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Pediatric Nephrology (Berlin, Germany) Oct 2021Nephritis is a recognised complication of IgA vasculitis (IgAV, Henoch-Schönlein purpura) contributing to 1-2% of all chronic kidney disease (CKD) stage 5. Improved...
BACKGROUND
Nephritis is a recognised complication of IgA vasculitis (IgAV, Henoch-Schönlein purpura) contributing to 1-2% of all chronic kidney disease (CKD) stage 5. Improved understanding may reduce irreversible damage in IgAV nephritis (IgAV-N).
OBJECTIVE
The aim of this study was to perform a comprehensive systematic literature review to identify promising clinical and pre-clinical urine biomarkers in children with IgAV-N that could predict the presence of nephritis and/or determine its severity.
METHODS
A systematic literature review was performed using four search engines and a predefined search term strategy. Promising biomarkers were divided in terms of clinical or pre-clinical and ability to predict the presence of nephritis or determine its severity. Results were described using statistical significance (p < 0.05) and area under the curve (AUC) values.
RESULTS
One hundred twenty-one studies were identified; 13 were eligible. A total of 2446 paediatric patients were included: healthy controls (n = 761), children with IgAV-N (n = 1236) and children with IgAV without nephritis (IgAV-noN, n = 449). Fifty-one percent were male, median age 7.9 years. The clinical markers, 24-h protein quantity and urine protein:creatinine ratio, were deemed acceptable for assessing severity of nephritis (AUC < 0.8). Urinary albumin concentration (Malb) performed well (AUC 0.81-0.98). The most promising pre-clinical urinary biomarkers in predicting presence of nephritis were as follows: kidney injury molecule-1 (KIM-1) (AUC 0.93), monocyte chemotactic protein-1 (MCP-1) (AUC 0.83), N-acetyl-β-glucosaminidase (NAG) (0.76-0.96), and angiotensinogen (AGT) (AUC not available). Urinary KIM-1, MCP-1, and NAG appeared to correlate with disease severity.
CONCLUSIONS
Longitudinal studies are needed to assess whether pre-clinical biomarkers enhance standard of care in IgAV-N.
Topics: Area Under Curve; Biomarkers; Child; Humans; IgA Vasculitis; Immunoglobulin A; Kidney Failure, Chronic; Male; Nephritis
PubMed: 33993342
DOI: 10.1007/s00467-021-05107-7 -
Advances in Therapy Jun 2021A network meta-analysis (NMA) was performed to assess the efficacy and safety of avatrombopag, relative to eltrombopag, romiplostim, and fostamatinib, for patients with... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
A network meta-analysis (NMA) was performed to assess the efficacy and safety of avatrombopag, relative to eltrombopag, romiplostim, and fostamatinib, for patients with chronic immune thrombocytopenia (ITP) not responding adequately to corticosteroids.
METHODS
A systematic search of publication and clinical trial databases was conducted to identify relevant randomized controlled trials (RCTs) and observational studies. Data from eligible studies were extracted and analyzed in a Bayesian framework using relative effect sizes vs placebo. Outcomes included durable platelet response; need for rescue therapy; reduction in use of concomitant ITP medication; incidence of any or World Health Organization (WHO) grade 2-4 bleeding events, and any adverse events. Results were reported as odds ratios or incidence rate ratios (IRR) with 95% credible intervals (CrIs).
RESULTS
The NMA included seven phase 3 RCTs. Compared with placebo, avatrombopag was associated with statistically significant improvements in durable platelet response, reduction in use of concomitant ITP medication, and incidence of any bleeding events. Statistically significant differences vs placebo were also observed for durable platelet response and need for rescue therapy (eltrombopag, romiplostim, and fostamatinib); reduction in use of concomitant ITP medication (eltrombopag and romiplostim); incidence of any bleeding events (fostamatinib); and incidence of WHO grade 2-4 bleeding events (romiplostim and fostamatinib). No statistically significant differences were observed for any adverse events. Avatrombopag was associated with a statistically significant lower incidence of any bleeding events vs eltrombopag (IRR 0.38 [95% CrI 0.19, 0.75]) and romiplostim (IRR 0.38 [95% Crl 0.17, 0.86]); no other between-treatment differences were observed.
CONCLUSION
In this NMA, avatrombopag significantly increased the chance of achieving durable platelet response and reducing the use of concomitant ITP medication vs placebo, and significantly reduced the incidence of any bleeding events compared with placebo, eltrombopag, and romiplostim. The study aims to help guide clinicians managing patients with chronic ITP and insufficient response to previous treatment.
Topics: Benzoates; Humans; Network Meta-Analysis; Purpura, Thrombocytopenic, Idiopathic; Randomized Controlled Trials as Topic; Recombinant Fusion Proteins; Thiazoles; Thiophenes
PubMed: 33934279
DOI: 10.1007/s12325-021-01752-4 -
Dermatology and Therapy Jun 2021Distinct skin lesions associated with coronavirus disease 2019 (COVID-19) have been described, but data regarding their time of onset during the COVID-19 course are... (Review)
Review
INTRODUCTION
Distinct skin lesions associated with coronavirus disease 2019 (COVID-19) have been described, but data regarding their time of onset during the COVID-19 course are scant. Our objective was to systematically review the studies reporting the time of onset of selected skin lesions with respect to the reported onset of the COVID-19 core symptoms.
METHODS
A comprehensive search of studies published before 21 January 2021 was performed on MEDLINE via PubMed database using a predefined strategy to identify relevant articles.
RESULTS
Out of 354 references, 87 were selected, reporting a total of 895 patients with skin lesions associated with COVID-19. The most frequent pattern was exanthema (n = 430, 48%), followed by vascular (n = 299, 33%), urticarial (n = 105, 12%) and others (n = 66, 7%). Skin lesions occurred more frequently in the first 4 weeks from the COVID-19 onset (n = 831, 92%), whereas prodromal or late lesions were rarer (n = 69, 8%). The urticarial and exanthema patterns were more frequent in the first 2 weeks. About the vascular pattern some differences were noted among its subtypes. Livedoid lesions occurred mainly in the first 2 weeks, while chilblain-like lesions between weeks 2 and 4. Purpuric/petechial lesions were equally distributed during the first 4 weeks. Several skin manifestations did not fall into the pattern classification, including erythema multiforme, generalized pruritus, Kawasaki disease and others.
CONCLUSION
The diversity in the time of onset of skin lesions as well as their polymorphic nature likely reflects the diversity of the pathogenetic underlying mechanisms.
PROSPERO DATABASE REGISTRATION NUMBER
CRD42021236331.
PubMed: 33811315
DOI: 10.1007/s13555-021-00526-8 -
Medicine Jan 2021The purpose of this study is to compare the clinical efficacy of laparoscopic splenectomy (LS) and open splenectomy (OS) in the treatment of Idiopathic thrombocytopenic... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
The purpose of this study is to compare the clinical efficacy of laparoscopic splenectomy (LS) and open splenectomy (OS) in the treatment of Idiopathic thrombocytopenic purpura.
METHODS
We systematically searched PubMed, Web of science, EMBASE, Clinicaltrials.gov, and Cochrane Central Register for studies (study published from July 1992-January 2020). This study analyzed the clinical effect of LS and OS on idiopathic thrombocytopenic purpur.
RESULTS
This study showed that compared with OS, the LS's Overall response (OR: 0.60, 95% confidence interval (CI): 0.23-1.59, P = .30), Complication (OR: 0.59, 95% CI: 0.18-1.94, P = .38), Accessory spleen(OR: 1.70, 95% CI: 0.98-2.98, P = .06), Wound infections (OR: 0.65, 95% CI: 0.26-1.59, P = .34), Pancreatic fistula (OR: 0.73, 95% CI: 0.16-3.30, P = .68), was no significant, the Operative time (weighted mean difference (WMD): 49.33, 95% CI: 36.29-62.37, P < .00001)was longer, and the Estimated blood loss (WMD: -172.59, 95% CI: -319.96 to -25.22, P = .02), Postoperative length of stay (WMD: -4.68, 95% CI: -7.75 to -1.62, P = .003)was less.
CONCLUSIONS
The therapeutic effect of LS was the same as that of OS in Overall response Complication Accessory spleen, while The operative time was longer, the Estimated blood loss was less, and the postoperative length of stay was shorter.
Topics: Adult; Blood Loss, Surgical; Female; Humans; Laparoscopy; Length of Stay; Male; Middle Aged; Operative Time; Purpura, Thrombocytopenic, Idiopathic; Splenectomy; Treatment Outcome
PubMed: 33530246
DOI: 10.1097/MD.0000000000024436 -
The Cochrane Database of Systematic... Jan 2021Portal hypertension commonly accompanies advanced liver disease and often gives rise to life-threatening complications, including bleeding (haemorrhage) from oesophageal...
Band ligation versus sham or no intervention for primary prophylaxis of oesophageal variceal bleeding in children and adolescents with chronic liver disease or portal vein thrombosis.
BACKGROUND
Portal hypertension commonly accompanies advanced liver disease and often gives rise to life-threatening complications, including bleeding (haemorrhage) from oesophageal and gastrointestinal varices. Variceal bleeding commonly occurs in children and adolescents with chronic liver disease or portal vein thrombosis. Prevention is, therefore, important. Randomised clinical trials have shown that non-selective beta-blockers and endoscopic variceal band ligation decrease the incidence of variceal bleeding in adults. In children and adolescents, band ligation, beta-blockers, and sclerotherapy have been proposed as primary prophylaxis alternatives for oesophageal variceal bleeding. However, it is unknown whether these interventions are of benefit or harm when used for primary prophylaxis in children and adolescents.
OBJECTIVES
To assess the benefits and harms of band ligation compared with sham or no intervention for primary prophylaxis of oesophageal variceal bleeding in children and adolescents with chronic liver disease or portal vein thrombosis.
SEARCH METHODS
We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, PubMed, Embase, and two other databases (April 2020). We scrutinised the reference lists of the retrieved publications, and we also handsearched abstract books of the two main paediatric gastroenterology and hepatology conferences from January 2008 to December 2019. We also searched clinicaltrials.gov, the United States Food and Drug Administration (FDA), the European Medicines Agency (EMA), and the World Health Organization (WHO) for ongoing clinical trials. We imposed no language or document type restrictions on our search.
SELECTION CRITERIA
We aimed to include randomised clinical trials irrespective of blinding, language, or publication status, to assess the benefits and harms of band ligation versus sham or no intervention for primary prophylaxis of oesophageal variceal bleeding in children with chronic liver disease or portal vein thrombosis. If the search for randomised clinical trials retrieved quasi-randomised and other observational studies, then we read them through to extract information on harm.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodology to perform this systematic review. We used GRADE to assess the certainty of evidence for each outcome. Our primary outcomes were all-cause mortality, serious adverse events and liver-related morbidity, and quality of life. Our secondary outcomes were oesophageal variceal bleeding and adverse events not considered serious. We used the intention-to-treat principle. We analysed data using Review Manager 5.
MAIN RESULTS
One conference abstract, describing a feasibility multi-centre randomised clinical trial, fulfilled our review inclusion criteria. We judged the trial at overall high risk of bias. This trial was conducted in three hospital centres in the United Kingdom. The aim of the trial was to determine the feasibility and safety of further larger randomised clinical trials of prophylactic band ligation versus no active treatment in children with portal hypertension and large oesophageal varices. Twelve children received prophylactic band ligation and 10 children received no active treatment. There was no information on the age of the children included, or about the diagnosis of any child included. All children were followed up for at least six months. Mortality was 8% (1/12) in the band ligation group versus 0% (0/10) in the no active intervention group (risk ratio (RR) 2.54, 95% confidence interval (CI) 0.11 to 56.25; very low certainty of evidence). The abstract did not report when the death occurred, but we assume it happened between the six-month follow-up and one year. No child (0%) in the band ligation group developed adverse events (RR 0.28, 95% CI 0.01 to 6.25; very low certainty of evidence) but one child out of 10 (10%) in the no active intervention group developed idiopathic thrombocytopaenic purpura. One child out of 12 (8%) in the band ligation group underwent liver transplantation versus none in the no active intervention group (0%) (RR 2.54, 95% CI 0.11 to 56.25; very low certainty of evidence). The trial reported no other serious adverse events or liver-related morbidity. Quality of life was not reported. Oesophageal variceal bleeding occurred in 8% (1/12) of the children in the band ligation group versus 30% (3/10) of the children in the no active intervention group (RR 0.28, 95% CI 0.03 to 2.27; very low certainty of evidence). No adverse events considered non-serious were reported. Two children were lost to follow-up by one-year. Ten children in total completed the trial at two-year follow-up. There was no information on funding. We found two observational studies on endoscopic variceal ligation when searching for randomised trials. One found no harm, and the other reported E nterobacter cloacae septicaemia in one child and mild, transient, upper oesophageal sphincter stenosis in another. We did not assess these studies for risk of bias. We did not find any ongoing randomised clinical trials of interest to our review.
AUTHORS' CONCLUSIONS
The evidence, obtained from only one feasibility randomised clinical trial at high risk of bias, is very scanty. It is very uncertain about whether prophylactic band ligation versus sham or no (active) intervention may affect mortality, serious adverse events and liver-related morbidity, or oesophageal variceal bleeding in children and adolescents with portal hypertension and large oesophageal varices. We have no data on quality of life. No adverse events considered non-serious were reported. The results presented in the trial need to be interpreted with caution. In addition, the highly limited data cover only part of our research question; namely, children with portal hypertension and large oesophageal varices. Data on children with portal vein thrombosis are lacking. Larger randomised clinical trials assessing the benefits and harms of band ligation compared with sham treatment for primary prophylaxis of oesophageal variceal bleeding in children and adolescents with chronic liver disease or portal vein thrombosis are needed. The trials should include important clinical outcomes such as death, quality of life, failure to control bleeding, and adverse events.
Topics: Adolescent; Child; Chronic Disease; Esophageal and Gastric Varices; Feasibility Studies; Gastrointestinal Hemorrhage; Humans; Ligation; Liver Diseases; Portal Vein; Primary Prevention; Venous Thrombosis
PubMed: 33522602
DOI: 10.1002/14651858.CD011561.pub2 -
Bioengineered Dec 2021The association of neutrophil-to-lymphocyte ratio (NLR) and mean platelet volume (MPV) with the severe gastrointestinal (GI) involvement in pediatric Henoch-Schonlein... (Meta-Analysis)
Meta-Analysis
The association of neutrophil-to-lymphocyte ratio (NLR) and mean platelet volume (MPV) with the severe gastrointestinal (GI) involvement in pediatric Henoch-Schonlein Purpura (HSP) has been reported in many studies. However, the conclusions from the previous studies were controversial. Therefore, for the first time, we performed a meta-analysis to systematically evaluate the relationship of NLR and MPV to the severe GI involvements. We retrieved PubMed, EMBASE, Web of Science, and Chinese National Knowledge Infrastructure (CNKI) (up to October 2020) thoroughly to acquire eligible studies. The pooled standard mean difference (SMD) with 95% confidence interval (CI) was used to describe the correlation of NLR and MPV with the severe GI involvement. A total of 1 studies comprising 2168 patients with HSP were included in this meta-analysis. Our combined analysis showed that NLR in HSP patients with the severe GI involvement was significantly higher than that in those without the severe GI involvement (SMD = 1.37; 95% CI: 0.70-2.05; p < 0.01). In addition, a lower MPV was observed in children with severe GI involvement (SMD = -0.29; 95% CI: -0.56 - -0.01, p = 0.042). Our sensitivity analysis and publication bias evaluation indicated that our combined results were reliable. Taken together, our study suggested NLR and MPV may be used as biomarkers for predicting or diagnosing the severe GI involvement in children with HSP. Nevertheless, more homogeneous studies with a larger sample size are required to validate these findings.
Topics: Child; Child, Preschool; Female; Gastrointestinal Hemorrhage; Humans; IgA Vasculitis; Intussusception; Leukocyte Count; Lymphocytes; Male; Mean Platelet Volume; Neutrophils
PubMed: 33412982
DOI: 10.1080/21655979.2020.1865607 -
Biology Dec 2020There have been increasing reports of skin manifestations in COVID-19 patients. We conducted a systematic review and included manuscripts describing patients with... (Review)
Review
There have been increasing reports of skin manifestations in COVID-19 patients. We conducted a systematic review and included manuscripts describing patients with positive RT-PCR coronavirus testing from nasopharyngeal swabs who also developed cutaneous manifestations. A total of 655 patients were selected, with different types of skin rashes: Erythematous maculopapular ( = 250), vascular ( = 146), vesicular ( = 99), urticarial ( = 98), erythema multiforme/generalized pustular figurate erythema/Stevens-Johnson syndrome ( = 22), ocular/periocular ( = 14), polymorphic pattern ( = 9), generalized pruritus ( = 8), Kawasaki disease ( = 5), atypical erythema nodosum ( = 3), and atypical Sweet syndrome ( = 1). Chilblain-like lesions were more frequent in the younger population and were linked to a milder disease course, while fixed livedo racemosa and retiform purpura appeared in older patients and seemed to predict a more severe prognosis. For vesicular rashes, PCR determined the presence of herpesviruses in the vesicle fluid, which raised the possibility of herpesvirus co-infections. The erythema-multiforme-like pattern, generalized pustular figurate erythema and Stevens-Johnson syndrome were most frequently linked to hydroxychloroquine intake. A positive PCR determination of SARS-COV-2 from conjunctival swabs suggest that eye discharge can also be contagious. These cutaneous manifestations may aid in identifying otherwise asymptomatic COVID-19 carriers in some cases or predict a more severe evolution in others.
PubMed: 33291502
DOI: 10.3390/biology9120449 -
The Journal of International Medical... Oct 2020We reviewed relevant research on rituximab (RTX) treatment for pediatric immune thrombocytopenia (ITP) to elucidate the efficacy and safety of RTX. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
We reviewed relevant research on rituximab (RTX) treatment for pediatric immune thrombocytopenia (ITP) to elucidate the efficacy and safety of RTX.
METHODS
Prospective clinical trials of RTX for the treatment of pediatric ITP were collected by searching the PubMed, Cochrane Library, Web of Science, and OVID: EMBASE databases and ClinicalTrials.gov. We examined rates of overall response (OR), complete response (CR), partial response (PR), sustained response (SR), relapse (R), and adverse drug reaction (ADR). The Methodological Index for Nonrandomized Studies scale was used, and sensitivity analyses were performed.
RESULTS
For five studies, including 100 patients, the pooled OR, CR, PR, SR, R, and ADR rates were 52% (95% CI: 0.36-0.77, = 78%), 52% (95% CI: 0.41-0.67, = 45%), 18% (95% CI: 0.10-0.33, = 33%), 43% (95% CI: 0.29-0.63, = 0%), 25% (95% CI: 0.06-0.96, = 52%), and 30% (95% CI: 0.15-0.58, = 64%), respectively.
CONCLUSION
There is evidence, albeit low quality, that RTX may be a better second-line therapy than splenectomy for children with ITP; however, its efficacy and safety need to be validated by further high-quality clinical trials, such as randomized controlled trials.
Topics: Child; Humans; Minors; Prospective Studies; Purpura, Thrombocytopenic, Idiopathic; Rituximab; Thrombocytopenia
PubMed: 33115308
DOI: 10.1177/0300060520962348 -
SN Comprehensive Clinical Medicine 2020Immune thrombocytopenia, often known as immune thrombocytopenic purpura (ITP), has emerged as an important complication of COVID-19. A systematic review was done to... (Review)
Review
Immune thrombocytopenia, often known as immune thrombocytopenic purpura (ITP), has emerged as an important complication of COVID-19. A systematic review was done to analyze the clinical profile and outcomes in a total of 45 cases of new-onset ITP in COVID-19 patients described in literature until date. A comprehensive approach is essential for diagnosing COVID-19-associated ITP after excluding several concomitant factors that can cause thrombocytopenia in COVID-19. Majority of ITP cases (71%) were found to be elderly (> 50 years) and 75% cases had moderate-to-severe COVID-19. Three patients (7%) were in the pediatric age group. Reports of ITP in asymptomatic COVID-19 patients (7%) underscore the need for COVID-19 testing in newly diagnosed patients with ITP irrespective of COVID-19 symptoms amid this pandemic. ITP onset occurred in 20% cases 3 weeks after onset of COVID-19 symptoms, with many reports after clinical recovery. SARS-CoV-2-mediated immune thrombocytopenia can be attributed to the underlying immune dysregulation, susceptibility mutations in SOCS 1, and other mechanisms, including molecular mimicry, cryptic antigen expression, and epitope spreading. No bleeding manifestations were reported in 31% cases at diagnosis. Severe life-threatening bleeding was uncommon. One case of mortality was attributed to intracranial hemorrhage. Secondary Evans syndrome was diagnosed in one case. Good initial response to short course of glucocorticoids and intravenous immunoglobulin has been found with the exception of delayed lag response in one case. Thrombopoietin receptor agonist usage as a second-line agent has been noted in few cases for short duration with no adverse events. In the relatively short follow-up period, four relapses of ITP were found.
PubMed: 32984764
DOI: 10.1007/s42399-020-00521-8 -
Microorganisms Sep 2020Evidence relating to the efficacy of eradication therapy for chronic immune thrombocytopenic purpura (cITP) in childhood is inadequate. The aim of this retrospective...
Evidence relating to the efficacy of eradication therapy for chronic immune thrombocytopenic purpura (cITP) in childhood is inadequate. The aim of this retrospective study was to determine the efficacy of eradication therapy for platelet response in pediatric patients with cITP in our hospital, and to perform a systematic review of previous reports about pediatric patients with cITP who were positive for infection and were treated with eradication therapy. Analysis of the data of pediatric patients with cITP in our hospital and a systematic review of digital literature databases of studies in pediatric patients with cITP were performed. Data of 33 pediatric patients with cITP from our hospital records showed that the prevalence of infection and the rate of response to platelet therapy were 15% and 33.3%, respectively. Data of 706 pediatric patients from 18 previous reports showed that the prevalence of infection and rate of platelet response were 23% and 43.8%, respectively. Eradication therapy for infection in pediatric cITP patients can be expected to result in a response equivalent to that in the adult population, with fewer adverse effects than other treatments for cITP.
PubMed: 32977477
DOI: 10.3390/microorganisms8101457