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Annals of Surgery Feb 2021This review assimilates and critically evaluates available literature regarding the use of metabolomic profiling in surgical decision-making. (Review)
Review
OBJECTIVE
This review assimilates and critically evaluates available literature regarding the use of metabolomic profiling in surgical decision-making.
BACKGROUND
Metabolomic profiling is performed by nuclear magnetic resonance spectroscopy or mass spectrometry of biofluids and tissues to quantify biomarkers (ie, sugars, amino acids, and lipids), producing diagnostic and prognostic information that has been applied among patients with cardiovascular disease, inflammatory bowel disease, cancer, and solid organ transplants.
METHODS
PubMed was searched from 1995 to 2019 to identify studies investigating metabolomic profiling of surgical patients. Articles were included and assimilated into relevant categories per PRISMA-ScR guidelines. Results were summarized with descriptive analytical methods.
RESULTS
Forty-seven studies were included, most of which were retrospective studies with small sample sizes using various combinations of analytic techniques and types of biofluids and tissues. Results suggest that metabolomic profiling has the potential to effectively screen for surgical diseases, suggest diagnoses, and predict outcomes such as postoperative complications and disease recurrence. Major barriers to clinical adoption include a lack of high-level evidence from prospective studies, heterogeneity in study design regarding tissue and biofluid procurement and analytical methods, and the absence of large, multicenter metabolome databases to facilitate systematic investigation of the efficacy, reproducibility, and generalizability of metabolomic profiling diagnoses and prognoses.
CONCLUSIONS
Metabolomic profiling research would benefit from standardization of study design and analytic approaches. As technologies improve and knowledge garnered from research accumulates, metabolomic profiling has the potential to provide personalized diagnostic and prognostic information to support surgical decision-making from preoperative to postdischarge phases of care.
Topics: Clinical Decision-Making; Humans; Magnetic Resonance Spectroscopy; Mass Spectrometry; Metabolomics; Prognosis; Surgical Procedures, Operative
PubMed: 32482979
DOI: 10.1097/SLA.0000000000003935 -
Asian Journal of Surgery Sep 2023Whether thymectomy (TM) or thymomectomy (TMM) is better for non-myasthenic patients with early-stage thymoma. We conducted a meta-analysis to compare the clinical... (Meta-Analysis)
Meta-Analysis Review
Whether thymectomy (TM) or thymomectomy (TMM) is better for non-myasthenic patients with early-stage thymoma. We conducted a meta-analysis to compare the clinical outcomes and prognoses of non-myasthenic patients with early-stage thymoma treated using thymectomy versus thymomectomy. PubMed, Embase, Cochrane Library and CNKI databases were systematically searched for relevant studies on the surgical treatment (TM and TMM) of non-myasthenic patients with early-stage thymoma published before March 2022. The Newcastle-Ottawa scale was used to evaluate the quality of the studies, and the data were analyzed using RevMan version 5.30. Fixed or random effect models were used for the meta-analysis depending on heterogeneity. Subgroup analyses were performed to compare short-term perioperative and long-term tumor outcomes. A total of 15 eligible studies, including 3023 patients, were identified in the electronic databases. Our analysis indicated that TMM patients might benefit from a shorter duration of surgery (p = 0.006), lower blood loss volume (p < 0.001), less postoperative drainage (p = 0.03), and a shorter hospital stay (p = 0.009). There were no significant differences in the overall survival rate (p = 0.47) or disease-free survival rate (p = 0.66) between the two surgery treatment groups. Likewise, TM and TMM were similar in the administration of adjuvant therapy (p = 0.29), resection completeness (p = 0.38), and postoperative thymoma recurrence (p = 0.99). Our study revealed that TMM might be a more appropriate option in treating non-myasthenic patients with early-stage thymoma.
Topics: Humans; Thymoma; Thymectomy; Neoplasm Staging; Retrospective Studies; Thymus Neoplasms; Prognosis; Disease-Free Survival
PubMed: 37005182
DOI: 10.1016/j.asjsur.2023.03.063 -
Biomedicine & Pharmacotherapy =... Jul 2021Long non-coding RNAs (lncRNAs) represent a group of ncRNAs with more than 200 nucleotides. These RNAs can specifically regulate gene expression at both the... (Review)
Review
Long non-coding RNAs (lncRNAs) represent a group of ncRNAs with more than 200 nucleotides. These RNAs can specifically regulate gene expression at both the transcriptional and the post-transcriptional levels, and increasing evidence indicates that they play vital roles in a variety of disease-related cellular processes. The lncRNA GAS8 antisense RNA 1 (GAS8-AS1, also known as C16orf3) is located in the second intron of GAS8 and has been reported to be both abnormally expressed in several diseases and closely correlated with many clinical characteristics. GAS8-AS1 has been shown to affect many biological functions, including cell proliferation, migration, invasiveness, and autophagy using several signaling pathways. In this review, we have summarized current studies on GAS8-AS1 roles in disease and discuss its potential clinical utility. GAS8-AS1 may be a promising biomarker for both diagnoses and prognoses, and a novel target for many disease therapies.
Topics: Animals; Biomarkers; Diagnosis; Disease; Humans; Prognosis; RNA, Long Noncoding
PubMed: 33838502
DOI: 10.1016/j.biopha.2021.111572 -
Translational Research : the Journal of... Apr 2023With the increasing prevalence of Alzheimer's disease (AD) among aging populations and the limited therapeutic options available to slow or reverse its progression, the... (Review)
Review
With the increasing prevalence of Alzheimer's disease (AD) among aging populations and the limited therapeutic options available to slow or reverse its progression, the need has never been greater for improved diagnostic tools for identifying patients in the preclinical and prodomal phases of AD. Biophysics models of the connectome-based spread of amyloid-beta (Aβ) and microtubule-associated protein tau (τ) have enjoyed recent success as tools for predicting the time course of AD-related pathological changes. However, given the complex etiology of AD, which involves not only connectome-based spread of protein pathology but also the interactions of many molecular and cellular players over multiple spatiotemporal scales, more robust, complete biophysics models are needed to better understand AD pathophysiology and ultimately provide accurate patient-specific diagnoses and prognoses. Here we discuss several areas of active research in AD whose insights can be used to enhance the mathematical modeling of AD pathology as well as recent attempts at developing improved connectome-based biophysics models. These efforts toward a comprehensive yet parsimonious mathematical description of AD hold great promise for improving both the diagnosis of patients at risk for AD and our mechanistic understanding of how AD progresses.
Topics: Humans; Alzheimer Disease; Connectome; tau Proteins; Amyloid beta-Peptides; Prognosis
PubMed: 36031051
DOI: 10.1016/j.trsl.2022.08.008 -
Epigenetics Dec 2023Patients with acute myeloid leukaemia (AML) have poor prognoses and low overall survival (OS) rates owing to its heterogeneity and the complexity of its tumour...
Patients with acute myeloid leukaemia (AML) have poor prognoses and low overall survival (OS) rates owing to its heterogeneity and the complexity of its tumour microenvironment (TME). N6-methyladenosine (mA) modification plays a key role in the initiation and progression of haematopoietic malignancies. However, the underlying function of mA regulators in AML remains elusive. This study thoroughly analysed the mA modification features of 177 AML patients based on 22 mA regulators. Utilizing unsupervised clustering, we determined three distinct mA modification patterns related to different biological functions, TME cell-infiltrating characteristics and clinical outcomes. Additionally, a risk score was constructed based on six mA regulators-associated prognostic signatures and was validated as an independent and valuable prognostic factor for AML. Patients with a low-risk score exhibited better survival than those with a high-risk score. Many mA regulators were aberrantly expressed in AML, among which and were observed to be associated with the OS of AML. In addition, these four mA regulators were found to be noticeably related to the immune checkpoint inhibitor (ICI) treatments. Finally, we verified the expression levels of these four mA regulators in AML and healthy samples and three groups of AML patients with different risk categories. Collectively, our study indicates that the mA modification pattern is involved in TME immune-infiltrating characteristics and prognosis in AML. A better understanding of the mA modification pattern will help enhance our knowledge of the molecular mechanisms of AML and develop potential prognosis prediction indicators and more effective immunotherapeutic strategies.
Topics: Humans; Tumor Microenvironment; DNA Methylation; Prognosis; Leukemia, Myeloid, Acute; RNA
PubMed: 36567510
DOI: 10.1080/15592294.2022.2160134 -
Medicine Feb 20223β-hydroxy-Δ5-C27-steroid dehydrogenase deficiency is a rare autosomal recessive condition. So far fewer than 100 cases have been reported and the factors affecting...
Prognosis and clinical characteristics of patients with 3β-hydroxy-Δ5-C27-steroid dehydrogenase deficiency diagnosed in childhood: A systematic review of the literature.
OBJECTIVES
3β-hydroxy-Δ5-C27-steroid dehydrogenase deficiency is a rare autosomal recessive condition. So far fewer than 100 cases have been reported and the factors affecting the prognosis are not yet established. The objective of this study is to explore a possible prediction of the outcome of this rare condition.
METHODS
This review was undertaken and reported in accordance with the preferred reporting items for systematic review and meta-analyses guidelines. Demographics, clinical features, gene data, treatment strategies and prognoses at the last follow-up were extracted and summarized. Patients were divided into 2 groups (alive with native liver and liver transplantation/died). Risk factors for the different clinical features were identified.
RESULTS
87 patients that were taken from 7 case reports and 9 case series were included. 38 (38/63, 63.0%) of them presented initial symptoms when they were younger than 1 month and 55 (55/63, 87.3%) less than 1 year. There is a larger proportion of patients younger than 1 month or 1 year at the age of symptom onset in the liver transplantation /died group than patients in alive with the native liver group. The majority of patients (53/62, 85.5%) were diagnosed before the age of 5 year. In all cases, 65 (predicted) pathogenic variants have been identified. Over 70% of patients carried an HSD3B7 variant on exon 1, 4, 5 or 6. 71 (81.6%) were alive at the last follow-up, 16 (18.4%) underwent liver transplantation or died. No significance was found between the group alive with native liver and group liver transplantation /died.
CONCLUSION
Age of onset of the symptoms may be a potential factor that determines the outcome of patients with 3β-HSD deficiency, patients presented with symptoms and signs at an age younger than 1 month or even 1 year may have a worse prognosis. Since there is no difference between clinical outcome and zygosity of gene mutation, we recommend a further study about any possible relationship between mutation site and clinical characteristics or prognosis.
Topics: 3-Hydroxysteroid Dehydrogenases; Bile Acids and Salts; Humans; Liver; Prognosis
PubMed: 35363177
DOI: 10.1097/MD.0000000000028834 -
Interventional Neuroradiology : Journal... Oct 2016Pediatric dural arteriovenous shunts (dAVSs) are a rare form of vascular disease: Fewer than 100 cases are reported in PubMed and the understanding of pediatric dAVS is... (Review)
Review
Pediatric dural arteriovenous shunts (dAVSs) are a rare form of vascular disease: Fewer than 100 cases are reported in PubMed and the understanding of pediatric dAVS is limited. For this study, we searched in PubMed, reviewed and summarized the literature related to pediatric dAVSs. Our review revealed that pediatric dAVSs have an unfavorable natural history: If left untreated, the majority of pediatric dAVSs deteriorate. In a widely accepted classification scheme developed by Lasjaunias et al., pediatric dAVSs are divided into three types: Dural sinus malformation (DMS) with dAVS, infantile dAVS (IDAVS) and adult-type dAVS (ADAVS). In general, the clinical manifestations of dAVS can be summarized as having symptoms due to high-flow arteriovenous shunts, symptoms from retrograde venous drainage, symptoms from cavernous sinus involvement and hydrocephalus, among other signs and symptoms. The pediatric dAVSs may be identified with several imaging techniques; however, the gold standard is digital subtraction angiography (DSA), which indicates unique anatomical details and hemodynamic features. Effectively treating pediatric dAVS is difficult and the prognosis is often unsatisfactory. Transarterial embolization with liquid embolic agents and coils is the treatment of choice for the safe stabilization and/or improvement of the symptoms of pediatric dAVS. In some cases, transumbilical arterial and transvenous approaches have been effective, and surgical resection is also an effective alternative in some cases. Nevertheless, pediatric dAVS can have an unsatisfactory prognosis, even when timely and appropriate treatment is administered; however, with the development of embolization materials and techniques, the potential for improved treatments and prognoses is increasing.
Topics: Central Nervous System Vascular Malformations; Child; Diagnostic Imaging; Humans; Prognosis
PubMed: 27306522
DOI: 10.1177/1591019916653254 -
Aging May 2023Epigenetic regulations of immune responses are essential for cancer development and growth. As a critical step, comprehensive and rigorous explorations of m6A...
Integrating machine learning and bioinformatics analysis to m6A regulator-mediated methylation modification models for predicting glioblastoma patients' prognosis and immunotherapy response.
BACKGROUND
Epigenetic regulations of immune responses are essential for cancer development and growth. As a critical step, comprehensive and rigorous explorations of m6A methylation are important to determine its prognostic significance, tumor microenvironment (TME) infiltration characteristics and underlying relationship with glioblastoma (GBM).
METHODS
To evaluate m6A modification patterns in GBM, we conducted unsupervised clustering to determine the expression levels of GBM-related m6A regulatory factors and performed differential analysis to obtain m6A-related genes. Consistent clustering was used to generate m6A regulators cluster A and B. Machine learning algorithms were implemented for identifying TME features and predicting the response of GBM patients receiving immunotherapy.
RESULTS
It is found that the m6A regulatory factor significantly regulates the mutation of GBM and TME. Based on Europe, America, and China data, we established m6Ascore through the m6A model. The model accurately predicted the results of 1206 GBM patients from the discovery cohort. Additionally, a high m6A score was associated with poor prognoses. Significant TME features were found among the different m6A score groups, which demonstrated positive correlations with biological functions (i.e., EMT2) and immune checkpoints.
CONCLUSIONS
m6A modification was important to characterize the tumorigenesis and TME infiltration in GBM. The m6Ascore provided GBM patients with valuable and accurate prognosis and prediction of clinical response to various treatment modalities, which could be useful to guide patient treatments.
Topics: Humans; Computational Biology; Glioblastoma; Immunotherapy; Machine Learning; Methylation; Prognosis; Tumor Microenvironment
PubMed: 37244287
DOI: 10.18632/aging.204495 -
Frontiers in Immunology 2022Pyrimidine metabolism is a hallmark of cancer and will soon become an essential part of cancer therapy. In the tumor microenvironment, cells reprogram pyrimidine...
Pyrimidine metabolism is a hallmark of cancer and will soon become an essential part of cancer therapy. In the tumor microenvironment, cells reprogram pyrimidine metabolism intrinsically and extracellularly, thereby promoting tumorigenesis. Metabolites in pyrimidine metabolism have a significant impact on promoting cancer advancement and modulating immune system responses. In preclinical studies and practical clinical applications, critical targets in pyrimidine metabolism are acted upon by drugs to exert promising therapeutic effects on tumors. However, the pyrimidine metabolism in breast cancer (BC) is still largely underexplored. In this study, 163 credible pyrimidine metabolism-related genes (PMGs) were retrieved, and their somatic mutations and expression levels were determined. In addition, by using The Cancer Genome Atlas (TCGA) and the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) databases, 12 PMGs related to the overall survival (OS) were determined using the univariate Cox regression analysis. Subsequently, by performing the LASSO Cox hazards regression analysis in the 12 PMGs in TCGA-BRCA dataset, we developed a prognosis nomogram using eight OS-related PMGs and then verified the same in the METABRIC, GSE96058, GSE20685, GSE42568 and GSE86166 data. Moreover, we validated relationships between the pyrimidine metabolism index (PMI) and the survival probability of patients, essential clinical parameters, including the TNM stage and the PAM50 subtypes. Next, we verified the predictive capability of the optimum model, including the signature, the PAM50 subtype, and age, using ROC analysis and calibration curve, and compared it with other single clinical factors for the predictive power of benefit using decision curve analysis. Finally, we investigated the potential effects of pyrimidine metabolism on immune checkpoints, tumor-infiltrating immune cells, and cytokine levels and determined the potential implications of pyrimidine metabolism in BC immunotherapy. In conclusion, our findings suggest that pyrimidine metabolism has underlying prognostic significance in BC and can facilitate a new management approach for patients with different prognoses and more precise immunotherapy.
Topics: Humans; Female; Breast Neoplasms; Prognosis; Immunosuppressive Agents; Immunotherapy; Pyrimidines; Tumor Microenvironment
PubMed: 36524129
DOI: 10.3389/fimmu.2022.1056680 -
Annals of Medicine Dec 2023Epstein-Barr virus (EBV)-associated hemophagocytic lymphohistiocytosis (EBV-HLH) is a common subtype of HLH with heterogeneous clinical presentations from self-limited...
BACKGROUND
Epstein-Barr virus (EBV)-associated hemophagocytic lymphohistiocytosis (EBV-HLH) is a common subtype of HLH with heterogeneous clinical presentations from self-limited to death, of which adults are worse than children.
OBJECTIVE
To establish predictors of mortality risk in adult EBV-HLH patients for timely and appropriate treatment.
METHODS
Patients with confirmed EBV-HLH admitted to Beijing Friendship Hospital from January 2015 to December 2019 were enrolled and statistical analysis of their laboratory test results was performed.
RESULTS
Among 246 adult patients with EBV-HLH, the deceased were older ( < 0.05), with fewer blood cells ( < 0.05), poorer renal function ( < 0.01), higher levels of procalcitonin (PCT) ( < 0.01), as well as soluble interleukin-2 receptor (sCD25) ( < 0.01). The overall median survival time of patients was 135 days, 87 days for patients without transplantation and 294 days with transplantation ( < 0.001). A combined index of sCD25, PCT, and estimated glomerular filtration rate (eGFR) was obtained to predict prognosis, named the Improved HLH index (IH index), and patients were divided into three groups meeting IH- (i.e. sCD25 ≤ 18,000 pg/mL, PCT ≤ 1.8 ng/mL, eGFR ≥ 90 mL/min/1.73m), IH1+ (i.e. only sCD25 > 18,000 pg/mL or only eGFR < 90 mL/min/1.73m), and IH2+ (i.e. the rest), respectively. In patients with the HScore ≥ 169 or meeting HLH-04, those meeting IH2+ had significantly worse prognoses than those who met IH1+ or IH- ( < 0.001). In the group meeting IH + or IH2+, patients who received allo-HSCT had better prognoses than those who did not ( < 0.05), but there was still a significant difference in prognosis among the three groups in transplanted patients ( < 0.001).
CONCLUSION
The IH index can early identify adult patients with a poor prognosis of EBV-HLH, initiating timely and appropriate treatment.KEY MESSAGESA combined index of sCD25, PCT, and eGFR was obtained to predict prognosis, named the Improved Hemophagocytic Lymphohistiocytosis index (IH index).IH index can early identify adult patients with a poor prognosis of EBV-HLH, initiating timely and appropriate treatment.
Topics: Child; Humans; Adult; Lymphohistiocytosis, Hemophagocytic; Herpesvirus 4, Human; Epstein-Barr Virus Infections; Retrospective Studies; Prognosis
PubMed: 36533966
DOI: 10.1080/07853890.2022.2149850