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Cancer Gene Therapy Jun 2023Chimeric Antigen Receptor (CAR) T cell therapy is an effective treatment approach for patients with relapsed or refractory acute lymphoblastic leukemia (R/R B-ALL).... (Meta-Analysis)
Meta-Analysis
Long-term response to autologous anti-CD19 chimeric antigen receptor T cells in relapsed or refractory B cell acute lymphoblastic leukemia: a systematic review and meta-analysis.
Chimeric Antigen Receptor (CAR) T cell therapy is an effective treatment approach for patients with relapsed or refractory acute lymphoblastic leukemia (R/R B-ALL). However, identifying the factors that influence long-term response to this therapy is necessary to optimize patient selection and treatment allocation. We conducted a literature review and meta-analysis to investigate the use of autologous anti-CD19 CAR T cell therapy in both pediatric and adult patients with R/R B-ALL, using several databases including MEDLINE, Cochrane Central, ScienceDirect, Web of Science, Journals@Ovid, Embase, and clinicaltrial.gov. A total of 38 reports were analyzed, which enrolled 2134 patients. Time-to-event endpoints were estimated using reconstructed patient survival data. The study explored key modulators of response, including costimulatory domains, disease status, age, and lymphodepletion. The median overall survival and event-free survival were 36.2 months [95% CI 28.9, NR] and 13.3 months [95% CI 12.2, 17], respectively. The overall response rate was 76% [95% CI 71, 81]. The use of 4-1BB costimulatory domain in the CAR construct, administration of low-dose cyclophosphamide lymphodepletion, and pretreatment morphologic remission were associated with better overall survival, with hazard ratios of 0.72, 0.56, and 0.66, respectively. Morphologic remission and 4-1BB domain were associated with better event-free survival, with hazard ratios of 0.66 and 0.72, respectively. These findings suggest that CAR T cell therapy may offer long-term benefits to patients with R/R B-ALL. However, further research is needed to optimize patient selection and better understand the impact of various factors on the outcome of CAR T cell therapy.
Topics: Adult; Humans; Child; Receptors, Chimeric Antigen; Receptors, Antigen, T-Cell; Immunotherapy, Adoptive; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Antigens, CD19; T-Lymphocytes
PubMed: 36750666
DOI: 10.1038/s41417-023-00593-3 -
Cancers Mar 2021Highly proliferative (G3) neuroendocrine neoplasms are divided into well differentiated tumors (NETs) and poorly differentiated carcinomas (NECs), based on the... (Review)
Review
BACKGROUND
Highly proliferative (G3) neuroendocrine neoplasms are divided into well differentiated tumors (NETs) and poorly differentiated carcinomas (NECs), based on the morphological appearance. This systematic review aims to evaluate the clinicopathological features and the treatment response of the NEC subgroup with a Ki67 labeling index (LI) < 55%.
METHODS
A literature search was performed using MEDLINE, Cochrane Library, and Scopus between December 2019 and April 2020, last update in October 2020. We included studies reporting data on the clinicopathological characteristics, survival, and/or therapy efficacy of patients with NECs, in which the Ki67 LI was specified.
RESULTS
8 papers were included, on a total of 268 NEC affected patients. NECs with a Ki67 LI < 55% have been reported in patients of both sexes, mainly of sixth decade, pancreatic origin, and large-cell morphology. The prevalent treatment choice was chemotherapy, followed by surgery and, in only one study, peptide receptor radionuclide therapy. The subgroup of patients with NEC with a Ki67 LI < 55% showed longer overall survival and progression free survival and higher response rates than the subgroup of patients with a tumor with higher Ki67 LI (≥55%).
CONCLUSIONS
NECs are heterogeneous tumors. The subgroup with a Ki67 LI < 55% has a better prognosis and should be treated and monitored differently from NECs with a Ki67 LI ≥ 55%.
PubMed: 33809007
DOI: 10.3390/cancers13061247 -
The Lancet. Haematology May 2023Given the paucity of high-certainty evidence, and differences in opinion on the use of nuclear medicine for hematological malignancies, we embarked on a consensus... (Review)
Review
Given the paucity of high-certainty evidence, and differences in opinion on the use of nuclear medicine for hematological malignancies, we embarked on a consensus process involving key experts in this area. We aimed to assess consensus within a panel of experts on issues related to patient eligibility, imaging techniques, staging and response assessment, follow-up, and treatment decision-making, and to provide interim guidance by our expert consensus. We used a three-stage consensus process. First, we systematically reviewed and appraised the quality of existing evidence. Second, we generated a list of 153 statements based on the literature review to be agreed or disagreed with, with an additional statement added after the first round. Third, the 154 statements were scored by a panel of 26 experts purposively sampled from authors of published research on haematological tumours on a 1 (strongly disagree) to 9 (strongly agree) Likert scale in a two-round electronic Delphi review. The RAND and University of California Los Angeles appropriateness method was used for analysis. Between one and 14 systematic reviews were identified on each topic. All were rated as low to moderate quality. After two rounds of voting, there was consensus on 139 (90%) of 154 of the statements. There was consensus on most statements concerning the use of PET in non-Hodgkin and Hodgkin lymphoma. In multiple myeloma, more studies are required to define the optimal sequence for treatment assessment. Furthermore, nuclear medicine physicians and haematologists are awaiting consistent literature to introduce volumetric parameters, artificial intelligence, machine learning, and radiomics into routine practice.
Topics: Humans; Consensus; Nuclear Medicine; Artificial Intelligence; Hematologic Neoplasms; Molecular Imaging
PubMed: 37142345
DOI: 10.1016/S2352-3026(23)00030-3 -
Frontiers in Plant Science 2023The C4 grass pearl millet is one of the most drought tolerant cereals and is primarily grown in marginal areas where annual rainfall is low and intermittent. It was...
The C4 grass pearl millet is one of the most drought tolerant cereals and is primarily grown in marginal areas where annual rainfall is low and intermittent. It was domesticated in sub-Saharan Africa, and several studies have found that it uses a combination of morphological and physiological traits to successfully resist drought. This review explores the short term and long-term responses of pearl millet that enables it to either tolerate, avoid, escape, or recover from drought stress. The response to short term drought reveals fine tuning of osmotic adjustment, stomatal conductance, and ROS scavenging ability, along with ABA and ethylene transduction. Equally important are longer term developmental plasticity in tillering, root development, leaf adaptations and flowering time that can both help avoid the worst water stress and recover some of the yield losses asynchronous tiller production. We examine genes related to drought resistance that were identified through individual transcriptomic studies and through our combined analysis of previous studies. From the combined analysis, we found 94 genes that were differentially expressed in both vegetative and reproductive stages under drought stress. Among them is a tight cluster of genes that are directly related to biotic and abiotic stress, as well as carbon metabolism, and hormonal pathways. We suggest that knowledge of gene expression patterns in tiller buds, inflorescences and rooting tips will be important for understanding the growth responses of pearl millet and the trade-offs at play in the response of this crop to drought. Much remains to be learnt about how pearl millet's unique combination of genetic and physiological mechanisms allow it to achieve such high drought tolerance, and the answers to be found may well be useful for crops other than just pearl millet.
PubMed: 36844091
DOI: 10.3389/fpls.2023.1059574 -
CNS Spectrums Apr 2022Blood platelets, due to shared biochemical and functional properties with presynaptic serotonergic neurons, constituted, over the years, an attractive peripheral... (Review)
Review
BACKGROUND
Blood platelets, due to shared biochemical and functional properties with presynaptic serotonergic neurons, constituted, over the years, an attractive peripheral biomarker of neuronal activity. Therefore, the literature strongly focused on the investigation of eventual structural and functional platelet abnormalities in neuropsychiatric disorders, particularly in depressive disorder. Given their impact in biological psychiatry, the goal of the present paper was to review and critically analyze studies exploring platelet activity, functionality, and morpho-structure in subjects with depressive disorder.
METHODS
According to the PRISMA guidelines, we performed a systematic review through the PubMed database up to March 2020 with the search terms: (1) platelets in depression [Title/Abstract]"; (2) "(platelets[Title]) AND depressive disorder[Title/Abstract]"; (3) "(Platelet[Title]) AND major depressive disorder[Title]"; (4) (platelets[Title]) AND depressed[Title]"; (5) (platelets[Title]) AND depressive episode[Title]"; (6) (platelets[Title]) AND major depression[Title]"; (7) platelet activation in depression[All fields]"; and (8) platelet reactivity in depression[All fields]."
RESULTS
After a detailed screening analysis and the application of specific selection criteria, we included in our review a total of 106 for qualitative synthesis. The studies were classified into various subparagraphs according to platelet characteristics analyzed: serotonergic system (5-HT2A receptors, SERT activity, and 5-HT content), adrenergic system, MAO activity, biomarkers of activation, responsivity, morphological changes, and other molecular pathways.
CONCLUSIONS
Despite the large amount of the literature examined, nonunivocal and, occasionally, conflicting results emerged. However, the findings on structural and metabolic alterations, modifications in the expression of specific proteins, changes in the aggregability, or in the responsivity to different pro-activating stimuli, may be suggestive of potential platelet dysfunctions in depressed subjects, which would result in a kind of hyperreactive state. This condition could potentially lead to an increased cardiovascular risk. In line with this hypothesis, we speculated that antidepressant treatments would seem to reduce this hyperreactivity while representing a potential tool for reducing cardiovascular risk in depressed patients and, maybe, in other neuropsychiatric conditions. However, the problem of the specificity of platelet biomarkers is still at issue and would deserve to be deepened in future studies.
Topics: Antidepressive Agents; Biomarkers; Blood Platelets; Depressive Disorder, Major; Humans; Serotonin
PubMed: 33092669
DOI: 10.1017/S1092852920001959 -
Immunoglobulin G4-related coronary periarteritis: a systematic literature review with a case series.Clinical Rheumatology Aug 2022We aimed to assess the clinical and radiological characteristics of immunoglobulin G4-related coronary periarteritis through a systematic literature review and from our... (Review)
Review
We aimed to assess the clinical and radiological characteristics of immunoglobulin G4-related coronary periarteritis through a systematic literature review and from our case series. In the systematic literature review, we assessed English language manuscripts on immunoglobulin G4-related coronary periarteritis cases. Additionally, we identified patients with immunoglobulin G4-related coronary periarteritis at St. Luke's International Hospital in Tokyo, Japan, from 2014 to 2020. We summarized patients' demographics, immunoglobulin-G and -G4 titers, site and morphological features of the coronary lesion, and other organ involvements. We identified 38 cases from the literature and four patients from our institute. Coronary lesions were detected using coronary computed tomography in 40 (95.2%) patients. Mass-like or diffuse wall-thickening lesion was the most frequently observed type in 33 (78.6%) patients. No trends at the site of the coronary arteries were identified. Overall, 32 (76.1%) patients had multiple-organ involvement, of which the most common lesion was peri-aortitis in 21 (50.0%) patients. Ten (23.8%) patients with an isolated coronary lesion had significantly lower immunoglobulin-G4 titers than those with other organ involvements (immunoglobulin-G4: 261 [161.0, 564.0] vs. 1355.0 [320.8, 2480.0] mg/dL, p = 0.033). The wall-thickening lesions responded well to immunosuppressive treatments. Mass-like or diffuse wall-thickening on coronary computed tomography is a characteristic radiographic finding of immunoglobulin G4-related coronary periarteritis, which can occur in any branch. Immunoglobulin G4-related coronary periarteritis showed similar characteristics to other organ lesions, including its relatively low serum immunoglobulin-G4 level in patients with a single-organ disease and its high responsiveness to glucocorticoids.
Topics: Aortitis; Arteritis; Coronary Vessels; Heart; Humans; Immunoglobulin G
PubMed: 35445950
DOI: 10.1007/s10067-022-06179-y -
International Journal of Environmental... Aug 2022Identifying potential gait deviations in patellofemoral instability (PI) can help with the development of effective rehabilitation strategies. The purpose of this... (Review)
Review
Identifying potential gait deviations in patellofemoral instability (PI) can help with the development of effective rehabilitation strategies. The purpose of this systematic review was to examine whether there are specific gait alterations in subjects with PI. The present review followed the PRISMA guidelines and was initially registered at PROSPERO (CRD42021236765). The literature search was carried out in the databases of PubMed, the Cochrane library, Web of Science, ClinicalTrials.gov, and Medline. The search strategy resulted in the identification of seven relevant publications. Subjects with PI show decreased walking speed, stride length, and cadence. Some studies reported changes not only in knee kinematics and kinetics but also in hip and ankle kinematics and kinetics. There is evidence that most subjects with PI walk with a quadriceps avoidance gait and show increased genu valgum posture, but there is still great variability in the coping responses within individuals with PI. The discrepancy among the study results might underpin the fact that PI is a multifactorial problem, and subjects cope with the different underlying morphological as well as functional deficits using a variety of gait strategies, which makes the interpretation and understanding of the gait of subjects with PI a clinically challenging task.
Topics: Ankle Joint; Biomechanical Phenomena; Gait; Humans; Knee Joint; Walking; Walking Speed
PubMed: 36078206
DOI: 10.3390/ijerph191710491 -
Scientific Reports Nov 2022Although learning disorders (LD) and developmental language disorder (DLD) can be linked to overlapping psychological and behavioral deficits, such as phonological,... (Meta-Analysis)
Meta-Analysis
Although learning disorders (LD) and developmental language disorder (DLD) can be linked to overlapping psychological and behavioral deficits, such as phonological, morphological, orthographic, semantic, and syntactic deficits, as well as academic (e.g., reading) difficulties, they are currently separate diagnoses in the DSM-5 with explicit phenotypic differences. At a neural level, it is yet to be determined to what extent they have overlapping or distinct signatures. The identification of such neural markers/endophenotypes could be important for the development of physiological diagnostic tools, as well as an understanding of disorders across different dimensions, as recommended by the Research Domain Criteria Initiative (RDoC). The current systematic review and meta-analysis examined whether the two disorders can be differentiated based on the auditory brainstem response (ABR). Even though both diagnoses require hearing problems to be ruled out, a number of articles have demonstrated associations of these disorders with the auditory brainstem response. We demonstrated that both LD and DLD are associated with longer latencies in ABR Waves III, V, and A, as well as reduced amplitude in Waves V and A. However, multilevel subgroup analyses revealed that LD and DLD do not significantly differ for any of these ABR waves. Results suggest that less efficient early auditory processing is a shared mechanism underlying both LD and DLD.
Topics: Humans; Evoked Potentials, Auditory, Brain Stem; Learning Disabilities; Auditory Perception; Deafness; Language Development Disorders
PubMed: 36418364
DOI: 10.1038/s41598-022-20438-7 -
The International Journal of Social... Aug 2021Grief is a common reaction to the feeling of loss and it is considered a physiological and instinctive response. The 'normal' grief evolves into an 'integrated' phase...
BACKGROUND
Grief is a common reaction to the feeling of loss and it is considered a physiological and instinctive response. The 'normal' grief evolves into an 'integrated' phase within 1 year from death, and it is a non-pathological condition, that do not require specific therapeutic interventions. When this 'integrated phase' does not occur, the subject could reach pathological manifestations related to the grief. The Persistent Complex Bereavement Disorder (PCBD) is a new DSM5 clinical category characterized by symptoms related to the detachment and to the post-traumatic distress and it differs from normal and uncomplicated grief, for the disability caused by these reactions and their persistence and pervasiveness.
AIM
The purpose of this work is the analysis of the pathways that led to this new definition, through a review of the main studies published in the last 20 years, with the aim to clarify the clinical utility of this new diagnostic category.
METHOD
Relevant publications done in the last 20 years were identified via electronic searches of Pubmed, Embase, and Elsevier databases using the terms 'complicated grief' AND 'persistent', according to PRISMA guideline and PICO study design.
RESULTS
PCBD results a new important clinical category showing specific symptoms, diagnostic criteria, and treatment. It presents many differences with other pathologies, that goes into differential diagnosis with PCBD, and it and can be treated with targeted therapeutic approaches. Diagnostic criteria for PCBD could allow an early diagnosis and a correct treatment avoiding underdiagnosis and misdiagnosis.
CONCLUSION
Further researches could focus on the evaluation of more neurobiological aspects, new psychometric tools, for assessing susceptibility to this pathology, and on the cultural aspects that may influence mourning reactions, in an ethno-psychiatric perspective.
Topics: Bereavement; Grief; Humans; International Classification of Diseases; Psychometrics
PubMed: 32972293
DOI: 10.1177/0020764020960202 -
Leukemia Dec 2022Measurable residual disease (MRD) is associated with relapse and survival in acute myeloid leukemia (AML). We aimed to quantify the impact of MRD on outcomes across... (Meta-Analysis)
Meta-Analysis
Association of hematologic response and assay sensitivity on the prognostic impact of measurable residual disease in acute myeloid leukemia: a systematic review and meta-analysis.
Measurable residual disease (MRD) is associated with relapse and survival in acute myeloid leukemia (AML). We aimed to quantify the impact of MRD on outcomes across clinical contexts, including its association with hematologic response and MRD assay sensitivity. We performed systematic literature review and meta-analysis of 48 studies that reported the association between MRD and overall survival (OS) or disease-free survival (DFS) in AML and provided information on the MRD threshold used and the hematologic response of the study population. Among studies limited to patients in complete remission (CR), the estimated 5-year OS for the MRD-negative and MRD-positive groups was 67% (95% Bayesian credible interval [CrI], 53-77%) and 31% (95% CrI, 18-44%), respectively. Achievement of an MRD-negative response was associated with superior DFS and OS, regardless of MRD threshold or analytic sensitivity. Among patients in CR, the benefit of MRD negativity was highest in studies using an MRD cutoff less than 0.1%. The beneficial impact of MRD negativity was observed across MRD assays and timing of MRD assessment. In patients with AML in morphological remission, achievement of MRD negativity is associated with superior DFS and OS, irrespective of hematologic response or the MRD threshold used.
Topics: Humans; Prognosis; Bayes Theorem; Neoplasm, Residual; Leukemia, Myeloid, Acute; Remission Induction; Hematopoietic Stem Cell Transplantation
PubMed: 36261575
DOI: 10.1038/s41375-022-01692-0