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Critical Reviews in Oncology/hematology Aug 2020Children with acute lymphoblastic leukemia (ALL) experience detrimental effects on motor function during and after chemotherapy. The objective of this systematic review...
The effect of exercise and motor interventions on physical activity and motor outcomes during and after medical intervention for children and adolescents with acute lymphoblastic leukemia: A systematic review.
BACKGROUND
Children with acute lymphoblastic leukemia (ALL) experience detrimental effects on motor function during and after chemotherapy. The objective of this systematic review was to evaluate the effect of exercise and motor interventions on physical activity and motor outcomes of children with ALL during and after chemotherapy.
METHODS
Ten databases were searched. Nineteen studies were included: 11 randomized clinical trials (RCT), 2 controlled clinical trials (CCT), and 6 cohort studies.
RESULTS
Participants included 508 children with ALL. Between-group results from RCTs and CCTs supported that exercise and motor intervention improved: fatigue during acute chemotherapy; physical activity, range of motion (ROM), strength, bone mineral density, aerobic capacity, and fatigue during maintenance chemotherapy; functional mobility, ROM, strength, and aerobic capacity during post-treatment survivorship; and participation, physical activity, ROM, strength, and coordination during multiple-phase interventions.
CONCLUSION
Low quality evidence supports the efficacy of motor and exercise interventions for children and adolescents with ALL.
Topics: Adolescent; Bone Density; Child; Exercise; Exercise Tolerance; Fatigue; Humans; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 32580035
DOI: 10.1016/j.critrevonc.2020.103004 -
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 -
Nutrients Mar 2020The aim of this review is to systematically review the evidence whether proper nutrition has a positive impact on the prevention or decline of depressive symptoms among...
The aim of this review is to systematically review the evidence whether proper nutrition has a positive impact on the prevention or decline of depressive symptoms among elderly people. In addition, possible connections between nutrition, microbiome, and serotonin molecules and its tryptophan precursor are discussed. The methodology follows the PRISMA guidelines, including the PRISMA flow chart. The authors systematically reviewed peer-review, English-written articles published in Web of Science and PubMed between 2013 and 2018. The findings of six original articles, detected on the set inclusion and exclusion criteria, indicate that there is an association between nutrition and depressive symptoms in the target group, i.e., that proper nutrition has a positive impact on the prevention or reduction of depressive symptoms among elderly people. The findings also reveal that there is a considerable correlation between the intakes of vitamin B and a decrease in the prevalence of depressive symptoms. Furthermore, sufficient nutrient intake of tryptophan appears to be an important factor in terms of nutrition and serotonin levels in the body. The authors consider it important to explore associations between the overall dietary intake and depression since diets are not consumed as individual nutrients. Returning to preventive approaches seems to be a rational way to promote the mental health of seniors. Future studies thus need to include interdisciplinary collaboration: from a good diagnosis of the disease by a psychiatrist, through an analysis of the need for nutrient metabolism by a biochemist to the development of a nutritional plan by a nutritional therapist. The limitations of this review consist in a relatively small number of the studies on this topic, including just few randomized controlled trials, which are a guarantee of efficacy and objectivity in comparison with cross-sectional studies.
Topics: Age Factors; Aged; Aged, 80 and over; Depression; Elder Nutritional Physiological Phenomena; Female; Gastrointestinal Microbiome; Humans; Male; Nutrition Therapy; Nutritional Status; Serotonin; Tryptophan; Vitamin B Complex
PubMed: 32156003
DOI: 10.3390/nu12030710 -
Transfusion Medicine Reviews Apr 2019Promising efficacy results of chimeric antigen receptor (CAR) T-cell therapy have been tempered by safety considerations. Our objective was to comprehensively summarize... (Meta-Analysis)
Meta-Analysis
Promising efficacy results of chimeric antigen receptor (CAR) T-cell therapy have been tempered by safety considerations. Our objective was to comprehensively summarize the efficacy and safety of CAR-T cell therapy in patients with relapsed or refractory hematologic or solid malignancies. MEDLINE, Embase, and the Cochrane Register of Controlled Trials (inception - November 21, 2017). Interventional studies investigating CAR-T cell therapy in patients with malignancies were included. Our primary outcome of interest was complete response (defined as the absence of detectable cancer). Two independent reviewers extracted relevant data, assessed risk of bias, and graded the quality of evidence using established methods. A total of 42 hematological malignancy studies and 18 solid tumor studies met were included (913 participants). Of 486 evaluable hematologic patients, 54.4% [95% CI, 42.5%-65.9%] experienced complete response in 27 CD19 CAR-T cell therapy studies. Of 65 evaluable hematologic patients, 24.4% [95% CI, 9.4%-50.3%] experienced complete response in seven non-CD19 CAR-T cell therapy studies. Cytokine release syndrome was experienced by 55.3% [95% CI, 40.3%-69.4%] of patients and neurotoxicity 37.2% [95% CI, 28.6%-46.8%] of patients with hematologic malignancies. Of 86 evaluable solid tumor patients, 4.1% [95% CI, 1.6%-10.6%] experienced complete response in eight CAR-T cell therapy studies. Limitations include heterogeneity of study populations, as well as high risk of bias of included studies. There was a strong signal for efficacy of CAR-T cell therapy in patients with CD19+ hematologic malignancies and no overall signal in solid tumor trials published to date. These results will help inform patients, physicians, and other stakeholders of the benefits and risks associated with CAR-T cell therapy.
Topics: Antigens, CD19; Hematologic Neoplasms; Humans; Immunotherapy; Immunotherapy, Adoptive; Lymphoma, Large B-Cell, Diffuse; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Receptors, Antigen, T-Cell; Receptors, Chimeric Antigen; Risk Assessment; T-Lymphocytes; Treatment Outcome
PubMed: 30948292
DOI: 10.1016/j.tmrv.2019.01.005 -
The Cochrane Database of Systematic... May 2021Intimate partner violence (IPV) includes any violence (physical, sexual or psychological/emotional) by a current or former partner. This review reflects the current... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Intimate partner violence (IPV) includes any violence (physical, sexual or psychological/emotional) by a current or former partner. This review reflects the current understanding of IPV as a profoundly gendered issue, perpetrated most often by men against women. IPV may result in substantial physical and mental health impacts for survivors. Women affected by IPV are more likely to have contact with healthcare providers (HCPs) (e.g. nurses, doctors, midwives), even though women often do not disclose the violence. Training HCPs on IPV, including how to respond to survivors of IPV, is an important intervention to improve HCPs' knowledge, attitudes and practice, and subsequently the care and health outcomes for IPV survivors.
OBJECTIVES
To assess the effectiveness of training programmes that seek to improve HCPs' identification of and response to IPV against women, compared to no intervention, wait-list, placebo or training as usual.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase and seven other databases up to June 2020. We also searched two clinical trials registries and relevant websites. In addition, we contacted primary authors of included studies to ask if they knew of any relevant studies not identified in the search. We evaluated the reference lists of all included studies and systematic reviews for inclusion. We applied no restrictions by search dates or language.
SELECTION CRITERIA
All randomised and quasi-randomised controlled trials comparing IPV training or educational programmes for HCPs compared with no training, wait-list, training as usual, placebo, or a sub-component of the intervention.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures outlined by Cochrane. Two review authors independently assessed studies for eligibility, undertook data extraction and assessed risks of bias. Where possible, we synthesised the effects of IPV training in a meta-analysis. Other analyses were synthesised in a narrative manner. We assessed evidence certainty using the GRADE approach.
MAIN RESULTS
We included 19 trials involving 1662 participants. Three-quarters of all studies were conducted in the USA, with single studies from Australia, Iran, Mexico, Turkey and the Netherlands. Twelve trials compared IPV training versus no training, and seven trials compared the effects of IPV training to training as usual or a sub-component of the intervention in the comparison group, or both. Study participants included 618 medical staff/students, 460 nurses/students, 348 dentists/students, 161 counsellors or psychologists/students, 70 midwives and 5 social workers. Studies were heterogeneous and varied across training content delivered, pedagogy and time to follow-up (immediately post training to 24 months). The risk of bias assessment highlighted unclear reporting across many areas of bias. The GRADE assessment of the studies found that the certainty of the evidence for the primary outcomes was low to very low, with studies often reporting on perceived or self-reported outcomes rather than actual HCPs' practices or outcomes for women. Eleven of the 19 included studies received some form of research grant funding to complete the research. Within 12 months post-intervention, the evidence suggests that compared to no intervention, wait-list or placebo, IPV training: · may improve HCPs' attitudes towards IPV survivors (standardised mean difference (SMD) 0.71, 95% CI 0.39 to 1.03; 8 studies, 641 participants; low-certainty evidence); · may have a large effect on HCPs' self-perceived readiness to respond to IPV survivors, although the evidence was uncertain (SMD 2.44, 95% CI 1.51 to 3.37; 6 studies, 487 participants; very low-certainty evidence); · may have a large effect on HCPs' knowledge of IPV, although the evidence was uncertain (SMD 6.56, 95% CI 2.49 to 10.63; 3 studies, 239 participants; very low-certainty evidence); · may make little to no difference to HCPs' referral practices of women to support agencies, although this is based on only one study (with 49 clinics) assessed to be very low certainty; · has an uncertain effect on HCPs' response behaviours (based on two studies of very low certainty), with one trial (with 27 participants) reporting that trained HCPs were more likely to successfully provide advice on safety planning during their interactions with standardised patients, and the other study (with 49 clinics) reporting no clear impact on safety planning practices; · may improve identification of IPV at six months post-training (RR 4.54, 95% CI 2.5 to 8.09) as in one study (with 54 participants), although three studies (with 48 participants) reported little to no effects of training on identification or documentation of IPV, or both. No studies assessed the impact of training HCPs on the mental health of women survivors of IPV compared to no intervention, wait-list or placebo. When IPV training was compared to training as usual or a sub-component of the intervention, or both, no clear effects were seen on HCPs' attitudes/beliefs, safety planning, and referral to services or mental health outcomes for women. Inconsistent results were seen for HCPs' readiness to respond (improvements in two out of three studies) and HCPs' IPV knowledge (improved in two out of four studies). One study found that IPV training improved HCPs' validation responses. No adverse IPV-related events were reported in any of the studies identified in this review.
AUTHORS' CONCLUSIONS
Overall, IPV training for HCPs may be effective for outcomes that are precursors to behaviour change. There is some, albeit weak evidence that IPV training may improve HCPs' attitudes towards IPV. Training may also improve IPV knowledge and HCPs' self-perceived readiness to respond to those affected by IPV, although we are not certain about this evidence. Although supportive evidence is weak and inconsistent, training may improve HCPs' actual responses, including the use of safety planning, identification and documentation of IPV in women's case histories. The sustained effect of training on these outcomes beyond 12 months is undetermined. Our confidence in these findings is reduced by the substantial level of heterogeneity across studies and the unclear risk of bias around randomisation and blinding of participants, as well as high risk of bias from attrition in many studies. Further research is needed that overcomes these limitations, as well as assesses the impacts of IPV training on HCPs' behavioral outcomes and the well-being of women survivors of IPV.
Topics: Adult; Bias; Dentists; Female; Health Personnel; Humans; Intimate Partner Violence; Medical Staff; Midwifery; Nursing Staff; Psychology; Randomized Controlled Trials as Topic; Social Workers; Students, Health Occupations
PubMed: 34057734
DOI: 10.1002/14651858.CD012423.pub2 -
The Cochrane Database of Systematic... Nov 2022Smith-Lemli-Opitz syndrome (SLOS) is a multiple congenital malformations syndrome caused by defective cholesterol biosynthesis. Affected individuals show cholesterol... (Review)
Review
BACKGROUND
Smith-Lemli-Opitz syndrome (SLOS) is a multiple congenital malformations syndrome caused by defective cholesterol biosynthesis. Affected individuals show cholesterol deficiency and accumulation of various precursor molecules, mainly 7-dehydrocholesterol and 8-dehydrocholesterol. There is currently no cure for SLOS, with cholesterol supplementation being primarily a biochemical therapy of limited evidence. However, several anecdotal reports and preclinical studies have highlighted statins as a potential therapy for SLOS.
OBJECTIVES
To evaluate the effects of statins, either alone or in combination with other non-statin therapies (e.g. cholesterol, bile acid, or vitamin co-supplementation), compared to cholesterol supplementation alone or in combination with other non-statin therapies (e.g. bile acid or vitamin supplementation) on several important outcomes including overall survival, neurobehavioral features, and adverse effects in individuals with SLOS.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, five other databases and three trials registers on 15 February 2022, together with reference checking, citation searching and contact with study authors to identify additional studies.
SELECTION CRITERIA
Randomized controlled trials (RCTs) and quasi-RCTs with parallel or cross-over designs, and non-randomized studies of interventions (NRSIs) including non-randomized trials, cohort studies, and controlled before-and-after studies, were eligible for inclusion in this review if they met our prespecified inclusion criteria, i.e. involved human participants with biochemically or genetically diagnosed SLOS receiving statin therapy or cholesterol supplementation, or both.
DATA COLLECTION AND ANALYSIS
Two authors screened titles and abstracts and subsequently full-texts for all potentially-relevant references. Both authors independently extracted relevant data from included studies and assessed the risks of bias. We analyzed the data extracted from the included NRSIs and cohort studies separately from the data extracted from the single included RCT. We used a random-effects model to account for the inherent heterogeneity and methodological variation between these different study designs. We used GRADE to assess the certainty of evidence.
MAIN RESULTS
We included six studies (61 participants with SLOS); one RCT (N = 18), three prospective NRSIs (N = 20), and two retrospective NRSIs (N = 22). Five studies included only children, and two limited their participant inclusion by disease severity. Overall, there were nearly twice as many males as females. All six studies compared add-on statin therapy to cholesterol supplementation alone. However, the dosages, formulations, and durations of treatment were highly variable across studies. We judged the RCT as having a high risk of bias due to missing data and selective reporting. All included NRSIs had a serious or critical overall risk of bias assessed by the Risk Of Bias In Non-randomized Studies of Interventions tool (ROBINS-I). None of the included studies evaluated survival or reported quality of life (QoL). Only the included RCT formally assessed changes in the neurobehavioral manifestations of SLOS, and we are uncertain whether statin therapy improves this outcome (very low-certainty evidence). We are also uncertain whether the adverse events reported in the RCT were statin-related (very low-certainty evidence). In contrast, the adverse events reported in the NRSIs seem to be possibly due to statin therapy (risk ratio 13.00, 95% confidence interval 1.85 to 91.49; P = 0.01; low-certainty evidence), with only one of the NRSIs retrospectively mentioning changes in the irritability of two of their participants. We are uncertain whether statins affect growth based on the RCT or NRSI results (very low-certainty evidence). The RCT showed that statins may make little or no difference to plasma biomarker levels (low-certainty evidence), while we are uncertain of their effects on such parameters in the NRSIs (very low-certainty evidence).
AUTHORS' CONCLUSIONS
Currently, there is no evidence on the potential effects of statin therapy in people with SLOS regarding survival or QoL, and very limited evidence on the effects on neurobehavioral manifestations. Likewise, current evidence is insufficient and of very low certainty regarding the effects of statins on growth parameters in children with SLOS and plasma or cerebrospinal fluid (CSF) levels of various disease biomarkers. Despite these limitations, current evidence seemingly suggests that statins may increase the risk of adverse reactions in individuals with SLOS receiving statins compared to those who are not. Given the insufficient evidence on potential benefits of statins in individuals with SLOS, and their potential for causing adverse reactions, anyone considering this therapy should take these findings into consideration. Future studies should address the highlighted gaps in evidence on the use of statins in individuals with SLOS by collecting prospective data on survival and performing serial standardized assessments of neurobehavioral features, QoL, anthropometric measures, and plasma and CSF biomarker levels after statin introduction. Future studies should also attempt to use consistent dosages, formulations and durations of cholesterol and statin therapy.
Topics: Child; Female; Humans; Male; Bile Acids and Salts; Cholesterol; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Smith-Lemli-Opitz Syndrome; Vitamins; Randomized Controlled Trials as Topic; Cross-Over Studies
PubMed: 36373961
DOI: 10.1002/14651858.CD013521.pub2 -
Molecular Neurodegeneration Nov 2022The family of VPS10p-Domain (D) receptors comprises five members named SorLA, Sortilin, SorCS1, SorCS2 and SorCS3. While their physiological roles remain incompletely... (Review)
Review
The family of VPS10p-Domain (D) receptors comprises five members named SorLA, Sortilin, SorCS1, SorCS2 and SorCS3. While their physiological roles remain incompletely resolved, they have been recognized for their signaling engagements and trafficking abilities, navigating a number of molecules between endosome, Golgi compartments, and the cell surface. Strikingly, recent studies connected all the VPS10p-D receptors to Alzheimer's disease (AD) development. In addition, they have been also associated with diseases comorbid with AD such as diabetes mellitus and major depressive disorder. This systematic review elaborates on genetic, functional, and mechanistic insights into how dysfunction in VPS10p-D receptors may contribute to AD etiology, AD onset diversity, and AD comorbidities. Starting with their functions in controlling cellular trafficking of amyloid precursor protein and the metabolism of the amyloid beta peptide, we present and exemplify how these receptors, despite being structurally similar, regulate various and distinct cellular events involved in AD. This includes a plethora of signaling crosstalks that impact on neuronal survival, neuronal wiring, neuronal polarity, and synaptic plasticity. Signaling activities of the VPS10p-D receptors are especially linked, but not limited to, the regulation of neuronal fitness and apoptosis via their physical interaction with pro- and mature neurotrophins and their receptors. By compiling the functional versatility of VPS10p-D receptors and their interactions with AD-related pathways, we aim to further propel the AD research towards VPS10p-D receptor family, knowledge that may lead to new diagnostic markers and therapeutic strategies for AD patients.
Topics: Humans; Alzheimer Disease; Amyloid beta-Peptides; Depressive Disorder, Major; Protein Transport; Nerve Growth Factors
PubMed: 36397124
DOI: 10.1186/s13024-022-00576-2 -
Frontiers in Nutrition 2023Despite the fact that obesity and overweight are serious major health problems worldwide, fighting against them is also considered a challenging issue. Several...
The effects of NAD+ precursor (nicotinic acid and nicotinamide) supplementation on weight loss and related hormones: a systematic review and meta-regression analysis of randomized controlled trials.
BACKGROUND
Despite the fact that obesity and overweight are serious major health problems worldwide, fighting against them is also considered a challenging issue. Several interventional studies have evaluated the potential weight-reduction effect of nicotinamide adenine dinucleotide (NAD+) precursor. In order to obtain a better viewpoint from them, this study aimed to comprehensively investigate the effects of NAD+ precursor supplementation on weight loss, adiponectin, and leptin.
METHODS
Scopus, PubMed/Medline, Web of Science, Cochrane, and Embase databases were searched using standard keywords to identify all controlled trials investigating the weight loss and related hormones effects of NAD+ precursor. Pooled weighted mean difference and 95% confidence intervals were achieved by random-effects model analysis for the best estimation of outcomes.
RESULTS
Twenty two treatment arms with 5,144 participants' were included in this systematic review and meta-regression analysis. The pooled findings showed that NAD+ precursor supplementation has an effect on lowering BMI (weighted mean difference (WMD): -0.19 kg/m2, 95% confidence interval (CI): -0.29 to -0.09, < 0.001) and increasing adiponectin (WMD: 1.59 μg/mL, 95% CI: 0.49 to 2.68, = 0.004) in humans compared with control groups. However, no significant effect was observed on body weight and leptin. There was a significant relationship between doses of intervention with changes in BMI. In addition, subgroup analysis showed that BMI reduction was greater when receiving nicotinic acid (NA) supplementation than nicotinamide (NE) supplementation.
CONCLUSION
NAD+ precursor had significant effects on weight management with the reduction of BMI and increasing adiponectin.
PubMed: 37854354
DOI: 10.3389/fnut.2023.1208734 -
Frontiers in Immunology 2023Chimeric antigen receptor (CAR) T-cells are an emerging therapy for the treatment of relapsed/refractory B-cell malignancies. While CD19 CAR-T cells have been... (Meta-Analysis)
Meta-Analysis
UNLABELLED
Chimeric antigen receptor (CAR) T-cells are an emerging therapy for the treatment of relapsed/refractory B-cell malignancies. While CD19 CAR-T cells have been FDA-approved, CAR T-cells targeting CD22, as well as dual-targeting CD19/CD22 CAR T-cells, are currently being evaluated in clinical trials. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of CD22-targeting CAR T-cell therapies. We searched MEDLINE, EMBASE, Web of Science, and the Cochrane Central Register of Controlled Trials from inception to March 3rd 2022 for full-length articles and conference abstracts of clinical trials employing CD22-targeting CAR T-cells in acute lymphocytic leukemia (ALL) and non-Hodgkin's lymphoma (NHL). The primary outcome was best complete response (bCR). A DerSimonian and Laird random-effects model with arcsine transformation was used to pool outcome proportions. From 1068 references screened, 100 were included, representing 30 early phase studies with 637 patients, investigating CD22 or CD19/CD22 CAR T-cells. CD22 CAR T-cells had a bCR of 68% [95% CI, 53-81%] in ALL (n= 116), and 64% [95% CI, 46-81%] in NHL (n= 28) with 74% and 96% of patients having received anti-CD19 CAR T-cells previously in ALL and NHL studies respectively. CD19/CD22 CAR T-cells had a bCR rate of 90% [95% CI, 84-95%] in ALL (n= 297) and 47% [95% CI, 34-61%] in NHL (n= 137). The estimated incidence of total and severe (grade ≥3) CRS were 87% [95% CI, 80-92%] and 6% [95% CI, 3-9%] respectively. ICANS and severe ICANS had an estimated incidence of 16% [95% CI, 9-25%] and 3% [95% CI, 1-5%] respectively. Early phase trials of CD22 and CD19/CD22 CAR T-cells show high remission rates in ALL and NHL. Severe CRS or ICANS were (1)rare and dual-targeting did not increase toxicity. Variability in CAR construct, dose, and patient factors amongst studies limits comparisons, with long-term outcomes yet to be reported.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero, identifier CRD42020193027.
Topics: Humans; Immunotherapy, Adoptive; T-Lymphocytes; Lymphoma, Non-Hodgkin; B-Lymphocytes; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Recurrence; Sialic Acid Binding Ig-like Lectin 2
PubMed: 37180149
DOI: 10.3389/fimmu.2023.1178403 -
International Journal of Molecular... Apr 2022Ovarian endometriosis may increase the risk of malignancy. Several studies have suggested atypical endometriosis as the direct precursor of endometriosis-associated... (Review)
Review
Ovarian endometriosis may increase the risk of malignancy. Several studies have suggested atypical endometriosis as the direct precursor of endometriosis-associated ovarian cancer. We performed an advanced, systematic search of the online medical databases PubMed and Medline. The search revealed = 40 studies eligible for inclusion in this systematic review. Of these, = 39 were finally included. The results from included studies are characterized by high heterogeneity, but some consistency has been found for altered expression in phosphoinositide 3-kinase (PI3K)/AKT/mTOR pathway, ARID1a, estrogen and progesterone receptors, transcriptional, nuclear, and growth factors in atypical endometriosis. Although many targets have been proposed as biomarkers for the presence of atypical endometriosis, none of them has such strong evidence to justify their systematic use in clinical practice, and they all need expensive molecular analyses. Further well-designed studies are needed to validate the evidence on available biomarkers and to investigate novel serum markers for atypical endometriosis.
Topics: Biomarkers; Carcinoma, Ovarian Epithelial; Endometriosis; Female; Humans; Ovarian Neoplasms; Phosphatidylinositol 3-Kinases; Precancerous Conditions
PubMed: 35457244
DOI: 10.3390/ijms23084425