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The Journal of Headache and Pain May 2023Neuroimaging studies have made an important contribution to our understanding of headache pathophysiology. This systematic review aims to provide a comprehensive... (Review)
Review
BACKGROUND
Neuroimaging studies have made an important contribution to our understanding of headache pathophysiology. This systematic review aims to provide a comprehensive overview and critical appraisal of mechanisms of actions of headache treatments and potential biomarkers of treatment response disclosed by imaging studies.
MAIN BODY
We performed a systematic literature search on PubMed and Embase databases for imaging studies investigating central and vascular effects of pharmacological and non-pharmacological treatments used to abort and prevent headache attacks. Sixty-three studies were included in the final qualitative analysis. Of these, 54 investigated migraine patients, 4 cluster headache patients and 5 patients with medication overuse headache. Most studies used functional magnetic resonance imaging (MRI) (n = 33) or molecular imaging (n = 14). Eleven studies employed structural MRI and a few used arterial spin labeling (n = 3), magnetic resonance spectroscopy (n = 3) or magnetic resonance angiography (n = 2). Different imaging modalities were combined in eight studies. Despite of the variety of imaging approaches and results, some findings were consistent. This systematic review suggests that triptans may cross the blood-brain barrier to some extent, though perhaps not sufficiently to alter the intracranial cerebral blood flow. Acupuncture in migraine, neuromodulation in migraine and cluster headache patients, and medication withdrawal in patients with medication overuse headache could promote headache improvement by reverting headache-affected pain processing brain areas. Yet, there is currently no clear evidence for where each treatment acts, and no firm imaging predictors of efficacy. This is mainly due to a scarcity of studies and heterogeneous treatment schemes, study designs, subjects, and imaging techniques. In addition, most studies used small sample sizes and inadequate statistical approaches, which precludes generalizable conclusions.
CONCLUSION
Several aspects of headache treatments remain to be elucidated using imaging approaches, such as how pharmacological preventive therapies work, whether treatment-related brain changes may influence therapy effectiveness, and imaging biomarkers of clinical response. In the future, well-designed studies with homogeneous study populations, adequate sample sizes and statistical approaches are needed.
Topics: Humans; Cluster Headache; Headache; Brain; Migraine Disorders; Headache Disorders, Secondary
PubMed: 37221469
DOI: 10.1186/s10194-023-01590-5 -
Biomedicine & Pharmacotherapy =... Oct 2021β-blockers are commonly prescribed to treat multiple cardiovascular (CV) diseases, but, frequently, adverse drug reactions and intolerance limit their use in clinical... (Meta-Analysis)
Meta-Analysis
β-blockers are commonly prescribed to treat multiple cardiovascular (CV) diseases, but, frequently, adverse drug reactions and intolerance limit their use in clinical practice. Interindividual variability in response to β-blockers may be explained by genetic differences. In fact, pharmacogenetic interactions for some of these drugs have been widely studied, such as metoprolol. But studies that explore genetic variants affecting bisoprolol response are inconclusive, limited or confusing because of mixed results with other β-Blockers, different genetic polymorphisms observed, endpoint studied etc. Because of this, we performed a systematic review in order to find relevant genetic variants affecting bisoprolol response. We have found genetic polymorphism in several genes, but most of the studies focused in ADRB variants. The ADRB1 Arg389Gly (rs1801253) was the most studied genetic polymorphism and it seems to influence the response to bisoprolol, although studies are inconclusive. Even, we performed a meta-analysis about its influence on systolic/diastolic blood pressure in patients treated with bisoprolol, but this did not show statistically significant results. In conclusion, many genetic polymorphisms have been assessed about their influence on patients´ response to bisoprolol and the ADRB1 Arg389Gly (rs1801253) seems the most relevant genetic polymorphism in this regard but results have not been confirmed with a meta-analysis. Our results support the need of further studies about the impact of genetic variants on bisoprolol response, considering different genetic polymorphisms and conducting single and multiple SNPs analysis, including other clinical parameters related to bisoprolol response in a multivariate study.
Topics: Adrenergic beta-1 Receptor Antagonists; Bisoprolol; Blood Pressure; Cardiovascular Diseases; Humans; Pharmacogenetics; Polymorphism, Single Nucleotide; Receptors, Adrenergic, beta-1; Treatment Outcome
PubMed: 34470728
DOI: 10.1016/j.biopha.2021.112069 -
Advances in Nutrition (Bethesda, Md.) Jan 2024Dairy intake may influence cognition through several molecular pathways. However, epidemiologic studies yield inconsistent results, and no dose-response meta-analysis... (Meta-Analysis)
Meta-Analysis Review
Dairy intake may influence cognition through several molecular pathways. However, epidemiologic studies yield inconsistent results, and no dose-response meta-analysis has been conducted yet. Therefore, we performed a systematic review with a dose-response meta-analysis about the association between dairy intake and cognitive decline or incidence of dementia. We investigated prospective studies with a follow-up ≥6 mo on cognitive decline or dementia incidence in adults without known chronic conditions through a systematic search of Embase, Medline, Cochrane Library, Web of Science, and Google Scholar from inception to 11 July 2023. We evaluated the dose-response association using a random-effects model. We identified 15 eligible cohort studies with >300,000 participants and a median follow-up of 11.4 y. We observed a negative nonlinear association between cognitive decline/dementia incidence and dairy intake as assessed through the quantity of consumption, with the nadir at ∼150 g/d (risk ratio: 0.88; 95% confidence interval: 0.78, 0.99). Conversely, we found an almost linear negative association when we considered the frequency of consumption (risk ratio for linear trend: 0.84; 95% confidence interval: 0.77, 0.92 for 1 time/d increase of dairy products). Stratified analysis by dairy products showed different shapes of the association with linear inverse relationship for milk intake, whereas possibly nonlinear for cheese. The inverse association was limited to Asian populations characterized by generally lower intake of dairy products, compared with the null association reported by European studies. In conclusion, our study suggests a nonlinear inverse association between dairy intake and cognitive decline or dementia, also depending on dairy types and population characteristics, although the heterogeneity was still high in overall and several subgroup analyses. Additional studies should be performed on this topic, including a wider range of intake and types of dairy products, to confirm a potential preventing role of dairy intake on cognitive decline and identify ideal intake doses. This review was registered at PROSPERO as CRD42020192395.
Topics: Animals; Humans; Cognitive Dysfunction; Dairy Products; Dementia; Diet; Milk; Prospective Studies; Risk Factors
PubMed: 38043604
DOI: 10.1016/j.advnut.2023.100160 -
The Lancet Regional Health. Western... Sep 2023The treatment of esophageal cancer has entered a new phase with the development of immunotherapy. The current investigation purpose is to investigate and contrast the...
Efficacy and safety of immunochemotherapy, immunotherapy, chemotherapy, and targeted therapy as first-line treatment for advanced and metastatic esophageal cancer: a systematic review and network meta-analysis.
BACKGROUND
The treatment of esophageal cancer has entered a new phase with the development of immunotherapy. The current investigation purpose is to investigate and contrast the efficacy and safety of immunotherapy, immunochemotherapy, chemotherapy, and targeted therapy as first-line treatment for individuals suffering from advanced and metastatic esophageal cancer.
METHODS
Within the framework of this systematic review and network meta-analysis, clinical trials published or reported in English up until 01 May, 2022, were retrieved from Embase, PubMed, Cochrane Central Register of Controlled Trials, the ClinicalTrials.gov databases, ESMO, and ASCO. The analysis incorporated randomized controlled trials (RCTs) from phase 2 to 3 that evaluated a minimum of two first-line therapeutic regimens for metastatic esophageal cancer were included in the analysis. The primary outcomes were overall survival (OS) and progression-free survival (PFS). Secondary clinical outcomes included the incidence of objective response rate (ORR), and adverse events (AEs) of any grade and ≥3 grade. Relative summary data were extracted from included studies by GZ, HS, WS, and TD. For clear statistical analysis, chemotherapy was divided into two categories of fluorouracil-based chemotherapy (FbCT) and fluorouracil-free chemotherapy (FfCT). Bayesian frequentist approach was employed to conduct the network meta-analysis. The indirect intercomparison between regimens was presented with league tables (HRs and 95% CI for OS and PFS, ORs and 95% CI for ORR and AEs). A greater surface value under the cumulative ranking (SUCRA) indicates a higher potential ranking for the corresponding treatment. A further calculation of relative results about esophageal squamous cell cancer was performed in the subgroup analysis. The current protocol for the systematic review has been properly registered on PROSPERO (registration number: CRD42021241145).
FINDINGS
The final analysis comprised 17 trials that involved 9128 patients and 19 distinct treatment regimens. Within the scope of investigated immunotherapy (IO) combinations, toripalimab + FfCT (tori + FfCT) demonstrated the best OS advantages (tori + FfCT vs. FbCT, HR 0.57, 95% CI 0.38-0.85; tori + FfCT vs. FfCT, HR 0.58, 95% CI 0.43-0.78). In terms of PFS, camrelizumab + FfCT (cam + FfCT) demonstrated the best PFS advantages (FbCT vs. cam + FfCT, HR 1.79, 95% CI 1.22-2.63; FfCT vs. cam + FfCT, HR 1.79, 95% CI 1.47-2.17). Nivolumab + FbCT (nivo + FbCT vs. FfCT, OR 3.29, 95% CI 1.43-7.56) showed the best objective responses. Compared to the conventional chemotherapy regimen, the toxicity was observed to be the slightest for the tori + FfCT (FbCT vs. tori + FfCT, OR 3.07, 95% CI 1.22-7.7) and sintilimab + FfCT (FbCT vs. sin + FfCT, OR 2.93, 95% CI 1.16-7.37). The results in this study were evaluated as having a low heterogeneity since the I value was ≤25% in all analyses.
INTERPRETATION
Compared to foreign IO combinations, sin + FfCT, tori + FfCT, cam + FfCT, and tisle + FbCT are superior first-line treatment options for patients with advanced and metastatic esophageal cancer. Although foreign IO combinations, such as pembro + FbCT and nivo + FbCT obtained better objective response rates than other IO combinations, the addition of chemotherapy to IO worsens the safety profiles. Our findings could provide complementary evidence for current guideline recommendations.
FUNDING
This work was supported by a grant from the Science and Technology Program of Guangzhou, China (202206010103); and Natural Science Foundation of Guangdong Province (2022A1515012469).
PubMed: 37457900
DOI: 10.1016/j.lanwpc.2023.100841 -
Biotechnology Advances Oct 2023Temperature affects cellular processes at different spatiotemporal scales, and identifying the genetic and molecular mechanisms underlying temperature responses paves... (Review)
Review
Temperature affects cellular processes at different spatiotemporal scales, and identifying the genetic and molecular mechanisms underlying temperature responses paves the way to develop approaches for mitigating the effects of future climate scenarios. A systems view of the effects of temperature on cellular physiology can be obtained by focusing on metabolism since: (i) its functions depend on transcription and translation and (ii) its outcomes support organisms' development, growth, and reproduction. Here we provide a systematic review of modelling efforts directed at investigating temperature effects on properties of single biochemical reactions, system-level traits, metabolic subsystems, and whole-cell metabolism across different prokaryotes and eukaryotes. We compare and contrast computational approaches and theories that facilitate modelling of temperature effects on key properties of enzymes and their consideration in constraint-based as well as kinetic models of metabolism. In addition, we provide a summary of insights from computational approaches, facilitating integration of omics data from temperature-modulated experiments with models of metabolic networks, and review the resulting biotechnological applications. Lastly, we provide a perspective on how different types of metabolic modelling can profit from developments in machine learning and models of different cellular layers to improve model-driven insights into the effects of temperature relevant for biotechnological applications.
Topics: Temperature; Metabolic Networks and Pathways; Phenotype; Models, Biological
PubMed: 37348662
DOI: 10.1016/j.biotechadv.2023.108203 -
Critical Reviews in Oncology/hematology Jun 2023The treatment of locally advanced rectal cancer often consists of neoadjuvant chemoradiotherapy followed by surgery. However, approximately 15% of patients show no... (Review)
Review
BACKGROUND AND AIMS
The treatment of locally advanced rectal cancer often consists of neoadjuvant chemoradiotherapy followed by surgery. However, approximately 15% of patients show no response to this neoadjuvant chemoradiotherapy. This systematic review aimed to identify biomarkers of innate radioresistant rectal cancer.
METHOD
Through a systematic literature search, 125 papers were included and analyzed using ROBINS-I, a Cochrane risk of bias tool for non-randomized studies of interventions. Both statistically significant and nonsignificant biomarkers were identified. Biomarkers mentioned more than once in the results or biomarkers with a low or moderate risk of bias were included as the final results.
RESULTS
Thirteen unique biomarkers, three genetic signatures, one specific pathway, and two combinations of two or four biomarkers were identified. In particular, the connection between HMGCS2, COASY, and PI3K-pathway seems promising. Future scientific research should focus on further validating these genetic resistance markers.
Topics: Humans; Phosphatidylinositol 3-Kinases; Chemoradiotherapy; Rectal Neoplasms; Neoadjuvant Therapy; Biomarkers, Tumor; Treatment Outcome; Neoplasm Staging
PubMed: 37059272
DOI: 10.1016/j.critrevonc.2023.103991 -
Clinical and Experimental Immunology Jul 2021Cytotoxic T lymphocyte antigen 4 (CTLA-4) haploinsufficiency (CHAI) and lipopolysaccharide-responsive beige-like anchor (LRBA) deficiency (LATAIE) are newly identified... (Review)
Review
Cytotoxic T lymphocyte antigen 4 (CTLA-4) haploinsufficiency (CHAI) and lipopolysaccharide-responsive beige-like anchor (LRBA) deficiency (LATAIE) are newly identified inborn errors of immunity with shared molecular pathomechanisms and clinical manifestations. In this review, we aimed to provide differential comparisons regarding demographic, clinical, immunological and molecular characteristics between these two similar conditions. A literature search was conducted in PubMed, Web of Science and Scopus databases and included studies were systematically evaluated. Overall, 434 (222 CHAI and 212 LATAIE) patients were found in 101 eligible studies. The CHAI patients were mainly reported from North America and western Europe, while LATAIE patients were predominantly from Asian countries. In CHAI, positive familial history (P < 0·001) and in LATAIE, consanguineous parents (P < 0·001) were more common. In CHAI patients the rates of granulomas (P < 0·001), malignancies (P = 0·001), atopy (P = 0·001), cutaneous disorders (P < 0·001) and neurological (P = 0·002) disorders were higher, while LATAIE patients were more commonly complicated with life-threatening infections (P = 0·002), pneumonia (P = 0·006), ear, nose and throat disorders (P < 0·001), organomegaly (P = 0·023), autoimmune enteropathy (P = 0·038) and growth failure (P < 0·001). Normal lymphocyte subsets and immunoglobulins except low serum levels of CD9 B cells (14·0 versus 38·4%, P < 0·001), natural killer (NK) cells (21 versus 41·1%, P < 0·001), immunoglobulin (Ig)G (46·9 versus 41·1%, P = 0·291) and IgA (54·5 versus 44·7%, P = 0·076) were found in the majority of CHAI and LATAIE patients, respectively. The most frequent biological immunosuppressive agents prescribed for CHAI and LATAIE patients were rituximab and abatacept, respectively. Further investigations into the best conditioning and treatment regimens pre- and post-transplantation are required to improve the survival rate of transplanted CHAI and LATAIE patients.
Topics: Adaptor Proteins, Signal Transducing; CTLA-4 Antigen; Haploinsufficiency; Humans; Immunoglobulins; Immunosuppressive Agents; Lymphocytes
PubMed: 33788257
DOI: 10.1111/cei.13600 -
The Cochrane Database of Systematic... Nov 2016Among pediatric patients, newborns are at highest risk of developing thromboembolism. Neonatal thromboembolic (TE) events may consist of both venous and arterial... (Review)
Review
BACKGROUND
Among pediatric patients, newborns are at highest risk of developing thromboembolism. Neonatal thromboembolic (TE) events may consist of both venous and arterial thromboses and often iatrogenic complications (eg, central catheterization). Treatment guidelines for pediatric patients with TE events most often are extrapolated from the literature regarding adults. Options for the management of neonatal TE events include expectant management; nitroglycerin ointment; thrombolytic therapy or anticoagulant therapy, or a combination of the two; and surgery. Since the 1990s, low molecular weight heparin (LMWH) has become the neonatal anticoagulant of choice. Reasons for its appeal include predictable dose response, no need for venous access, and limited monitoring requirements. The overall major complication rate is around 5%. Whether preterm infants are at increased risk is unclear. No data are available on the frequency of osteoporosis, heparin-induced thrombocytopenia (HIT), or other hypersensitivity reactions in children and neonates exposed to LMWH.
OBJECTIVES
To assess whether heparin treatment (both unfractionated heparin [UFH] and LMWH) reduces mortality and morbidity rates in preterm and term newborn infants with diagnosed thrombosis. The intervention is compared with placebo or no treatment. Also, to assess the safety of heparin therapy (both UFH and LMWH) for potential harms.Subgroup analyses were planned to examine gestational age, birth weight, mode of thrombus diagnosis, presence of a central line, positive family history for genetic disorders (thrombophilia, deficiency of protein S and protein C, methylenetetrahydrofolate reductase [MTHFR] mutation), route of heparin administration, type of heparin used, and location of thrombus (see "Subgroup analysis and investigation of heterogeneity").
SEARCH METHODS
We used the standard search strategy of the Cochrane Neonatal Review Group to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 4), MEDLINE via PubMed (1966 to May 9, 2016), Embase (1980 to May 9, 2016), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to May 9, 2016). We searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomized controlled trials and quasi-randomized trials.
SELECTION CRITERIA
Randomized, quasi-randomized, and cluster-randomized controlled trials comparing heparin versus placebo or no treatment in preterm and term neonates with a diagnosis of thrombosis.
DATA COLLECTION AND ANALYSIS
We used the standard methods of the Cochrane Neonatal Review Group. Two review authors independently assessed studies identified by the search strategy for inclusion.
MAIN RESULTS
Our search strategy yielded 1160 references. Two review authors independently assessed all references for inclusion. We found no completed studies and no ongoing trials for inclusion.
AUTHORS' CONCLUSIONS
We found no studies that met our inclusion criteria and no evidence from randomized controlled trials to recommend or refute the use of heparin for treatment of neonates with thrombosis.
Topics: Anticoagulants; Heparin; Heparin, Low-Molecular-Weight; Humans; Infant, Newborn; Thrombosis
PubMed: 27820879
DOI: 10.1002/14651858.CD012185.pub2 -
Autoimmunity Reviews Mar 2021Regulatory T cells (Tregs) are a subset of T cells responsible for the regulation of immune responses, thereby maintaining immune homeostasis and providing immune... (Review)
Review
Regulatory T cells (Tregs) are a subset of T cells responsible for the regulation of immune responses, thereby maintaining immune homeostasis and providing immune tolerance to both self and non-self-antigens. An increasing number of studies revealed Treg numbers and functions in a variety of autoimmune diseases. Treg deficiency can cause the development of several autoimmune skin diseases including vitiligo, alopecia areata, pemphigoid and pemphigus, psoriasis, and systemic sclerosis. Many clinical trials have been performed for autoimmune conditions using polyclonal Tregs, but efficiency can be significantly improved using antigen-specific Tregs engineered using T cell receptor (TCR) or chimeric antigen receptor (CAR) constructs. In this review, we systematically reviewed altered frequencies, impaired functions, and phenotypic features of Tregs in autoimmune skin conditions. We also summarized new advances in TCR and CAR based antigen-specific Tregs tested both in animal models and in clinics. The advantages and limitations of each approach were carefully discussed emphasizing possible clinical relevance to patients with autoimmune skin diseases. Moreover, we have reviewed potential approaches for engineering antigen-specific Tregs, and strategies for overcoming possible hurdles in clinical applications. Thereby, antigen-specific Tregs can be infused using autologous adoptive cell transfer to restore Treg numbers and to provide local immune tolerance for autoimmune skin disorders.
Topics: Animals; Autoimmune Diseases; Humans; Immune Tolerance; Receptors, Antigen, T-Cell; Skin Diseases; T-Lymphocytes, Regulatory
PubMed: 33476816
DOI: 10.1016/j.autrev.2021.102761 -
EJNMMI Research Dec 2017Mesenchymal-epithelial transition factor also named c-MET is a receptor tyrosine kinase for the hepatocyte growth factor that plays a pivotal role in tumorigenesis.... (Review)
Review
BACKGROUND
Mesenchymal-epithelial transition factor also named c-MET is a receptor tyrosine kinase for the hepatocyte growth factor that plays a pivotal role in tumorigenesis. c-MET-targeted therapies have been tested in preclinical models and patients, with significant benefits for cancer treatment. In recent years, many studies have shown that the expression level and activation status of c-MET are closely correlated to c-MET-targeted therapy response and clinical prognosis, thus highlighting the importance of evaluating the c-MET status during and prior to targeted therapy. Molecular imaging allows the monitoring of abnormal alterations of c-MET in real time and in vivo.
RESULTS
In this review, we initially summarize the recent advances in c-MET-targeted molecular imaging, with a special focus on the development of imaging agents ranging in size from monoclonal antibody to small molecule. The aim of this review is to report the preclinical results and clinical application of all molecular imaging studies completed until now for in vivo detection of c-MET in cancer, in order to be beneficial to development of molecular probe and the combination of molecular imaging technologies for in vivo evaluation of c-MET. Various molecular probe targeted to c-MET possesses distinctive advantages and disadvantages. For example, antibody-based probes have high binding affinity but with long metabolic cycle as well as remarkable immunogenicity.
CONCLUSIONS
Although studies for c-MET-targeted molecular imaging have made many important advances, most of imaging agents specifically target to extracellular area of c-MET receptor; however, it is difficult to reflect entirely activation of c-MET. Therefore, small molecule probes based on tyrosine kinase inhibitors, which could target to intracellular area of c-MET without any immunogenicity, should be paid more attention.
PubMed: 28485003
DOI: 10.1186/s13550-017-0286-z