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Mutation Research. Genetic Toxicology... Sep 2019Drug-induced kidney injury is one of the most significant adverse events and dose limiting factor in chemotherapy as well a major cause of prospective drug attrition...
Drug-induced kidney injury is one of the most significant adverse events and dose limiting factor in chemotherapy as well a major cause of prospective drug attrition during pharmaceutical development. Moreover, kidney injury can also occur as a consequence of exposures to environmental xenobiotics such as heavy metals, fungal toxins and nanomaterials. The lack of adequate in vitro human kidney models that mimic more realistically the in vivo conditions and the absence of suitable and robust, cost-effective and predictive cell-based in vitro assays contribute to an underestimation of the kidney toxic potential of new drugs and xenobiotics. Therefore, a rapid screening system capable to detect potential nephrotoxicity at early stages of drug discovery is an urgent need. Here we provide an overview of human cell lines currently used as a surrogate in vitro kidney models in nephrotoxicity studies, including their advantages and limitations. In addition, the capacity of the single cell gel electrophoresis (SCGE)/comet assay as a potential tool in kidney toxicants screening is discussed. Despite a limited number of studies using the comet assay to evaluate the drug-induced kidney damage potential, a considerable variability in SCGE methodology (e.g. lysis, unwinding, and electrophoresis conditions) has been observed. Before the comet assay can be included in nephrotoxicity testing, a basic guideline has to be developed. To test its feasibility, additional in vitro experiments including inter-laboratory validation studies based on this guideline have to be performed.
Topics: Animals; Automation; Cell Line; Comet Assay; DNA Damage; Drug Development; Drug Evaluation, Preclinical; Forecasting; Guidelines as Topic; HEK293 Cells; Humans; Image Processing, Computer-Assisted; Kidney; Miniaturization; Nanostructures; Reproducibility of Results; Risk Assessment; Single-Cell Analysis; Th1 Cells; Toxicity Tests
PubMed: 31561894
DOI: 10.1016/j.mrgentox.2018.11.012 -
Frontiers in Pharmacology 2023Head and neck squamous cell carcinoma (HNSCC) accounts for approximately 3% of new cancer cases and 3% of all deaths worldwide. Most HNSCC patients are locally advanced... (Review)
Review
Head and neck squamous cell carcinoma (HNSCC) accounts for approximately 3% of new cancer cases and 3% of all deaths worldwide. Most HNSCC patients are locally advanced (LA) at diagnosis. The combination of radiotherapy (RT), chemotherapy, targeted therapy, and immunotherapy are the primary LA-HNSCC treatment options. Nevertheless, the choice of optimal LA-HNSCC treatment remains controversial. We systematically searched public databases for LA-HNSCC-related studies and assess treatment effectiveness and safety by assessing the objective response rate (ORR), ≥3 adverse events (AEs), overall survival (OS), progression-free survival (PFS), disease-free survival (DFS), local-region control (LRC), and disease-specific survival (DSS). 126 randomized controlled clinical trials (RCTs) were included in this study. We show that concurrent RT with nimotuzumab or conventional concurrent chemo-radiotherapy (CCRT) had significantly better efficacy and long-term survival without increasing AEs than RT alone. Accelerated fractionated radiotherapy (AFRT) showed better efficiency than conventional fractionated RT, although it had higher AEs. In addition, concurrent cetuximab combined with RT failed to show a significant advantage over RT alone. PROSPERO CRD42022352127.
PubMed: 37795033
DOI: 10.3389/fphar.2023.1269863 -
International Journal of Health Policy... 2023Circular economy (CE) has raised great interest as a concept and as a development model worldwide. This concept aims to provide a substitute for the linear economic... (Review)
Review
BACKGROUND
Circular economy (CE) has raised great interest as a concept and as a development model worldwide. This concept aims to provide a substitute for the linear economic model, which was based on production and consumption, continuous growth, and resources depletion. CE allows a greener economy with sustainable development and promotes more balanced societies. The healthcare sector is a major contributor to the climate crisis, with a carbon footprint representing 4.4% of global net emissions. It is thus essential to rethink the applicability of CE in healthcare.
METHODS
We conducted a scoping review guided by the Arksey and O'Malley methodological framework and utilised PRISMA-ScR (Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews) checklist. A systematic search from MEDLINE complete, SCOPUS, and Web of Science databases published between 1992 and 2022.
RESULTS
Through database searching a total of 1018 records were identified and 475 duplicates were removed. From the total search, 543 articles were screened by title/abstract according to the inclusion and exclusion criteria. After screening, 38 full-text articles were selected and assessed for eligibility. Forty-seven additional records were also identified through other sources and screened for eligibility. Other sources included: 12 articles from snowballing of previous papers; 9 articles following peer-reviewers suggestions; 19 reports from relevant organisations in CE and healthcare; two webpage, and one book.
CONCLUSION
Specific areas were identified where hospitals could reduce their greenhouse gas (GHG) emissions and consequently their negative environmental impact, namely through waste management, energy, water, transportation/travel, hospital design, food optimisation, green procurement, and behaviour. Also, lack of staff awareness and knowledge of the environmental impact of healthcare, and hospitals sustainability were identified as major contributors.
Topics: Humans; Conservation of Natural Resources; Hospitals; Delivery of Health Care
PubMed: 37579377
DOI: 10.34172/ijhpm.2023.6947 -
The Cochrane Database of Systematic... Mar 2017This is an update of the review published in Issue 4, 2003. Bone metastasis cause severe pain as well as pathological fractures, hypercalcaemia and spinal cord... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This is an update of the review published in Issue 4, 2003. Bone metastasis cause severe pain as well as pathological fractures, hypercalcaemia and spinal cord compression. Treatment strategies currently available to relieve pain from bone metastases include analgesia, radiotherapy, surgery, chemotherapy, hormone therapy, radioisotopes and bisphosphonates.
OBJECTIVES
To determine efficacy and safety of radioisotopes in patients with bone metastases to improve metastatic pain, decrease number of complications due to bone metastases and improve patient survival.
SEARCH METHODS
We sought randomised controlled trials (RCTs) in MEDLINE, EMBASE, CENTRAL, and the PaPaS Trials Register up to October 2010.
SELECTION CRITERIA
Studies selected had metastatic bone pain as a major outcome after treatment with a radioisotope, compared with placebo or another radioisotope.
DATA COLLECTION AND ANALYSIS
We assessed the risk of bias of included studies by their sequence generation, allocation concealment, blinding of study participants, researchers and outcome assessors, and incomplete outcome data. Two review authors extracted data. We performed statistical analysis as an "available case" analysis, and calculated global estimates of effect using a random-effects model. We also performed an intention-to-treat (ITT) sensitivity analysis.
MAIN RESULTS
This update includes 15 studies (1146 analyzed participants): four (325 participants) already included and 11 new (821 participants). Only three studies had a low risk of bias. We observed a small benefit of radioisotopes for complete relief (risk ratio (RR) 2.10, 95% CI 1.32 to 3.35; Number needed to treat to benefit (NNT) = 5) and complete/partial relief (RR 1.72, 95% CI 1.13 to 2.63; NNT = 4) in the short and medium term (eight studies, 499 participants). There is no conclusive evidence to demonstrate that radioisotopes modify the use of analgesia with respect to placebo. Leucocytopenia and thrombocytopenia are secondary effects significantly associated with the administration of radioisotopes (RR 5.03; 95% CI 1.35 to 18.70; Number needed to treat to harm (NNH) = 13). Pain flares were not higher in the radioisotopes group (RR 0.74; 95% CI 0.27 to 2.06). There are scarce data of moderate quality when comparing Strontium-89 (Sr) with Samarium-153 (Sm), Rhenium-186 (Re) and Phosphorus-32 (P). We observed no significant differences between treatments. Similarly, we observed no differences when we compared different doses of Sm (0.5 versus 1.0 mCi).
AUTHORS' CONCLUSIONS
This update adds new evidence on efficacy of radioisotopes versus placebo, Sr compared with other radioisotopes, and dose-comparisons of Sm and Re. There is some evidence indicating that radioisotopes may provide complete reduction in pain over one to six months with no increase in analgesic use, but severe adverse effects (leucocytopenia and thrombocytopenia) are frequent.
Topics: Bone Neoplasms; Fractures, Bone; Humans; Hypercalcemia; Pain; Pain Measurement; Phosphorus Radioisotopes; Radioisotopes; Randomized Controlled Trials as Topic; Ruthenium Radioisotopes; Samarium; Spinal Cord Compression; Strontium Radioisotopes
PubMed: 28334435
DOI: 10.1002/14651858.CD003347.pub3 -
Brachytherapy 2014To review and analyze the published data on high-dose-rate brachytherapy as monotherapy in the treatment of prostate cancer. (Review)
Review
PURPOSE
To review and analyze the published data on high-dose-rate brachytherapy as monotherapy in the treatment of prostate cancer.
METHODS
A literature search and a systematic review of the high-dose-rate (HDR) brachytherapy (monotherapy) prostate literature were performed on PubMed using "high-dose-rate, brachytherapy, prostate, monotherapy" as search terms. More than 80 articles and abstracts published between 1990 and 2013 were identified. Data tables were generated and summary descriptions created. Commentary and opinion was formulated through discussion and consensus based on the critical review of the literature and the author's combined personal experience and knowledge.
RESULTS
Thirteen articles reported clinical outcome and toxicity with followup ranging from 1.5 to 8.0 years. Results were available for all risk groups. A variety of dose and fractionation schedules were described. Prostate-specific antigen progression-free survival ranged from 79% to 100% and local control from 97% to 100%. The toxicity rates were low. Genitourinary toxicity, mainly frequency/urgency, was 0-16% (Grade 3). Gastrointestinal toxicity was 0-2% (Grade 3). Erectile function preservation was 67-89%. The radiobiological, clinical, and technical features of HDR brachytherapy were reviewed and discussed.
CONCLUSIONS
Consistently high local tumor control and low complications rates are reported with HDR monotherapy. It provides reproducible high-quality dosimetry, it has an advantage from a radiobiology perspective, and it has a good radiation safety profile. HDR brachytherapy is a safe and effective local treatment modality for prostate cancer.
Topics: Brachytherapy; Disease-Free Survival; Humans; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Radiotherapy Dosage; Tomography, X-Ray Computed
PubMed: 25085454
DOI: 10.1016/j.brachy.2014.03.002 -
Strahlentherapie Und Onkologie : Organ... Dec 2023Tumor-associated macrophages (TAMs) are the most represented cells of the immune system in the tumor microenvironment (TME). Besides its effects on cancer cells,... (Review)
Review
OBJECTIVE
Tumor-associated macrophages (TAMs) are the most represented cells of the immune system in the tumor microenvironment (TME). Besides its effects on cancer cells, radiation therapy (RT) can alter TME composition. With this systematic review, we provide a better understanding on how RT can regulate macrophage characterization, namely the M1 antitumor and the M2 protumor polarization, with the aim of describing new effective RT models and exploration of the possibility of integrating radiation with other available therapies.
METHODS
A systematic search in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was carried out in PubMed, Google Scholar, and Scopus. Articles from January 2000 to April 2020 which focus on the role of M1 and M2 macrophages in the response to RT were identified.
RESULTS
Of the 304 selected articles, 29 qualitative summary papers were included in our analysis (16 focusing on administration of RT and concomitant systemic molecules, and 13 reporting on RT alone). Based on dose intensity, irradiation was classified into low (low-dose irradiation, LDI; corresponding to less than 1 Gy), moderate (moderate-dose irradiation, MDI; between 1 and 10 Gy), and high (high-dose irradiation, HDI; greater than 10 Gy). While HDI seems to be responsible for induced angiogenesis and accelerated tumor growth through early M2-polarized TAM infiltration, MDI stimulates phagocytosis and local LDI may represent a valid treatment option for possible combination with cancer immunotherapeutic agents.
CONCLUSION
TAMs seem to have an ambivalent role on the efficacy of cancer treatment. Radiation therapy, which exerts its main antitumor activity via cell killing, can in turn interfere with TAM characterization through different modalities. The plasticity of TAMs makes them an attractive target for anticancer therapies and more research should be conducted to explore this potential therapeutic strategy.
Topics: Humans; Tumor-Associated Macrophages; Neoplasms; Macrophages; Tumor Microenvironment
PubMed: 37347290
DOI: 10.1007/s00066-023-02097-3 -
European Journal of Cancer (Oxford,... Jun 2023The faecal immunochemical test (FIT) suffers from suboptimal performance and participation in colorectal cancer (CRC) screening. Urinary volatile organic compounds... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The faecal immunochemical test (FIT) suffers from suboptimal performance and participation in colorectal cancer (CRC) screening. Urinary volatile organic compounds (VOCs) may be a useful alternative. We aimed to determine the diagnostic potential of urinary VOCs for CRC/adenomas. By relating VOCs to known pathways, we aimed to gain insight into the pathophysiology of colorectal neoplasia.
METHODS
A systematic search was performed in PubMed, EMBASE and Web of Science. Original studies on urinary VOCs for CRC/adenoma detection with a control group were included. QUADAS-2 tool was used for quality assessment. Meta-analysis was performed by adopting a bivariate model for sensitivity/specificity. Fagan's nomogram estimated the performance of combined FIT-VOC. Neoplasm-associated VOCs were linked to pathways using the KEGG database.
RESULTS
Sixteen studies-involving 837 CRC patients and 1618 controls-were included; 11 performed chemical identification and 7 chemical fingerprinting. In all studies, urinary VOCs discriminated CRC from controls. Pooled sensitivity and specificity for CRC based on chemical fingerprinting were 84% (95% CI 73-91%) and 70% (95% CI 63-77%), respectively. The most distinctive individual VOC was butanal (AUC 0.98). The estimated probability of having CRC following negative FIT was 0.38%, whereas 0.09% following negative FIT-VOC. Combined FIT-VOC would detect 33% more CRCs. In total 100 CRC-associated urinary VOCs were identified; particularly hydrocarbons, carboxylic acids, aldehydes/ketones and amino acids, and predominantly involved in TCA-cycle or alanine/aspartate/glutamine/glutamate/phenylalanine/tyrosine/tryptophan metabolism, which is supported by previous research on (colorectal)cancer biology. The potential of urinary VOCs to detect precancerous adenomas or gain insight into their pathophysiology appeared understudied.
CONCLUSION
Urinary VOCs hold potential for non-invasive CRC screening. Multicentre validation studies are needed, especially focusing on adenoma detection. Urinary VOCs elucidate underlying pathophysiologic processes.
Topics: Humans; Volatile Organic Compounds; Biomarkers, Tumor; Early Detection of Cancer; Colorectal Neoplasms; Adenoma; Colonic Neoplasms
PubMed: 37030079
DOI: 10.1016/j.ejca.2023.03.002 -
World Journal of Surgery Sep 2017Individualised risk prediction is crucial if targeted pre-operative risk reduction strategies are to be deployed effectively. Radiologically determined sarcopenia has... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Individualised risk prediction is crucial if targeted pre-operative risk reduction strategies are to be deployed effectively. Radiologically determined sarcopenia has been shown to predict outcomes across a range of intra-abdominal pathologies. Access to pre-operative cross-sectional imaging has resulted in a number of studies investigating the predictive value of radiologically assessed sarcopenia over recent years. This systematic review and meta-analysis aimed to determine whether radiologically determined sarcopenia predicts post-operative morbidity and mortality following abdominal surgery.
METHOD
CENTRAL, EMBASE and MEDLINE databases were searched using terms to capture the concept of radiologically assessed sarcopenia used to predict post-operative complications in abdominal surgery. Outcomes included 30 day post-operative morbidity and mortality, 1-, 3- and 5-year overall and disease-free survival and length of stay. Data were extracted and meta-analysed using either random or fixed effects model (Revman 5.3).
RESULTS
A total of 24 studies involving 5267 patients were included in the review. The presence of sarcopenia was associated with a significant increase in major post-operative complications (RR 1.61 95% CI 1.24-4.15 p = <0.00001) and 30-day mortality (RR 2.06 95% CI 1.02-4.17 p = 0.04). In addition, sarcopenia predicted 1-, 3- and 5-year survival (RR 1.61 95% CI 1.36-1.91 p = <0.0001, RR 1.45 95% CI 1.33-1.58 p = <0.0001, RR 1.25 95% CI 1.11-1.42 p = 0.0003, respectively) and 1- and 3-year disease-free survival (RR 1.30 95% CI 1.12-1.52 p = 0.0008).
CONCLUSION
Peri-operative cross-sectional imaging may be utilised in order to predict those at risk of complications following abdominal surgery. These findings should be interpreted in the context of retrospectively collected data and no universal sarcopenic threshold. Targeted prehabilitation strategies aiming to reverse sarcopenia may benefit patients undergoing abdominal surgery.
Topics: Abdomen; Disease-Free Survival; Humans; Mortality; Postoperative Complications; Predictive Value of Tests; Radiology; Risk Factors; Sarcopenia; Survival Rate
PubMed: 28386715
DOI: 10.1007/s00268-017-3999-2 -
Radiography (London, England : 1995) Aug 2022Advances in Radiotherapy (RT) technology and increase of complexity in cancer care have enabled the implementation of new treatment techniques. Subsequently, a greater... (Review)
Review
INTRODUCTION
Advances in Radiotherapy (RT) technology and increase of complexity in cancer care have enabled the implementation of new treatment techniques. Subsequently, a greater level of autonomy, responsibility, and accountability in the practice of Therapeutic Radiographers/Radiation Therapists (TR/RTTs) has led to Advanced Practice (AP) roles. The published evidence of this role is scattered with confusing terminology and divergence regarding the perception of whether a specific role represents AP internationally. This study aims to establish an international baseline of evidence on AP roles in RT to identify roles and activities performed by TR/RTTs at advanced level practice and to summarise the impact.
METHODS
A systematic PRISMA review of the literature was undertaken. Thematic analysis was used to synthesise the roles and associated activities. Six RT external experts validated the list. The impact was scrutinised in terms of clinical, organisational, and professional outcomes.
RESULTS
Studies (n = 87) were included and categorised into four groups. AP roles were listed by clinical area, site-specific, and scope of practice, and advanced activities were organised into seven dimensions and 27 sub-dimensions. Three most-reported outcomes were: enhanced service capacity, higher patient satisfaction, and safety maintenance.
CONCLUSION
Evidence-based AP amongst TR/RTTs show how AP roles were conceptualised, implemented, and evaluated. Congruence studies have shown that TR/RTTs are at par with the gold-standard across the various AP roles.
IMPLICATIONS FOR PRACTICE
This is the first systematic literature review synthetisising AP roles and activities of TR/RTTs. This study also identified the main areas of AP that can be used to develop professional frameworks and education guiding policy by professional bodies, educators and other stakeholders.
Topics: Allied Health Personnel; Humans; Radiation Oncology
PubMed: 35550932
DOI: 10.1016/j.radi.2022.04.009 -
Head & Neck Dec 2023This systematic review study aims to provide comprehensive data on different radiobiological models, parameters, and endpoints used for calculating the normal tissue... (Review)
Review
This systematic review study aims to provide comprehensive data on different radiobiological models, parameters, and endpoints used for calculating the normal tissue complication probability (NTCP) based on clinical data from head and neck cancer patients treated with conformal radiotherapy. A systematic literature search was carried out according to the PRISMA guideline for the identification of relevant publications in six electronic databases of Embase, PubMed, Scopus, and Google Scholar to July 2022 using specific keywords in the paper's title and abstract. The initial search resulted in 1368 articles for all organs for the review article about the NTCP parameters. One hundred and seventy-eight articles were accepted for all organs with complete parameters for the mentioned models and finally, 20 head and neck cancer articles were accepted for review. Analysis of the studies shows that the Lyman-Kutcher-Burman (LKB) model properly links the NTCP curve parameters to the postradiotherapy endpoints. In the LKB model for esophagus, the minimum, and maximum corresponding parameters were reported as TD = 2.61 Gy with grade ≥3 radiation-induced esophagitis endpoints as the minimum TD and TD = 68 Gy as the maximum ones. n = 0.06, n = 1.04, m = 0.1, and m = 0.65, respectively. Unfortunately, there was not a wide range of published articles on other organs at risk like ear or cauda equina except Burman et al. (Fitting of normal tissue tolerance data to an analytic function. Int J Radiat Oncol Biol Phys Ther. 1991;21:123-135). Findings suggest that the validation of different radiobiological models and their corresponding parameters need to be investigated in vivo and in vitro for developing a more accurate NTCP model to be used for radiotherapy treatment planning optimization.
Topics: Humans; Radiotherapy, Conformal; Probability; Head and Neck Neoplasms; Radiotherapy Planning, Computer-Assisted; Radiobiology; Radiotherapy Dosage
PubMed: 37767820
DOI: 10.1002/hed.27469