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Nutrients Aug 2023β-alanine does not have an ergogenic effect by itself, but it does as a precursor for the synthesis of carnosine in human skeletal muscle. β-alanine and carnosine... (Review)
Review
β-Alanine Supplementation in Combat Sports: Evaluation of Sports Performance, Perception, and Anthropometric Parameters and Biochemical Markers-A Systematic Review of Clinical Trials.
β-alanine does not have an ergogenic effect by itself, but it does as a precursor for the synthesis of carnosine in human skeletal muscle. β-alanine and carnosine together help improve the muscles' functionality, especially in high-intensity exercises such as combat sports. Therefore, β-alanine could be considered a nutritional ergogenic aid to improve sports performance in combat athletes. We aimed to critically review clinical trial evidence on the impact of β-alanine supplementation on sports performance, perception, and anthropometric parameters, as well as circulating biochemical markers in combat athletes. This systematic review was conducted following the specific methodological guidelines of the Preferred Report Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA), the PICOS question model, the Critical Review Form of McMaster, and the PEDro scale. Furthermore, the Cochrane risk-of-bias assessment tool was used. The search was carried out in the SCOPUS, Web of Science (WOS), and Medline (PubMed) databases for studies published from the beginning of the database until July 31, 2023. Of the 41 registers identified, only 7 met the established criteria and were included in this systematic review. Overall, performance parameters related to strength, power, total exercise work capacity, and combat-specific parameters were significantly improved ( < 0.05). Perception parameters increased non-significantly ( > 0.05). Regarding biochemical parameters, carnosine increased significantly ( < 0.05), pH decreased non-significantly ( > 0.05), and the results for blood bicarbonate and blood lactate were heterogeneous. Finally, there was a non-significant ( > 0.05) improvement in the anthropometric parameters of lean mass and fat mass. β-alanine supplementation appears to be safe and could be a suitable nutritional ergogenic aid for combat athletes.
Topics: Humans; Athletes; Athletic Performance; Carnosine; Dietary Supplements; Perception; Performance-Enhancing Substances; Clinical Trials as Topic
PubMed: 37686787
DOI: 10.3390/nu15173755 -
International Journal of Molecular... Aug 2023Muscular dystrophy is a heterogenous group of hereditary muscle disorders caused by mutations in the genes responsible for muscle development, and is generally defined... (Review)
Review
Muscular dystrophy is a heterogenous group of hereditary muscle disorders caused by mutations in the genes responsible for muscle development, and is generally defined by a disastrous progression of muscle wasting and massive loss in muscle regeneration. is closely associated with myogenesis, which is governed by various signaling pathways throughout a lifetime and is frequently used as an indicator in muscle research. In this review, an extensive literature search adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was performed to identify research that examined signaling pathways in living models, while quantifying expression in myogenesis. A total of 247 articles were retrieved from the Web of Science (WoS), PubMed and Scopus databases and were thoroughly examined and evaluated, resulting in 19 articles which met the inclusion criteria. Admittedly, we were only able to discuss the quantification of carried out in research affecting various type of genes and signaling pathways, rather than the expression of itself, due to the massive differences in approach, factor molecules and signaling pathways analyzed across the research. However, we highlighted the thorough evidence for the alteration of the muscle stem cell precursor in multiple signaling pathways described in different living models, with an emphasis on the novel approach that could be taken in manipulating expression itself in dystrophic muscle, towards the discovery of an effective treatment for muscular dystrophy. Therefore, we believe that this could be applied to the potential gap in muscle research that could be filled by tuning the well-established marker expression to improve dystrophic muscle.
Topics: Humans; Muscular Dystrophies; Muscles; Databases, Factual; Muscle Development; Signal Transduction; PAX7 Transcription Factor
PubMed: 37685856
DOI: 10.3390/ijms241713051 -
Journal of Pediatric Surgery Nov 2023Nephrogenic rests (NR) may represent precursor lesions for Wilms tumor (WT), but their clinical course is not fully understood and no guidelines for treatment exist.... (Review)
Review
BACKGROUND
Nephrogenic rests (NR) may represent precursor lesions for Wilms tumor (WT), but their clinical course is not fully understood and no guidelines for treatment exist. This study sought to evaluate the outcomes of pediatric patients with NRs related to traditional chemotherapy and surgery.
METHODS
A PRISMA-P-compliant literature search was conducted in MEDLINE, Embase, CINAHL, Web of Science, COCHRANE, and SCOPUS from inception to June 2021. Clinical questions regarding the treatment of NRs, including chemotherapy and surgery, were developed in the population, intervention, comparison, and outcome format.
RESULTS
Twenty-five studies including 1445 patients met inclusion criteria for evaluating chemotherapy compared to observation for NRs. Eighteen studies including 1392 patients met inclusion criteria for evaluating the role of surgery for NRs. Patients with isolated NRs who underwent observation progressed to WT 33% of the time; chemotherapy reduced the rate of WT to 3.9%. Observation of multiple NRs and diffuse hyperplastic perilobar nephroblastomatosis (DHPLN) led to progression to WT 50% and 100% of the time, respectively. Chemotherapy reduced the rate of WT to 34% for multiple NRs and 46% for DHPLN. Surgery for isolated NRs reduced the risk of WT development from 23.7% in patients with incomplete excision to 3.3% with complete excision; however, 96% of patients with incompletely excised NRs had bilateral disease.
CONCLUSIONS
Observation with close surveillance for isolated NRs is safe. Treatment with chemotherapy is recommended for patients with multiple NRs and DHPLN. Surgical management of NRs should focus on renal function preservation.
LEVEL OF EVIDENCE
Treatment study, Level III.
PubMed: 37625940
DOI: 10.1016/j.jpedsurg.2023.07.011 -
EClinicalMedicine Aug 2023Anal cancer prevention has two critical points: the incidence rate is several fold higher for some groups, such as people living with human immunodeficiency virus (HIV)...
BACKGROUND
Anal cancer prevention has two critical points: the incidence rate is several fold higher for some groups, such as people living with human immunodeficiency virus (HIV) and men who have sex with men (MSM), and there is not a well-defined guideline for its screening. This systematic review evaluates the accuracy of DNA HRHPV (high-risk human papillomavirus), mRNA HPV, DNA HPV16 isolated and p16 staining biomarkers in anal canal smears for identifying anal intraepithelial neoplasia (AIN) 2 or 3, summarised as anal high-grade squamous intraepithelial lesions (aHSIL), and cancer.
METHODS
We searched the MEDLINE, Cochrane Library and Embase electronic databases as well as Grey literature to identify eligible papers published up to 31st July 2022. This systematic review and meta-analysis included observational studies comparing biomarker tests to histopathology after HRA (High-resolution Anoscopy) as a reference standard. We (ACM, TF) analysed studies in which patients of both sexes were screened for anal cancer using DNA HRHPV, mRNA HPV, DNA HPV16 and/or p16 biomarkers. The analysis was performed in pairs, for instance AIN2 or worse (AIN2+) vs. AIN1, HPV infection and normal (AIN1-). PROSPERO CRD42015024201.
FINDINGS
We included 21 studies with 7445 patients. DNA HR HPV showed a higher sensitivity 92.4% (95% CI 84.2-96.5), specificity 41.7% (95% CI 33.9-44.9) and AUC 0.67, followed by the mRNA HPV test, with a sensitivity 77.3% (95% CI 73.2%-80.9%), specificity 61.9% (95% CI 56.6-66.9) and AUC 0.78. DNA HPV16 showed higher specificity 71.7% (95% CI 55.3-83.8), followed by p16 test, 64.1% (95% CI 51.0-75.4); Sensitivity of DNA HPV16 was 53.3% (95% CI 35.4-70.3) and AUC 0.69, while p16 had a sensitivity of 68.8% (95% CI 47.9-84.1) and AUC 0.74. Subgroup analysis of MSM with HIV, with 13 studies and 5123 patients, showed similar accuracy, with a bit higher sensitivities and lower specificities. Considering the measure of the total between-study variability, mRNA HPV tests showed the smallest area of the 95% prediction ellipse, 6.0%, influenced by the low logit sensitivity, 0.011. All other groups of tests exceed 50% prediction ellipse area, which represent a high heterogeneity.
INTERPRETATION
Our findings suggested that DNA HR HPV can be a useful tool for screening for aHSIL and anal cancer if followed by biomarker with a higher specificity. As an isolated test, mRNA HPV had better performance.
FUNDING
There was no funding source for this study.
PubMed: 37588624
DOI: 10.1016/j.eclinm.2023.102128 -
Advances in Nutrition (Bethesda, Md.) Nov 2023Accumulation of deoxyribonucleic acid (DNA) damage diminishes cellular health, increases risk of developmental and degenerative diseases, and accelerates aging.... (Review)
Review
Protective Effects of Micronutrient Supplements, Phytochemicals and Phytochemical-Rich Beverages and Foods Against DNA Damage in Humans: A Systematic Review of Randomized Controlled Trials and Prospective Studies.
Accumulation of deoxyribonucleic acid (DNA) damage diminishes cellular health, increases risk of developmental and degenerative diseases, and accelerates aging. Optimizing nutrient intake can minimize accrual of DNA damage. The objectives of this review are to: 1) assemble and systematically analyze high-level evidence for the effect of supplementation with micronutrients and phytochemicals on baseline levels of DNA damage in humans, and 2) use this knowledge to identify which of these essential micronutrients or nonessential phytochemicals promote DNA integrity in vivo in humans. We conducted systematic literature searches of the PubMed database to identify interventional, prospective, cross-sectional, or in vitro studies that explored the association between nutrients and established biomarkers of DNA damage associated with developmental and degenerative disease risk. Biomarkers included lymphocyte chromosome aberrations, lymphocyte and buccal cell micronuclei, DNA methylation, lymphocyte/leukocyte DNA strand breaks, DNA oxidation, telomere length, telomerase activity, and mitochondrial DNA mutations. Only randomized, controlled interventions and uncontrolled longitudinal intervention studies conducted in humans were selected for evaluation and data extraction. These studies were ranked for the quality of their study design. In all, 96 of the 124 articles identified reported studies that achieved a quality assessment score ≥ 5 (from a maximum score of 7) and were included in the final review. Based on these studies, nutrients associated with protective effects included vitamin A and its precursor β-carotene, vitamins C, E, B1, B12, folate, minerals selenium and zinc, and phytochemicals such as curcumin (with piperine), lycopene, and proanthocyanidins. These findings highlight the importance of nutrients involved in (i) DNA metabolism and repair (folate, vitamin B, and zinc) and (ii) prevention of oxidative stress and inflammation (vitamins A, C, E, lycopene, curcumin, proanthocyanidins, selenium, and zinc). Supplementation with certain micronutrients and their combinations may reduce DNA damage and promote cellular health by improving the maintenance of genome integrity.
Topics: Humans; Prospective Studies; Selenium; Lycopene; Cross-Sectional Studies; Curcumin; Proanthocyanidins; Randomized Controlled Trials as Topic; Vitamins; Vitamin A; Micronutrients; Folic Acid; Zinc; Beverages; Phytochemicals; DNA; DNA Damage; Biomarkers; Dietary Supplements
PubMed: 37573943
DOI: 10.1016/j.advnut.2023.08.004 -
Life (Basel, Switzerland) Jun 2023SEIC is a non-invasive lesion of the endometrial epithelium considered to be the precursor to uterine serous carcinoma (USC) and is just as aggressive as USC. Currently,... (Review)
Review
SEIC is a non-invasive lesion of the endometrial epithelium considered to be the precursor to uterine serous carcinoma (USC) and is just as aggressive as USC. Currently, there are no reliable data about the behavior and prognosis of SEIC; therefore, the therapeutic management approach is not clear. : A systematic search of the Pubmed, Scopus and Embase databases was conducted, following the recommendations in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). : Of the 296 studies that matched the search criteria, only 9 met the inclusion criteria, covering a total of 81 patients. The main disease-presenting pattern was AUB (abnormal uterine bleeding). In 31 cases, SEIC was associated with extrauterine disease. All patients underwent hysterectomy and salpingo-oophorectomy, while only 15 of the 81 patients received adjuvant treatments. In the patients receiving adjuvant therapy, the RR was 42.67%, the DFS was 35.71% and the OS was 57.13%. In patients subjected to follow-up alone, the RR was only 28.78%, the DFS was 59.1% and the OS was 66.6%. : The presence of an extrauterine disease significantly worsens outcomes, regardless of adjuvant treatment. In cases of disease confined to the uterine mucosa alone, the prognosis is good and follow-up allows a good control of the disease; however, adjuvant therapy could further increase survival rates and reduce relapse rates.
PubMed: 37511804
DOI: 10.3390/life13071429 -
Interactive Journal of Medical Research Jul 2023Nonalcoholic fatty liver disease (NAFLD) is one of the common causes of chronic liver disease globally. Obesity, metabolic diseases, and exposure to some environmental... (Review)
Review
BACKGROUND
Nonalcoholic fatty liver disease (NAFLD) is one of the common causes of chronic liver disease globally. Obesity, metabolic diseases, and exposure to some environmental agents contribute to NAFLD. NAFLD is commonly considered a precursor for some types of cancers. Since the leading causes of death in people with NAFLD are cardiovascular disease and extrahepatic cancers, it is important to understand the mechanisms of the progression of NAFLD to control its progression and identify its association with extrahepatic cancers. Thus, this review aims to estimate the global prevalence of NAFLD in association with the risk of extrahepatic cancers.
OBJECTIVE
We aimed to determine the prevalence of various cancers in NAFLD patients and the association between NAFLD and cancer.
METHODS
We searched PubMed, ProQuest, Scopus, and Web of Science from database inception to March 2022 to identify eligible studies reporting the prevalence of NAFLD and the risk of incident cancers among adult individuals (aged ≥18 years). Data from selected studies were extracted, and meta-analysis was performed using random effects models to obtain the pooled prevalence with the 95% CI. The quality of the evidence was assessed with the Newcastle-Ottawa Scale.
RESULTS
We identified 11 studies that met our inclusion criteria, involving 222,523 adults and 3 types of cancer: hepatocellular carcinoma (HCC), breast cancer, and other types of extrahepatic cancer. The overall pooled prevalence of NAFLD and cancer was 26% (95% CI 16%-35%), while 25% of people had NAFLD and HCC (95% CI 7%-42%). NAFLD and breast cancer had the highest prevalence out of the 3 forms of cancer at 30% (95% CI 14%-45%), while the pooled prevalence for NAFLD and other cancers was 21% (95% CI 12%-31%).
CONCLUSIONS
The review suggests that people with NAFLD may be at an increased risk of cancer that might not affect not only the liver but also other organs, such as the breast and bile duct. The findings serve as important evidence for policymakers to evaluate and recommend measures to reduce the prevalence of NAFLD through lifestyle and environmental preventive approaches.
TRIAL REGISTRATION
PROSPERO CRD42022321946; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=321946.
PubMed: 37467012
DOI: 10.2196/40653 -
Dental Research Journal 2023These days minimally invasive micro-osteoperforation (MOPs) has accelerated orthodontic tooth movement (OTM). However, there are some conflicting reports about their...
The effect of micro-osteoperforation on root resorption, pulp vitality, and biological changes of teeth subjected to orthodontic tooth movement: A systematic review study.
BACKGROUND
These days minimally invasive micro-osteoperforation (MOPs) has accelerated orthodontic tooth movement (OTM). However, there are some conflicting reports about their various impacts; hence, the present systematic review study aimed to evaluate the effect of MOP on root resorption, pulp vitality, and the biological changes of teeth subjected to OTM.
MATERIALS AND METHODS
Search in electronic databases of English literature including PubMed, Scopus, Web of sciences, Cochrane, and Google scholar as well as a manual search was performed from 2013 to 2022. Most of the studies included in this article were randomized controlled trials.
RESULTS
From the total number of 321 found articles, 31 duplicated and 268 irrelevant articles were excluded regarding the defined inclusion and exclusion criteria. Consequently, 22 articles were subjected to the quality assessment process, and finally, 18 articles were selected for the review phase. Root resorption during tooth movement using the MOP approach was reported only in one study. Besides, except for two animal studies, all of the relevant included articles showed that MOPs significantly increased the expression of some inflammatory biomarkers known to recruit osteoclast precursors and increase the number of osteoclast cells. On the other hand, two animal studies showed no differences in osteoclast counts by using MOPs in comparison to their control groups, which was consequently the result of biologic variability between animal and human and also probably the small sample sizes of these two studies.
CONCLUSION
In this systematic review, according to the adverse effects of MOP on root resorption, one study showed higher levels of root resorption among patients undergoing MOP. However, this outcome was due to the different methods used to evaluate the effect of MOPs on root resorption. Moreover, a high certainty of evidence supports that MOP causes biological changes and an elevation in cytokines, chemokines, and other biomarkers that stimulates osteoclasts differentiation which in turn accelerate OTM. There was no change in pulp vitality status based on available evidence.
PubMed: 37304419
DOI: No ID Found -
The Cochrane Database of Systematic... Jun 2023Amputation is described as the removal of an external part of the body by trauma, medical illness or surgery. Amputations caused by vascular diseases (dysvascular... (Review)
Review
BACKGROUND
Amputation is described as the removal of an external part of the body by trauma, medical illness or surgery. Amputations caused by vascular diseases (dysvascular amputations) are increasingly frequent, commonly due to peripheral arterial disease (PAD), associated with an ageing population, and increased incidence of diabetes and atherosclerotic disease. Interventions for motor rehabilitation might work as a precursor to enhance the rehabilitation process and prosthetic use. Effective rehabilitation can improve mobility, allow people to take up activities again with minimum functional loss and may enhance the quality of life (QoL). Strength training is a commonly used technique for motor rehabilitation following transtibial (below-knee) amputation, aiming to increase muscular strength. Other interventions such as motor imaging (MI), virtual environments (VEs) and proprioceptive neuromuscular facilitation (PNF) may improve the rehabilitation process and, if these interventions can be performed at home, the overall expense of the rehabilitation process may decrease. Due to the increased prevalence, economic impact and long-term rehabilitation process in people with dysvascular amputations, a review investigating the effectiveness of motor rehabilitation interventions in people with dysvascular transtibial amputations is warranted.
OBJECTIVES
To evaluate the benefits and harms of interventions for motor rehabilitation in people with transtibial (below-knee) amputations resulting from peripheral arterial disease or diabetes (dysvascular causes).
SEARCH METHODS
We used standard, extensive Cochrane search methods. The latest search date was 9 January 2023.
SELECTION CRITERIA
We included randomised controlled trials (RCT) in people with transtibial amputations resulting from PAD or diabetes (dysvascular causes) comparing interventions for motor rehabilitation such as strength training (including gait training), MI, VEs and PNF against each other.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcomes were 1. prosthesis use, and 2.
ADVERSE EVENTS
Our secondary outcomes were 3. mortality, 4. QoL, 5. mobility assessment and 6. phantom limb pain. We use GRADE to assess certainty of evidence for each outcome.
MAIN RESULTS
We included two RCTs with a combined total of 30 participants. One study evaluated MI combined with physical practice of walking versus physical practice of walking alone. One study compared two different gait training protocols. The two studies recruited people who already used prosthesis; therefore, we could not assess prosthesis use. The studies did not report mortality, QoL or phantom limb pain. There was a lack of blinding of participants and imprecision as a result of the small number of participants, which downgraded the certainty of the evidence. We identified no studies that compared VE or PNF with usual care or with each other. MI combined with physical practice of walking versus physical practice of walking (one RCT, eight participants) showed very low-certainty evidence of no difference in mobility assessment assessed using walking speed, step length, asymmetry of step length, asymmetry of the mean amount of support on the prosthetic side and on the non-amputee side and Timed Up-and-Go test. The study did not assess adverse events. One study compared two different gait training protocols (one RCT, 22 participants). The study used change scores to evaluate if the different gait training strategies led to a difference in improvement between baseline (day three) and post-intervention (day 10). There were no clear differences using velocity, Berg Balance Scale (BBS) or Amputee Mobility Predictor with PROsthesis (AMPPRO) in training approaches in functional outcome (very low-certainty evidence). There was very low-certainty evidence of little or no difference in adverse events comparing the two different gait training protocols.
AUTHORS' CONCLUSIONS
Overall, there is a paucity of research in the field of motor rehabilitation in dysvascular amputation. We identified very low-certainty evidence that gait training protocols showed little or no difference between the groups in mobility assessments and adverse events. MI combined with physical practice of walking versus physical practice of walking alone showed no clear difference in mobility assessment (very low-certainty evidence). The included studies did not report mortality, QoL, and phantom limb pain, and evaluated participants already using prosthesis, precluding the evaluation of prosthesis use. Due to the very low-certainty evidence available based on only two small trials, it remains unclear whether these interventions have an effect on the prosthesis use, adverse events, mobility assessment, mortality, QoL and phantom limb pain. Further well-designed studies that address interventions for motor rehabilitation in dysvascular transtibial amputation may be important to clarify this uncertainty.
Topics: Humans; Phantom Limb; Amputation, Surgical; Walking; Peripheral Arterial Disease; Diabetes Mellitus
PubMed: 37276273
DOI: 10.1002/14651858.CD013711.pub2 -
The Cochrane Database of Systematic... May 2023Asparaginase has played a crucial role in the improvement of survival in children with acute lymphoblastic leukaemia (ALL), which is the commonest cancer among children.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Asparaginase has played a crucial role in the improvement of survival in children with acute lymphoblastic leukaemia (ALL), which is the commonest cancer among children. Survival rates have steadily increased over decades since the introduction of asparaginase to ALL therapy, and overall survival rates reach 90% with the best contemporary protocols. Currently, polyethylene glycolated native Escherichia coli-derived L-asparaginase (PEG-asparaginase) is the preferred first-line asparaginase preparation. Besides its clinical benefits, PEG-asparaginase is well known for severe toxicities. Agreement on the optimal dose, treatment duration, and frequency of administration has never been reached among clinicians.
OBJECTIVES
Primary objective To assess the effect of the number of PEG-asparaginase doses on survival and relapse in children and adolescents with ALL. Secondary objectives To assess the association between the number of doses of PEG-asparaginase and asparaginase-associated toxicities (e.g. hypersensitivity, thromboembolism, pancreatitis and osteonecrosis). To undertake a network meta-analysis at dose-level in order to generate rankings of the number of doses of PEG-asparaginase used in the treatment for ALL, according to their benefits (survival and relapse) and harms (toxicity).
SEARCH METHODS
We searched CENTRAL, PubMed, Embase, Web of Science databases and three trials registers in November 2021, together with reference checking, citation searching and contact with study authors to identify additional studies.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) comparing different PEG-asparaginase treatment regimens in children and adolescents (< 18 years of age) with first-line ALL treated with multiagent chemotherapy including PEG-asparaginase.
DATA COLLECTION AND ANALYSIS
Using a standardised data collection form, two review authors independently screened and selected studies, extracted data, assessed risk of bias for each outcome using a standardised tool (RoB 2.0) and assessed the certainty of evidence for each outcome using the GRADE approach. Primary outcomes included overall survival, event-free survival and leukaemic relapse. Secondary outcomes included asparaginase-associated toxicities (hypersensitivity, thromboembolism, pancreatitis, sinusoidal obstruction syndrome and osteonecrosis as well as overall asparaginase-associated toxicity). We conducted the review and performed the analyses in accordance with the guidelines of the Cochrane Handbook for Systematic Reviews of Interventions.
MAIN RESULTS
We included three RCTs in the review, and identified an additional four ongoing studies. We judged outcomes of two RCTs to be at low risk of bias in all the Cochrane risk of bias (RoB 2) domains. We rated the remaining study as having some concerns regarding bias. Due to concerns about imprecision, we rated all outcomes as having low- to moderate-certainty evidence. One study compared intermittent PEG-asparaginase treatment (eight doses of PEG-asparaginase, 1000 IU/m, intramuscular (IM) administration) versus continuous PEG-asparaginase treatment (15 doses of PEG-asparaginase, 1000 IU/m, IM) in 625 participants with non-high risk ALL aged 1.0 to 17.9 years. We found that treatment with eight doses probably results in little to no difference in event-free survival compared to treatment with 15 doses (RR 1.01, 95% CI 0.97 to 1.06; moderate-certainty evidence). Compared to treatment with 15 doses, treatment with eight doses may result in either no difference or a slight reduction in hypersensitivity (RR 0.64, 95% CI 0.21 to 1.93; low-certainty evidence), thromboembolism (RR 0.55, 95% CI 0.22 to 1.36; low-certainty evidence) or osteonecrosis (RR 0.68, 95% CI 0.35 to 1.32; low-certainty evidence). Furthermore, we found that treatment with eight doses probably reduces pancreatitis (RR 0.31, 95% CI 0.12 to 0.75; moderate-certainty evidence) and asparaginase-associated toxicity (RR 0.53, 95% CI 0.35 to 0.78; moderate-certainty evidence) compared to treatment with 15 doses. One study compared low-risk standard treatment with additional PEG-asparaginase (six doses, 2500 IU/m, IM) versus low-risk standard treatment (two doses, 2500 IU/m, IM) in 1857 participants aged one to nine years old with standard low-risk ALL. We found that, compared to treatment with two doses, treatment with six doses probably results in little to no difference in overall survival (RR 0.99, 95% CI 0.98 to 1.00; moderate-certainty evidence) and event-free survival (RR 1.01, 95% CI 0.99 to 1.04; moderate-certainty evidence), and may result in either no difference or a slight increase in osteonecrosis (RR 1.65, 95% CI 0.91 to 3.00; low-certainty evidence). Furthermore, we found that treatment with six doses probably increases hypersensitivity (RR 12.05, 95% CI 5.27 to 27.58; moderate-certainty evidence), pancreatitis (RR 4.84, 95% CI 2.15 to 10.85; moderate-certainty evidence) and asparaginase-associated toxicity (RR 4.49, 95% CI 3.05 to 6.59; moderate-certainty evidence) compared to treatment with two doses. One trial compared calaspargase (11 doses, 2500 IU/m, intravenous (IV)) versus PEG-asparaginase (16 doses, 2500 IU/m, IV) in 239 participants aged one to 21 years with standard- and high-risk ALL and lymphoblastic lymphoma. We found that treatment with 11 doses of calaspargase probably results in little to no difference in event-free survival compared to treatment with 16 doses of PEG-asparaginase (RR 1.06, 95% CI 0.97 to 1.16; moderate-certainty evidence). However, treatment with 11 doses of calaspargase probably reduces leukaemic relapse compared to treatment with 16 doses of PEG-asparaginase (RR 0.32, 95% CI 0.12 to 0.83; moderate-certainty evidence). Furthermore, we found that treatment with 11 doses of calaspargase results in either no difference or a slight reduction in hypersensitivity (RR 1.17, 95% CI 0.64 to 2.13; low-certainty evidence), pancreatitis (RR 0.85, 95% CI 0.47 to 1.52; low-certainty evidence), thromboembolism (RR 0.83, 95% CI 0.48 to 1.42; low-certainty evidence), osteonecrosis (RR 0.63, 95% CI 0.15 to 2.56; low-certainty evidence) and asparaginase-associated toxicity (RR 1.00, 95% CI 0.71 to 1.40; low-certainty evidence) compared to treatment with 16 doses of PEG-asparaginase.
AUTHORS' CONCLUSIONS
We were not able to conduct a network meta-analysis, and could not draw clear conclusions because it was not possible to rank the interventions. Overall, we found that different numbers of doses of PEG-asparaginase probably result in little to no difference in event-free survival across all studies. In two studies, we found that a higher number of PEG-asparaginase doses probably increases pancreatitis and asparaginase-associated toxicities.
Topics: Adolescent; Child; Child, Preschool; Humans; Infant; Asparaginase; Neoplasm Recurrence, Local; Network Meta-Analysis; Pancreatitis; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Systematic Reviews as Topic; Thromboembolism; Recurrence
PubMed: 37260073
DOI: 10.1002/14651858.CD014570.pub2