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Biology of Blood and Marrow... Mar 2020Relapse after stem cell transplantation for Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) remains a significant challenge. In this systematic... (Review)
Review
Relapse after stem cell transplantation for Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) remains a significant challenge. In this systematic review, we compare survival outcomes of second-generation tyrosine kinase inhibitors (TKIs) nilotinib and dasatinib with first-generation TKI imatinib when these agents are used after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in Ph+ ALL. In addition, we review the literature on TKI use to prevent relapse in patients who proceed to allo-HSCT beyond first complete response (>CR1). We performed database searches (inception to January 2018) using PubMed, Cochrane Library, and Embase. After exclusions, 17 articles were included in this analysis. Imatinib was used post-transplant either prophylactically or preemptively in 12 studies, 7 prospective studies and 5 retrospective studies. Overall survival (OS) for most prospective studies at 1.5 to 3 and 5 years ranged between 62% to 92% and 74.5% to 86.7%. Disease-free survival at 1.5 to 5 years was 60.4% to 92%. Additionally, imatinib failed to show survival benefit in patients who were >CR1 at the time of allo-HSCT. The cumulative OS for most retrospective studies using imatinib at 1 to 2 and 3 to 5 years was 42% to 100% and 33% to 40% respectively. Event-free survival at 1 to 2 and 3 to 5 years was 33.3% to 67% and 20% to 31% respectively. Dasatinib was used as maintenance treatment in 3 retrospective studies (n = 34). The OS for patients with Ph+ ALL using dasatinib as maintenance regimen after allo-HSCT at 1.4 to 3 years was 87% to 100% and disease-free survival at 1.4 to 3 years was 89% to 100%. Ninety-three percent of patients with minimal residual disease (MRD) positive status after allo-HSCT became MRD negative. Three prospective studies used nilotinib. In 2 studies where investigators studied patients with advanced chronic myeloid leukemia and Ph+ ALL, the cumulative OS and event-free survival at 7.5 months to 2 years were 69% to 84% and 56% to 84%, respectively. In the third study (n = 5) in patients with Ph+ ALL, nilotinib use resulted in OS at 5 years of 60%. Our review showed that use of TKIs (all generations) after allo-HSCT for patients in CR1 improved OS when given as a prophylactic or preemptive regimen. Limited data suggest that second-generation TKIs (ie, dasatinib) have a better OS, especially in patients with MRD-positive status. Imatinib did not improve OS in patients who were >CR1 at the time of allo-HSCT; for this population, no data were available with newer generation TKIs. The evaluation of survival benefit with newer generation TKIs and their efficacy in patients in >CR1 needs further study in large randomized clinical trials.
Topics: Hematopoietic Stem Cell Transplantation; Humans; Philadelphia Chromosome; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prospective Studies; Protein Kinase Inhibitors; Retrospective Studies; Secondary Prevention; Transplantation, Homologous
PubMed: 31557532
DOI: 10.1016/j.bbmt.2019.09.022 -
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 -
Seminars in Vascular Surgery Dec 2022In this article, we compare and contrast methods of reviewing, summarizing, and synthesizing the literature, including systematic reviews, scoping reviews, and narrative... (Review)
Review
In this article, we compare and contrast methods of reviewing, summarizing, and synthesizing the literature, including systematic reviews, scoping reviews, and narrative reviews. Review articles are essential to help investigators wade through the plethora of exponentially growing medical literature. In the era of evidence-based medicine, a systematic approach is required. A systematic review is a formalized method to address a specific clinical question by analyzing the breadth of published literature while minimizing bias. Systematic reviews are designed to answer narrow clinical questions in the PICO (population, intervention, comparison, and outcome) format. Alternatively, scoping reviews use a similar systematic approach to a literature search in order to determine the breadth and depth of knowledge on a topic; to clarify definitions, concepts, and themes; or sometimes as a precursor to a systematic review or hypothesis generator to guide future research. However, scoping reviews are less constrained by a priori decisions about which interventions, controls, and outcomes may be of interest. Traditional narrative reviews still have a role in informing practice and guiding research, particularly when there is a paucity of high-quality evidence on a topic.
Topics: Humans; Evidence-Based Medicine; Research Design
PubMed: 36414363
DOI: 10.1053/j.semvascsurg.2022.09.001 -
Cephalalgia : An International Journal... Feb 2015Migraine has been associated with stroke as well as with several non-atherosclerotic vascular conditions leading to discussions about the potential role of endothelium... (Review)
Review
AIM
Migraine has been associated with stroke as well as with several non-atherosclerotic vascular conditions leading to discussions about the potential role of endothelium in the etiopathogenesis of migraine and migraine-associated stroke. We present a systematic review of the literature on vascular biomarkers in migraine, including those suggesting endothelial activation and damage.
METHODS
We conducted a systematic literature search from 1990 to 2013 using multiple research databases with the keywords "migraine," "headache," "vascular," and "biomarkers." We used selected inclusion and exclusion criteria to create a final pool of studies for this review.
RESULTS
The literature search identified a total of 639 citations of which 129 were included in our review. The final pool of clinical- and population-based studies assessed the level of various biomarkers (e.g. inflammatory, prothrombotic, endothelial activation, endothelial repair) in migraineurs of varying ages, gender, and demographic characteristics. Although for each biomarker there is at least one study suggesting an association with migraine, in many cases the quality of evidence is poor and there are conflicting studies showing no relationship. The results were, therefore, in each case inconclusive.
CONCLUSION
This systematic review indicated that in migraine populations there are a number of positive vascular biomarker studies, including some involving novel biomarkers such as endothelial microparticles and endothelial precursor cells. These lend insight into possible pathophysiological mechanisms by which migraine may be associated with stroke. More high-quality studies are needed to establish whether a true association between promising vascular biomarkers and migraine exists.
Topics: Biomarkers; Humans; Migraine Disorders
PubMed: 25281220
DOI: 10.1177/0333102414544976 -
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 -
Sleep Medicine Reviews Oct 2018Insomnia is a prevalent sleep disorder that is associated with a multitude of health consequences. Particularly, insomnia has been associated with cardiovascular disease... (Review)
Review
Insomnia is a prevalent sleep disorder that is associated with a multitude of health consequences. Particularly, insomnia has been associated with cardiovascular disease and its precursors, such as hypertension and blood pressure (BP) non-dipping. The present systematic review aimed to summarize the evidence on the concurrent and prospective associations between insomnia and hypertension and/or BP. Using electronic search engines (PubMed, SCOPUS, PsycINFO), 5,618 articles published from January 1970 to December 2017 were identified, and 64 met the inclusion criteria (26 to 162,121 participants; age range: 18-100; 46.4% male). Insomnia was based on diagnostic or non-diagnostic criteria. Hypertension was based on self-or physician-reports, antihypertensive medication use, and/or measured BP. Findings indicate that when insomnia is frequent, chronic, and/or accompanied with short sleep duration or objective markers of arousal, there is a strong association with hypertension/BP. Based on limited studies, hypertension did not significantly predict future insomnia in middle-aged adults, but did in older adults. Based on a majority of case-control studies, no differences in BP were found between participants with and without insomnia. Further research is needed to identify putative pathophysiological mechanisms underlying the link between insomnia and hypertension. The impact of insomnia therapy on BP should also be further examined in the future.
Topics: Antihypertensive Agents; Blood Pressure; Humans; Hypertension; Risk Factors; Sleep Initiation and Maintenance Disorders; Time Factors
PubMed: 29576408
DOI: 10.1016/j.smrv.2018.02.003 -
Journal of the American Academy of... Feb 2022To evaluate which early neurocognitive and behavioral precursors are associated with the development of attention-deficit/hyperactivity disorder (ADHD) and whether these... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To evaluate which early neurocognitive and behavioral precursors are associated with the development of attention-deficit/hyperactivity disorder (ADHD) and whether these are currently targeted in early interventions.
METHOD
We conducted 2 systematic reviews and meta-analyses of empirical studies to examine the following: (1) early-life (0-5 years) neurocognitive and behavioral precursors associated with familial likelihood for ADHD, an early ADHD diagnosis/elevated ADHD symptoms, and/or the presence of later-childhood ADHD; and (2) interventions delivered to children aged 0 to 5 years targeting the identified precursors or measuring these as outcomes. Standardized mean differences (Hedges' g) and pre-post-treatment change scores (SMD) were computed.
RESULTS
A total of 149 studies (165,095 participants) investigating 8 neurocognitive and behavioral domains met inclusion criteria for part 1. Multi-level random-effects meta-analyses on 136 studies revealed significant associations between ADHD and poorer cognitive (g = -0.46 [95% CIs: -0.59, -0.33]), motor (g = -0.35 [CIs: -0.48, -0.21]) and language (g = -0.43 [CIs: -0.66, -0.19]) development, social (g = 0.23 [CIs: 0.03, 0.43]) and emotional (g = 0.46 [CIs: 0.33, 0.58]) difficulties, early regulatory (g = 0.30 [CIs: 0.18, 0.43]) and sleep (g = 0.29 [CIs: 0.14, 0.44]) problems, sensory atypicalities (g = 0.52 [CIs: 0.16, 0.88]), elevated activity levels (g = 0.54 [CIs: 0.37, 0.72]), and executive function difficulties (g = 0.34 [CIs: 0.05, 0.64] to -0.87 [CIs: -1.35, -0.40]). A total of 32 trials (28 randomized, 4 nonrandomized, 3,848 participants) testing early interventions that targeted the identified precursors met inclusion criteria for part 2. Multi-level random-effects meta-analyses on 22 studies revealed significant intervention-related improvements in ADHD symptoms (SMD = 0.43 [CIs: 0.22, 0.64]) and working memory (SMD = 0.37 [CIs: 0.06, 0.69]).
CONCLUSION
Children aged 0 to 5 years with current or later-emerging ADHD are likely to experience difficulties in multiple neurocognitive/behavioral functions. Early interventions show some effectiveness in reducing ADHD symptoms, but their effects on neurocognitive/behavioral difficulties require further study.
Topics: Attention Deficit Disorder with Hyperactivity; Child; Child, Preschool; Executive Function; Humans; Infant; Infant, Newborn; Memory, Short-Term
PubMed: 33864938
DOI: 10.1016/j.jaac.2021.03.016 -
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 -
The Primary Care Companion For CNS... Sep 2019The primary objective of this narrative review is to provide clinicians an in-depth analysis of the mechanism of action, pharmacokinetics, toxicology, and efficacy of...
OBJECTIVE
The primary objective of this narrative review is to provide clinicians an in-depth analysis of the mechanism of action, pharmacokinetics, toxicology, and efficacy of levomilnacipran. We propose that unlike selective serotonin reuptake inhibitors (SSRIs), or even their precursor serotonin-norepinephrine reuptake inhibitors (SNRIs), levomilnacipran demonstrates a potentially unique ability to alleviate the fatigue symptom cluster of major depressive disorder (MDD).
DATA SOURCES
A literature review was completed in PubMed using the MeSH term levomilnacipran.
STUDY SELECTION
Inclusion criteria were English-language only, randomized controlled trials and systematic reviews published through March 2019. Analyses using product labels and anecdotal or uncontrolled reports of clinical applications were excluded. Only published data from short-term and long-term trials were analyzed. The search resulted in 73 articles. The evidence-based review comprises a total of 31 articles.
DATA SYNTHESIS
The data analyzed suggest that levomilnacipran has evidence in the treatment of MDD. More specifically, data suggest that levomilnacipran may be unique among SSRI and SNRI antidepressants in its ability to improve the fatigue symptom cluster in MDD.
CONCLUSIONS
Further investigations are warranted into levomilnacipran's potentially unique ability to alleviate the fatigue symptom cluster of MDD. Future head-to-head studies and studies that assess for clinically relevant improvements in fatigue are needed.
Topics: Depressive Disorder, Major; Humans; Levomilnacipran; Serotonin and Noradrenaline Reuptake Inhibitors
PubMed: 31509357
DOI: 10.4088/PCC.19nr02475 -
Neuropsychiatric Disease and Treatment 2023Subthreshold depression (StD) is considered to be the "precursor" stage of major depressive disorder (MDD), which could cause higher risk of suicide, disease burden and... (Review)
Review
BACKGROUND
Subthreshold depression (StD) is considered to be the "precursor" stage of major depressive disorder (MDD), which could cause higher risk of suicide, disease burden and functional impairment. There have been various non-pharmacological interventions for StD. However, the comparison of their effectiveness still lacks sufficient evidence. We performed a systematic review and network meta-analysis to evaluate and rank the efficacy of multiple non-pharmacological interventions targeting StD.
METHODS
We conducted a thorough search across various databases including PubMed, Medline, Embase, Web of Science and PsycINFO from inception to December 2022. All included studies were randomized controlled trials (RCTs) of non-pharmacological interventions for patients with StD compared with control group (CG). Several universal scales for measuring depression severity were used as efficacy outcomes. The surface under the cumulative ranking curve (SUCRA) was used to separately rank each intervention using the "Stata 17.0" software.
RESULTS
A total of thirty-six trials were included, involving twenty-eight interventions and 7417 participants. The research found that most non-pharmacological interventions were superior to controls for StD. In each outcome evaluation by different scales for measuring depression, psychotherapy always ranked first in terms of treatment effectiveness, especially Problem-solving Therapy (PST), Behavioral Activation Therapy (BAT), Cognitive Behavioral Therapy (CBT)/Internet-based CBT (I-CBT)/Telephone-based CBT (T-CBT). Since different groups could not be directly compared, the total optimal intervention could not be determined.
CONCLUSION
Here, we show that psychotherapy may be the better choice for the treatment of StD. This study provides some evidence on StD management selection for clinical workers. However, to establish its intervention effect more conclusively, the content, format and operators of psychotherapy still require extensive exploration to conduct more effective, convenient and cost-effective implementation in primary healthcare. Notably, further research is also urgently needed to find the biological and neural mechanisms of StD by examining whether psychotherapy alters neuroplasticity in patients with StD.
PubMed: 37867932
DOI: 10.2147/NDT.S425509