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European Journal of Nuclear Medicine... Dec 2023Transthyretin (ATTR) amyloidosis is a progressive protein misfolding disease with frequent cardiac involvement. This review aims to determine the value of PET in... (Review)
Review
PURPOSE
Transthyretin (ATTR) amyloidosis is a progressive protein misfolding disease with frequent cardiac involvement. This review aims to determine the value of PET in diagnosis, assessment of disease progression or treatment response and its relation to clinical outcome in follow-up of ATTR amyloid cardiomyopathy (ATTR-CM) patients.
METHODS
Medline, Cochrane Library, Embase and Web of Science databases were searched, from the earliest date available until December 2022, for studies investigating the use of PET in ATTR-CM patients. Studies containing original data were included, except for case reports. Risk of bias was assessed by QUADAS-2.
RESULTS
Twenty-one studies were included in this systematic review, investigating five different tracers: carbon-11 Pittsburgh compound B ([C]PIB), fluorine-18 Florbetaben ([F]FBB), fluorine-18 Florbetapir ([F]FBP), fluorine-18 Flutemetamol ([F]FMM) and fluorine-18 Sodium Fluoride (Na[F]F). In total 211 ATTR amyloidosis patients were included. A majority of studies concluded that [C]PIB, [F]FBP and Na[F]F can distinguish ATTR amyloidosis patients from controls, and that [C]PIB and Na[F]F, but not [F]FBP, can distinguish ATTR-CM patients from patients with cardiac light chain amyloidosis. Evidence on the performance of [F]FBB and [F]FMM was contradictory. No studies on the use of PET in follow-up were found.
CONCLUSION
[C]PIB, Na[F]F and [F]FBP can be used to diagnose cardiac amyloidosis, although [F]FBP may not be suitable for the distinction of different types of amyloid cardiomyopathy. No studies on PET in the follow-up of ATTR amyloidosis patients were found. Future research should focus on the use of these PET tracers in the follow-up of ATTR amyloidosis patients.
Topics: Humans; Prealbumin; Follow-Up Studies; Amyloidosis; Positron-Emission Tomography; Cardiomyopathies
PubMed: 37561144
DOI: 10.1007/s00259-023-06381-3 -
Journal of Geriatric Oncology Sep 2023Blood biomarkers are potentially useful prognostic markers and may support treatment decisions, but it is unknown if and which biomarkers are most useful in older... (Review)
Review
INTRODUCTION
Blood biomarkers are potentially useful prognostic markers and may support treatment decisions, but it is unknown if and which biomarkers are most useful in older patients with solid tumors. The aim of this systematic review was to evaluate the evidence on the association of blood biomarkers with treatment response and adverse health outcomes in older patients with solid tumors.
MATERIALS AND METHODS
A literature search was conducted in five databases in December 2022 to identify studies on blood biomarkers measured before treatment initiation, not tumor specific, and outcomes in patients with solid tumors aged ≥60 years. Studies on any type or line of oncologic treatment could be included. Titles and abstracts were screened by three authors. Data extraction and quality assessment, using the Quality in Prognosis Studies (QUIPS) checklist, were performed by two authors.
RESULTS
Sixty-three studies were included, with a median sample size of 138 patients (Interquartile range [IQR] 99-244) aged 76 years (IQR 72-78). Most studies were retrospective cohort studies (63%). The risk of bias was moderate in 52% and high in 43%. Less than one-third reported geriatric parameters. Eighty-six percent examined mortality outcomes, 37% therapeutic response, and 37% adverse events. In total, 77 unique markers were studied in patients with a large variety of tumor types and treatment modalities. Neutrophil-to-lymphocyte ratio (20 studies), albumin (19), C-reactive protein (16), hemoglobin (14) and (modified) Glasgow Prognostic Score ((m)GPS) (12) were studied most often. The vast majority showed no significant association of these biomarkers with outcomes, except for associations between low albumin and adverse events and high (m)GPS with mortality.
DISCUSSION
Most studies did not find a significant association between blood biomarkers and clinical outcomes. The interpretation of current evidence on prognostic blood biomarkers is hampered by small sample sizes and inconsistent results across heterogeneous studies. The choice for blood biomarkers in the majority of included studies seemed driven by availability in clinical practice in retrospective cohort studies. Ageing biomarkers are rarely studied in older patients with solid tumors. Further research is needed in larger and more homogenous cohorts that combine clinical parameters and biomarkers before these can be used in clinical practice.
Topics: Humans; Aged; Retrospective Studies; Neoplasms; Prognosis; Biomarkers; Outcome Assessment, Health Care
PubMed: 37453811
DOI: 10.1016/j.jgo.2023.101567 -
Life (Basel, Switzerland) Aug 2023The COVID-19 pandemic, caused by the SARS-CoV-2 virus, mainly causes respiratory and intestinal symptoms and changes in the microbiota of patients. We performed a... (Review)
Review
The COVID-19 pandemic, caused by the SARS-CoV-2 virus, mainly causes respiratory and intestinal symptoms and changes in the microbiota of patients. We performed a systematic search in major databases using "" and "COVID-19" or "SARS-CoV-2" as key terms to assess the relationship of the genus to COVID-19. After the selection steps, 25 articles were analyzed. Of these, eighteen were observational, and seven were interventional articles that evaluated the use of alone or in mix as probiotics for additional treatment of patients with COVID-19. All stages and severities were contemplated, including post-COVID-19 patients. Overall, was associated with both protective effects and reduced abundance in relation to the disease. The genus has been found to be abundant in some cases and linked to disease severity. The studies evaluating the use of as probiotics have demonstrated the potential of this genus in reducing symptoms, improving pulmonary function, reducing inflammatory markers, alleviating gastrointestinal symptoms, and even contributing to better control of mortality. In summary, Bifidobacterium may offer protection against COVID-19 through its ability to modulate the immune response, reduce inflammation, compete with pathogenic microbes, and maintain gut barrier function. The findings provide valuable insights into the relationship between the disease and the genus , highlighting the potential of microbiota modulation in the treatment of COVID-19.
PubMed: 37763251
DOI: 10.3390/life13091847 -
The Journal of Allergy and Clinical... May 2024Access to the molecular culprits of allergic reactions allows for the leveraging of molecular allergology as a new precision medicine approach-one built on... (Review)
Review
Access to the molecular culprits of allergic reactions allows for the leveraging of molecular allergology as a new precision medicine approach-one built on interdisciplinary, basic, and clinical knowledge. Molecular allergology relies on the use of allergen molecules as tools for the diagnosis and management of allergic patients. It complements the conventional approach based on skin and allergen extract testing. Major applications of molecular allergology comprise accurate identification of the offending allergen thanks to discrimination between genuine sensitization and allergen cross-reactivity, evaluation of potential severity, patient-tailored choice of the adequate allergen immunotherapy, and prediction of its expected efficacy and safety. Allergen cross-reactivity, defined as the recognition of 2 or more allergen molecules by antibodies or T cells of the same specificity, frequently interferes with allergen extract testing. At the mechanistic level, allergen cross-reactivity depends on the allergen, the host's immune response, and the context of their interaction. The multiplicity of allergen molecules and families adds further difficulty. Understanding allergen cross-reactivity at the immunologic level and translating it into a daily tool for the management of allergic patients is further complicated by the ever-increasing number of characterized allergenic molecules, the lack of dedicated resources, and the need for a personalized, patient-centered approach. Conversely, knowledge sharing paves the way for improved clinical use, innovative diagnostic tools, and further interdisciplinary research. Here, we aimed to provide a comprehensive and unbiased state-of-the art systematic review on allergen cross-reactivity. To optimize learning, we enhanced the review with basic, translational, and clinical definitions, clinical vignettes, and an overview of online allergen databases.
PubMed: 38524786
DOI: 10.1016/j.jacig.2024.100230 -
Mutation Research. Reviews in Mutation... 2024Head and neck cancer is the seventh most common malignancy globally. Head and neck squamous cell carcinoma (HNSCC) originates from squamous cells and 90% of HNC are... (Comparative Study)
Comparative Study Review
Head and neck cancer is the seventh most common malignancy globally. Head and neck squamous cell carcinoma (HNSCC) originates from squamous cells and 90% of HNC are HNSCC. The gold standard for diagnosing HNSCC is tissue biopsy. However, given tumour heterogeneity, biopsies may miss important cancer-associated molecular signatures, and more importantly, after the tumour is excised, there is no means of tracking response to treatment in patients. Captured under liquid biopsy, circulating tumour DNA (ctDNA), may identify in vivo molecular genotypes and complements tumour tissue analysis in cancer management. A systematic search was conducted in PubMed, Embase, Scopus and the Cochran Library between 2012 to early 2023 on ctDNA in HNSCC using publications written in English. We summarise 20 studies that compared mutational profiles between tumour tissue DNA (tDNA) and ctDNA, using a cohort of 631 HNSCC patients and 139 controls. Among these studies, the concordance rates varied greatly and the most mutated and the most concordant gene was TP53, followed by PIK3CA, CDKN2A, NOTCH1 and FAT1. Concordant variants were mainly found in Stage IV tumours, and the mutation type is mostly single nucleotide variants (SNV). We conclude that, as a biomarker for HNSCC, ctDNA demonstrates great promise as it recapitulates tumour genotypes, however additional multi-central trials are needed.
Topics: Humans; Circulating Tumor DNA; Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms; Mutation; Class I Phosphatidylinositol 3-Kinases; Biomarkers, Tumor; Tumor Suppressor Protein p53; Receptor, Notch1; DNA, Neoplasm; Cyclin-Dependent Kinase Inhibitor p16; Cadherins
PubMed: 37977279
DOI: 10.1016/j.mrrev.2023.108477 -
Arthritis Research & Therapy May 2024Targeted small-molecule drugs in the treatment of systemic lupus erythematosus (SLE) have attracted increasing attention from clinical investigators. However, there is... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Targeted small-molecule drugs in the treatment of systemic lupus erythematosus (SLE) have attracted increasing attention from clinical investigators. However, there is still a lack of evidence on the difference in the efficacy and safety of different targeted small-molecule drugs. Therefore, this study was conducted to assess the efficacy and safety of different targeted small-molecule drugs for SLE.
METHODS
Randomized controlled trials (RCTs) on targeted small-molecule drugs in the treatment of SLE in PubMed, Web of Science, Embase, and Cochrane Library were systematically searched as of April 25, 2023. Risk of bias assessment was performed for included studies using the Cochrane's tool for evaluating the risk of bias. The primary outcome indicators were SRI-4 response, BICLA response, and adverse reaction. Because different doses and courses of treatment were used in the included studies, Bayesian network meta-regression was used to investigate the effect of different doses and courses of treatment on efficacy and safety.
RESULTS
A total of 13 studies were included, involving 3,622 patients and 9 targeted small-molecule drugs. The results of network meta-analysis showed that, in terms of improving SRI-4, Deucravacitinib was significantly superior to that of Baricitinib (RR = 1.32, 95% CI (1.04, 1.68), P < 0.05). Deucravacitinib significantly outperformed the placebo in improving BICLA response (RR = 1.55, 95% CI (1.20, 2.02), P < 0.05). In terms of adverse reactions, targeted small-molecule drugs did not significantly increase the risk of adverse events as compared to placebo (P > 0.05).
CONCLUSION
Based on the evidence obtained in this study, the differences in the efficacy of targeted small-molecule drugs were statistically significant as compared to placebo, but the difference in the safety was not statistically significant. The dose and the course of treatment had little impact on the effect of targeted small-molecule drugs. Deucravacitinib could significantly improve BICLA response and SRI-4 response without significantly increasing the risk of AEs. Therefore, Deucravacitinib is very likely to be the best intervention measure. Due to the small number of included studies, more high-quality clinical evidence is needed to further verify the efficacy and safety of targeted small-molecule drugs for SLE.
Topics: Humans; Lupus Erythematosus, Systemic; Randomized Controlled Trials as Topic; Treatment Outcome; Azetidines; Purines; Molecular Targeted Therapy; Sulfonamides; Pyrazoles
PubMed: 38730460
DOI: 10.1186/s13075-024-03331-8 -
European Urology Jan 2024In prostate cancer (PCa), questions remain on indications for prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging and PSMA radioligand...
BACKGROUND
In prostate cancer (PCa), questions remain on indications for prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging and PSMA radioligand therapy, integration of advanced imaging in nomogram-based decision-making, dosimetry, and development of new theranostic applications.
OBJECTIVE
We aimed to critically review developments in molecular hybrid imaging and systemic radioligand therapy, to reach a multidisciplinary consensus on the current state of the art in PCa.
DESIGN, SETTING, AND PARTICIPANTS
The results of a systematic literature search informed a two-round Delphi process with a panel of 28 PCa experts in medical or radiation oncology, urology, radiology, medical physics, and nuclear medicine. The results were discussed and ratified in a consensus meeting.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS
Forty-eight statements were scored on a Likert agreement scale and six as ranking options. Agreement statements were analysed using the RAND appropriateness method. Ranking statements were analysed using weighted summed scores.
RESULTS AND LIMITATIONS
After two Delphi rounds, there was consensus on 42/48 (87.5%) of the statements. The expert panel recommends PSMA PET to be used for staging the majority of patients with unfavourable intermediate and high risk, and for restaging of suspected recurrent PCa. There was consensus that oligometastatic disease should be defined as up to five metastases, even using advanced imaging modalities. The group agreed that [Lu]Lu-PSMA should not be administered only after progression to cabazitaxel and that [Ra]RaCl remains a valid therapeutic option in bone-only metastatic castration-resistant PCa. Uncertainty remains on various topics, including the need for concordant findings on both []FDG and PSMA PET prior to [Lu]Lu-PSMA therapy.
CONCLUSIONS
There was a high proportion of agreement among a panel of experts on the use of molecular imaging and theranostics in PCa. Although consensus statements cannot replace high-certainty evidence, these can aid in the interpretation and dissemination of best practice from centres of excellence to the wider clinical community.
PATIENT SUMMARY
There are situations when dealing with prostate cancer (PCa) where both the doctors who diagnose and track the disease development and response to treatment, and those who give treatments are unsure about what the best course of action is. Examples include what methods they should use to obtain images of the cancer and what to do when the cancer has returned or spread. We reviewed published research studies and provided a summary to a panel of experts in imaging and treating PCa. We also used the research summary to develop a questionnaire whereby we asked the experts to state whether or not they agreed with a list of statements. We used these results to provide guidance to other health care professionals on how best to image men with PCa and what treatments to give, when, and in what order, based on the information the images provide.
Topics: Humans; Male; Molecular Imaging; Nuclear Medicine; Positron-Emission Tomography; Precision Medicine; Prostatic Neoplasms
PubMed: 37743194
DOI: 10.1016/j.eururo.2023.09.003 -
Clinical and Translational Radiation... Nov 2023Pain is the most common acute symptom following radiation therapy (RT) for head and neck cancer (HNC). The multifactorial origin of RT-induced pain makes it highly... (Review)
Review
BACKGROUND/OBJECTIVE
Pain is the most common acute symptom following radiation therapy (RT) for head and neck cancer (HNC). The multifactorial origin of RT-induced pain makes it highly challenging to manage. Multiple studies were conducted to identify genetic variants associated with cancer pain, however few of them focused on RT-induced acute pain. In this review, we summarize the potential mechanisms of acute pain after RT in HNC and identify genetic variants associated with RT-induced acute pain and relevant acute toxicities.
METHODS
A comprehensive search of Ovid Medline, EMBASE and Web of Science databases using terms including "Variants", "Polymorphisms", "Radiotherapy", "Acute pain", "Acute toxicity" published up to February 28, 2022, was performed by two reviewers. Review articles and citations were reviewed manually. The identified SNPs associated with RT-induced acute pain and toxicities were reported, and the molecular functions of the associated genes were described based on genetic annotation using The Human Gene Database; GeneCards.
RESULTS
A total of 386 articles were identified electronically and 8 more articles were included after manual search. 21 articles were finally included. 32 variants in 27 genes, of which 25% in inflammatory/immune response, 20% had function in DNA damage response and repair, 20% in cell death or cell cycle, were associated with RT-inflammatory pain and acute oral mucositis or dermatitis. 4 variants in 4 genes were associated with neuropathy and neuropathic pain. 5 variants in 4 genes were associated with RT-induced mixed types of post-RT-throat/neck pain.
CONCLUSION
Different types of pain develop after RT in HNC, including inflammatory pain; neuropathic pain; nociceptive pain; and mixed oral pain. Genetic variants involved in DNA damage response and repair, cell death, inflammation and neuropathic pathways may affect pain presentation post-RT. These variants could be used for personalized pain management in HNC patients receiving RT.
PubMed: 37954025
DOI: 10.1016/j.ctro.2023.100669 -
Journal of Clinical Medicine May 2024: Chordomas pose a challenge in treatment due to their local invasiveness, high recurrence, and potential lethality. Despite being slow-growing and rarely metastasizing,... (Review)
Review
: Chordomas pose a challenge in treatment due to their local invasiveness, high recurrence, and potential lethality. Despite being slow-growing and rarely metastasizing, these tumors often resist conventional chemotherapies (CTs) and radiotherapies (RTs), making surgical resection a crucial intervention. However, achieving radical resection for chordomas is seldom possible, presenting therapeutic challenges. The accurate diagnosis of these tumors is vital for their distinct prognoses, yet differentiation is hindered by overlapping radiological and histopathological features. Fortunately, recent molecular and genetic studies, including extracranial location analysis, offer valuable insights for precise diagnosis. This literature review delves into the genetic aberrations and molecular biology of chordomas, aiming to provide an overview of more successful therapeutic strategies. : A systematic search was conducted across major medical databases (PubMed, Embase, and Cochrane Library) up to 28 January 2023. The search strategy utilized relevant Medical Subject Heading (MeSH) terms and keywords related to "chordomas", "molecular biology", "gene aberrations", and "target therapies". The studies included in this review consist of preclinical cell studies, case reports, case series, randomized controlled trials, non-randomized controlled trials, and cohort studies reporting on genetic and biological aberrations in chordomas. : Of the initial 297 articles identified, 40 articles were included in the article. Two tables highlighted clinical studies and ongoing clinical trials, encompassing 18 and 22 studies, respectively. The clinical studies involved 185 patients diagnosed with chordomas. The tumor sites were predominantly sacral ( = 8, 44.4%), followed by clivus ( = 7, 38.9%) and lumbar spine ( = 3, 16.7%). Primary treatments preceding targeted therapies included surgery ( = 10, 55.6%), RT ( = 9, 50.0%), and systemic treatments ( = 7, 38.9%). Various agents targeting specific molecular pathways were analyzed in the studies, such as imatinib (a tyrosine kinase inhibitor), erlotinib, and bevacizumab, which target EGFR/VEGFR. Common adverse events included fatigue (47.1%), skin reactions (32.4%), hypertension (23.5%), diarrhea (17.6%), and thyroid abnormalities (5.9%). Clinical outcomes were systematically assessed based on progression-free survival (PFS), overall survival (OS), and tumor response evaluated using RECIST or CHOI criteria. Notably, stable disease (SD) occurred in 58.1% of cases, and partial responses (PRs) were observed in 28.2% of patients, while 13.7% experienced disease progression (PD) despite targeted therapy. Among the 22 clinical trials included in the analysis, Phase II trials were the most prevalent (40.9%), followed by I-II trials (31.8%) and Phase I trials (27.3%). PD-1 inhibitors were the most frequently utilized, appearing in 50% of the trials, followed by PD-L1 inhibitors (36.4%), CTLA-4 inhibitors (22.7%), and mTOR inhibitors (13.6%). : This systematic review provides an extensive overview of the state of targeted therapy for chordomas, highlighting their potential to stabilize the illness and enhance clinical outcomes.
PubMed: 38731241
DOI: 10.3390/jcm13092711 -
The Japanese Dental Science Review Dec 2023The mechanisms modulated by periodontal pathogens in atherosclerosis are not fully understood. Aim: to perform an integrative analysis of gene and protein expression... (Review)
Review
UNLABELLED
The mechanisms modulated by periodontal pathogens in atherosclerosis are not fully understood. Aim: to perform an integrative analysis of gene and protein expression modulated by periodontal pathogens in cells and animal models for atherosclerosis.
METHODS
Cochrane, PRISMA and AMSTAR2 guidelines for systematic reviews were followed. Data search was conducted in Pub-med, LILACS and Science Direct databases. Gene and protein expression data were collected from the included papers to perform an overrepresentation analysis using the Reactome Pathway Analysis tool and the KEGG database.
RESULTS
Thirty-two papers were included in the review, they analyzed the effect of , , , , , and or/and their virulent factors on gene and protein expression in human cells and animal models of atherosclerosis. Some of the modulated pathways include the immune system, programmed cell death, cellular responses to external stimuli, transport of small molecules, and signal transduction (p < 0.05). Those pathways are known to be involved in different stages of atherosclerosis progression.
CONCLUSION
Based on the performed analysis, it is possible to state that periodontal pathogens have the potential to be a contributing factor for atherosclerosis even in absence of a high-fat diet or high shear stress.
PubMed: 36654677
DOI: 10.1016/j.jdsr.2022.12.001