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The Oncologist May 2024The use of immune checkpoint inhibitors (ICIs) has revolutionized cancer care, particularly in immune-inflamed tumors and tumors with a high mutational burden, like...
The use of immune checkpoint inhibitors (ICIs) has revolutionized cancer care, particularly in immune-inflamed tumors and tumors with a high mutational burden, like microsatellite instable colorectal cancer (CRC). However, their effectiveness in microsatellite stable (MSS) CRC is limited. This systematic review aims to evaluate the efficacy of ICIs in MSS CRC and explore promising combination strategies. A comprehensive search from the Web of Science, Medline, and Embase databases, for studies published until 14 November 2022, identified 53 clinical trials included in the review. ICI monotherapy or ICI-ICI combinations demonstrated limited clinical activity for patients with MSS CRC, with overall response rates below (ORR) 10% in most studies. The ICI and tyrosine kinase inhibitor (TKI) garnered ORRs ranging from 10% to 40% and indicated a higher benefit for patients, particularly those without active liver metastases. The combination of ICIs with anti-VEGF agents showed modest ORRs, especially in the earlier treatment lines and in combination with chemotherapy. While these combinations could lead to modest improvements, well-defined biomarkers for long-term benefit are yet to be delineated. Combinations involving BRAF inhibitors with ICIs were studied, showing promising responses with combination approaches in molecularly defined subgroups. In conclusion, while ICI monotherapy has limited efficacy in MSS CRC, combination strategies hold promise to enhance survival outcomes. Further research is necessary to identify optimal combination approaches, predictive biomarkers for treatment response, as well as enrollment according to tumor molecular characteristics.
Topics: Humans; Immune Checkpoint Inhibitors; Colorectal Neoplasms; Microsatellite Instability
PubMed: 38309719
DOI: 10.1093/oncolo/oyae013 -
JAMA Network Open Feb 2024Physical activity is associated with the risk for cognitive decline, but much of the evidence in this domain comes from studies with short follow-ups, which is prone to... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Physical activity is associated with the risk for cognitive decline, but much of the evidence in this domain comes from studies with short follow-ups, which is prone to reverse causation bias.
OBJECTIVE
To examine how length of follow-up, baseline age, physical activity amount, and study quality modify the longitudinal associations of physical activity with cognition.
DATA SOURCES
Observational studies of adults with a prospective follow-up of at least 1 year, a valid baseline cognitive measure or midlife cohort, and an estimate of the association of baseline physical activity and follow-up cognition were sought from PsycInfo, Scopus, CINAHL, Web of Science, SPORTDiscus, and PubMed, with the final search conducted on November 2, 2022.
STUDY SELECTION
Two independent researchers screened titles with abstracts and full-text reports.
DATA EXTRACTION AND SYNTHESIS
Two reviewers independently assessed study quality and extracted data. Pooled estimates of association were calculated with random-effects meta-analyses. An extensive set of moderators, funnel plots, and scatter plots of physical activity amount were examined. This study is reported following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline.
MAIN OUTCOMES AND MEASURES
Pooled estimates of the associations between physical activity and global cognition, as well as specific cognitive domains, were examined.
RESULTS
A total of 104 studies with 341 471 participants were assessed. Analysis of binary outcomes included 45 studies with 102 452 individuals, analysis of follow-up global cognition included 14 studies with 41 045 individuals, and analysis of change in global cognition included 25 studies with 67 463 individuals. Physical activity was associated with a decreased incidence of cognitive impairment or decline after correction for funnel plot asymmetry (pooled risk ratio, 0.97; 95% CI, 0.97-0.99), but there was no significant association in follow-ups longer than 10 years. Physical activity was associated with follow-up global cognition (standardized regression coefficient, 0.03; 95% CI, 0.02-0.03) and change in global cognition (standardized regression coefficient, 0.01; 95% CI, 0.01 to 0.02) from trim-and-fill analyses, with no clear dose-response or moderation by follow-up length, baseline age, study quality or adjustment for baseline cognition. The specific cognitive domains associated with physical activity were episodic memory (standardized regression coefficient, 0.03; 95% CI, 0.02-0.04) and verbal fluency (standardized regression coefficient, 0.05; 95% CI, 0.03-0.08).
CONCLUSIONS AND RELEVANCE
In this meta-analysis of the association of physical activity with cognitive decline, physical activity was associated with better late-life cognition, but the association was weak. However, even a weak association is important from a population health perspective.
Topics: Humans; Aged; Prospective Studies; Cognitive Dysfunction; Cognition; Exercise; Memory, Episodic
PubMed: 38300618
DOI: 10.1001/jamanetworkopen.2023.54285 -
Neurotrauma Reports 2024This systematic review focuses on an increasing subset of traumatic brain injury (TBI) survivors who develop post-traumatic parkinsonism (PTP), characterized by slowness...
This systematic review focuses on an increasing subset of traumatic brain injury (TBI) survivors who develop post-traumatic parkinsonism (PTP), characterized by slowness of movement (bradykinesia), rigidity (stiffness), postural instability, and resting tremors caused by obstruction or damage to deep brain structures of the basal ganglia. PTP is rare, and one hypothesis to explain PTP rarity is that TBIs severe enough to affect deep brain structures are often lethal; however, with increasing survivability of TBIs, these numbers are expected to increase. The goal of this review is to raise awareness of an expected global increase of a subgroup of TBI patients who are treatment responsive and report therapeutic results aiding providers in diagnosing, educating, and treating PTP patients. Literature over the past 100 years was considered, and 44,663 peer-reviewed articles were identified. Inclusion criteria required a clinical indication of parkinsonian signs and TBI. Twenty-six case reports were ultimately included from which 36 individual patient data points were extracted for this review. Between 1980 and 2010, there has been an increase in reporting of PTP decade after decade. Forty-seven percent of PTP cases have 1-6 months of latency to symptom onset, and 83% of cases were male. PTP can occur with or without presence of brain lesions, and the most common type of injuries that cause PTP are motor vehicle accidents followed by falls. PTP patients are responsive to surgery or medication treatments. Further detail on PTP symptomology, treatment responsiveness, and injury types is provided.
PubMed: 38292732
DOI: 10.1089/neur.2023.0104 -
Frontiers in Plant Science 2023The molecular and physiological mechanisms activated in plants during drought stress tolerance are regulated by several key genes with both metabolic and regulatory...
INTRODUCTION
The molecular and physiological mechanisms activated in plants during drought stress tolerance are regulated by several key genes with both metabolic and regulatory roles. Studies focusing on crop gene expression following plant growth-promoting rhizobacteria (PGPR) inoculation may help understand which bioinoculant is closely related to the induction of abiotic stress responses.
METHODS
Here, we performed a meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to summarise information regarding plant-PGPR interactions, focusing on the regulation of nine genes involved in plant drought stress response. The literature research yielded 3,338 reports, of which only 41 were included in the meta-analysis based on the chosen inclusion criteria. The meta-analysis was performed on four genes (ACO, APX, ACS and ); the other five genes (ERD15, MYB, MYC, acdS, WRKY) had an insufficient number of eligible articles.
RESULTS
Forest plots obtained through each meta-analysis showed that the overexpression of ACO, APX, ACS and genes was not statistically significant. Unlike the other genes, showed statistically significant results in both the presence and absence of PGPR. Considering I2>75 %, the results showed a high heterogeneity among the studies included, and the cause for this was examined using subgroup analysis. Moreover, the funnel plot and Egger's test showed that the analyses were affected by strong publication bias.
DISCUSSION
This study argues that the presence of PGPR may not significantly influence the expression of drought stress response-related crop genes. This finding may be due to high heterogeneity, lack of data on the genes examined, and significant publication bias.
PubMed: 38288406
DOI: 10.3389/fpls.2023.1282553 -
BMC Cancer Jan 2024Esophageal cancer (EC) is a deadly disease with limited therapeutic options. Although circulating tumor DNA (ctDNA) could be a promising tool in this regard, the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Esophageal cancer (EC) is a deadly disease with limited therapeutic options. Although circulating tumor DNA (ctDNA) could be a promising tool in this regard, the availiable evidence is limited. We performed a systematic review and meta-analysis to summarize the clinical applicability of the next-generation sequencing (NGS) and droplet digital polymerase chain reaction (ddPCR) technology on the ctDNA detection of the EC and listed the current challenges.
METHODS
We systematically searched MEDLINE (via PubMed), Embase (via OVID), ISI Web of Science database and Cochrane Library from January, 2000 to April, 2023. Progression-free survival (PFS) and overall survival (OS) were set as primary outcome endpoints. Pathologic response was evaluated by tumor regression grade (TRG), according to the eighth edition of the American Joint Committee on Cancer (AJCC). Major pathologic regression (MPR) was defined as TRG 1 and 2. The MPR was set as secondary endpoint. Hazard rate (HR) and associated 95% CI were used as the effect indicators the association between ctDNA and prognosis of EC. MPR rates were also calculated. Fixed-effect model (Inverse Variance) or random-effect model (Mantel-Haenszel method) was performed depending on the statistically heterogeneity.
RESULTS
Twenty-two studies, containing 1144 patients with EC, were included in this meta-analysis. The results showed that OS (HR = 3.87; 95% CI, 2.86-5.23) and PFS (HR = 4.28; 95% CI, 3.34-5.48) were shorter in ctDNA-positive patients. In the neoadjuvant therapy, the sensitivity analysis showed the clarified HR of ctDNA-positive was 1.13(95% CI, 1.01-1.28). We also found that TP53, NOTCH1, CCND1 and CNKN2A are the most frequent mutation genes.
CONCLUSIONS
Positive ctDNA is associated with poor prognosis, which demonstrated clinical value of ctDNA. Longitudinal ctDNA monitoring showed potential prognostic value in the neoadjuvant therapy. In an era of precision medicine, ctDNA could be a promising tool to individualize treatment planning and to improve outcomes in EC.
PROSPERO REGISTRATION NUMBER
CRD42023412465.
Topics: Humans; Circulating Tumor DNA; Esophageal Neoplasms; Databases, Factual; Gene Library; Genes, cdc
PubMed: 38267901
DOI: 10.1186/s12885-024-11879-6 -
International Journal of Molecular... Jan 2024The number of children suffering from cardiovascular diseases (CVDs) is rising globally. Therefore, there is an urgent need to acquire a better understanding of the...
The number of children suffering from cardiovascular diseases (CVDs) is rising globally. Therefore, there is an urgent need to acquire a better understanding of the genetic factors and molecular mechanisms related to the pathogenesis of CVDs in order to develop new prevention and treatment strategies for the future. MicroRNAs (miRNAs) constitute a class of small non-coding RNA fragments that range from 17 to 25 nucleotides in length and play an essential role in regulating gene expression, controlling an abundance of biological aspects of cell life, such as proliferation, differentiation, and apoptosis, thus affecting immune response, stem cell growth, ageing and haematopoiesis. In recent years, the concept of miRNAs as diagnostic markers allowing discrimination between healthy individuals and those affected by CVDs entered the purview of academic debate. In this review, we aimed to systematise available information regarding miRNAs associated with arrhythmias, cardiomyopathies, myocarditis and congenital heart diseases in children. We focused on the targeted genes and metabolic pathways influenced by those particular miRNAs, and finally, tried to determine the future of miRNAs as novel biomarkers of CVD.
Topics: Child; Humans; Aging; Apoptosis; Cardiovascular Diseases; Cell Cycle; MicroRNAs
PubMed: 38256030
DOI: 10.3390/ijms25020956 -
International Journal of Molecular... Jan 2024Craniopharyngiomas present unique challenges in surgical management due to their proximity to critical neurovascular structures. This systematic review investigates... (Review)
Review
Craniopharyngiomas present unique challenges in surgical management due to their proximity to critical neurovascular structures. This systematic review investigates genetic and immunological markers as potential targets for therapy in craniopharyngiomas, assessing their involvement in tumorigenesis, and their influence on prognosis and treatment strategies. The systematic review adhered to PRISMA guidelines, with a thorough literature search conducted on PubMed, Ovid MED-LINE, and Ovid EMBASE. Employing MeSH terms and Boolean operators, the search focused on craniopharyngiomas, targeted or molecular therapy, and clinical outcomes or adverse events. Inclusion criteria encompassed English language studies, clinical trials (randomized or non-randomized), and investigations into adamantinomatous or papillary craniopharyngiomas. Targeted therapies, either standalone or combined with chemotherapy and/or radiotherapy, were examined if they included clinical outcomes or adverse event analysis. Primary outcomes assessed disease response through follow-up MRI scans, categorizing responses as follows: complete response (CR), near-complete response (NCR), partial response, and stable or progressive disease based on lesion regression percentages. Secondary outcomes included treatment type and duration, as well as adverse events. A total of 891 papers were initially identified, of which 26 studies spanning from 2000 to 2023 were finally included in the review. Two tables highlighted adamantinomatous and papillary craniopharyngiomas, encompassing 7 and 19 studies, respectively. For adamantinomatous craniopharyngiomas, Interferon-2α was the predominant targeted therapy (29%), whereas dabrafenib took precedence (70%) for papillary craniopharyngiomas. Treatment durations varied, ranging from 1.7 to 28 months. Positive responses, including CR or NCR, were observed in both types of craniopharyngiomas (29% CR for adamantinomatous; 32% CR for papillary). Adverse events, such as constitutional symptoms and skin changes, were reported, emphasizing the need for vigilant monitoring and personalized management to enhance treatment tolerability. Overall, the data highlighted a diverse landscape of targeted therapies with encouraging responses and manageable adverse events, underscoring the importance of ongoing research and individualized patient care in the exploration of treatment options for craniopharyngiomas. In the realm of targeted therapies for craniopharyngiomas, tocilizumab and dabrafenib emerged as prominent choices for adamantinomatous and papillary cases, respectively. While adverse events were common, their manageable nature underscored the importance of vigilant monitoring and personalized management. Acknowledging limitations, future research should prioritize larger, well-designed clinical trials and standardized treatment protocols to enhance our understanding of the impact of targeted therapies on craniopharyngioma patients.
Topics: Humans; Ameloblastoma; Craniopharyngioma; Imidazoles; Oximes; Pituitary Neoplasms
PubMed: 38255797
DOI: 10.3390/ijms25020723 -
Biomolecules Jan 2024Ocular graft-versus-host disease (oGVHD) affects ~50% of post-stem cell transplant patients and is the only form of GVHD diagnosed without a biopsy. As it must be... (Review)
Review
Ocular graft-versus-host disease (oGVHD) affects ~50% of post-stem cell transplant patients and is the only form of GVHD diagnosed without a biopsy. As it must be distinguished from other dry eye diseases, there is a need to identify oGVHD biomarkers to improve diagnosis and treatment. We conducted a systematic review of 19 scholarly articles published from 2018 to 2023 including articles focused on adult patients diagnosed with oGVHD following allogeneic hematopoietic stem cell transplant and used biomarkers as the outcome measure. Articles that were not original investigations or were not published in English were excluded. These clinical investigations explored different molecular oGVHD biomarkers and were identified on 3 October 2023 from the Scopus, PubMed, and Embase databases by using search terms including ocular graft-versus-host disease, biomarkers, cytokines, proteomics, genomics, immune response, imaging techniques, and dry-eye-related key terms. The Newcastle-Ottawa scale for case-control studies was used to assess bias. From the 19 articles included, cytokine, proteomic, lipid, and leukocyte profiles were studied in tear film, as well as ocular surface microbiota and fluorescein staining. Our findings suggest that cytokine profiling is the most studied oGVHD biomarker. Additionally, variations correlating these biomarkers with disease state may lead to a more targeted diagnosis and therapeutic approach. Limitations include language bias, publication bias, and sampling bias, as well as a lack of appropriate controls for included studies.
Topics: Adult; Humans; Proteomics; Biomarkers; Biopsy; Cytokines; Graft vs Host Disease
PubMed: 38254702
DOI: 10.3390/biom14010102 -
EXCLI Journal 2023Hesperidin and hesperetin, two flavonoids with potential therapeutic value, have been extensively studied in the context of diabetes management. The main objective of... (Review)
Review
Hesperidin and hesperetin, two flavonoids with potential therapeutic value, have been extensively studied in the context of diabetes management. The main objective of this research is to ascertain their potential as therapeutic options for managing diabetes and its complications. The present study utilized a systematic review methodology and comprehensively explored relevant literature from databases, including PubMed, Scopus, and Web of Science, from inception until July 2023. The review summarized the outcomes related to the molecular, cellular, and metabolic effects of hesperidin and hesperetin in diabetes and its complications. Hesperetin exhibits a potential treatment for preventing diabetes and its associated complications through modulation of inflammatory cytokine release and expression via the pathway of signaling through Toll-like receptor/Myeloid differentiation factor 88/Nuclear factor-kappa B. Hesperidin shows promise as a biomolecule for treating diabetic neuropathy, primarily through activation of nuclear factor erythroid 2-related factor 2 (Nrf-2), as an antioxidant-response element signaling, leading to neuroprotective effects. Both compounds demonstrated the ability to normalize blood glucose levels and reduce serum and liver lipid levels, making them potential candidates for managing hypoglycemia and hypolipidemia in diabetes. Hesperidin also showed potential benefits against diabetic nephropathy by suppressing transforming growth factor-β1-integrin-linked kinase-Akt signaling and enhancing renal function. Furthermore, hesperidin's antioxidant, anti-inflammatory, and anti-depressant effects in diabetic conditions expanded its potential therapeutic applications. This systematic review provides substantial evidence supporting the consideration of hesperidin and hesperetin for diabetes and its complications. It offers exciting possibilities for developing novel, cost-effective treatment options to enhance diabetes management and patient outcomes.
PubMed: 38234970
DOI: 10.17179/excli2023-6577 -
Clinical Nutrition ESPEN Feb 2024Body composition reflects nutritional status, disease status and progression, and treatment responses. Mounting evidence supports the use of bioelectrical impedance...
BACKGROUND
Body composition reflects nutritional status, disease status and progression, and treatment responses. Mounting evidence supports the use of bioelectrical impedance analysis (BIA) as a non-invasive tool to assess body composition. Patients with benign gastrointestinal (GI) disease experience disease-related alterations in their body composition, and bioimpedance outcomes in patients with benign GI diseases have not previously been summarized. We aimed to evaluate BIA as a clinical body composition marker for benign GI diseases and describe its association with physical health status.
METHODS
We systematically searched PubMed, Scopus, Web of Science, Embase, and CINAHL from inception to October 2023 (PROSPERO registration: CRD42021265866). Of 971 screened studies, 26 studies were included in the final analysis, comprising a total of 2398 adult patients with benign GI disease. The main outcome was raw impedance data.
RESULTS
The most frequently reported BIA outcome was phase angle (PhA) (reported in 18 of 26 studies), followed by fat-free-mass (FFM) (reported in 13 of 26 studies). The consensus view of the included studies illustrates that BIA can be a useful tool for evaluating body composition in patients with benign GI diseases, and low PhA and FFM were associated with increased nutritional risk, abnormal physical characteristics, and increased mortality risk.
CONCLUSION
To fully utilize BIA as a clinical marker of health in patients with benign GI disease, standardized protocols specific to this population are needed and prospective studies testing cut-offs and ranges, accuracy, and other raw BIA parameters for classifying disease status.
Topics: Adult; Humans; Electric Impedance; Prospective Studies; Health Status; Body Composition; Gastrointestinal Diseases; Biomarkers
PubMed: 38220401
DOI: 10.1016/j.clnesp.2023.12.145