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Pharmacological Research Sep 2021Glioblastoma multiforme (GBM) is a WHO grade IV glioma and the most common malignant, primary brain tumor with a 5-year survival of 7.2%. Its highly infiltrative nature,...
Glioblastoma multiforme (GBM) is a WHO grade IV glioma and the most common malignant, primary brain tumor with a 5-year survival of 7.2%. Its highly infiltrative nature, genetic heterogeneity, and protection by the blood brain barrier (BBB) have posed great treatment challenges. The standard treatment for GBMs is surgical resection followed by chemoradiotherapy. The robust DNA repair and self-renewing capabilities of glioblastoma cells and glioma initiating cells (GICs), respectively, promote resistance against all current treatment modalities. Thus, durable GBM management will require the invention of innovative treatment strategies. In this review, we will describe biological and molecular targets for GBM therapy, the current status of pharmacologic therapy, prominent mechanisms of resistance, and new treatment approaches. To date, medical imaging is primarily used to determine the location, size and macroscopic morphology of GBM before, during, and after therapy. In the future, molecular and cellular imaging approaches will more dynamically monitor the expression of molecular targets and/or immune responses in the tumor, thereby enabling more immediate adaptation of tumor-tailored, targeted therapies.
Topics: Animals; Antineoplastic Agents; Brain Neoplasms; Drug Resistance, Neoplasm; Glioblastoma; Humans
PubMed: 34302977
DOI: 10.1016/j.phrs.2021.105780 -
Annals of the Rheumatic Diseases May 2018To develop evidence-based recommendations for the use of imaging modalities in primary large vessel vasculitis (LVV) including giant cell arteritis (GCA) and Takayasu...
To develop evidence-based recommendations for the use of imaging modalities in primary large vessel vasculitis (LVV) including giant cell arteritis (GCA) and Takayasu arteritis (TAK). European League Against Rheumatism (EULAR) standardised operating procedures were followed. A systematic literature review was conducted to retrieve data on the role of imaging modalities including ultrasound, MRI, CT and [F]-fluorodeoxyglucose positron emission tomography (PET) in LVV. Based on evidence and expert opinion, the task force consisting of 20 physicians, healthcare professionals and patients from 10 EULAR countries developed recommendations, with consensus obtained through voting. The final level of agreement was voted anonymously. A total of 12 recommendations have been formulated. The task force recommends an early imaging test in patients with suspected LVV, with ultrasound and MRI being the first choices in GCA and TAK, respectively. CT or PET may be used alternatively. In case the diagnosis is still in question after clinical examination and imaging, additional investigations including temporal artery biopsy and/or additional imaging are required. In patients with a suspected flare, imaging might help to better assess disease activity. The frequency and choice of imaging modalities for long-term monitoring of structural damage remains an individual decision; close monitoring for aortic aneurysms should be conducted in patients at risk for this complication. All imaging should be performed by a trained specialist using appropriate operational procedures and settings. These are the first EULAR recommendations providing up-to-date guidance for the role of imaging in the diagnosis and monitoring of patients with (suspected) LVV.
Topics: Europe; Fluorodeoxyglucose F18; Giant Cell Arteritis; Humans; Magnetic Resonance Imaging; Positron-Emission Tomography; Radiopharmaceuticals; Rheumatology; Takayasu Arteritis; Tomography, X-Ray Computed; Ultrasonography; Vasculitis
PubMed: 29358285
DOI: 10.1136/annrheumdis-2017-212649 -
The Lancet. Psychiatry Jul 2016Many countries are developing suicide prevention strategies for which up-to-date, high-quality evidence is required. We present updated evidence for the effectiveness of... (Review)
Review
BACKGROUND
Many countries are developing suicide prevention strategies for which up-to-date, high-quality evidence is required. We present updated evidence for the effectiveness of suicide prevention interventions since 2005.
METHODS
We searched PubMed and the Cochrane Library using multiple terms related to suicide prevention for studies published between Jan 1, 2005, and Dec 31, 2014. We assessed seven interventions: public and physician education, media strategies, screening, restricting access to suicide means, treatments, and internet or hotline support. Data were extracted on primary outcomes of interest, namely suicidal behaviour (suicide, attempt, or ideation), and intermediate or secondary outcomes (treatment-seeking, identification of at-risk individuals, antidepressant prescription or use rates, or referrals). 18 suicide prevention experts from 13 European countries reviewed all articles and rated the strength of evidence using the Oxford criteria. Because the heterogeneity of populations and methodology did not permit formal meta-analysis, we present a narrative analysis.
FINDINGS
We identified 1797 studies, including 23 systematic reviews, 12 meta-analyses, 40 randomised controlled trials (RCTs), 67 cohort trials, and 22 ecological or population-based investigations. Evidence for restricting access to lethal means in prevention of suicide has strengthened since 2005, especially with regard to control of analgesics (overall decrease of 43% since 2005) and hot-spots for suicide by jumping (reduction of 86% since 2005, 79% to 91%). School-based awareness programmes have been shown to reduce suicide attempts (odds ratio [OR] 0·45, 95% CI 0·24-0·85; p=0·014) and suicidal ideation (0·5, 0·27-0·92; p=0·025). The anti-suicidal effects of clozapine and lithium have been substantiated, but might be less specific than previously thought. Effective pharmacological and psychological treatments of depression are important in prevention. Insufficient evidence exists to assess the possible benefits for suicide prevention of screening in primary care, in general public education and media guidelines. Other approaches that need further investigation include gatekeeper training, education of physicians, and internet and helpline support. The paucity of RCTs is a major limitation in the evaluation of preventive interventions.
INTERPRETATION
In the quest for effective suicide prevention initiatives, no single strategy clearly stands above the others. Combinations of evidence-based strategies at the individual level and the population level should be assessed with robust research designs.
FUNDING
The Expert Platform on Mental Health, Focus on Depression, and the European College of Neuropsychopharmacology.
Topics: Humans; Program Evaluation; Randomized Controlled Trials as Topic; Suicide Prevention
PubMed: 27289303
DOI: 10.1016/S2215-0366(16)30030-X -
European Urology Jul 2023Whether prostate-specific membrane antigen positron emission tomography (PSMA-PET) should replace conventional imaging modalities (CIM) for initial staging of... (Meta-Analysis)
Meta-Analysis Review
Head-to-head Comparison of the Diagnostic Accuracy of Prostate-specific Membrane Antigen Positron Emission Tomography and Conventional Imaging Modalities for Initial Staging of Intermediate- to High-risk Prostate Cancer: A Systematic Review and Meta-analysis.
CONTEXT
Whether prostate-specific membrane antigen positron emission tomography (PSMA-PET) should replace conventional imaging modalities (CIM) for initial staging of intermediate-high risk prostate cancer (PCa) requires definitive evidence on their relative diagnostic abilities.
OBJECTIVE
To perform head-to-head comparisons of PSMA-PET and CIM including multiparametric magnetic resonance imaging (mpMRI), computed tomography (CT) and bone scan (BS) for upfront staging of tumour, nodal, and bone metastasis.
EVIDENCE ACQUISITION
A search of the PubMed, EMBASE, CENTRAL, and Scopus databases was conducted from inception to December 2021. Only studies in which patients underwent both PSMA-PET and CIM and imaging was referenced against histopathology or composite reference standards were included. Quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) checklist and its extension for comparative reviews (QUADAS-C). Pairwise comparisons of the sensitivity and specificity of PSMA-PET versus CIM were performed by adding imaging modality as a covariate to bivariate mixed-effects meta-regression models. The likelihood ratio test was applied to determine whether statistically significant differences existed.
EVIDENCE SYNTHESIS
A total of 31 studies (2431 patients) were included. PSMA-PET/MRI was more sensitive than mpMRI for detection of extra-prostatic extension (78.7% versus 52.9%) and seminal vesicle invasion (66.7% versus 51.0%). For nodal staging, PSMA-PET was more sensitive and specific than mpMRI (73.7% versus 38.9%, 97.5% versus 82.6%) and CT (73.2% versus 38.5%, 97.8% versus 83.6%). For bone metastasis staging, PSMA-PET was more sensitive and specific than BS with or without single-photon emission computerised tomography (98.0% versus 73.0%, 96.2% versus 79.1%). A time interval between imaging modalities >1 month was identified as a source of heterogeneity across all nodal staging analyses.
CONCLUSIONS
Direct comparisons revealed that PSMA-PET significantly outperforms CIM, which suggests that PSMA-PET should be used as a first-line approach for the initial staging of PCa.
PATIENT SUMMARY
We reviewed direct comparisons of the ability of a scan method called PSMA-PET (prostate-specific membrane antigen positron emission tomography) and current imaging methods to detect the spread of prostate cancer outside the prostate gland. We found that PSMA-PET is more accurate for detection of the spread of prostate cancer to adjacent tissue, nearby lymph nodes, and bones.
Topics: Male; Humans; Prostate; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Prostatic Neoplasms; Magnetic Resonance Imaging; Gallium Radioisotopes; Neoplasm Staging
PubMed: 37032189
DOI: 10.1016/j.eururo.2023.03.001 -
The American Journal of Psychiatry Jul 2021The authors sought to identify scalable evidence-based suicide prevention strategies.
OBJECTIVE
The authors sought to identify scalable evidence-based suicide prevention strategies.
METHODS
A search of PubMed and Google Scholar identified 20,234 articles published between September 2005 and December 2019, of which 97 were randomized controlled trials with suicidal behavior or ideation as primary outcomes or epidemiological studies of limiting access to lethal means, using educational approaches, and the impact of antidepressant treatment.
RESULTS
Training primary care physicians in depression recognition and treatment prevents suicide. Educating youths on depression and suicidal behavior, as well as active outreach to psychiatric patients after discharge or a suicidal crisis, prevents suicidal behavior. Meta-analyses find that antidepressants prevent suicide attempts, but individual randomized controlled trials appear to be underpowered. Ketamine reduces suicidal ideation in hours but is untested for suicidal behavior prevention. Cognitive-behavioral therapy and dialectical behavior therapy prevent suicidal behavior. Active screening for suicidal ideation or behavior is not proven to be better than just screening for depression. Education of gatekeepers about youth suicidal behavior lacks effectiveness. No randomized trials have been reported for gatekeeper training for prevention of adult suicidal behavior. Algorithm-driven electronic health record screening, Internet-based screening, and smartphone passive monitoring to identify high-risk patients are understudied. Means restriction, including of firearms, prevents suicide but is sporadically employed in the United States, even though firearms are used in half of all U.S. suicides.
CONCLUSIONS
Training general practitioners warrants wider implementation and testing in other nonpsychiatrist physician settings. Active follow-up of patients after discharge or a suicide-related crisis should be routine, and restricting firearm access by at-risk individuals warrants wider use. Combination approaches in health care systems show promise in reducing suicide in several countries, but evaluating the benefit attributable to each component is essential. Further suicide rate reduction requires evaluating newer approaches, such as electronic health record-derived algorithms, Internet-based screening methods, ketamine's potential benefit for preventing attempts, and passive monitoring of acute suicide risk change.
Topics: Evidence-Based Practice; Humans; Mass Screening; Suicide Prevention
PubMed: 33596680
DOI: 10.1176/appi.ajp.2020.20060864 -
International Journal of Molecular... Apr 2022Positron emission tomography (PET) uses radioactive tracers and enables the functional imaging of several metabolic processes, blood flow measurements, regional chemical... (Review)
Review
Positron emission tomography (PET) uses radioactive tracers and enables the functional imaging of several metabolic processes, blood flow measurements, regional chemical composition, and/or chemical absorption. Depending on the targeted processes within the living organism, different tracers are used for various medical conditions, such as cancer, particular brain pathologies, cardiac events, and bone lesions, where the most commonly used tracers are radiolabeled with 18F (e.g., [F]-FDG and NA [F]). Oxygen-15 isotope is mostly involved in blood flow measurements, whereas a wide array of C-based compounds have also been developed for neuronal disorders according to the affected neuroreceptors, prostate cancer, and lung carcinomas. In contrast, the single-photon emission computed tomography (SPECT) technique uses gamma-emitting radioisotopes and can be used to diagnose strokes, seizures, bone illnesses, and infections by gauging the blood flow and radio distribution within tissues and organs. The radioisotopes typically used in SPECT imaging are iodine-123, technetium-99m, xenon-133, thallium-201, and indium-111. This systematic review article aims to clarify and disseminate the available scientific literature focused on PET/SPECT radiotracers and to provide an overview of the conducted research within the past decade, with an additional focus on the novel radiopharmaceuticals developed for medical imaging.
Topics: Fluorodeoxyglucose F18; Humans; Male; Positron-Emission Tomography; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed
PubMed: 35563414
DOI: 10.3390/ijms23095023 -
Annals of the Rheumatic Diseases May 2024To update the EULAR recommendations for the use of imaging modalities in primary large vessel vasculitis (LVV).
OBJECTIVES
To update the EULAR recommendations for the use of imaging modalities in primary large vessel vasculitis (LVV).
METHODS
A systematic literature review update was performed to retrieve new evidence on ultrasound, MRI, CT and [F]-fluorodeoxyglucose positron emission tomography (FDG-PET) for diagnosis, monitoring and outcome prediction in LVV. The task force consisted of 24 physicians, health professionals and patients from 14 countries. The recommendations were updated based on evidence and expert opinion, iterating until voting indicated consensus. The level of agreement was determined by anonymous votes.
RESULTS
Three overarching principles and eight recommendations were agreed. Compared to the 2018 version, ultrasound is now recommended as first-line imaging test in all patients with suspected giant cell arteritis, and axillary arteries should be included in the standard examination. As an alternative to ultrasound, cranial and extracranial arteries can be examined by FDG-PET or MRI. For Takayasu arteritis, MRI is the preferred imaging modality; FDG-PET, CT or ultrasound are alternatives. Although imaging is not routinely recommended for follow-up, ultrasound, FDG-PET or MRI may be used for assessing vessel abnormalities in LVV patients with suspected relapse, particularly when laboratory markers of inflammation are unreliable. MR-angiography, CT-angiography or ultrasound may be used for long-term monitoring of structural damage, particularly at sites of preceding vascular inflammation.
CONCLUSIONS
The 2023 EULAR recommendations provide up-to-date guidance for the role of imaging in the diagnosis and assessment of patients with LVV.
Topics: Humans; Giant Cell Arteritis; Takayasu Arteritis; Ultrasonography; Magnetic Resonance Imaging; Fluorodeoxyglucose F18; Positron-Emission Tomography; Vasculitis; Tomography, X-Ray Computed; Axillary Artery
PubMed: 37550004
DOI: 10.1136/ard-2023-224543 -
PloS One 2022Public health and epidemiologic research have established that social connectedness promotes overall health. Yet there have been no recent reviews of findings from... (Review)
Review
Public health and epidemiologic research have established that social connectedness promotes overall health. Yet there have been no recent reviews of findings from research examining social connectedness as a determinant of mental health. The goal of this review was to evaluate recent longitudinal research probing the effects of social connectedness on depression and anxiety symptoms and diagnoses in the general population. A scoping review was performed of PubMed and PsychInfo databases from January 2015 to December 2021 following PRISMA-ScR guidelines using a defined search strategy. The search yielded 66 unique studies. In research with other than pregnant women, 83% (19 of 23) studies reported that social support benefited symptoms of depression with the remaining 17% (5 of 23) reporting minimal or no evidence that lower levels of social support predict depression at follow-up. In research with pregnant women, 83% (24 of 29 studies) found that low social support increased postpartum depressive symptoms. Among 8 of 9 studies that focused on loneliness, feeling lonely at baseline was related to adverse outcomes at follow-up including higher risks of major depressive disorder, depressive symptom severity, generalized anxiety disorder, and lower levels of physical activity. In 5 of 8 reports, smaller social network size predicted depressive symptoms or disorder at follow-up. In summary, most recent relevant longitudinal studies have demonstrated that social connectedness protects adults in the general population from depressive symptoms and disorders. The results, which were largely consistent across settings, exposure measures, and populations, support efforts to improve clinical detection of high-risk patients, including adults with low social support and elevated loneliness.
Topics: Adult; Anxiety Disorders; Depression; Depressive Disorder, Major; Female; Humans; Loneliness; Mental Health; Pregnancy; Social Support
PubMed: 36228007
DOI: 10.1371/journal.pone.0275004 -
Frontiers in Psychiatry 2019Recently discovered relationships between the gastrointestinal microbiome and the brain have implications for psychiatric disorders, including major depressive disorder...
Recently discovered relationships between the gastrointestinal microbiome and the brain have implications for psychiatric disorders, including major depressive disorder (MDD). Bacterial transplantation from MDD patients to rodents produces depression-like behaviors. In humans, case-control studies have examined the gut microbiome in healthy and affected individuals. We systematically reviewed existing studies comparing gut microbial composition in MDD and healthy volunteers. A PubMed literature search combined the terms "depression," "depressive disorder," "stool," "fecal," "gut," and "microbiome" to identify human case-control studies that investigated relationships between MDD and microbiota quantified from stool. We evaluated the resulting studies, focusing on bacterial taxa that were different between MDD and healthy controls. Six eligible studies were found in which 50 taxa exhibited differences ( < 0.05) between patients with MDD and controls. Patient characteristics and methodologies varied widely between studies. Five phyla-, and -were represented; however, divergent results occurred across studies for all phyla. The largest number of differentiating taxa were within phylum , in which nine families and 12 genera differentiated the diagnostic groups. The majority of these families and genera were found to be statistically different between the two groups in two identified studies. Family differentiated the diagnostic groups in four studies (with an even split in directionality). Across all five phyla, nine genera were higher in MDD (, and ), six were lower (, and ), and six were divergent (, and ). We highlight mechanisms and products of bacterial metabolism as they may relate to the etiology of depression. No consensus has emerged from existing human studies of depression and gut microbiome concerning which bacterial taxa are most relevant to depression. This may in part be due to differences in study design. Given that bacterial functions are conserved across taxonomic groups, we propose that studying microbial functioning may be more productive than a purely taxonomic approach to understanding the gut microbiome in depression.
PubMed: 30804820
DOI: 10.3389/fpsyt.2019.00034 -
European Urology Apr 2020Accurate staging of high-risk localised, advanced, and metastatic prostate cancer is becoming increasingly more important in guiding local and systemic treatment.... (Meta-Analysis)
Meta-Analysis
Gallium-68 Prostate-specific Membrane Antigen Positron Emission Tomography in Advanced Prostate Cancer-Updated Diagnostic Utility, Sensitivity, Specificity, and Distribution of Prostate-specific Membrane Antigen-avid Lesions: A Systematic Review and Meta-analysis.
CONTEXT
Accurate staging of high-risk localised, advanced, and metastatic prostate cancer is becoming increasingly more important in guiding local and systemic treatment. Gallium-68 prostate-specific membrane antigen (PSMA) positron emission tomography (PET) has increasingly been utilised globally to assess the local and metastatic burden of prostate cancer, typically in biochemically recurrent or advanced disease. Following our previous meta-analysis, a high-volume series has been reported highlighting the utility of Ga-PSMA PET in this setting.
OBJECTIVE
To perform a systematic review and meta-analysis to update reported predictors of positive Ga-PSMA PET according to prior therapy and proportion of positivity in various anatomical locations with sensitivity and specificity profiles.
EVIDENCE ACQUISITION
We performed critical reviews of MEDLINE, EMBASE, ScienceDirect, Cochrane Libraries, and Web of Science databases in July 2018 according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. Quality assessment was performed using Quality Assessment if Diagnostic Accuracy Studies-2 tool. Meta-analyses of proportions were performed using a random-effect model. Summary sensitivity and specificity values were obtained by fitting bivariate hierarchical regression models.
EVIDENCE SYNTHESIS
A total of 37 articles including 4790 patients were analysed. For patients with biochemical recurrence, positive Ga-PSMA PET scans increased with higher pre-PET prostate-specific antigen (PSA) levels. For PSA categories 0-0.19, 0.2-0.49, 0.5-0.99, 1-1.99, and ≥2ng/ml, the percentages of positive scans were 33%, 45%, 59%, 75%, and 95%, respectively. No significant differences in positivity were noted between Gleason sums ≤7 and ≥8. Significant differences in positivity after biochemical recurrence in the prostate bed were noted between radical prostatectomy (22%) and radiotherapy (52%) patients. On per-node analysis, high sensitivity (75%) and specificity (99%) were observed.
CONCLUSIONS
Ga-68-PSMA PET improves detection of metastases with biochemical recurrence, particularly at low pre-PET PSA levels of >0.2ng/ml (33%) and 0.2-0.5ng/ml (45%). Ga-68-PSMA-PET produces favourable sensitivity and specificity profiles on meta-analysis of pooled data. This analysis highlights different anatomic patterns of metastatic spread according to PSMA PET in the primary and biochemically recurrent settings.
PATIENT SUMMARY
Gallium-68 prostate-specific membrane antigen positron emission tomography is now an established imaging technique that has been developed in response to inadequacies in standard of care imaging modalities to improve the detection of metastatic disease in prostate cancer, particularly in the setting of disease recurrence. To date, this imaging modality in the setting of primary staging is controversial, given the paucity of data. In light of the growing body of evidence, we summarised the data to date to provide clinicians with an overview of this imaging modality.
Topics: Antigens, Surface; Edetic Acid; Gallium Isotopes; Gallium Radioisotopes; Glutamate Carboxypeptidase II; Humans; Male; Neoplasm Staging; Oligopeptides; Positron-Emission Tomography; Prostatic Neoplasms; Radiopharmaceuticals; Sensitivity and Specificity
PubMed: 30773328
DOI: 10.1016/j.eururo.2019.01.049