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Pharmaceuticals (Basel, Switzerland) Apr 2022Platinum-based chemotherapy regimens have been proven to be effective in various cancers; however, considerable toxicities may develop and can even lead to treatment... (Review)
Review
Platinum-based chemotherapy regimens have been proven to be effective in various cancers; however, considerable toxicities may develop and can even lead to treatment discontinuation. Diverse factors may influence adverse treatment events, with pharmacogenetic variations being one prime example. Polymorphisms within the glutathione S-transferase pi 1 (GSTP1) gene may especially alter enzyme activity and, consequently, various toxicities in patients receiving platinum-based chemotherapy. Due to a lack of consistency in the degree of elevated complication risk, we performed a systematic literature review and meta-analysis to determine the level of platinum-associated toxicity in patients with the GSTP1 rs1695 polymorphism. We conducted a systematic search for eligible studies published before January 2022 from PubMed, Web of Science, and EMBASE based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the strength of the association between the rs1695 polymorphism and various toxicities. Ten eligible studies met the inclusion criteria. The pooled ORs for hematological toxicity and neutropenia in the patients with the variant (G) allele were 1.7- and 2.6-times higher than those with the AA genotype (95% CI 1.06-2.73 and 1.07-6.35), respectively. In contrast, the rs1695 polymorphism resulted in a 44% reduced gastrointestinal toxicity compared to wild-type homozygotes. Our study found that the GSTP1 rs1695 polymorphism was significantly correlated with platinum-induced toxicities. The study also revealed that rs1695 expression exhibited tissue-specific patterns and thus yielded opposite effects in different tissues. A personalized chemotherapy treatment based on these polymorphisms may be considered for cancer patients in the future.
PubMed: 35455437
DOI: 10.3390/ph15040439 -
World Journal of Gastroenterology Mar 2016To construct a global "metabolic phenotype" of pancreatic ductal adenocarcinoma (PDAC) reflecting tumour-related metabolic enzyme expression. (Review)
Review
AIM
To construct a global "metabolic phenotype" of pancreatic ductal adenocarcinoma (PDAC) reflecting tumour-related metabolic enzyme expression.
METHODS
A systematic review of the literature was performed using OvidSP and PubMed databases using keywords "pancreatic cancer" and individual glycolytic and mitochondrial oxidative phosphorylation (MOP) enzymes. Both human and animal studies investigating the oncological effect of enzyme expression changes and inhibitors in both an in vitro and in vivo setting were included in the review. Data reporting changes in enzyme expression and the effects on PDAC cells, such as survival and metastatic potential, were extracted to construct a metabolic phenotype.
RESULTS
Seven hundred and ten papers were initially retrieved, and were screened to meet the review inclusion criteria. 107 unique articles were identified as reporting data involving glycolytic enzymes, and 28 articles involving MOP enzymes in PDAC. Data extraction followed a pre-defined protocol. There is consistent over-expression of glycolytic enzymes and lactate dehydrogenase in keeping with the Warburg effect to facilitate rapid adenosine-triphosphate production from glycolysis. Certain isoforms of these enzymes were over-expressed specifically in PDAC. Altering expression levels of HK, PGI, FBA, enolase, PK-M2 and LDA-A with metabolic inhibitors have shown a favourable effect on PDAC, thus identifying these as potential therapeutic targets. However, the Warburg effect on MOP enzymes is less clear, with different expression levels at different points in the Krebs cycle resulting in a fundamental change of metabolite levels, suggesting that other essential anabolic pathways are being stimulated.
CONCLUSION
Further characterisation of the PDAC metabolic phenotype is necessary as currently there are few clinical studies and no successful clinical trials targeting metabolic enzymes.
Topics: Animals; Carcinoma, Pancreatic Ductal; Energy Metabolism; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Glucose; Humans; Pancreatic Neoplasms; Phenotype
PubMed: 27022229
DOI: 10.3748/wjg.v22.i12.3471 -
PloS One 2023Systematic review.
STUDY DESIGN
Systematic review.
OBJECTIVES
To conduct a systematic review identifying existing definitions of cauda equina syndrome (CES) and time to surgery in the literature for patients with CES.
METHODS
A systematic review was conducted in accordance with the PRISMA statement. Ovid Medline, Embase, CINAHL Plus, and trial registries were searched from October 1st, 2016, to 30th December 2022, and combined with articles identified from a previous systematic review by the same authors (studies published 1990-2016).
RESULTS
A total of 110 studies (52,008 patients) were included. Of these only 16 (14.5%) used established definitions in defining CES, including Fraser criteria (n = 6), British Association of Spine Surgeons (BASS) (n = 5), Gleave and MacFarlane (n = 2), and other (n = 3). Most reported symptoms were urinary dysfunction (n = 44, 40%%), altered sensation in the perianal region (n = 28, 25.5%) and bowel dysfunction (n = 20, 18.2%). Sixty-eight (61.8%) studies included details on time to surgery. There was an increase in percentage of studies defining CES published in the last 5 years compared to ones from 1990-2016 (58.6% vs 77.5.%, P = .045).
CONCLUSIONS
Despite Fraser recommendations, substantial heterogeneity exists in reporting of CES definitions, and a start point for time to surgery, with most authors using self-defined criteria. A consensus is required to define CES and time to surgery, to allow consistency in reporting and study analysis.
Topics: Humans; Cauda Equina Syndrome; Spine; Consensus; Patients; Registries; Cauda Equina
PubMed: 37141301
DOI: 10.1371/journal.pone.0285006 -
Frontiers in Genetics 2021Huntington's disease (HD) is a chronic neurodegenerative disorder caused by an expansion of polyglutamine repeats in exon 1 of the Huntingtin gene. Transcriptional... (Review)
Review
Huntington's disease (HD) is a chronic neurodegenerative disorder caused by an expansion of polyglutamine repeats in exon 1 of the Huntingtin gene. Transcriptional dysregulation accompanied by epigenetic alterations is an early and central disease mechanism in HD yet, the exact mechanisms and regulators, and their associated gene expression programs remain incompletely understood. This systematic review investigates genome-wide transcriptional studies that were conducted using RNA sequencing (RNA-seq) technology in HD patients and models. The review protocol was registered at the Open Science Framework (OSF). The biomedical literature and gene expression databases, PubMed and NCBI BioProject, Array Express, European Nucleotide Archive (ENA), European Genome-Phenome Archive (EGA), respectively, were searched using the defined terms specified in the protocol following the PRISMA guidelines. We conducted a complete literature and database search to retrieve all RNA-seq-based gene expression studies in HD published until August 2020, retrieving 288 articles and 237 datasets from PubMed and the databases, respectively. A total of 27 studies meeting the eligibility criteria were included in this review. Collectively, comparative analysis of the datasets revealed frequent genes that are consistently dysregulated in HD. In postmortem brains from HD patients, and genes were commonly upregulated across all brain regions and cell types except for medium spiny neurons (MSNs) at symptomatic disease stage, and and genes were altered in expression in all symptomatic brain datasets, indicating early and sustained changes in the expression of genes related to heat shock response as well as response to misfolded proteins. Specifically in indirect pathway medium spiny neurons (iMSNs), mitochondria related genes were among the top uniquely dysregulated genes. Interestingly, blood from HD patients showed commonly differentially expressed genes with a number of brain regions and cells, with the highest number of overlapping genes with MSNs and BA9 region at symptomatic stage. We also found the differential expression and predicted altered activity of a set of transcription factors and epigenetic regulators, including and , respectively, which may underlie the observed transcriptional changes in HD. Altogether, our work provides a complete overview of the transcriptional studies in HD, and by data synthesis, reveals a number of common and unique gene expression and regulatory changes across different cell and tissue types in HD. These changes could elucidate new insights into molecular mechanisms of differential vulnerability in HD. https://osf.io/pm3wq.
PubMed: 34721539
DOI: 10.3389/fgene.2021.751033 -
The Annals of Pharmacotherapy Feb 2022Ibuprofen is a widely used nonsteroidal anti-inflammatory drug, which has been occasionally associated with hypokalemia and metabolic acidosis. The objective of this...
OBJECTIVE
Ibuprofen is a widely used nonsteroidal anti-inflammatory drug, which has been occasionally associated with hypokalemia and metabolic acidosis. The objective of this report is to analyze the literature on this issue and to address the underlying pathophysiology.
DATA SOURCES
Excerpta Medica, the National Library of Medicine, and Web of Science were searched from inception to July 16, 2021.
STUDY SELECTION AND DATA EXTRACTION
Papers reporting individually documented humans on ibuprofen with hypokalemia, acidosis, or both were retained. Data were extracted using a checklist.
DATA SYNTHESIS
For the final analysis, we evaluated 41 reports describing 50 cases (26 males and 24 females; 36 adults and 14 children) with often profound hypokalemia, acidosis, or both after ingestion of ibuprofen. Twenty-six cases were acute and 24 long term. Hypokalemia and acidosis occurred not only after ingestion of very high doses but also after ingestion of moderately high or even normal doses of ibuprofen. Laboratory values consistent with an excessive urinary potassium excretion or an altered urinary acidification were often disclosed in most cases. Discontinuation of ibuprofen resulted in a resolution of hypokalemia and acidosis within days in 47 cases. The course was lethal in 3 cases.
RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE
This review highlights potentially fatal side effects of ibuprofen and can help doctors who are confronted with such a situation.
CONCLUSIONS
These data highlight the potential of ibuprofen to occasionally induce hypokalemia and acidosis of renal origin. Discontinuation of ibuprofen results in a resolution within days.
PubMed: 35135381
DOI: 10.1177/10600280221075362 -
Oncotarget Nov 2019To assess the association of tumor mutational burden (TMB) with clinical outcomes, other biomarkers and patient/disease characteristics in patients receiving therapy... (Review)
Review
To assess the association of tumor mutational burden (TMB) with clinical outcomes, other biomarkers and patient/disease characteristics in patients receiving therapy for lung cancer. In total, 4,303 publications were identified; 81 publications were included. The majority of publications assessing clinical efficacy of immunotherapy reported an association with high TMB, particularly when assessing progression-free survival and objective response rate. High TMB was consistently associated with alterations, and negatively associated with EGFR mutations. High TMB was also associated with smoking, squamous cell non-small cell lung carcinoma, and being male. A systematic literature review based upon an a priori protocol was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Cochrane methodologies. Searches were conducted in EMBASE, SCOPUS, Ovid MEDLINE, and Emcare (from January 2012 until April 2018) and in two clinical trial registries. Conference abstracts were identified in EMBASE, and in targeted searches of recent major conference proceedings (from January 2016 until April 2018). Publications reporting data in patients receiving therapy for lung cancer that reported TMB and its association with clinical efficacy, or with other biomarkers or patient/disease characteristics, were included. Results are presented descriptively. This systematic literature review identified several clinical outcomes, biomarkers, and patient/disease characteristics associated with high TMB, and highlights the need for standardized definitions and testing practices. Further studies using standardized methodology are required to inform treatment decisions.
PubMed: 31762941
DOI: 10.18632/oncotarget.27287 -
Headache Mar 2022To summarize the evidence regarding static and dynamic balance alterations among patients with headache. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To summarize the evidence regarding static and dynamic balance alterations among patients with headache.
METHODS
Electronic databases (PubMed, CINAHL, and Web of Science) were searched by two researchers independently up to September 2021. Two reviewers selected eligible studies, extracted the data, and assessed the quality of evidence using the Downs and Black checklist. Case-control studies were included if they involved balance assessment of any kind of headache, including objective outcome measures of dynamic and static tests such as body sway displacement, limits of stability (LOS), gait, and tandem walk tests. A meta-analysis and post hoc sensitivity analyses were performed when possible.
RESULTS
Twenty-two studies (1202 patients with headache and 597 controls) were included in this review and 16 of them in the meta-analysis. Risk of bias ranged from low to moderate among all studies. Greater sway area in static posturography was shown by patients with migraine in comparison to controls, with more consistent differences in more challenging test conditions, such as over a foam surface with eyes closed (difference of 4.8 cm , 95% CI: 3.8-5.9). Lower performance of patients with migraine during the tandem walk test (difference of -7.8 cm/s, 95% CI: -9.0 to -6.5) and slower reaction time in the LOS test (difference of 0.3 s, 95% CI: 0.2-0.4) were also verified. There is no evidence of altered sway velocity and length in static posturography among patients with migraine (p > 0.05). The level of evidence is very low for balance alteration of any kind among patients with tension-type and cervicogenic headache owing to the limited number of studies and high heterogeneity.
CONCLUSION
This review confirmed the presence of static and dynamic balance alterations among patients with migraine. Future studies with low risk of bias are needed to decrease heterogeneity in methodology and explore the role of subdiagnosis on the balance of patients with headache.
Topics: Case-Control Studies; Headache; Humans; Migraine Disorders; Post-Traumatic Headache; Postural Balance
PubMed: 35315066
DOI: 10.1111/head.14281 -
The American Journal of Drug and... 2015Exteroception involves processes related to the perception of environmental stimuli important for an organism's ability to adapt to its environment. As such,... (Review)
Review
BACKGROUND
Exteroception involves processes related to the perception of environmental stimuli important for an organism's ability to adapt to its environment. As such, exteroception plays a critical role in conditioned response. In addiction, behavioral and neuroimaging studies show that the conditioned response to drug-related cues is often associated with alterations in brain regions including the precuneus/posterior cingulate cortex, an important node within the default mode network dedicated to processes such as self-monitoring.
OBJECTIVE
This review aimed to summarize the growing, but largely fragmented, literature that supports a central role of exteroceptive processes in addiction.
METHODS
We performed a systematic review of empirical research via PubMed and Google Scholar with keywords including 'addiction', 'exteroception', 'precuneus', and 'self-awareness', to identify human behavioral and neuroimaging studies that report mechanisms of self-awareness in healthy populations, and altered self-awareness processes, specifically exteroception, in addicted populations.
RESULTS
Results demonstrate that exteroceptive processes play a critical role in conditioned cue response in addiction and serve as targets for interventions such as mindfulness training. Further, a hub of the default mode network, namely, the precuneus, is (i) consistently implicated in exteroceptive processes, and (ii) widely demonstrated to have increased activation and connectivity in addicted populations.
CONCLUSION
Heightened exteroceptive processes may underlie cue-elicited craving, which in turn may lead to the maintenance and worsening of substance use disorders. An exteroception model of addiction provides a testable framework from which novel targets for interventions can be identified.
Topics: Behavior, Addictive; Conditioning, Psychological; Gyrus Cinguli; Humans; Models, Psychological; Perception
PubMed: 26154169
DOI: 10.3109/00952990.2015.1049701 -
Biomolecules Sep 2023Previous studies have suggested that bile acids (BAs) may participate in the development and/or progression of metabolic dysfunction-associated steatotic liver disease... (Meta-Analysis)
Meta-Analysis Review
Previous studies have suggested that bile acids (BAs) may participate in the development and/or progression of metabolic dysfunction-associated steatotic liver disease (MASLD). The present study aimed to define whether specific BA molecular species are selectively associated with MASLD development, disease severity, or geographic region. We comprehensively identified all eligible studies reporting circulating BAs in both MASLD patients and healthy controls through 30 July 2023. The pooled results were expressed as the standard mean difference (SMD) and 95% confidence interval (CI). Subgroup, sensitivity, and meta-regression analyses were performed to address heterogeneity. Nineteen studies with 154,807 individuals were included. Meta-analysis results showed that total BA levels in MASLD patients were higher than those in healthy controls (SMD = 1.03, 95% CI: 0.63-1.42). When total BAs were divided into unconjugated and conjugated BAs or primary and secondary BAs, the pooled results were consistent with the overall estimates except for secondary BAs. Furthermore, we examined each individual BA and found that 9 of the 15 BAs were increased in MASLD patients, especially ursodeoxycholic acids (UDCA), taurococholic acid (TCA), chenodeoxycholic acids (CDCA), taurochenodeoxycholic acids (TCDCA), and glycocholic acids (GCA). Subgroup analysis revealed that different geographic regions or disease severities led to diverse BA profiles. Notably, TCA, taurodeoxycholic acid (TDCA), taurolithocholic acids (TLCA), and glycolithocholic acids (GLCA) showed a potential ability to differentiate metabolic dysfunction-associated steatohepatitis (MASH) (all 0.05). An altered profile of circulating BAs was shown in MASLD patients, providing potential targets for the diagnosis and treatment of MASLD.
Topics: Humans; Bile Acids and Salts; Metabolic Diseases; Ursodeoxycholic Acid; Chenodeoxycholic Acid; Fatty Liver
PubMed: 37759756
DOI: 10.3390/biom13091356 -
Journal of Personalized Medicine Feb 2022: Diabetes mellitus (DM) refers to a group of metabolic disorders characterized by hyperglycemia resulting from impaired secretion or action of insulin. The high levels... (Review)
Review
: Diabetes mellitus (DM) refers to a group of metabolic disorders characterized by hyperglycemia resulting from impaired secretion or action of insulin. The high levels of glucose in the blood can negatively affect the healing processes through alterations in vascularization, bone remodeling, and with increased susceptibility to infections. Diabetes mellitus is therefore a risk factor not only for many systemic diseases, but also for localized problems such as peri-implantitis. The objective of this systematic review was to identify a clear relationship between peri-implant inflammation indices and glycemic levels, through the investigation of prospective studies that report data on a short-term follow-up period. Our hypothesis was that peri-implant inflammatory indices may already present themselves in a statistically significant way as altered in patients with DM compared to patients without DM. : This review was reported according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA). : More than 992 records were identified in the PubMed, Scopus, and Cochrane Central Register of Controlled Trial electronic databases and only seven studies were included in the meta-analysis. The results of the meta-analysis report worse outcomes in patients with DM, even in the short period of six months, for peri-implatitis inflammation indices, such as Marginal bone loss (standardized (Std). mean difference (MD) 12\6 months 0.81 [0.45, 1.17]\1.82 [0.53, 3.10]), Bleeding on probing (Std. MD 12\6 months 2.84 [1.34, 4.34]\3.44 [1.41, 5.50]), Probing depth (Std. MD 12\6 months 1.14 [0.60, 1.68]\2.24 [0.66, 3.83]), and the plaque index (Std. MD 12 months 2.83 [0.09, 5.57]). : The literature linking glycaemic control to peri-implant disease is highly heterogeneous due to lack of consistency of the definition of peri-implantitis and its clinical indicators among studies. Therefore, interpretation of finding and relevance to clinical practice should be considered on individual bases. In the era of personalized medicine, the clinician should utilize individualized information from translational researches and analyze all risk factors to provide the patient with evidence-based treatment options.
PubMed: 35207724
DOI: 10.3390/jpm12020235