-
Cerebellum (London, England) Jun 2021Superficial siderosis describes haemosiderin deposition on the surface of the brain. When present on infratentorial structures, it can cause ataxia, sensorineural...
Superficial siderosis describes haemosiderin deposition on the surface of the brain. When present on infratentorial structures, it can cause ataxia, sensorineural hearing loss and pyramidal signs. There is no proven treatment and patients experience slow progression of symptoms. Iron-chelating agents have been suggested as a therapeutic option and deferiprone is suited as it crosses the blood-brain barrier. However, deferiprone is reported to have a 1-2% risk of agranulocytosis. We performed a systematic review on treatment of infratentorial superficial siderosis with deferiprone based on PRISMA guidelines. Studies were included if in English or an English language translation was available, were about human subjects and referred to patients with ataxia. Studies were excluded if they did not possess an English translation, included animal studies or did not have ataxia. Studies were excluded if they discussed cerebral amyloid angiopathy or siderosis of other regions. Eleven papers were included. We identified 69 patients. Seventeen patients (25%) discontinued the drug. The most encountered adverse effect was anaemia (21.7%). Neutropaenia was observed in 8.7% and agranulocytosis in 5.8% of patients. Clinically, response varied, and stability or improvement was seen across neurological domains in 6 studies while 5 showed a mixed response. On imaging, 13 (28.9%) patients improved, 24 (53.3%) stabilised and 8 (17.8%) deteriorated. A prospective international centralised register of patients should be developed to inform the design and conduct of a multicentre, placebo-controlled, randomised clinical trial to evaluate the efficacy of deferiprone. The evidence from this systematic review is that deferiprone is a promising intervention.
Topics: Animals; Deferiprone; Hemosiderin; Humans; Iron Chelating Agents; Randomized Controlled Trials as Topic; Siderosis
PubMed: 33409768
DOI: 10.1007/s12311-020-01222-7 -
Pediatric Blood & Cancer Oct 2019Routinely measurable biomarkers as predictors for adverse outcomes in febrile neutropenia could improve management through risk stratification. This systematic review... (Meta-Analysis)
Meta-Analysis
Updated systematic review and meta-analysis of the predictive value of serum biomarkers in the assessment and management of fever during neutropenia in children with cancer.
Routinely measurable biomarkers as predictors for adverse outcomes in febrile neutropenia could improve management through risk stratification. This systematic review assesses the predictive role of biomarkers in identifying events such as bacteraemia, clinically documented infections, microbiologically documented infection, severe sepsis requiring intensive care or high dependency care and death. This review collates 8319 episodes from 4843 patients. C-reactive protein (CRP), interleukin (IL)-6, IL-8 and procalcitonin (PCT) consistently predict bacteraemia and severe sepsis; other outcomes have highly heterogeneous results. Performance of the biomarkers at admission using different thresholds demonstrates that PCT > 0.5 ng/mL offers the best compromise between sensitivity and specificity: sensitivity 0.67 (confidence interval [CI] 0.53-0.79) specificity 0.73 (CI 0.66-0.77). Seventeen studies describe the use of serial biomarkers, with PCT having the greatest discriminatory role. Biomarkers, potentially with serial measurements, may predict adverse outcomes in paediatric febrile neutropenia and their role in risk stratification is promising.
Topics: Adolescent; Biomarkers; Child; Child, Preschool; Febrile Neutropenia; Female; Humans; Infant; Male; Neoplasms; Predictive Value of Tests; Young Adult
PubMed: 31250539
DOI: 10.1002/pbc.27887 -
Haematologica Apr 20246-mercaptopurine (6-MP) serves as the backbone in the maintenance regimens of acute lymphoblastic leukemia (ALL). We aimed to evaluate the influence of NUDT15 gene... (Meta-Analysis)
Meta-Analysis
Association of gene polymorphism with adverse reaction, treatment efficacy, and dose of 6-mercaptopurine in patients with acute lymphoblastic leukemia: a systematic review and meta-analysis.
6-mercaptopurine (6-MP) serves as the backbone in the maintenance regimens of acute lymphoblastic leukemia (ALL). We aimed to evaluate the influence of NUDT15 gene polymorphism on the risk of myelosupression, hepatotoxicity and interruption of 6-MP, as well as treatment efficacy and dose of 6-MP in ALL patients. A total of 24 studies with 3,374 patients were included in this meta-analysis. We found 9-fold higher risk of 6-MP induced leukopenia (odds ratio [OR] =9.00, 95% confidence interval [CI]: 3.73-21.74) and 2.5-fold higher risk of 6-MP-induced neutropenia (OR=2.52, 95% CI: 1.72-3.69) for NUDT15 c.415C>T variant carriers in the dominant model. Moreover, we found that the dose intensity of 6-MP in ALL patients with one NUDT15 c.415C>T variant alleles (CT) was 19% less than that in wild-type patients (CC) (mean differences: 19.43%, 95% CI: -25.36 to -13.51). The tolerable dose intensity of 6-MP in NUDT15 c.415C>T homozygote variant (TT) and heterozygote variant (CT) carriers was 49% and 15% less than that in wild-type patients, respectively. The NUDT15 c.415C>T variant group (CT+TT) had seven times (OR=6.98, 95% CI: 2.83-17.22) higher risk of developing 6-MP intolerance than the CC group. However, NUDT15 c.415C>T polymorphism did not appear significantly associated with hepatotoxicity, treatment interruption or relapse incidence. We concluded that NUDT15 c.415C>T was a good predictor for 6-MP-induced myelosuppression in ALL patients. The dose intensity of 6-MP in ALL patients with NUDT15 c.415C>T variants was significantly lower than that in wild-type patients. This research provided a basis for further investigation into relations between NUDT15 gene and adverse reaction, treatment efficacy and dose intensity of 6-MP.
Topics: Humans; Mercaptopurine; Pyrophosphatases; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Polymorphism, Genetic; Neutropenia; Treatment Outcome; Chemical and Drug Induced Liver Injury
PubMed: 37794799
DOI: 10.3324/haematol.2023.282761 -
Frontiers in Endocrinology 2019Granulocyte-colony-stimulating factor (G-CSF) is highly beneficial as a general treatment for anti-thyroid drug (ATD)-induced agranulocytosis. This meta-analysis aimed...
Granulocyte-colony-stimulating factor (G-CSF) is highly beneficial as a general treatment for anti-thyroid drug (ATD)-induced agranulocytosis. This meta-analysis aimed to assess the clinical effects of G-CSF and non-G-CSF on recovery duration in patients with ATD-induced agranulocytosis by analyzing the overall clinical outcomes. The PubMed, Embase, Ovid, Cochrane, Google Scholar, China National Knowledge Infrastructure (CNKI) databases were searched for published studies from 1900 to 2018. No language restriction was implemented. This meta-analysis included 10 published retrospective studies and one prospective study. Data were obtained from 11 trials (474 patients: 247 with G-CSF and 227 with non-G-CSF treatment). Compared with the non-G-CSF group, the G-CSF group presented shorter recovery duration [weighted mean difference (WMD) = -3.04 days, 95% confidence interval (95% CI): -4.38 to -1.69 ( = 4.43 = 0.000)]. However, the recovery duration varied across regions and recovery criteria. Asian patients achieved significant clinical outcomes [WMD = -3.16 days (95% CI: -4.58 to -1.74, = 0.000)] compared with European and South American patients [WMD = -2.19 days (95% CI: -7.38 to 3.01, = 0.409)]. Also, according to various recovery criteria, a duration of granulocyte count increase of more than 1.5 or 1.0 × 10/L [WMD = -3.50 days (95% CI: -4.82 to -2.18 = 0.000)] revealed a better treatment effect. G-CSF can significantly shorten the recovery duration in patients with ATD-induced agranulocytosis.
PubMed: 31824417
DOI: 10.3389/fendo.2019.00789 -
Critical Reviews in Oncology/hematology May 2020We compared the Multinational Association of Supportive Care in Cancer (MASCC) and Clinical Index of Stable Febrile Neutropenia (CISNE) scores for identifying serious... (Meta-Analysis)
Meta-Analysis
Accuracy of the Multinational Association of Supportive Care in Cancer (MASCC) and Clinical Index of Stable Febrile Neutropenia (CISNE) scores for predicting serious complications in adult patients with febrile neutropenia: A systematic review and meta-analysis.
We compared the Multinational Association of Supportive Care in Cancer (MASCC) and Clinical Index of Stable Febrile Neutropenia (CISNE) scores for identifying serious complications in febrile neutropenia patients. We searched MEDLINE, PubMed, EMBASE, and Cochrane Database of Systematic Reviews from inception to March 19, 2019. Two reviewers independently screened citations, extracted data, and assessed quality. We included 26 studies, totalling 6617 patients. Pooled sensitivity and specificity for MASCC < 21 was 55.6 % (95 % CI: 46.2 %-64.5%) and 86.0 % (95 % CI: 81.3 %-89.7 %), respectively. Pooled sensitivity and specificity for CISNE ≥ 3 was 78.9 % (95 % CI: 65.3 %-88.1 %) and 64.9 % (95 % CI: 49.6 %-77.7 %), respectively. Pooled sensitivity and specificity for CISNE ≥ 1 was 96.7 % (95 % CI: 93.6 %-98.3 %) and 22.2 % (95 % CI: 15.6 %-30.4 %), respectively. The CISNE score had higher sensitivity and may be more useful than the MASCC score in the acute setting.
Topics: Adult; Antineoplastic Agents; Febrile Neutropenia; Fever; Humans; Neoplasms; Predictive Value of Tests; Prognosis; Risk Assessment; Sensitivity and Specificity; Severity of Illness Index; Treatment Outcome
PubMed: 32244162
DOI: 10.1016/j.critrevonc.2020.102922 -
Multiple Sclerosis and Related Disorders Dec 2022Neutropenia is an infrequent complication of treatment with CD20 depleting agents and may require the administration of granulocyte-colony stimulating factors (G-CSF),...
BACKGROUND
Neutropenia is an infrequent complication of treatment with CD20 depleting agents and may require the administration of granulocyte-colony stimulating factors (G-CSF), which have been associated with an increased relapse risk in patients with multiple sclerosis (PwMS). The management of this side effect is still matter of debate.
METHODS
Aim of this study is to evaluate the clinical features and the management of neutropenia occurring in anti-CD20 treated PwMS through a single-center case series and a systematic review of the literature, performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.
RESULTS
A total of 19 patients were included (3 from our clinical experience, 16 from the systematic review). Median age was 38 years-old (25-69) and nearly 70% were female, most of these patients had already received a median of 3 (0-4) previous treatments. Neutropenia occurred in 11 patients treated with ocrelizumab and 8 with rituximab, after a median of 2 (1-7) infusions and 9.5 (1-42) months from the first infusion. Most of these patients had late-onset neutropenia, that occurred after a median time of 90 days (2-156). About 70% of patients were symptomatic and most were treated with G-CSF or antibiotics. No relapses after G-CSF were reported. In those who did not suspend anti-CD20 (68.8%), neutropenia reoccurred in 18.2% of cases. Finally, switching between rituximab and ocrelizumab seem not to affect the occurrence of neutropenia.
CONCLUSION
Our data provides practical evidence regarding the occurrence and the management of neutropenia during treatment with anti-CD20 in PwMS.
Topics: Adult; Female; Humans; Male; Granulocyte Colony-Stimulating Factor; Multiple Sclerosis; Neutropenia; Retrospective Studies; Rituximab
PubMed: 35994977
DOI: 10.1016/j.msard.2022.104090 -
Pediatric Hematology and Oncology Nov 2022Febrile neutropenia is the most frequent complication in children treated with chemotherapy. Nevertheless, neutropenic children are a very heterogeneous group and... (Meta-Analysis)
Meta-Analysis
Febrile neutropenia is the most frequent complication in children treated with chemotherapy. Nevertheless, neutropenic children are a very heterogeneous group and invasive bacterial infections concern a minority of patients. Reducing antibiotics would bring many benefits. Yet, we can only explore this strategy if the safety of children is preserved. The main aims of this review were to study the safety and effectiveness of reducing antibiotic use in children with febrile neutropenia in terms of duration, route of administration (oral versus intravenous) and narrowing of antimicrobial spectrum. Cochrane Library, Pubmed and Embase were searched for relevant articles until February 2020. We have included all articles describing controlled trials written in French or in English. The risk of bias was assessed with ROB-2 (. 2019, Chap. 8) or ROBINS-1 (. 2019, Chap. 25). On 2351 articles, the systematic research retained 13 studies. Nine were used for a meta-analysis comparing oral versus intravenous treatment. We found no pediatric studies concerning de-escalation of empiric broad-spectrum antibiotics. No publication biases were found and almost all of the selected studies were at low risk or with some concern for bias. In comparing oral versus intravenous treatment and early cessation versus continuing antibiotics when no infection is proven, we found no difference in terms of safety (mortality and admission in intensive care unit) and efficacy (need of readmission/antibiotic modification/recurrence of fever). It seems safe and effective to provide oral treatment in low-risk febrile neutropenia and to stop antibiotics when no bacterial infection is proven. Spectrum reduction remains an important topic in pediatric research.Supplemental data for this article is available online at https://doi.org/10.1080/08880018.2022.2055245.
Topics: Anti-Bacterial Agents; Bacterial Infections; Child; Febrile Neutropenia; Humans
PubMed: 35465847
DOI: 10.1080/08880018.2022.2055245 -
Brazilian Journal of Otorhinolaryngology 2021Tonsillectomy is the 2nd most common outpatient surgery performed on children in the United States of America. Its main complication is pain, which varies in intensity... (Review)
Review
INTRODUCTION
Tonsillectomy is the 2nd most common outpatient surgery performed on children in the United States of America. Its main complication is pain, which varies in intensity from moderate to severe. Dipyrone is one of the most widely used painkillers in the postoperative period in children. Its use, however, is controversial in the literature, to the point that it is banned in many countries due to its potential severe adverse effects. Because of this controversy, reviewing the analgesic use of dipyrone in the postoperative period of tonsillectomy in children is essential.
OBJECTIVE
The aim of this study was to review the analgesic use of dipyrone in the postoperative period of tonsillectomy in children.
METHODS
Systematic review of the literature, involving an evaluation of the quality of articles in the databases MEDLINE/Pubmed, EMBASE and Virtual Health Library, selected with a preestablished search strategy. Only studies with a randomised clinical trial design evaluating the use of dipyrone in the postoperative period of tonsillectomy in children were included.
RESULTS AND CONCLUSION
Only 2 randomised clinical trials were found. Both compared dipyrone, paracetamol, and placebo. We were unable to carry out a metanalysis because the studies were too heterogenous (dipyrone was used as pre-emptive analgesic in one and only postoperatively in another). The analgesic effect of dipyrone, measured by validated pain scales in childhood, was shown to be superior to placebo and similar to paracetamol. It appears that dipyrone exhibits a profile suitable for use in children. However, the scarcity of randomised clinical trials evaluating its analgesic effect in this age group leads to the conclusion that more well-designed studies are still needed to establish the role of dipyrone in the postoperative period of tonsillectomy in children.
Topics: Analgesia; Child; Dipyrone; Humans; Pain Measurement; Pain, Postoperative; Randomized Controlled Trials as Topic; Tonsillectomy
PubMed: 33485779
DOI: 10.1016/j.bjorl.2020.12.005 -
BMC Infectious Diseases May 2021Sepsis is a life-threatening and time-critical medical emergency; therefore, the early diagnosis of sepsis is essential to timely treatment and favorable outcomes for... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Sepsis is a life-threatening and time-critical medical emergency; therefore, the early diagnosis of sepsis is essential to timely treatment and favorable outcomes for patients susceptible to sepsis. Eosinopenia has been identified as a potential biomarker of sepsis in the past decade. However, its clinical application progress is slow and its recognition is low. Recent studies have again focused on the potential association between Eosinopenia and severe infections. This study analyzed the efficacy of Eosinopenia as a biomarker for diagnosis of sepsis and its correlation with pathophysiology of sepsis.
METHOD
The protocol for this meta-analysis is available in PROSPERO (CRD42020197664). We searched PubMed, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials CENTRAL databases to identify studies that met the inclusion criteria. Two authors performed data extraction independently. The pooled outcomes were calculated by TP (true positive), FP (false positive), FN (false negative), TN (true negative) by using bivariate meta-analysis model in STATA 14.0 software. Meanwhile, possible mechanisms of sepsis induced Eosinopenia was also analyzed.
RESULTS
Seven studies were included in the present study with a total number of 3842 subjects. The incidence of Eosinopenia based on the enrolled studies varied from 23.2 to 92.7%. For diagnosis of sepsis, the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio of Eosinopenia were 0.66 (95%CI [0.53-0.77]), 0.68 (95%CI [0.56-0.79]), 2.09 (95%CI [1.44-3.02]), 0.49 (95%CI [0.34-0.71]) and 4.23 (95%CI [2.15-8.31]), respectively. The area under the summary receiver operator characteristic curve (SROC) was 0.73 (95%CI [0.68-0.76]). Meta-regression analysis revealed that no single parameter accounted for the heterogeneity of pooled outcomes. For each subgroup of different eosinopenia cutoff values (50, 40, ≤25, 100), the sensitivity was 0.61, 0.79, 0.57, 0.54, and the specificity was 0.61, 0.75, 0.83, 0.51, respectively.
CONCLUSIONS
Our findings suggested that Eosinopenia has a high incidence in sepsis but has no superiority in comparison with conventional biomarkers for diagnosis of sepsis. However, eosinopenia can still be used in clinical diagnosis for sepsis as a simple, convenient, fast and inexpensive biomarker. Therefore, further large clinical trials are still needed to re-evaluate eosinopenia as a biomarker of sepsis.
Topics: Agranulocytosis; Biomarkers; Early Diagnosis; Eosinophils; Humans; Incidence; Odds Ratio; Sensitivity and Specificity; Sepsis
PubMed: 34030641
DOI: 10.1186/s12879-021-06150-3 -
Journal of Neuroimmunology Jul 2021N-methyl-d-aspartate receptor (NMDAR) encephalitis is a potentially treatable condition, although a small proportion of patients remains refractory to immunotherapy....
N-methyl-d-aspartate receptor (NMDAR) encephalitis is a potentially treatable condition, although a small proportion of patients remains refractory to immunotherapy. Bortezomib is a proteasome inhibitor that has a promising role in autoimmune conditions. We performed an independent PubMed search employing "Anti-N-Methyl‑D-Aspartate encephalitis AND bortezomib", including papers published between January 1st, 2007 to April 15th, 2021. Fourteen articles were included, with 29 patients. 16 patients (55,2%) had a favorable outcome after bortezomib and 11 (37,9%) patients developed side effects. Quality of studies was overall poor and future trials should aim to include more homogeneous and larger cohorts.
Topics: Anti-N-Methyl-D-Aspartate Receptor Encephalitis; Bortezomib; Chemotherapy-Induced Febrile Neutropenia; Humans; Immunologic Factors; Immunotherapy
PubMed: 33975246
DOI: 10.1016/j.jneuroim.2021.577586