathy of posterior reversible encephalopathy type. Haemorrhagic patients had higher ferritin levels at the time of stroke (1554.3 versus 519.2, P = 0.004). Ischaemic strokes were unexpectedly frequent in the vertebrobasilar territory (6/17, 35.3%). In the haemorrhagic group, a characteristic radiological pattern was identified showing subarachnoid haemorrhage, parieto-occipital leukoencephalopathy, microbleeds and single or multiple focal haematomas. Brain biopsies performed showed signs of thrombotic microangiopathy and endothelial injury, with no evidence of vasculitis or necrotizing encephalitis. The functional prognosis during the hospital period was unfavourable in 73.9% (17/23 modified Rankin scale 4-6), and age was the main predictive variable (odds ratio = 1.5; 95% confidence interval 1.012-2.225; P = 0.043). Our series shows cerebrovascular disease incidence of 1.4% in patients with COVID-19 with high morbidity and mortality. We describe pathological and radiological data consistent with thrombotic microangiopathy caused by endotheliopathy with a haemorrhagic predisposition. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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18. Nephrotic-range proteinuria and central nervous involvement in typical hemolytic uremic syndrome: a case report.
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Shi, Chuan, Li, Chao, Ye, Wei, Ye, Wen-ling, and Li, Ming-xi
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HEMOLYTIC-uremic syndrome ,THROMBOTIC thrombocytopenic purpura ,ESCHERICHIA coli diseases ,PROTEINURIA ,CENTRAL nervous system ,ACUTE kidney failure - Abstract
Background: Hemolytic uremic syndrome (HUS), a common subtype of thrombotic microangiopathy (TMA), is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. Shiga toxin-producing Escherichia coli infection is the most common cause of post-diarrheal HUS. Kidney and central nervous system are the primary target organs.Case Presentation: A 64-year-old male presented with HUS following bloody diarrhea. Nephrotic-range proteinuria and hypoalbuminemia were present at the acute stage and renal histology revealed common TMA features. Neurological involvement presented as confusion and impaired cognitive function. Cranial magnetic resonance imaging demonstrated bilateral T2 hyperintensities in the brainstem and insula. The patient received plasma exchange and supportive care. Both the renal and neurological impairments were completely recovered 3 months after the onset.Conclusion: We report an adult patient presenting with nephrotic-range proteinuria and central nervous system involvement at the acute phase of post-diarrheal HUS. The reversibility of the organ damages might predict a favorable outcome. [ABSTRACT FROM AUTHOR]- Published
- 2020
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19. Increased history of ischemic stroke and decreased neurocognitive performance in children with chronic kidney disease.
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Kupferman, Juan C., Matheson, Matthew B., Lande, Marc B., Flynn, Joseph T., Furth, Susan, Warady, Bradley A., and Hooper, Stephen R.
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CHRONIC kidney failure complications ,STROKE risk factors ,CONFIDENCE intervals ,ISCHEMIA ,MEDICAL records ,PSYCHOLOGY of movement ,QUESTIONNAIRES ,SELF-evaluation ,EFFECT sizes (Statistics) ,DESCRIPTIVE statistics ,ACQUISITION of data methodology ,MANN Whitney U Test ,DISEASE risk factors ,CHILDREN - Abstract
Background: This study aimed to determine stroke incidence and assess the association between stroke and neurocognitive functioning in children with chronic kidney disease (CKD). Methods: Data was derived from the Chronic Kidney Disease in Children (CKiD) cohort study. Stroke incidence was calculated after confirming self-reports of stroke occurrence by chart review. Each participant with stroke was matched with three stroke-free participants and performance on selected neurocognitive measures was compared. Wilcoxon rank-sum tests were used to compare neurocognitive test scores. Effect size (ES) was estimated using a modified version of Cohen's U
3 metric that measures the excess percentage of the stroke group worse than the median of the control group. Results: Of 891 subjects, five (0.56%) had a confirmed stroke prior to study entry. Median time at risk was 15.7 years [interquartile range, 12.5–18.4]. Estimated incidence rate of history of stroke was 36.8 per 100,000 children per year (95% confidence interval 15.3, 88.5). Controls and subjects with stroke were similar in age, CKD duration, race, and maternal education. ES for many of the neurocognitive comparisons was moderate to large. Subjects in the CKID cohort with a history of stroke had lower scores on spatial span reverse, spatial span forward, and design fluency, and worse parent ratings on BRIEF Metacognition Index compared to a matched sample of children with CKD without stroke. Conclusions: Children with CKD have an increased incidence of prior ischemic stroke compared to the general pediatric population. A stroke history was associated with poorer performance on neurocognitive measures. [ABSTRACT FROM AUTHOR]- Published
- 2020
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20. Shiga-Toxin E. coli Hemolytic Uremic Syndrome: Review of Management and Long-term Outcome.
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Harkins, V. J., McAllister, D. A., and Reynolds, B. C.
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- 2020
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21. C3 levels and acute outcomes in Shiga toxin–related hemolytic uremic syndrome.
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Balestracci, Alejandro, Meni Bataglia, Luciana, Toledo, Ismael, Beaudoin, Laura, and Alvarado, Caupolican
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BACTERIAL toxins ,COMPARATIVE studies ,COMPLEMENT (Immunology) ,CONFIDENCE intervals ,ESCHERICHIA coli ,ESCHERICHIA coli diseases ,HEMOLYTIC-uremic syndrome ,HOSPITAL admission & discharge ,IMMUNITY ,EVALUATION of medical care ,MULTIVARIATE analysis ,PATIENTS ,STATISTICS ,DATA analysis ,RECEIVER operating characteristic curves ,DESCRIPTIVE statistics ,ODDS ratio - Abstract
Background: The correlation between complement activation and severity of hemolytic uremic syndrome related to Shiga toxin–producing Escherichia coli (STEC-HUS) has been examined in few studies, with conflicting results. We investigated whether C3 levels on admission are associated with worse acute outcomes. Methods: Demographic, clinical, and laboratory variables were compared between dialyzed and non-dialyzed patients and between those with or without extrarenal complications. Univariate and multivariate analyses were performed; odds ratio (OR) and 95% confidence interval (95%CI) were calculated. C3 concentrations were correlated with dialysis length (Spearman test) and ROC curves with area under the curves (AUC) were calculated to identify C3 concentrations able to discriminate patients with dialysis requirements and complicated course. Results: Among 49 children, 33 had normal and 16 had decreased C3 concentrations. Higher hemoglobin, lactic dehydrogenase, urea and creatinine and lower albumin, sodium, and C3 and C4 concentrations at admission were associated with dialysis requirement; only creatinine remained significant (p = 0.03, OR 2.1, 95%CI 1.34–2.7) by multivariate analysis. Patients with a complicated course presented higher leukocyte count, hemoglobin and lactic dehydrogenase and lower albumin, sodium, and C3 and C4. In the multivariate analysis, leukocyte count (p = 0.02, OR 2.6, 95%CI 1.4–4.3) and C3 concentration (p = 0.039, OR 1.7, 95%CI 1.1–2.73) were independently associated with a complicated disease. C3 levels correlated with dialysis length (r = − 0.42, p = 0.002); nevertheless, they were unable to discriminate dialysis requirement (AUC = 0.25, 95%CI 0.11–0.38) and extrarenal complications (AUC = 0.24, 95%CI 0.11–0.4). Conclusions: Our study suggests that decreased C3 levels at admission are associated with a more complicated STEC-HUS episode. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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22. Extrarenal manifestations of the hemolytic uremic syndrome associated with Shiga toxin-producing Escherichia coli (STEC HUS).
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Khalid, Myda and Andreoli, Sharon
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TREATMENT of escherichia coli diseases ,HEMOLYTIC-uremic syndrome treatment ,MORTALITY prevention ,ESCHERICHIA coli diseases ,HEMOLYTIC-uremic syndrome ,DISEASE complications ,SYMPTOMS - Abstract
Hemolytic uremic syndrome is commonly caused by Shiga toxin-producing Escherichia coli (STEC). Up to 15% of individuals with STEC-associated hemorrhagic diarrhea develop hemolytic uremic syndrome (STEC HUS). Hemolytic uremic syndrome (HUS) is a disorder comprising of thrombocytopenia, microangiopathic hemolytic anemia, and acute kidney injury. The kidney is the most commonly affected organ and approximately half of the affected patients require dialysis. Other organ systems can also be affected including the central nervous system and the gastrointestinal, cardiac, and musculoskeletal systems. Neurological complications include altered mental status, seizures, stroke, and coma. Gastrointestinal manifestations may present as hemorrhagic colitis, bowel ischemia/necrosis, and perforation. Pancreatitis and pancreatic beta cell dysfunction resulting in both acute and chronic insulin dependant diabetes mellitus can occur. Thrombotic microangiopathy (TMA) in cardiac microvasculature and troponin elevation has been reported, and musculoskeletal involvement manifesting as rhabdomyolysis has also been described. Extrarenal complications occur not only in the acute setting but may also be seen well after recovery from the acute phase of HUS. This review will focus on the extrarenal complications of STEC HUS. To date, management remains mainly supportive, and while there is no specific therapy for STEC HUS, supportive therapy has significantly reduced the mortality rate. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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23. Eculizumab in the treatment of Shiga toxin haemolytic uraemic syndrome.
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Walsh, Patrick R. and Johnson, Sally
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THERAPEUTIC use of monoclonal antibodies ,ACUTE kidney failure ,ALTERNATIVE medicine ,BACTERIAL toxins ,DISEASES ,ESCHERICHIA coli ,HEMOLYTIC-uremic syndrome ,SYMPTOMS ,SEROTYPES ,DISEASE complications - Abstract
Haemolytic uraemic syndrome (HUS) remains a leading cause of paediatric acute kidney injury (AKI). Haemolytic uraemic syndrome is characterised by the triad of microangiopathic haemolytic anaemia, thrombocytopenia and AKI. In ~ 90% of cases, HUS is a consequence of infection with Shiga toxin-producing E. coli (STEC), most commonly serotype O157:H7. Acute mortality from STEC-HUS is now less than 5%; however, there is significant long-term renal morbidity in one third of survivors. Currently, no specific treatment exists for STEC-HUS. There is growing interest in the role of complement in the pathogenesis of STEC-HUS due to the discovery of inherited and acquired dysregulation of the alternative complement system in the closely related disorder, atypical HUS (aHUS). The treatment of aHUS has been revolutionised by the introduction of the anti-C5 monoclonal antibody, eculizumab. However, the role of complement and anti-complement therapy in STEC-HUS remains unclear. Herein, we review the current evidence of the role of complement in STEC-HUS focusing on the use of eculizumab in this disease. [ABSTRACT FROM AUTHOR]
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- 2019
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24. Hemolytic uremic syndrome in a developing country: Consensus guidelines.
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Bagga, Arvind, Khandelwal, Priyanka, Mishra, Kirtisudha, Thergaonkar, Ranjeet, Vasudevan, Anil, Sharma, Jyoti, Patnaik, Saroj Kumar, Sinha, Aditi, Sethi, Sidharth, Hari, Pankaj, and Dragon-Durey, Marie-Agnes
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HEMOLYTIC-uremic syndrome treatment ,THERAPEUTIC use of monoclonal antibodies ,HEMOLYTIC-uremic syndrome diagnosis ,IMMUNOSUPPRESSIVE agents ,ALGORITHMS ,BACTERIAL toxins ,BIOPSY ,BLOOD vessels ,COMPLEMENT (Immunology) ,DEVELOPING countries ,DIFFERENTIAL diagnosis ,GENETIC techniques ,HEMOLYTIC-uremic syndrome ,HOMOGRAFTS ,INFECTION ,MEDICAL equipment ,MEDICAL protocols ,PEDIATRICS ,PLASMA exchange (Therapeutics) ,STREPTOCOCCAL diseases ,DISEASE management ,DISEASE relapse ,DISEASE remission ,DISEASE complications - Abstract
Background: Hemolytic uremic syndrome (HUS) is a leading cause of acute kidney injury in children. Although international guidelines emphasize comprehensive evaluation and treatment with eculizumab, access to diagnostic and therapeutic facilities is limited in most developing countries. The burden of Shiga toxin-associated HUS in India is unclear; school-going children show high prevalence of anti-factor H (FH) antibodies. The aim of the consensus meeting was to formulate guidelines for the diagnosis and management of HUS in children, specific to the needs of the country. Methods: Four workgroups performed literature review and graded research studies addressing (i) investigations, biopsy, genetics, and differential diagnosis; (ii) Shiga toxin, pneumococcal, and infection-associated HUS; (iii) atypical HUS; and (iv) complement blockade. Consensus statements developed by the workgroups were discussed during a consensus meeting in March 2017. Results: An algorithm for classification and evaluation was developed. The management of Shiga toxin-associated HUS is supportive; prompt plasma exchanges (PEX) is the chief therapy in patients with atypical HUS. Experts recommend that patients with anti-FH-associated HUS be managed with a combination of PEX and immunosuppressive medications. Indications for eculizumab include incomplete remission with plasma therapy, life-threatening features, complications of PEX or vascular access, inherited defects in complement regulation, and recurrence of HUS in allografts. Priorities for capacity building in regional and national laboratories are highlighted. Conclusions: Limited diagnostic capabilities and lack of access to eculizumab prevent the implementation of international guidelines for HUS in most developing countries. We propose practice guidelines for India, which will perhaps be applicable to other developing countries. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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25. Factors affecting mortality in children requiring continuous renal replacement therapy in pediatric intensive care unit.
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Miklaszewska, Monika, Korohoda, Przemysław, Zachwieja, Katarzyna, Sobczak, Alina, Kobylarz, Krzysztof, Stefanidis, Constantinos J., Goździk, Jolanta, and Drożdż, Dorota
- Subjects
PEDIATRIC intensive care ,CHILD mortality ,INTENSIVE care units ,PEDIATRIC therapy ,KIDNEY injuries - Abstract
Background. Acute kidney injury (AKI) occurs in up to 30% of pediatric intensive care unit (PICU) patients and is associated with a high mortality rate. Objectives. The objective of the study was to evaluate factors associated with the outcome and to identify the prognostic factors in children receiving continuous renal replacement therapy (CRRT). Material and methods. This was a retrospective, single-center study, including 46 patients. Results. Logistic regression analysis demonstrated significant effects on patient survival exerted by the percentage of fluid overload (FO%) (odds ratio (OR): 1.030; p = 0.044). In the group of patients with FO% <25%, the mortality was 33.3%, and in the FO% .25% group, the mortality was 67.9% (p < 0.001). The probability of death without multi-organ failure (MOF) was 13%, while with MOF it was 74%. There was no difference in the duration of hospitalization between the CRRT patients (mean: 21.9 days) and the general population of children hospitalized in PICU in the same period (n = 3,255; mean: 25.4 days); however, a significant difference was noted in mortality between the 2 groups of patients (54% vs 6.5%; p < 0.001). Conclusions. The mortality of PICU CRRT patients is more than 8-fold higher than the mortality of the total PICU population. Coexisting MOF increases the mortality almost 6 times. The mortality of children with FO% =25% was more than 2-fold higher than the mortality of children with FO% <25%. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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26. A pediatric neurologic assessment score may drive the eculizumab-based treatment of Escherichia coli-related hemolytic uremic syndrome with neurological involvement.
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Giordano, Paolo, Santangelo, Luisa, Carbone, Vincenza, Torres, Diletta Domenica, Martino, Marida, Giordano, Mario, Netti, Giuseppe Stefano, Castellano, Giuseppe, Gesualdo, Loreto, Sesta, Michela, Di Cuonzo, Franca, Resta, Maria Chiara, Gaeta, Alberto, Milella, Leonardo, Chironna, Maria, Germinario, Cinzia, and Scavia, Gaia
- Subjects
THERAPEUTIC use of monoclonal antibodies ,HEMOLYTIC-uremic syndrome diagnosis ,BACTERIAL toxins ,BRAIN injuries ,CENTRAL nervous system diseases ,ESCHERICHIA coli diseases ,HEMOLYTIC-uremic syndrome ,LONGITUDINAL method ,NEUROLOGIC examination ,PEDIATRICS ,TREATMENT effectiveness ,RETROSPECTIVE studies ,SEVERITY of illness index ,TERTIARY care ,DISEASE complications ,DIAGNOSIS - Abstract
Background: Thrombotic microangiopathy (TMA) is a clinical syndrome encompassing a large group of rare but severe disorders including thrombotic thrombocytopenic purpura (TTP) and both typical and atypical forms of hemolytic uremic syndrome (HUS). The key role of the complement system is well known in TTP and atypical HUS, but recent reports describe its involvement in the pathogenesis of HUS secondary to gastrointestinal infections due to Shiga toxin-producing Escherichia coli (STEC).Methods: TMA mainly affects the kidney, but extra-renal complications are frequently described. The involvement of the central nervous system (CNS) represents often a life-threatening condition and it can result in serious long-term disability in HUS patients who overcome the acute phase of illness. In the present study, we retrospectively analyzed a pediatric cohort of a single tertiary pediatric hospital in Southern Italy, in which this complication occurred in 12/54 children (22% of cases), of whom five with severe neurological involvement had been successfully treated with eculizumab.Results: The great clinical variability of brain injury in our cohort has led us to retrospectively build a "neurological score" useful to assess the clinical severity of neurologic involvement. Subjects with higher neurologic score due to the most severe CNS involvement resulted in the group of patients early treated with eculizumab, obtaining a good clinical response (four out five patients). In conclusion, the early treatment with eculizumab in children with severe neurological involvement during STEC-HUS was associated with complete regression of both acute kidney injury (AKI) and neurological lesions observed at magnetic resonance imaging (MRI).Conclusions: A "neurological score" may be a useful tool to drive the early treatment of CNS complications in STEC-HUS with eculizumab, although future perspective controlled studies are urgently needed to validate this therapeutic approach. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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27. Shiga toxin 2 from enterohemorrhagic Escherichia coli induces reactive glial cells and neurovascular disarrangements including edema and lipid peroxidation in the murine brain hippocampus.
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Berdasco, Clara, Pinto, Alipio, Calabró, Valeria, Arenas, David, Cangelosi, Adriana, Geoghegan, Patricia, Evelson, Pablo, and Goldstein, Jorge
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ESCHERICHIA coli O157:H7 ,HIPPOCAMPUS (Brain) ,NEUROGLIA ,ONE-way analysis of variance ,TOXINS - Abstract
Background: Shiga toxin 2 from enterohemorrhagic Escherichia coli is the etiologic agent of bloody diarrhea, hemolytic uremic syndrome and derived encephalopathies that may result to death in patients. Being a Gram negative bacterium, lipopolysaccharide is also released. Particularly, the hippocampus has been found affected in patients intoxicated with Shiga toxin 2. In the current work, the deleterious effects of Shiga toxin 2 and lipopolysaccharide are investigated in detail in hippocampal cells for the first time in a translational murine model, providing conclusive evidences on how these toxins may damage in the observed clinic cases. Methods: Male NIH mice (25 g) were injected intravenously with saline solution, lipopolysaccharide, Shiga toxin 2 or a combination of Shiga toxin 2 with lipopolysaccharide. Brain water content assay was made to determine brain edema. Another set of animals were intracardially perfused with a fixative solution and their brains were subjected to immunofluorescence with lectins to determine the microvasculature profile, and anti-GFAP, anti-NeuN, anti-MBP and anti-Iba1 to study reactive astrocytes, neuronal damage, myelin dysarrangements and microglial state respectively. Finally, the Thiobarbituric Acid Reactive Substances Assay was made to determine lipid peroxidation. In all assays, statistical significance was performed using the One-way analysis of variance followed by Bonferroni post hoc test. Results: Systemic sublethal administration of Shiga toxin 2 increased the expressions of astrocytic GFAP and microglial Iba1, and decreased the expressions of endothelial glycocalyx, NeuN neurons from CA1 pyramidal layer and oligodendrocytic MBP myelin sheath from the fimbria of the hippocampus. In addition, increased interstitial fluids and Thiobarbituric Acid Reactive Substances-derived lipid peroxidation were also found. The observed outcomes were enhanced when sublethal administration of Shiga toxin 2 was co-administered together with lipopolysaccharide. Conclusion: Systemic sublethal administration of Shiga toxin 2 produced a deterioration of the cells that integrate the vascular unit displaying astrocytic and microglial reactive profiles, while edema and lipid peroxidation were also observed. The contribution of lipopolysaccharide to pathogenicity caused by Shiga toxin 2 resulted to enhance the observed hippocampal damage. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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28. Complement activation is associated with more severe course of diarrhea-associated hemolytic uremic syndrome, a preliminary study.
- Author
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Karnisova, Lucia, Hradsky, Ondrej, Blahova, Kveta, Fencl, Filip, Dolezel, Zdenek, Zaoral, Tomas, and Zieg, Jakub
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HEMOLYTIC-uremic syndrome ,DIARRHEA ,HEMOLYTIC anemia ,THROMBOCYTOPENIA ,ESCHERICHIA coli - Abstract
Diarrhea-associated hemolytic uremic syndrome is characterized by hemolytic anemia, thrombocytopenia, and acute kidney injury secondary to enteric infection, typically Shiga toxin-producing Escherichia coli. Shiga toxin 2 is able to activate alternative complement pathways; therefore, the aim of the study was to analyze C3 as a predictor of clinical courses in patients with diarrhea-associated hemolytic uremic syndrome. We hypothesized that the patients with increased complement activation at admission suffered from a more severe course. We retrospectively analyzed data of 33 pediatric patients between 1999 and 2015 in the Czech Republic. We tested the association of a C3 concentration with biochemical parameters and the clinical data reflecting the severity of the disease. We found significant correlation between the initial C3 and the duration of renal replacement therapy (r = - 0.62, p = 0.0001) and the initial glomerular filtration rate (r = 0.36, p = 0.026). Patients with C3 < 0.825 g/L needed renal replacement therapy and also had significantly more renal complications (p = 0.015).Conclusion: Based on our study, decreased C3 concentrations can be used as one of the risk factors that can help predict the need for acute dialysis and a more severe course of disease in children with diarrhea-associated hemolytic uremic syndrome. What is Known: • Shiga toxin modulates the function of complement regulatory proteins and thus contributes to complement activation in patients with diarrhea-associated hemolytic uremic syndrome. • Risk factors that can predict the need for acute renal replacement therapy and poor outcome in patients with diarrhea-associated hemolytic uremic syndrome are mainly the combination of oligoanuria, dehydration, leukocytosis, high hematocrit > 23%, and neurological involvement. What is New: • A lowered concentration of C3 at the time of initial presentation of diarrhea-associated hemolytic uremic syndrome was associated with more severe renal failure and the need for renal replacement therapy along with the development of more extra renal complications. • Decreased C3 at admission can predict complicated course of diarrhea-associated hemolytic uremic syndrome. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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29. Combined and sequential liver-kidney transplantation in children.
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Grenda, Ryszard and Kaliciński, Piotr
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ORGAN donation ,ALGORITHMS ,GRAFT rejection ,KIDNEY diseases ,KIDNEY transplantation ,LIVER diseases ,LIVER transplantation ,MULTIPLE organ failure ,SURVIVAL ,AUTOSOMAL recessive polycystic kidney ,SYMPTOMS ,CHILDREN ,THERAPEUTICS ,PSYCHOLOGY - Abstract
Combined and sequential liver-kidney transplantation (CLKT and SLKT) is a definitive treatment in children with end-stage organ failure. There are two major indications: - terminal insufficiency of both organs, or - need for transplanting new liver as a source of lacking enzyme or specific regulator of the immune system in a patient with renal failure. A third (uncommon) option is secondary end-stage renal failure in liver transplant recipients. These three clinical settings use distinct qualification algorithms. The most common indications include primary hyperoxaluria type 1 (PH1) and autosomal recessive polycystic kidney disease (ARPKD), followed by liver diseases associated with occasional kidney failure. Availability of anti-C5a antibody (eculizumab) has limited the validity of CLKT in genetic atypical hemolytic uremic syndrome (aHUS). The liver coming from the same donor as renal graft (in CLKT) is immunologically protective for the kidney and this provides long-term rejection-free follow-up. No such protection is observed in SLKT, when both organs come from different donors, except uncommon cases of living donation of both organs. Overall long-term outcome in CLKT in terms of graft survival is good and not different from isolated liver or kidney transplantation, however patient survival is inferior due to complexity of this procedure. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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30. Is eculizumab efficacious in Shigatoxin-associated hemolytic uremic syndrome? A narrative review of current evidence.
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Keenswijk, Werner, Raes, Ann, and Vande Walle, Johan
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ECULIZUMAB ,HEMOLYTIC-uremic syndrome ,DRUG efficacy ,DRUG administration ,RANDOMIZED controlled trials ,THERAPEUTIC use of monoclonal antibodies ,IMMUNOSUPPRESSIVE agents ,BACTERIAL toxins ,MEDICAL information storage & retrieval systems ,MEDLINE ,ONLINE information services ,SYSTEMATIC reviews - Abstract
Severe complications due to Shigatoxin-associated hemolytic uremic syndrome (STEC-HUS) currently present a serious challenge since no specific treatment for this condition is available. Eculizumab, a terminal complement inhibitor, has been used especially in STEC-HUS patients with severe neurological involvement, but the efficacy remains undetermined. In order to determine its efficacy, we searched the databases Pubmed, Web of Science, Embase, and LiLACS for reports describing outcomes of eculizumab administration in STEC-HUS. We retrieved 11 reports ranging from case reports to cohort studies with the largest study population emanating from the 2011 German outbreak. Outcomes were variable and difficult to interpret in light of the absence of high-quality studies but seemed to point towards potential efficacy of eculizumab if administered early in the course.
Conclusion: The efficacy of eculizumab in STEC-HUS could not be established nor disproven based on current data, and there is a desperate need for randomized controlled trials. What is known? • Eculizumab has been used in complicated cases of Shigatoxin-associated hemolytic uremic syndrome but the efficacy remains unknown? What is new? • Eculizumab might be efficacious if given early in selected cases of Shigatoxin-associated hemolytic uremic syndrome; however, randomized trials are needed to assess this. [ABSTRACT FROM AUTHOR]- Published
- 2018
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31. Successful long-term outcome of pediatric liver-kidney transplantation: a single-center study.
- Author
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Quintero Bernabeu, Jesús, Juamperez, Javier, Muñoz, Marina, Rodriguez, Olalla, Vilalta, Ramon, Molino, José A., Asensio, Marino, Bilbao, Itxarone, Ariceta, Gema, Rodrigo, Carlos, and Charco, Ramón
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TREATMENT effectiveness ,FISHER exact test ,GRAFT rejection ,HOMOGRAFTS ,IMMUNOGLOBULINS ,KIDNEY transplantation ,LIVER transplantation ,LONG-term health care ,ORGAN donors ,OXALIC acid ,PEDIATRICS ,SURVIVAL ,DATA analysis software ,KAPLAN-Meier estimator ,AUTOSOMAL recessive polycystic kidney ,DISEASE complications - Abstract
Introduction: Liver-kidney transplantation is a rare procedure in children, with just ten to 30 cases performed annually worldwide. The main indications are autosomal recessive polycystic liver-kidney disease and primary hyperoxaluria. This study aimed to report outcomes of liver-kidney transplantation in a cohort of pediatric patients. Methods: We retrospectively analyzed all pediatric liver-kidney transplantations performed in our center between September 2000 and August 2015. Patient data were obtained by reviewing inpatient and outpatient medical records and our transplant database. Results: A total of 14 liver-kidney transplants were performed during the study period, with a median patient age and weight at transplant of 144.4 months (131.0-147.7) and 27.3 kg (12.0-45.1), respectively. The indications for liver-kidney transplants were autosomal recessive polycystic liver-kidney disease (8/14), primary hyperoxaluria −1 (5/14), and idiopathic portal hypertension with end-stage renal disease (1/14). Median time on waiting list was 8.5 months (5.7-17.3). All but two liver-kidney transplants were performed simultaneously. Patients with primary hyperoxaluria-1 tended to present a delayed recovery of renal function compared with patients transplanted for other indications (62.5 vs 6.5 days, respectively, P 0.076). Patients with liver-kidney transplants tended to present a lower risk of acute kidney rejection than patients transplanted with an isolated kidney transplant (7.2% vs 32.7%, respectively; P < 0.07). Patient and graft survival at 1, 3, and 5 years were 100%, 91.7%, 91.7%, and 91.7%, 83.3%, 83.3%, respectively. No other grafts were lost. Conclusion: Long-term results of liver-kidney transplants in children are encouraging, being comparable with those obtained in isolated liver transplantation. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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32. Blood urea nitrogen to serum creatinine ratio as a prognostic factor in diarrhea-associated hemolytic uremic syndrome: a validation study.
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Balestracci, Alejandro, Meni Battaglia, Luciana, Toledo, Ismael, Martin, Sandra Mariel, and Alvarado, Caupolican
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HEMOLYTIC-uremic syndrome ,PROGNOSIS ,DIARRHEA in children ,BLOOD urea nitrogen ,CREATININE ,COMORBIDITY ,HEMOLYTIC-uremic syndrome diagnosis ,COMPARATIVE studies ,DIARRHEA ,RESEARCH methodology ,MEDICAL cooperation ,RESEARCH ,EVALUATION research ,RETROSPECTIVE studies ,DISEASE complications - Abstract
The article discusses research on the relation of a blood urea nitrogen to serum creatinine ratio (BCR) to diarrhea-associated hemolytic uremic syndrome (D+HUS) in children. Topics include the use of BCR as a prognostic measure at the time of hospital admission, the impact of various comorbidities on prognosis, and the notion of a complicated course for children with D+HUS.
- Published
- 2018
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33. Filter Size Not the Anticoagulation Method is the Decisive Factor in Continuous Renal Replacement Therapy Circuit Survival.
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Miklaszewska, Monika, Korohoda, Przemysław, Zachwieja, Katarzyna, Kobylarz, Krzysztof, Stefanidis, Constantinos J., Sobczak, Alina, and Drożdż, Dorota
- Subjects
ANTICOAGULANTS ,BLOOD coagulation disorders ,TREATMENT of acute kidney failure ,PATIENT compliance ,DIAGNOSIS ,BLOOD disease treatment - Abstract
Background/Aim: As continuous renal replacement therapy (CRRT) has emerged as a standard therapy in pediatric intensive care units (PICU), many related issues that may have an impact on circuit survival have gained in importance. Objective of the study was an evaluation of factors associated with circuit survival, including anticoagulation (ACG). Methods: Retrospective study that included 40 patients, who in total received 7636 hours of CRRT during 150 sessions (84 filters, 4260 hours with heparin anticoagulation (Hep-ACG); 66 filters, 3376 hours with regional citrate anticoagulation (RCA)). Results: The Kaplan-Meier analysis of the total circuit survival time depending on the type of ACG did not demonstrate a significant difference between Hep-ACG and RCA. The percentage of clotted filters was significantly higher in case of smaller filters (HF20: 58.8%; ST60:29.5%; ST100: 15.8%), and their lifetime was significantly lower regardless of ACG (the mean and median lifetime for HF20: 38.7/27.0 h; for ST60: 54.1/72.0 h., for ST100: 62.1/72.0 h, respectively). Conclusions: Irrespectively of filter size, filter clotting occurs within the first 24 hours after the initiation of CRRT. Most commonly, clotting affects small filters, and their lifetime is significantly shorter as compared to larger filters regardless of the type of the ACG. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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34. Blood urea nitrogen to serum creatinine ratio is an accurate predictor of outcome in diarrhea-associated hemolytic uremic syndrome, a preliminary study.
- Author
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Keenswijk, Werner, Vanmassenhove, Jill, Raes, Ann, Dhont, Evelyn, and Vande Walle, Johan
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BLOOD urea nitrogen ,CREATININE ,HEMOLYTIC-uremic syndrome ,THROMBOTIC thrombocytopenic purpura ,KIDNEY diseases ,DIARRHEA ,LONGITUDINAL method ,RETROSPECTIVE studies ,DISEASE complications - Abstract
Diarrhea-associated hemolytic uremic syndrome (D+HUS) is a common thrombotic microangiopathy during childhood and early identification of parameters predicting poor outcome could enable timely intervention. This study aims to establish the accuracy of BUN-to-serum creatinine ratio at admission, in addition to other parameters in predicting the clinical course and outcome. Records were searched for children between 1 January 2008 and 1 January 2015 admitted with D+HUS. A complicated course was defined as developing one or more of the following: neurological dysfunction, pancreatitis, cardiac or pulmonary involvement, hemodynamic instability, and hematologic complications while poor outcome was defined by death or development of chronic kidney disease. Thirty-four children were included from which 11 with a complicated disease course/poor outcome. Risk of a complicated course/poor outcome was strongly associated with oliguria (p = 0.000006) and hypertension (p = 0.00003) at presentation. In addition, higher serum creatinine (p = 0.000006) and sLDH (p = 0.02) with lower BUN-to-serum creatinine ratio (p = 0.000007) were significantly associated with development of complications. A BUN-to-sCreatinine ratio ≤40 at admission was a sensitive and highly specific predictor of a complicated disease course/poor outcome.
Conclusion: A BUN-to-serum Creatinine ratio can accurately identify children with D+HUS at risk for a complicated course and poor outcome. What is Known: • Oliguria is a predictor of poor long-term outcome in D+HUS What is New: • BUN-to-serum Creatinine ratio at admission is an entirely novel and accurate predictor of poor outcome and complicated clinical outcome in D+HUS • Early detection of the high risk group in D+HUS enabling early treatment and adequate monitoring. [ABSTRACT FROM AUTHOR]- Published
- 2017
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35. Shiga toxin-producing Escherichia coli hemolytic uremic syndrome.
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Peco-Antić, Amira
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- 2016
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36. Diarrhea-associated hemolytic uremic syndrome with severe neurological manifestations treated with IgG depletion through immunoadsorption.
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Flam, Benjamin, Sackey, Peter, Berge, Andreas, Zachau, Anne, Brink, Bo, and Lundberg, Sigrid
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- 2016
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37. Health-related quality of life and mental health in parents of children with hemolytic uremic syndrome.
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Buder, Kathrin, Werner, Helene, Landolt, Markus, Neuhaus, Thomas, Laube, Guido, and Spartà, Giuseppina
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DIAGNOSIS of post-traumatic stress disorder ,HEMOLYTIC-uremic syndrome ,ACADEMIC medical centers ,CHI-squared test ,STATISTICAL correlation ,HEALTH surveys ,MENTAL health ,PARENTS ,POST-traumatic stress disorder ,PROBABILITY theory ,QUALITY of life ,QUESTIONNAIRES ,RESEARCH funding ,STATISTICS ,T-test (Statistics) ,DATA analysis ,MULTIPLE regression analysis ,CROSS-sectional method ,DATA analysis software ,DESCRIPTIVE statistics ,MANN Whitney U Test ,BRIEF Symptom Inventory ,CHILDREN ,PSYCHOLOGY - Abstract
Background: Little is known about health-related quality of life (HRQoL) and mental health of parents having children with a history of hemolytic uremic syndrome (HUS). Methods: This study included 63 mothers and 58 fathers of a cohort of 63 HUS-affected children. At assessment, the mean time since a child experienced an acute episode of HUS was 6.4 years. Parental HRQoL, mental health and posttraumatic stress disorder (PTSD) were assessed with standardized self-report questionnaires. Medical data were extracted from patients' hospital records. Results: The HRQoL and mental health of both the mothers and fathers were not impaired compared to normative data. However, a shorter time since a child's acute HUS episode was a significant predictor of lower HRQoL among the mothers, while no such effect was found among the fathers. Two fathers (3 %), but no mothers, met the criteria for a diagnosis of HUS-related full PTSD; one father (2 %) and four mothers (6 %) met the criteria for a diagnosis of HUS-related partial PTSD. Conclusions: Our study shows that most parents of our study sample were doing well in terms of HRQoL and mental health, although a small number met the criteria for full or partial PTSD diagnosis due to their child's HUS. We therefore recommend that healthcare providers pay special attention to parents regarding PTSD symptoms during the clinical follow-up of a HUS-affected child since some parents may benefit from psychological support. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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38. Guidelines on the Use of Therapeutic Apheresis in Clinical Practice-Evidence-Based Approach from the Writing Committee of the American Society for Apheresis: The Seventh Special Issue.
- Author
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Schwartz, Joseph, Padmanabhan, Anand, Aqui, Nicole, Balogun, Rasheed A., Connelly‐Smith, Laura, Delaney, Meghan, Dunbar, Nancy M., Witt, Volker, Wu, Yanyun, and Shaz, Beth H.
- Abstract
The American Society for Apheresis (ASFA) Journal of Clinical Apheresis (JCA) Special Issue Writing Committee is charged with reviewing, updating, and categorizing indications for the evidence-based use of therapeutic apheresis in human disease. Since the 2007 JCA Special Issue (Fourth Edition), the Committee has incorporated systematic review and evidence-based approaches in the grading and categorization of apheresis indications. This Seventh Edition of the JCA Special Issue continues to maintain this methodology and rigor to make recommendations on the use of apheresis in a wide variety of diseases/conditions. The JCA Seventh Edition, like its predecessor, has consistently applied the category and grading system definitions in the fact sheets. The general layout and concept of a fact sheet that was used since the fourth edition has largely been maintained in this edition. Each fact sheet succinctly summarizes the evidence for the use of therapeutic apheresis in a specific disease entity. The Seventh Edition discusses 87 fact sheets (14 new fact sheets since the Sixth Edition) for therapeutic apheresis diseases and medical conditions, with 179 indications, which are separately graded and categorized within the listed fact sheets. Several diseases that are Category IV which have been described in detail in previous editions and do not have significant new evidence since the last publication are summarized in a separate table. The Seventh Edition of the JCA Special Issue serves as a key resource that guides the utilization of therapeutic apheresis in the treatment of human disease. J. Clin. Apheresis 31:149-162, 2016. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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39. Atipik Hemolitik Üremik Sendrom.
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GÜLLEROĞLU, Kaan, GÜLLEROĞLU, Başak, and BASKIN, Esra
- Abstract
Copyright of Journal of Pediatric Disease / Türkiye Çocuk Hastalıkları Dergisi is the property of Turkish Journal of Pediatric Disease and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
- Published
- 2015
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40. Success of eculizumab in the treatment of atypical hemolytic uremic syndrome.
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Baskin, Esra, Gulleroglu, Kaan, Kantar, Asli, Bayrakci, Umut, and Ozkaya, Ozan
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HEMOLYTIC-uremic syndrome treatment ,THERAPEUTIC use of monoclonal antibodies ,BIOTHERAPY ,BLOOD plasma ,HEMOLYTIC-uremic syndrome ,TREATMENT effectiveness ,RETROSPECTIVE studies ,DESCRIPTIVE statistics - Abstract
Background: Disorders of complement regulation are the most important etiology of atypical hemolytic uremic syndrome (aHUS). Recent studies demonstrate that eculizumab is beneficial in long-term aHUS treatment. We present a series of children with aHUS resistant to/dependent on plasma exchange (PE) who were treated with eculizumab. Methods: This was a retrospective study in which data were retrieved from the medical files of children who had received PE as treatment for aHUS. The data retrieved included age, sex, presenting symptoms, presence of diarrhea/vomiting, hospitalization duration, laboratory data on admission and follow-up, need for transfusion or dialysis, response to PE, response to eculizumab and outcome. Results: Of the 15 children diagnosed with aHUS in 2011 and 2012 in our departments, ten were resistant to, or dependent on, plasma therapy and treated with eculizumab; these children were enrolled in the study. Three patients had relapses, and seven had a new diagnosis. Nine children had oliguria or anuria, and eight required dialysis. Hypertension was observed in six patients. Neurologic involvement developed in six patients, with the symptoms including seizures, loss of balance, vision loss and severe confusion. Five and five patients were resistant to and dependent on plasma therapy, respectively. Following the start of eculizumab treatment, all patients achieved full recovery of renal function and hematologic parameters. Conclusions: In our ten pediatric patients with aHUS who did not respond to PE, eculizumab was a lifesaving therapy and improved their quality of life. Early eculizumab use was a rescue therapy for renal function. Our results show that eculizumab is an effective treatment for aHUS. However, more studies are needed on the long-term efficacy and safety of eculizumab in children with aHUS and to determine the optimal duration of treatment. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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41. Neurodevelopmental long-term outcome in children after hemolytic uremic syndrome.
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Buder, Kathrin, Latal, Beatrice, Nef, Samuel, Neuhaus, Thomas, Laube, Guido, and Spartà, Giuseppina
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ACADEMIC medical centers ,CHILD development ,FISHER exact test ,GLOMERULAR filtration rate ,HEMOLYTIC-uremic syndrome ,NERVOUS system ,T-test (Statistics) ,MULTIPLE regression analysis ,RETROSPECTIVE studies ,DATA analysis software ,DESCRIPTIVE statistics ,MANN Whitney U Test ,DISEASE complications ,CHILDREN - Abstract
Background: To investigate the long-term neurodevelopmental outcome in children after hemolytic uremic syndrome (HUS) and to compare outcome dependent on central nervous system (CNS) involvement during HUS. Methods: A single-center retrospective cohort of 47 children was examined at a median age of 10.6 (range 6-16.9) years and a median follow-up of 7.8 (range 0.4-15.3) years after having had HUS. Intellectual performance was assessed with the German version of the Wechsler Intelligence Scale 4th version and neuromotor performance with the Zurich Neuromotor Assessment (ZNA). The occurrence of neurological symptoms during the acute phase of HUS was evaluated retrospectively. Results: Mean IQ of the whole study population fell within the normal range (median full scale IQ 104, range 54-127). Neuromotor performance was significantly poorer in the domains 'adaptive fine,' 'gross motor,' 'static balance' (all p < 0.05) and 'associated movements' ( p < 0.001); only the 'pure motor' domain was within the normal reference range. Neurological findings occurred in 16/47 patients (34 %) during acute HUS. Neurodevelopmental outcome was not significantly different between children with or without CNS involvement. Conclusions: Our follow-up of children after HUS showed a favorable cognitive outcome. However, neuromotor outcome was impaired in all study participants. Neurological impairment during acute HUS was not predictive of outcome. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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42. Upregulation of Shiga Toxin Receptor CD77/Gb3 and Interleukin-1β Expression in the Brain of EHEC Patients with Hemolytic Uremic Syndrome and Neurologic Symptoms.
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Hagel, Christian, Krasemann, Susanne, Löffler, Judith, Püschel, Klaus, Magnus, Tim, and Glatzel, Markus
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TOXIN receptors ,INTERLEUKINS ,GENE expression ,BRAIN physiology ,ESCHERICHIA coli O157:H7 ,HEMOLYTIC-uremic syndrome ,NEUROLOGY - Abstract
In 2011, a large outbreak of Shiga toxin-producing enterohemorrhagic Escherichia coli (EHEC) infections occurred in northern Germany, which mainly affected adults. Out of 3842 patients, 104 experienced a complicated course comprising hemolytic uremic syndrome and neurological complications, including cognitive impairment, aphasia, seizures and coma. T2 hyperintensities on magnet resonance imaging (MRI) bilateral in the thalami and in the dorsal pons were found suggestive of a metabolic toxic effect. Five of the 104 patients died because of toxic heart failure. In the present study, the post-mortem neuropathological findings of the five EHEC patients are described. Histological investigation of 13 brain regions (frontal, temporal, occipital cortex, corpora mammillaria, thalamus, frontal operculum, corona radiata, gyrus angularis, pons, medulla oblongata, cerebellar vermis and cerebellar hemisphere) showed no thrombosis, ischemic changes or fresh infarctions. Further, no changes were found in electron microscopy. In comparison with five age-matched controls, slightly increased activation of microglia and a higher neuronal expression of interleukin-1β and of Shiga toxin receptor CD77/globotriaosylceramide 3 was observed. The findings were confirmed by Western blot analyses. It is suggested that CD77/globotriaosylceramide upregulation may be a consequence to Shiga toxin exposure, whereas increased interleukin-1β expression may point to activation of inflammatory cascades. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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43. Early erythropoietin in post-diarrheal hemolytic uremic syndrome: a case-control study.
- Author
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Balestracci, Alejandro, Martin, Sandra, Toledo, Ismael, Alvarado, Caupolican, and Wainsztein, Raquel
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THERAPEUTICS ,HEMOLYTIC-uremic syndrome treatment ,CHI-squared test ,DIARRHEA ,RED blood cell transfusion ,ERYTHROPOIETIN ,FISHER exact test ,HEMOLYTIC-uremic syndrome ,T-test (Statistics) ,RETROSPECTIVE studies ,CASE-control method ,DATA analysis software ,DESCRIPTIVE statistics ,CHILDREN - Abstract
The article focuses on a study related to reporting of erythropoietin (EPO) deficiency in post-diarrheal hemolytic uremic syndrome (D+HUS). Topics discussed include use of rHuEPO in patients with D+HUS, progression of hemoglobin levels along the course of the disease, and treatment with EPO do not reduce the number of RBC transfusions in D+HUS children.
- Published
- 2015
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44. Hemoconcentration: a major risk factor for neurological involvement in hemolytic uremic syndrome.
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Ardissino, Gianluigi, Daccò, Valeria, Testa, Sara, Civitillo, Cristina, Tel, Francesca, Possenti, Ilaria, Belingheri, Mirco, Castorina, Pierangela, Bolsa-Ghiringhelli, Nicolò, Tedeschi, Silvana, Paglialonga, Fabio, Salardi, Stefania, Consonni, Dario, Zoia, Elena, Salice, Patrizia, and Chidini, Giovanna
- Subjects
HEMOLYTIC-uremic syndrome treatment ,NEUROLOGICAL disorders ,BACTERIAL toxins ,BLOOD plasma ,BLOOD volume ,CONFIDENCE intervals ,STATISTICAL correlation ,HEMOLYTIC-uremic syndrome ,KIDNEY diseases ,PEDIATRICS ,RESEARCH funding ,STATISTICS ,THERAPEUTICS ,LOGISTIC regression analysis ,DATA analysis ,RETROSPECTIVE studies ,SEVERITY of illness index ,DESCRIPTIVE statistics ,ODDS ratio ,DISEASE complications ,DISEASE risk factors - Abstract
Background: Shigatoxin-associated hemolytic uremic syndrome (STEC-HUS) is a common thrombotic microangiopathy (TMA) in which central nervous system (CNS) involvement is responsible for the majority of deaths and for severe long-term sequelae. We have analyzed the role of hemoconcentration in disease severity. Methods: This was a retrospective review of the records and laboratory data at presentation of all patients with STEC-HUS cases ( n = 61) over a 10-year period. The patients were grouped into three severity classes: group A, comprising patients who did not require dialysis; group B, patients who were dialyzed without CNS involvement; group C, patients with CNS involvement. Results: Patients with CNS involvement (group C) had a higher mean hemoglobin level (11.2 ± 2.3 g/dL) than those of group A or B ( 9.4 ± 2.1 and 7.5 ± 1.9 g/dL, respectively; p < 0.0001). We also observed that the higher the initial hemoglobin level, the more severe the long-term renal damage ( p < 0.007). Conclusions: In patients with STEC-HUS, hemoconcentration and hypovolemia may be responsible for more severe ischemic organ damage (both short and long term) at disease onset, and these signs should be regarded as risk factors for CNS damage and for more severe TMA. Therefore, we recommend that hydration status should be actively monitored in HUS patients and that dehydration, when diagnosed, should be promptly corrected. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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45. Current evidence for the role of complement in the pathogenesis of Shiga toxin haemolytic uraemic syndrome.
- Author
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Keir, Lindsay and Saleem, Moin
- Subjects
BACTERIAL toxins ,BLOOD coagulation ,COMPLEMENT (Immunology) ,HEMOLYTIC-uremic syndrome ,KIDNEY glomerulus ,MONOCLONAL antibodies - Abstract
Shiga toxin-associated haemolytic uraemic syndrome (Stx HUS) is the leading cause of paediatric acute kidney injury. This toxin-mediated disease carries a significant morbidity and mortality but has no direct treatments. Rare familial atypical HUS (aHUS) is now understood to result from over-activation of the alternative complement pathway causing glomerular endothelial damage. By understanding the pathogenic mechanisms of this disease, the monoclonal antibody eculizumab, which blocks the final common pathway of complement, is now being used to treat aHUS. For this reason, clinicians and scientists are studying the role of the alternative complement pathway in Stx HUS with the aim of targeting treatment in a similar way. There is some evidence suggesting that complement plays a role in the pathogenesis of Stx HUS, but other mechanisms may also be important. Clinically, modulating the complement system using plasma exchange provides no proven benefit in Stx HUS, and the use of eculizumab has provided conflicting results. Understanding the local effect of Stx on the glomerulus, in particular regulation of the complement and coagulation systems, may lead to advances in defining the precise pathogenesis of this disease. Then, targeted treatment strategies could be devised and clinical trials undertaken. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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46. Neurological involvement in children with E. coli O104:H4-induced hemolytic uremic syndrome.
- Author
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Bauer, Angela, Loos, Sebastian, Wehrmann, Carola, Horstmann, Dirk, Donnerstag, Frank, Lemke, Johanna, Hillebrand, Georg, Löbel, Ulrike, Pape, Lars, Haffner, Dieter, Bindt, Carola, Ahlenstiel, Thurid, Melk, Anette, Lehnhardt, Anja, Kemper, Markus, Oh, Jun, and Hartmann, Hans
- Subjects
ACADEMIC medical centers ,BRAIN ,CENTRAL nervous system diseases ,CHI-squared test ,ELECTROENCEPHALOGRAPHY ,ESCHERICHIA coli diseases ,HEMOLYTIC-uremic syndrome ,INTERVIEWING ,MAGNETIC resonance imaging ,NEUROPSYCHOLOGICAL tests ,RESEARCH methodology ,NEUROLOGIC manifestations of general diseases ,T-test (Statistics) ,RETROSPECTIVE studies ,DATA analysis software ,DESCRIPTIVE statistics ,DISEASE complications - Abstract
Background: The aim of this study was to analyze the neurological involvement and outcome in pediatric patients with hemolytic uremic syndrome (HUS) during the 2011 epidemic caused by Escherichia coli O104:H4. Methods: Clinical data and data from magnetic resonance imaging (MRI) scans and electroencephalography (EEG) during the acute phase of the disease and during follow-up at 3 and 6 months were analyzed in 50 patients. Twenty-five of these patients underwent neuropsychological testing (WISC IV) during follow-up. Results: Neurological involvement (stupor or coma, seizures, visual disturbances, paresis, myocloni) was initially observed in 14/50 (28 %) patients. One patient died. EEG abnormalities were more frequent in patients with neurological involvement than in those without (12/14 vs. 13/25, respectively). Cranial MRI scans were analyzed in nine patients with neurological involvement, of whom five showed abnormal findings. At the 3- and 6-month follow-ups, EEG abnormalities were found in 14/40 (35 %) and 7/36 (19 %) patients, respectively, whereas 28/42 (67 %) and 17/39 (44 %) patients, respectively, complained about on-going reduced performance. Neuropsychological testing showed a slightly lower global intelligence quotient in patients with neurological involvement versus those without (113.4 ± 2.8 vs. 119.4 ± 1.8, respectively). Conclusions: Neurological involvement was frequent in our cohort. Accordingly, the incidence of pathological EEG findings was high, even in patients without clinical signs of neurological involvement. Nevertheless, major neurological sequelae were rare, and neuropsychological outcome was favorable after 6 months. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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47. Psychiatric Symptoms in Patients with Shiga Toxin-Producing E. coli O104:H4 Induced Haemolytic-Uraemic Syndrome.
- Author
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Kleimann, Alexandra, Toto, Sermin, Eberlein, Christian K., Kielstein, Jan T., Bleich, Stefan, Frieling, Helge, and Sieberer, Marcel
- Subjects
PSYCHIATRIC diagnosis ,VEROCYTOTOXINS ,ESCHERICHIA coli ,HEMOLYTIC anemia diagnosis ,NEUROLOGY ,EPIDEMICS - Abstract
Background: In May 2011 an outbreak of Shiga toxin-producing enterohaemorrhagic E. coli (STEC) O104:H4 in Northern Germany led to a high number of in-patients, suffering from post-enteritis haemolytic-uraemic syndrome (HUS) and often severe affection of the central nervous system. To our knowledge so far only neurological manifestations have been described systematically in literature. Aim: To examine psychiatric symptoms over time and search for specific symptom clusters in affected patients. Methods: 31 in-patients suffering from E. coli O104:H4 associated HUS, were examined and followed up a week during the acute hospital stay. Psychopathology was assessed by clinical interview based on the AMDP Scale, the Brief Symptom Inventory and the Clinical Global Impressions Scale. Results: At baseline mental disorder due to known physiological condition (ICD-10 F06.8) was present in 58% of the examined patients. Patients suffered from various manifestations of cognitive impairment (n = 27) and hallucinations (n = 4). Disturbances of affect (n = 28) included severe panic attacks (n = 9). Psychiatric disorder was significantly associated with higher age (p<0.0001), higher levels of C-reactive protein (p<0.05), and positive family history of heart disease (p<0.05). Even within the acute hospital stay with a median follow up of 7 days, symptoms improved markedly over time (p <0.0001). Conclusions: Aside from severe neurological symptoms the pathology in E.coli O104:H4 associated HUS frequently includes particular psychiatric disturbances. Long term follow up has to clarify whether or not these symptoms subside. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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48. Cerebral Magnetic Resonance Imaging Findings in Adults with Haemolytic Uraemic Syndrome Following an Infection with Escherichia coli, Subtype O104:H4.
- Author
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Löbel, U., Eckert, B., Simova, O., Meier-Cillien, M., Kluge, S., Gerloff, C., Röther, J., Magnus, T., and Fiehler, J.
- Abstract
Purpose: Infections with Enterohaemorrhagic Escherichia coli typically occur in children causing haemolytic uraemic syndrome (HUS) and neurological symptoms in 20-50 %. Little information is available on the morphology of brain manifestations in adults. The purpose of this study was to identify a characteristic magnetic resonance imaging (MRI) pattern during the outbreak of a novel mutation of Escherichia coli O104:H4. Methods: Patients were recruited from two hospitals between May and July 2011. The MRI protocol included standard anatomical, diffusion-weighted, and susceptibility-sensitive sequences. Results: A total of 104 MRIs of 57 (32 female, 25 male) patients (mean 45.5 ± 18.4 years) showed abnormal signal intensity on 51 MRIs (49 %). Bilateral thalamus (39 %), bilateral pons (35 %), centrum semiovale and splenium of corpus callosum (33 %) were most often involved. Acute lesions were reversible in 81 % of cases. There was no statistically significant association between symptom onset and the MRI findings ( P = 0.2). Conclusions: Neuroimaging findings in this adult patient cohort were non-specific and similar to previous findings in children. A characteristic neuroimaging pattern of an infection with Escherichia coli O104:H4 was not identified. However, bilateral symmetric T2 hyperintense lesions of the thalami and dorsal pons characterized by restricted diffusion suggest a metabolic toxic effect of the disease on the brain. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
49. Combined liver and kidney transplantation in children.
- Author
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Jalanko, Hannu and Pakarinen, Mikko
- Subjects
IMMUNOSUPPRESSION ,TREATMENT of chronic kidney failure ,HEMOLYTIC-uremic syndrome treatment ,LIVER disease treatment ,AUTOSOMAL recessive polycystic kidney ,INBORN errors of carbohydrate metabolism ,KIDNEY transplantation ,LIVER transplantation ,HEALTH outcome assessment ,PEDIATRICS ,TREATMENT effectiveness ,THERAPEUTICS - Abstract
Simultaneous combined liver-kidney transplantation (CLKT) is a rare operation in pediatric patients so that annually only 10-30 operations are performed worldwide. The main indications for CLKT are primary hyperoxaluria type 1 and autosomal recessive polycystic kidney disease. In addition, CLKT is indicated in individual patients with metabolic or cirrhotic liver diseases and end-stage kidney disease. The surgery and immediate post-operative management of CLKT remain challenging in infants and small children. The patients should be operated on before they become severely ill or develop major systemic manifestations of their metabolic disorder. The liver allograft is immunologically protective of the kidney graft in simultaneous CLKT, often resulting in well-preserved kidney function. The long-term outcome after CLKT is nowadays comparable to that of isolated liver and kidney transplantations. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
50. Long-term outcomes of Shiga toxin hemolytic uremic syndrome.
- Author
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Spinale, Joann, Ruebner, Rebecca, Copelovitch, Lawrence, and Kaplan, Bernard
- Subjects
ACUTE kidney failure ,BACTERIAL toxins ,DIABETES ,GASTROINTESTINAL diseases ,HEMOLYTIC-uremic syndrome ,HYPERTENSION ,KIDNEY diseases ,NEUROLOGICAL disorders ,PROTEINURIA ,DISEASE complications ,PROGNOSIS - Abstract
Shiga toxin-producing Escherichia coli (STEC) hemolytic uremic syndrome (HUS) is an important cause of acute kidney injury (AKI). The outcomes of STEC HUS have improved, and the acute mortality rate in children is 1-4 %. About 70 % of patients recover completely from the acute episode and the remainder have varying degrees of sequelae. Only a few retrospective studies have reviewed these patients over long periods. Methodological flaws include a lack of strict definitions, changing modes of treatment, ascertainment bias and loss of subjects to follow-up. The kidneys bear the brunt of the long-term damage: proteinuria (15-30 % of cases); hypertension (5-15 %); chronic kidney disease (CKD; 9-18 %); and end-stage kidney disease (ESKD; 3 %). A smaller number have extra-renal sequelae: colonic strictures, cholelithiasis, diabetes mellitus or brain injury. Most renal sequelae are minor abnormalities, such as treatable hypertension and/or variable proteinuria. Most of the patients who progress to ESKD do not recover normal renal function after the acute episode. Length of anuria (more than 10 days) and prolonged dialysis are the most important risk factors for a poor acute and long-term renal outcome. After the acute episode all patients must be followed for at least 5 years, and severely affected patients should be followed indefinitely if there is proteinuria, hypertension or a reduced glomerular filtration rate (GFR). [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
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