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Haematologica Mar 2024CNS relapse in patients with diffuse large B-cell lymphoma (DLBCL) carries a dismal prognosis with most clinical guidelines recommending CNS prophylaxis to patients...
Efficacy of intravenous high-dose methotrexate in preventing relapse to the central nervous system in R-CHOP(-like)-treated, high-risk, diffuse large B-cell lymphoma patients and its effect on mortality: a systematic review and meta-analysis.
UNLABELLED
CNS relapse in patients with diffuse large B-cell lymphoma (DLBCL) carries a dismal prognosis with most clinical guidelines recommending CNS prophylaxis to patients deemed at high risk for CNS relapse. However, results from observational studies investigating the effect of CNS prophylaxis have yielded conflicting results.
OBJECTIVES
To evaluate: 1) whether addition of prophylactic intravenous HD-MTX reduces the risk of CNS relapse in high-risk DLBCL patients treated with R-CHOP or similar and 2) whether HD-MTX prophylaxis confers an overall survival benefit, irrespective of CNS relapse.
METHODS
A systematic search of MEDLINE/PubMed and EMBASE on DLBCL patients at high risk of CNS relapse treated with R-CHOP or similar receiving HD-MTX as intervention and a comparator arm receiving no prophylaxis and/or IT prophylaxis. Risk of Bias was estimated using the ROBINS-I tool and the quality of the evidence by the GRADE approach. Finally, a meta-analysis based on the systematic review was conducted.
RESULTS
A total of 1812 studies were screened. No RCT's were identified. Seven observational studies comprising 1661 patients met inclusion criteria. We found a statistically non-significant relative risk of 0.54 [0.27-1.07, 95% CI] of CNS relapse for patients receiving HD-MTX vs. controls. The meta-analysis investigating mortality demonstrated a relative risk of death of 0.70 [0.44-1.11, 95% CI] for HD-MTX treated vs. controls. The overall risk of bias was adjudged as "serious" and the quality of the evidence was rated as low.
CONCLUSION
Our data indicate that HD-MTX does not prevent, or at best, only slightly reduces the risk of CNS relapse and confers no survival benefit.
PubMed: 38497149
DOI: 10.3324/haematol.2023.284281 -
Journal of Cancer Research and Clinical... Mar 2024The clinical significance of tertiary lymphoid structure (TLS) in gastric cancer (GC) was uncertain. (Meta-Analysis)
Meta-Analysis
Analyzing the associations between tertiary lymphoid structures and postoperative prognosis, along with immunotherapy response in gastric cancer: findings from pooled cohort studies.
BACKGROUND
The clinical significance of tertiary lymphoid structure (TLS) in gastric cancer (GC) was uncertain.
METHODS
A systematic search was performed in public databases for eligible studies as of April 2, 2023. Meta-analyses were performed to interrogate the associations between TLS levels and prognosis and immunotherapy response of GC. Bioinformatic analyses based on the nine-gene signature of TLS were further conducted to capture the biological underpinnings.
RESULTS
Eleven studies containing 4224 GC cases were enrolled in the meta-analysis. TLS levels positively correlated with smaller tumor size, earlier T stage and N stage. Moreover, higher TLS levels were detected in diffuse and mix subtypes of GC (P < 0.001). Higher TLS levels strongly predicted favorable postoperative overall survival of GC, with HR of 0.36 (95%CI 0.26-0.50, P < 0.001) and 0.55 (95%CI 0.45-0.68, P < 0.001) of univariate and multivariate Cox analysis, respectively. Higher TLS levels were also in favor of the treatment response of anti-PD-1 inhibitors as later-line therapy of GC. TLS levels positively correlated with immune effector cells infiltration, diversity and richness of T cell receptor and B cell receptor repertoire, immune checkpoint genes expression, and immune-related genes mutation of GC in the TCGA-STAD cohort, representing higher immunogenicity and immunoactivity. Moreover, moderate accuracy of TLS levels in predicting benefit from anti-PD-1 inhibitors in the PRJEB25780 cohort was also validated (AUC 0.758, 95%CI 0.583-0.933), higher than the microsatellite instability-score and Epstein-Barr virus status.
CONCLUSIONS
TLS levels demonstrated potential in predicting the postoperative prognosis and immunotherapy response of GC.
Topics: Humans; Cohort Studies; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Immune Checkpoint Inhibitors; Immunotherapy; Prognosis; Stomach Neoplasms; Tertiary Lymphoid Structures; Tumor Microenvironment
PubMed: 38519621
DOI: 10.1007/s00432-024-05672-y -
Clinical and Experimental Medicine Mar 2024Investigating the role of circulating tumor cells (CTCs) and their characteristics is still controversial in patients with gastric cancer (GC). Therefore, in this study,... (Meta-Analysis)
Meta-Analysis Review
Investigating the role of circulating tumor cells (CTCs) and their characteristics is still controversial in patients with gastric cancer (GC). Therefore, in this study, to provide a comprehensive review and meta-analyses of the literature on association of CTCs with gastric cancer, Scopus, Web of Science, Embase, and Medline were searched for systematic reviews and meta-analyses conducted during February 2022 using the keywords. Risk of bias, hazard ratios (HRs), and risk differences (RD) were assessed. Forty-five studies containing 3,342 GC patients from nine countries were assessed. The overall prevalence of CTC in GC was 69.37% (60.27, 77.78). The pooled result showed that increased mortality in GC patients was significantly associated with positive CTCs, poor overall survival (HR = 2.73, 95%CI 2.34-3.24, p < 0.001), and progression-free survival rate (HR = 2.78, 95%CI 2.01-3.85, p < 0.001). Subgroup analyses regarding markers, detection methods, treatment type, presence of distance metastasis, presence of lymph node metastasis, and overall risk of bias showed significant associations between the groups in terms of the incidence rates of CTCs, OS, and PFS. In addition, the results of risk differences based on sampling time showed that the use of the cell search method (RD: - 0.19, 95%CI (- 0.28, - 0.10), p < 0.001), epithelial marker (RD: - 0.12, 95%CI (- 0.25, 0.00), p 0.05) and mesenchymal markers (RD: - 0.35, 95%CI (- 0.57, - 0.13), p 0.002) before the treatment might have a higher diagnostic power to identify CTCs and also chemotherapy treatment (RD: - 0.17, 95%CI (- 0.31, - 0.03), p 0.016) could significantly reduce the number of CTCs after the treatment. We also found that the risk differences between the clinical early and advanced stages were not statistically significant (RD: - 0.10, 95%CI (- 0.23, 0.02), P 0.105). Also, in the Lauren classification, the incidence of CTC in the diffuse type (RD: - 0.19, 95%CI (- 0.37, - 0.01), P0.045) was higher than that in the intestinal type. Meta-regression analysis showed that baseline characteristics were not associated with the detection of CTCs in GC patients. According to our systematic review and meta-analysis, CTCs identification may be suggested as a diagnostic technique for gastric cancer screening, and the outcomes of CTC detection may also be utilized in the future to create personalized medicine programs.
Topics: Humans; Neoplastic Cells, Circulating; Prognosis; Stomach Neoplasms; Proportional Hazards Models; Lymphatic Metastasis; Biomarkers, Tumor
PubMed: 38554188
DOI: 10.1007/s10238-024-01310-6 -
The Indian Journal of Radiology &... Oct 2023High-grade gliomas (HGGs) are the most prevalent primary malignancy of the central nervous system. The tumor results in vasogenic and infiltrative edema . Exact... (Review)
Review
High-grade gliomas (HGGs) are the most prevalent primary malignancy of the central nervous system. The tumor results in vasogenic and infiltrative edema . Exact anatomical differentiation of these edemas is so important for surgical planning. Multimodal imaging could be used to differentiate the edema type. The aim of this study was to investigate the role of multimodal imaging in the differentiation of vasogenic edema from infiltrative edema in patients with HGG (grade III and grade IV). A search on PubMed, EMBASE, Scopus, and ISI Web of Science Core Collection up to June 2022 using terms related to (a) multimodal imaging AND (b) HGG AND (c) edema. (PROSPERO registration number: CRD42022336131) Two reviewers screened the articles and independently extracted the data. We included original articles assessing the role of multimodal imaging in differentiating vasogenic from infiltrative edema in patients with HGG. Six high-quality articles remained for the narrative synthesis. Dynamic susceptibility contrast imaging showed that relative cerebral blood volume and relative cerebral blood flow were higher in the infiltrative edema component than in the vasogenic edema component. Diffusion tensor imaging revealed a dispute on fractional anisotropy. The apparent diffusion coefficient was comparable between the two edematous components. Magnetic resonance spectroscopy exhibited an increment in choline/creatinine ratio and choline/N-acetyl aspartate ratio in the infiltrative edema component. Strict study selection, low sample size of relevant published studies, and heterogeneity in endpoint variables were the major drawbacks. Multimodal imaging, including dynamic susceptibility contrast and magnetic resonance spectroscopy, might help differentiate between vasogenic and infiltrative edema.
PubMed: 37811185
DOI: 10.1055/s-0043-1772466 -
Frontiers in Neurology 2024Magnetic resonance diffusion-weighted imaging (DWI) is the most sensitive modality for ischemic stroke diagnosis. However, DWI may fail to detect ischemic lesions in a...
BACKGROUND
Magnetic resonance diffusion-weighted imaging (DWI) is the most sensitive modality for ischemic stroke diagnosis. However, DWI may fail to detect ischemic lesions in a proportion of patients.
METHODS
Following PRISMA statement, a systematic search of Medline, Embase, and Web of Science was conducted until January 3, 2024. The inclusion was confined to English literature with sufficient reporting. Proportions of DWI-negative ischemic stroke were pooled. For binary variables, odds ratios (ORs) were computed using the random-effects model.
RESULTS
Fourteen studies constituting 16,268 patients with a clinical diagnosis of ischemic stroke and available DWI findings were included. Intravenous thrombolysis (IVT) was administered to 19.6% of the DWI-negative group and 15.3% of the DWI-positive group. DWI-negative ischemic stroke was reported in 16% (95% CI: 10-24%; after sensitivity analysis: 11% [95% CI: 8-15%]) of stroke patients. Among minor stroke patients (National Institutes of Health Stroke scale [NIHSS] of 5 or less), 24% (95% CI 12-42%) had negative DWI findings. Predictors of DWI-negative scans included posterior circulation stroke, history of ischemic heart disease, prior stroke, or prior transient ischemic attack. Cardioembolic stroke (OR, 0.62, 95% CI: 0.41-0.93) and history of atrial fibrillation increased the likelihood of positive DWI findings (OR, 0.56, 95% CI: 0.45-0.71). Patients with DWI-negative ischemic stroke had higher odds of good functional outcomes (modified Rankin scale [mRS] of 0-1) (OR, 2.26; 95% CI: 1.03-4.92), lower odds of stroke recurrence (OR, 0.68; 95% CI: 0.48-0.96), and lower odds of severe disability or mortality (mRS of 3-6) (OR, 0.44; 95% CI: 0.34-0.57) compared to patients with positive DWI. Rates of symptomatic intracerebral hemorrhage after IVT were comparable between groups.
CONCLUSION
DWI-negative findings were present in a significant proportion of ischemic stroke patients and may be utilized as a marker for favorable prognosis.
PubMed: 38737347
DOI: 10.3389/fneur.2024.1376439 -
Translational Stroke Research Jun 2024In intracerebral hemorrhage (ICH) with pathology-proven etiology, we performed a systematic review and meta-analysis to elucidate the association between cerebral... (Meta-Analysis)
Meta-Analysis
In intracerebral hemorrhage (ICH) with pathology-proven etiology, we performed a systematic review and meta-analysis to elucidate the association between cerebral amyloid angiopathy (CAA) and arteriolosclerosis, and directly compared MRI and pathological changes of markers of cerebral small vessel disease (CSVD). Studies enrolling primary ICH who had received an etiological diagnosis through biopsy or autopsy were searched using Ovid MEDLINE, PubMed, and Web of Science from inception to June 8, 2022. We extracted pathological changes of CSVD for each patient whenever available. Patients were grouped into CAA + arteriolosclerosis, strict CAA, and strict arteriolosclerosis subgroups. Of 4155 studies identified, 28 studies with 456 ICH patients were included. The frequency of lobar ICH (p<0.001) and total microbleed number (p=0.015) differed among patients with CAA + arteriolosclerosis, strict CAA, and strict arteriolosclerosis. Concerning pathology, severe CAA was associated with arteriolosclerosis (OR 6.067, 95% CI 1.107-33.238, p=0.038), although this association was not statistically significant after adjusting for age and sex. Additionally, the total microbleed number (median 15 vs. 0, p=0.006) was higher in ICH patients with CAA evidence than those without CAA. The pathology of CSVD imaging markers was mostly investigated in CAA-ICH. There was inconsistency concerning CAA severity surrounding microbleeds. Small diffusion-weighted imaging lesions could be matched to acute microinfarct histopathologically. Studies that directly correlated MRI and pathology of lacunes, enlarged perivascular spaces, and atrophy were scarce. Arteriolosclerosis might be associated with severe CAA. The pathological changes of CSVD markers by ICH etiology are needed to be investigated further.
Topics: Humans; Cerebral Hemorrhage; Cerebral Small Vessel Diseases; Cerebral Amyloid Angiopathy; Arteriolosclerosis
PubMed: 37280502
DOI: 10.1007/s12975-023-01154-4 -
Journal of Medical Radiation Sciences Jun 2024Brain metastases (BMs) are common in lung cancer (LC) and are associated with poor prognosis. Magnetic resonance imaging (MRI) plays a vital role in the detection,... (Review)
Review
INTRODUCTION
Brain metastases (BMs) are common in lung cancer (LC) and are associated with poor prognosis. Magnetic resonance imaging (MRI) plays a vital role in the detection, diagnosis and management of BMs. This review summarises recent advances in MRI techniques for BMs from LC.
METHODS
This systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive literature search was conducted in three electronic databases: PubMed, Scopus and the Web of Science. The search was limited to studies published between January 2000 and March 2023. The quality of the included studies was evaluated using appropriate tools for different study designs. A narrative synthesis was carried out to describe the key findings of the included studies.
RESULTS
Sixty-five studies were included. Standard MRI sequences such as T1-weighted (T1w), T2-weighted (T2w) and fluid-attenuated inversion recovery (FLAIR) were commonly used. Advanced techniques included perfusion-weighted imaging (PWI), diffusion-weighted imaging (DWI) and radiomics analysis. DWI and PWI parameters could distinguish tumour recurrence from radiation necrosis. Radiomics models predicted genetic mutations and the risk of BMs. Diagnostic accuracy was improved with deep learning (DL) approaches. Prognostic factors such as performance status and concurrent chemotherapy impacted survival.
CONCLUSION
Advanced MRI techniques and specialised MRI methods have emerging roles in managing BMs from LC. PWI and DWI improve diagnostic accuracy in treated BMs. Radiomics and DL facilitate personalised prognosis and treatment. Magnetic resonance imaging plays a key role in the continuum of care for BMs of patients with LC, from screening to treatment monitoring.
Topics: Humans; Brain Neoplasms; Lung Neoplasms; Magnetic Resonance Imaging; Neuroimaging
PubMed: 38234262
DOI: 10.1002/jmrs.756 -
JMIR Medical Informatics Apr 2024Semantic interoperability facilitates the exchange of and access to health data that are being documented in electronic health records (EHRs) with various semantic... (Review)
Review
BACKGROUND
Semantic interoperability facilitates the exchange of and access to health data that are being documented in electronic health records (EHRs) with various semantic features. The main goals of semantic interoperability development entail patient data availability and use in diverse EHRs without a loss of meaning. Internationally, current initiatives aim to enhance semantic development of EHR data and, consequently, the availability of patient data. Interoperability between health information systems is among the core goals of the European Health Data Space regulation proposal and the World Health Organization's Global Strategy on Digital Health 2020-2025.
OBJECTIVE
To achieve integrated health data ecosystems, stakeholders need to overcome challenges of implementing semantic interoperability elements. To research the available scientific evidence on semantic interoperability development, we defined the following research questions: What are the key elements of and approaches for building semantic interoperability integrated in EHRs? What kinds of goals are driving the development? and What kinds of clinical benefits are perceived following this development?
METHODS
Our research questions focused on key aspects and approaches for semantic interoperability and on possible clinical and semantic benefits of these choices in the context of EHRs. Therefore, we performed a systematic literature review in PubMed by defining our study framework based on previous research.
RESULTS
Our analysis consisted of 14 studies where data models, ontologies, terminologies, classifications, and standards were applied for building interoperability. All articles reported clinical benefits of the selected approach to enhancing semantic interoperability. We identified 3 main categories: increasing the availability of data for clinicians (n=6, 43%), increasing the quality of care (n=4, 29%), and enhancing clinical data use and reuse for varied purposes (n=4, 29%). Regarding semantic development goals, data harmonization and developing semantic interoperability between different EHRs was the largest category (n=8, 57%). Enhancing health data quality through standardization (n=5, 36%) and developing EHR-integrated tools based on interoperable data (n=1, 7%) were the other identified categories. The results were closely coupled with the need to build usable and computable data out of heterogeneous medical information that is accessible through various EHRs and databases (eg, registers).
CONCLUSIONS
When heading toward semantic harmonization of clinical data, more experiences and analyses are needed to assess how applicable the chosen solutions are for semantic interoperability of health care data. Instead of promoting a single approach, semantic interoperability should be assessed through several levels of semantic requirements A dual model or multimodel approach is possibly usable to address different semantic interoperability issues during development. The objectives of semantic interoperability are to be achieved in diffuse and disconnected clinical care environments. Therefore, approaches for enhancing clinical data availability should be well prepared, thought out, and justified to meet economically sustainable and long-term outcomes.
PubMed: 38686541
DOI: 10.2196/53535 -
European Radiology May 2024To determine the role of diffusion-weighted imaging (DWI) for predicting response to neoadjuvant therapy (NAT) in pancreatic cancer. (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To determine the role of diffusion-weighted imaging (DWI) for predicting response to neoadjuvant therapy (NAT) in pancreatic cancer.
MATERIALS AND METHODS
MEDLINE, EMBASE, and Cochrane Library databases were searched for studies evaluating the performance of apparent diffusion coefficient (ADC) to assess response to NAT. Data extracted included ADC pre- and post-NAT, for predicting response as defined by imaging, histopathology, or clinical reference standards. ADC values were compared with standardized mean differences. Risk of bias was assessed using the Quality Assessment of Diagnostic Studies (QUADAS-2).
RESULTS
Of 337 studies, 7 were included in the analysis (161 patients). ADC values reported for the pre- and post-NAT assessments overlapped between responders and non-responders. One study reported inability of ADC increase after NAT for distinguishing responders and non-responders. A correlation with histopathological response was reported for pre- and post-NAT ADC in 4 studies. DWI's diagnostic performance was reported to be high in three studies, with a 91.6-100% sensitivity and 62.5-94.7% specificity. Finally, heterogeneity and high risk of bias were identified across studies, affecting the domains of patient selection, index test, reference standard, and flow and timing.
CONCLUSION
DWI might be useful for determining response to NAT in pancreatic cancer. However, there are still too few studies on this matter, which are also heterogeneous and at high risk for bias. Further studies with standardized procedures for data acquisition and accurate reference standards are needed.
CLINICAL RELEVANCE STATEMENT
Diffusion-weighted MRI might be useful for assessing response to neoadjuvant therapy in pancreatic cancer. However, further studies with robust data are needed to provide specific recommendations for clinical practice.
KEY POINTS
•The role of DWI with ADC measurements for assessing response to neoadjuvant therapy in pancreatic cancer is still unclear. •Pre- and post-neoadjuvant therapy ADC values overlap between responders and non-responders. •DWI has a reported high diagnostic performance for determining response when using histopathological or clinical reference standards; however, studies are still few and at high risk for bias.
Topics: Humans; Pancreatic Neoplasms; Diffusion Magnetic Resonance Imaging; Neoadjuvant Therapy; Treatment Outcome; Sensitivity and Specificity
PubMed: 37907761
DOI: 10.1007/s00330-023-10381-0 -
Molecules (Basel, Switzerland) Aug 2023As some of the most widely used biocatalysts, lipases have exhibited extreme advantages in many processes, such as esterification, amidation, and transesterification... (Review)
Review
As some of the most widely used biocatalysts, lipases have exhibited extreme advantages in many processes, such as esterification, amidation, and transesterification reactions, which causes them to be widely used in food industrial production. However, natural lipases have drawbacks in terms of organic solvent resistance, thermostability, selectivity, etc., which limits some of their applications in the field of foods. In this systematic review, the application of lipases in various food processes was summarized. Moreover, the general structure of lipases is discussed in-depth, and the engineering strategies that can be used in lipase engineering are also summarized. The protocols of some classical methods are compared and discussed, which can provide some information about how to choose methods of lipase engineering. Thermostability engineering and solvent tolerance engineering are highlighted in this review, and the basic principles for improving thermostability and solvent tolerance are summarized. In the future, comput er-aided technology should be more emphasized in the investigation of the mechanisms of reactions catalyzed by lipases and guide the engineering of lipases. The engineering of lipase tunnels to improve the diffusion of substrates is also a promising prospect for further enhanced lipase activity and selectivity.
Topics: Lipase; Enzyme Stability; Solvents; Food Industry; Computers
PubMed: 37570817
DOI: 10.3390/molecules28155848