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Blood Purification 2012Attempts at achieving cytokine homeostasis include blood purification to deliver cytokine removal. Assessment of ex vivo studies for optimal operating conditions is a... (Review)
Review
BACKGROUND AND AIMS
Attempts at achieving cytokine homeostasis include blood purification to deliver cytokine removal. Assessment of ex vivo studies for optimal operating conditions is a vital step.
METHODS
We conducted a systematic search for ex vivo studies on cytokine removal using known modalities of extracorporeal circulation. We selected 29 articles and analyzed data according to clearance, sieving coefficient, ultrafiltrate concentration and percentage removal.
RESULTS
We identified four main techniques for cytokine removal: standard techniques, high cut-off (HCO) techniques, adsorption techniques and combined plasma filtration adsorption. HCO hemofiltration (HCO/HF) showed greatest consistency in cytokine removal among all approaches. Mean albumin clearance with HCO filters was 3.74 ml/min.
CONCLUSION
Ex vivo data support the view that HCO/HF is the most consistently effective approach in terms of sieving and clearance. Further investigation of HCO/HF in randomized controlled trials in animal models and humans seems desirable.
Topics: Adsorption; Animals; Cytokines; Hemofiltration; Humans; Plasma Exchange; Plasmapheresis; Renal Replacement Therapy
PubMed: 22248671
DOI: 10.1159/000333845 -
Rheumatology International Aug 2011Lupus protein-losing enteropathy (LUPLE) is a well reported but a rare manifestation of systemic lupus erythematosus (SLE). The main objectives of this study are to... (Review)
Review
Lupus protein-losing enteropathy (LUPLE) is a well reported but a rare manifestation of systemic lupus erythematosus (SLE). The main objectives of this study are to raise awareness of LUPLE that can be easily missed by internist, rheumatologist, gastroenterologist and nephrologist, and then to be considered in any patient with unexplained edema, ascites, and hypoalbuminemia. A systematic review was performed with 112 patients who met the eligibility criteria and were critically appraised. The LUPLE was ultimately diagnosed by either Tc-(99m) albumin scintography ((99m)Tc-HAS) or fecal alpha-1-antitrypsin clearance test. Clinical features of patients, at the time of LUPLE diagnosis, were as follows: age was 34 ± 14.2 years; the female to male ratio was 5.8:1; the mean time to development of LUPLE after diagnosis of SLE was 4.19 ± 4.7 years. There was a predominance of Asian (64.7%) while 29.5% were white or Hispanic patients. Eighty percent had peripheral edema, 48% had ascites, 38% had pleural effusion, and 21% had pericardial effusion. Forty-six percent had diarrhea, 27% had abdominal pain, 22% had nausea, and 19% had vomiting. Hypoalbuminemia was the most common characteristic laboratory finding (96%). A 24-h urine protein was less than 0.5 gm in (71%). Almost all patients (96%) had positive ANA with predominant speckled patterns (55%) and hypocomplementemia (79%). Colonoscopy showed mucosal thickening in 44% of patients, and the majority of patients (52%) revealed no abnormalities; on the other hand, intestinal histology either revealed mucosal edema, inflammatory cell infiltrate, lymphangiectasia, mucosal atrophy or vasculitis in 80% of patients. All patients were started on steroids. Thirty-four percent responded to steroids alone. Sixty-six percent were started with other immunosuppressive therapies, which include cyclophosphamide (46%), azathioprine (33%), and a combination of cyclophosphamide and azathioprine (7%). A few reported cases responded to either cyclosporine or etanercept. Prognosis was very good with steroids combined with immunosuppressive therapy. This is the first systematic review of LUPLE and should be considered as an etiology of unidentified edema, ascites, and hypoalbuminemia.
Topics: Adult; Drug Therapy, Combination; Endoscopy, Gastrointestinal; Female; Glucocorticoids; Humans; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Male; Protein-Losing Enteropathies
PubMed: 21344315
DOI: 10.1007/s00296-011-1827-9 -
Health Technology Assessment... 2007To assess the clinical effectiveness and cost-effectiveness of treatments for children with idiopathic steroid-resistant nephrotic syndrome (SRNS). (Review)
Review
OBJECTIVES
To assess the clinical effectiveness and cost-effectiveness of treatments for children with idiopathic steroid-resistant nephrotic syndrome (SRNS).
DATA SOURCES
Electronic databases from inception to February 2006, bibliographies of studies, and experts in the field.
REVIEW METHODS
Studies were selected, quality assessed and data were extracted using recognised methods agreed a priori. Meta-analysis was undertaken where appropriate using the random effects model. Where data allowed, subgroup analysis was undertaken according to renal histopathology.
RESULTS
Two systematic reviews and 11 trials were included in the clinical effectiveness review; however, the quality of reporting and methodology of the included studies was generally poor. No economic evaluations were identified. No statistically significant difference in remission rates was found between cyclophosphamide plus prednisone and prednisone alone for all children or those with focal segmental glomerulosclerosis (FSGS), also the time to response was statistically significantly less with cyclophosphamide (38.4 days versus 95.5 days). Remission rates were not statistically significantly different between intravenous and oral cyclophosphamide. Vomiting was common with intravenous cyclophosphamide, while pneumonia and alopecia occurred in the oral group. Ciclosporin statistically significantly increased the number of children with complete remission compared with placebo or supportive treatment, but not for the FSGS subgroup, adverse effects including infection and hypertension differed little between groups. No differences were found between azathioprine and placebo, with about 13% of each group having remission. Complete or partial remission occurred in six out of seven patients on the 18-month methylprednisolone regimen and three out of five patients on the 6-month regimen, for both groups renal function improved and adverse events such as hypertension and frequent infections occurred. Intravenous dexamethasone and methylprednisolone produced similar complete remission rates, partial remission rates, median time to response (about 10 days) and total number of adverse events, with hypertension as the most common. Six-hour urinary albumin and urinary albumin to creatinine ratio decreased statistically significantly with high-dose but not low-dose enalapril. Tuna fish oil was not associated with any statistically significant improvements in proteinuria, creatinine clearance, serum creatinine or lipid profiles compared with placebo. A very limited literature was found on costs associated with SRNS in children. The pharmaceutical cost of treatment varied considerably: an 8-week course of cyclophosphamide cost less than 6 pounds, while a course of ciclosporin cost almost 900 pounds per year. Treatment with tacrolimus, an alternative to ciclosporin, was estimated to cost in excess of 3400 pounds per year. Healthcare medical management costs were estimated; varying by treatment strategy, they ranged from 250 pounds to 930 pounds per year in patients not experiencing complications. Other longer term costs may also be incurred. Lack of data meant that cost-effectiveness modelling was not feasible.
CONCLUSIONS
The clinical effectiveness literature on treatments for idiopathic SRNS in children is very limited. The available evidence suggests a beneficial effect of ciclosporin on remission rates and of cyclophosphamide on time to remission; however, the strength of the conclusions drawn is limited by the poor quality of the included studies. The other treatments included in this review were each evaluated by only one study, and none found a statistically significant effect. There is insufficient evidence to determine whether or not there is a clinically significant difference. The available data on costs and outcomes are sparse and do not permit the reliable modelling of the cost-effectiveness of treatments for SRNS at present. A modelling framework is suggested, should more relevant data become available. A well-designed adequately powered randomised controlled trial comparing ciclosporin with other treatments in children with SRNS without genetic mutation is required.
Topics: Adolescent; Anti-Inflammatory Agents, Non-Steroidal; Child; Child, Preschool; Cost-Benefit Analysis; Drug Resistance; Humans; Immunosuppressive Agents; Infant; Meta-Analysis as Topic; Nephrotic Syndrome; Treatment Outcome; United Kingdom
PubMed: 17537341
DOI: 10.3310/hta11210 -
The Cochrane Database of Systematic... Oct 2006Terlipressin may reverse some of the circulatory changes associated with hepatorenal syndrome. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Terlipressin may reverse some of the circulatory changes associated with hepatorenal syndrome.
OBJECTIVES
To assess the beneficial and harmful effects of terlipressin for hepatorenal syndrome.
SEARCH STRATEGY
Electronic searches in The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Renal Group Register, the Cochrane Central Register of Controlled Trials in The Cochrane Library, MEDLINE, and EMBASE were combined with scanning of bibliographies and conference proceedings, and correspondence with experts and pharmaceutical companies. Last search update was July 2006.
SELECTION CRITERIA
Randomised clinical trials were included irrespective of dose or treatment duration. Included patients had type 1 or type 2 hepatorenal syndrome. Co-interventions were allowed if administered equally to both treatment and control groups.
DATA COLLECTION AND ANALYSIS
Data were retrieved from trial reports and correspondence with the authors of included trials. Mortality was the primary outcome. Meta-analyses were performed to calculate risk differences (RD) for binary outcomes and weighted mean differences (WMD) for continuous outcomes. Both were presented with 95% confidence intervals (CI). Due to the limited number of trials, no subgroup analyses were performed.
MAIN RESULTS
The initial searches identified 645 potentially relevant references. Six randomised trials were eligible for inclusion. Three trials are still ongoing. Three trials with a total of 51 patients assessed terlipressin 1 mg bid for 2 to 15 days. Co-interventions included albumin, fresh frozen plasma, and cimetidine 800 mg daily. One trial reported adequate bias control assessed by randomisation and blinding. All trials reported mortality. Terlipressin reduced mortality rates by 34% (RD -0.34, 95% CI -0.56 to -0.12). The control group mortality rate was 65%. Terlipressin improved renal function assessed by creatinine clearance (WMD 21 ml/min, 95% CI 17 to 26), serum creatinine (WMD -219 micromol/l, 95% CI -244 to -194), and urine output (WMD 707 ml/day, 95% CI -212 to 1625). Adverse events included headache, abdominal pain, cardiac arrhythmia, and hypertension.
AUTHORS' CONCLUSIONS
Additional evidence on terlipressin for hepatorenal syndrome is needed before reliable treatment recommendations can be made. The dose and duration of therapy, and the influence of co-interventions remain to be established.
Topics: Hepatorenal Syndrome; Humans; Lypressin; Randomized Controlled Trials as Topic; Terlipressin; Vasoconstrictor Agents
PubMed: 17054242
DOI: 10.1002/14651858.CD005162.pub2