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Current Pharmaceutical Design Jun 2023Although chemotherapy and radiotherapy are effective in cancer treatment, different adverse effects induced by these therapeutic modalities (such as ototoxicity)...
BACKGROUND
Although chemotherapy and radiotherapy are effective in cancer treatment, different adverse effects induced by these therapeutic modalities (such as ototoxicity) restrict their clinical use. Co-treatment of melatonin may alleviate the chemotherapy/radiotherapy-induced ototoxicity.
OBJECTIVE
In the present study, the otoprotective potentials of melatonin against the ototoxicity induced by chemotherapy and radiotherapy were reviewed.
METHODS
According to the PRISMA guideline, a systematic search was carried out to identify all relevant studies on "the role of melatonin against ototoxic damage associated with chemotherapy and radiotherapy" in the different electronic databases up to September 2022. Sixty-seven articles were screened based on a predefined set of inclusion and exclusion criteria. Seven eligible studies were finally included in this review.
RESULTS
The in vitro findings showed that cisplatin chemotherapy significantly decreased the auditory cell viability compared to the control group; in contrast, the melatonin co-administration increased the cell viability of cisplatin-treated cells. The results obtained from the distortion product otoacoustic emission (DPOAE) and auditory brainstem response (ABR) tests demonstrated a decreased amplitude of DPOAE and increased values of ABR I-IV interval and ABR threshold in mice/rats receiving radiotherapy and cisplatin; nevertheless, melatonin co-treatment indicated an opposite pattern on these evaluated parameters. It was also found that cisplatin and radiotherapy could significantly induce the histological and biochemical changes in the auditory cells/tissue. However, melatonin co-treatment resulted in alleviating the cisplatin/radiotherapy-induced biochemical and histological changes.
CONCLUSION
According to the findings, it was shown that melatonin co-treatment alleviates the ototoxic damage induced by chemotherapy and radiotherapy. Mechanically, melatonin may exert its otoprotective effects via its anti-oxidant, anti-apoptotic, and anti-inflammatory activities and other mechanisms.
Topics: Rats; Mice; Animals; Cisplatin; Antineoplastic Agents; Melatonin; Ototoxicity; Antioxidants
PubMed: 37138418
DOI: 10.2174/1381612829666230503145707 -
Advances in Radiation Oncology 2023The aim of this study was to comprehensively review all studies examining clinical outcomes of craniospinal irradiation with proton radiotherapy for medulloblastoma (MB)... (Review)
Review
PURPOSE
The aim of this study was to comprehensively review all studies examining clinical outcomes of craniospinal irradiation with proton radiotherapy for medulloblastoma (MB) to determine whether theoretical dosimetric advantages have translated into superior clinical outcomes (including survival and toxicities) compared with traditional photon-based techniques.
METHODS AND MATERIALS
We performed a systematic review based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Articles reporting on clinical outcomes of pediatric and/or adult patients with MB treated with proton radiotherapy were included. Evidence quality was assessed using a modified Newcastle Ottawa scale and GRADE score.
RESULTS
Thirty-five studies were included, with a total of 2059 patients reported (representing an estimated 630-654 unique patients). None of the studies were randomized, 12 were comparative, 9 were prospective, 3 were mixed, and 22 were retrospective. Average mean/median follow-up was 5.0 years (range, 4 weeks to 12.6 years). The majority of studies (n = 19) reported on treatment with passive scatter proton beams exclusively. Average study quality was 6.0 out of 9 (median, 6; standard deviation, 1.6). Nine studies scored ≥8 out of 9 on the modified Newcastle Ottawa Scale; an overall "moderate" GRADE score was assigned. Well-designed comparative cohort studies with adequate follow-up demonstrate superior neurocognitive outcomes, lower incidence of hypothyroidism (23% vs 69%), sex hormone deficiency (3% vs 19%), greater heights, and reduced acute toxicities in patients treated with protons compared to photons. Overall survival (up to 10 years), progression-free survival (up to 10 years), brain stem injury, and other endocrine outcomes were similar to those reported for photon radiation. There was insufficient evidence to make conclusions on endpoints of quality of life, ototoxicity, secondary malignancy, alopecia, scoliosis, cavernomas, and cerebral vasculopathy.
CONCLUSIONS
Moderate-grade evidence supports proton radiotherapy as a preferred treatment for craniospinal irradiation of MB based on equivalent disease control and comparable-to-improved toxicity versus photon beam radiation therapy.
PubMed: 37008255
DOI: 10.1016/j.adro.2023.101189 -
Otolaryngology--head and Neck Surgery :... Jun 2023The objective of this meta-analysis is to evaluate the impact of genetic polymorphisms on platinum-based chemotherapy (PBC)-induced ototoxicity. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The objective of this meta-analysis is to evaluate the impact of genetic polymorphisms on platinum-based chemotherapy (PBC)-induced ototoxicity.
DATA SOURCES
Systematic searches of PubMed, Embase, Cochrane, and Web of Science were conducted from the inception of the databases to May 31, 2022. Abstracts and presentations from conferences were also reviewed.
REVIEW METHODS
Four investigators independently extracted data in adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Differences in the prevalence of PBC-induced ototoxicity between reference and variant (i) genotypes and (ii) alleles were analyzed. The overall effect size was presented using the random-effects model as an odds ratio (OR) with a 95% confidence interval (CI).
RESULTS
From 32 included articles, 59 single nucleotide polymorphisms on 28 genes were identified, with 4406 total unique participants. For allele frequency analysis, the A allele in ACYP2 rs1872328 was positively associated with ototoxicity (OR: 2.61; 95% CI: 1.06-6.43; n = 2518). Upon limiting to cisplatin use only, the T allele of COMT rs4646316 and COMT rs9332377 revealed significant results. For genotype frequency analysis, the CT/TT genotype in ERCC2 rs1799793 demonstrated an otoprotective effect (OR: 0.50; 95% CI: 0.27-0.94; n = 176). Excluding studies using carboplatin or concomitant radiotherapy revealed significant effects with COMT rs4646316, GSTP1 rs1965, and XPC rs2228001. Major sources of variations between studies include differences in patient demographics, ototoxicity grading systems, and treatment protocols.
CONCLUSION
Our meta-analysis presents polymorphisms that exert ototoxic or otoprotective effects in patients undergoing PBC. Importantly, several of these alleles are observed at high frequencies globally, highlighting the potential for polygenic screening and cumulative risk evaluation for personalized care.
Topics: Humans; Antineoplastic Agents; Ototoxicity; Platinum; Cisplatin; Polymorphism, Single Nucleotide; Xeroderma Pigmentosum Group D Protein; Acid Anhydride Hydrolases
PubMed: 36802061
DOI: 10.1002/ohn.222 -
Journal of Cancer Survivorship :... Feb 2023A cornerstone of treatment for many cancers is the administration of platinum-based chemotherapies and/or ionizing radiation, which can be ototoxic. An accurate... (Review)
Review
PURPOSE
A cornerstone of treatment for many cancers is the administration of platinum-based chemotherapies and/or ionizing radiation, which can be ototoxic. An accurate ototoxicity risk assessment would be useful for counseling, treatment planning, and survivorship follow-up in patients with cancer.
METHODS
This systematic review evaluated the literature on predictive models for estimating a patient's risk for chemotherapy-related auditory injury to accelerate development of computational approaches for the clinical management of ototoxicity in cancer patients. Of the 1195 articles identified in a PubMed search from 2010 forward, 15 studies met inclusion for the review.
CONCLUSIONS
All but 1 study used an abstraction of the audiogram as a modeled outcome; however, specific outcome measures varied. Consistently used predictors were age, baseline hearing, cumulative cisplatin dose, and radiation dose to the cochlea. Just 5 studies were judged to have an overall low risk of bias. Future studies should attempt to minimize bias by following statistical best practices including not selecting multivariate predictors based on univariate analysis, validation in independent cohorts, and clearly reporting the management of missing and censored data. Future modeling efforts should adopt a transdisciplinary approach to define a unified set of clinical, treatment, and/or genetic risk factors. Creating a flexible model that uses a common set of predictors to forecast the full post-treatment audiogram may accelerate work in this area. Such a model could be adapted for use in counseling, treatment planning, and follow-up by audiologists and oncologists and could be incorporated into ototoxicity genetic association studies as well as clinical trials investigating otoprotective agents.
IMPLICATIONS FOR CANCER SURVIVORS
Improvements in the ability to model post-treatment hearing loss can help to improve patient quality of life following cancer care. The improvements advocated for in this review should allow for the acceleration of advancements in modeling the auditory impact of these treatments to support treatment planning and patient counseling during and after care.
Topics: Child; Humans; Adult; Antineoplastic Agents; Prognosis; Ototoxicity; Quality of Life; Cancer Survivors; Neoplasms
PubMed: 36729346
DOI: 10.1007/s11764-022-01315-8 -
BMC Cancer Dec 2022Osteosarcoma is the most common bone tumor in children and adolescents. Despite multiagent chemotherapy, only 71% of patients survives and these survivors often...
BACKGROUND
Osteosarcoma is the most common bone tumor in children and adolescents. Despite multiagent chemotherapy, only 71% of patients survives and these survivors often experience long-term toxicities. The main objective of this systematic review is to provide an overview of the discovery of novel associations of germline polymorphisms with treatment response and/or chemotherapy-induced toxicities in osteosarcoma. METHODS: MEDLINE and Embase were systematically searched (2010-July 2022). Genetic association studies were included if they assessed > 10 germline genetic variants in > 5 genes in relevant drug pathways or if they used a genotyping array or other large-scale genetic analysis. Quality was assessed using adjusted STrengthening the REporting of Genetic Association studies (STREGA)-guidelines. To find additional evidence for the identified associations, literature was searched to identify replication studies.
RESULTS
After screening 1999 articles, twenty articles met our inclusion criteria. These range from studies focusing on genes in relevant pharmacokinetic pathways to whole genome sequencing. Eleven articles reported on doxorubicin-induced cardiomyopathy. For seven genetic variants in CELF4, GPR35, HAS3, RARG, SLC22A17, SLC22A7 and SLC28A3, replication studies were performed, however without consistent results. Ototoxicity was investigated in one study. Five small studies reported on mucosistis or bone marrow, nephro- and/or hepatotoxicity. Six studies included analysis for treatment efficacy. Genetic variants in ABCC3, ABCC5, FasL, GLDC, GSTP1 were replicated in studies using heterogeneous efficacy outcomes.
CONCLUSIONS
Despite that results are promising, the majority of associations were poorly reproducible due to small patient cohorts. For the future, hypothesis-generating studies in large patient cohorts will be necessary, especially for cisplatin-induced ototoxicity as these are largely lacking. In order to form large patient cohorts, national and international collaboration will be essential.
Topics: Child; Adolescent; Humans; Pharmacogenetics; Ototoxicity; Osteosarcoma; Cisplatin; Bone Neoplasms
PubMed: 36536332
DOI: 10.1186/s12885-022-10434-5 -
Journal of the Association For Research... Feb 2023Identifying risk factors for tinnitus could facilitate not only the recommendations for prevention measures, but also identifying potential pathways for new... (Meta-Analysis)
Meta-Analysis
AIMS/HYPOTHESIS
Identifying risk factors for tinnitus could facilitate not only the recommendations for prevention measures, but also identifying potential pathways for new interventions. This study reports the first comprehensive systematic review of analytical observational studies able to provide information about causality (i.e., case-control and cohort designs).
METHODS
A literature search of four electronic databases identified epidemiological studies published on tinnitus and different exposures. Independent raters screened all studies, extracted data, and evaluated study quality using the Newcastle-Ottawa Scale. Reported relative risks (RR), hazard ratios (HR), odds ratios (OR), and prevalence ratios (PR) with 95% confidence intervals (CI) were used to compute crude estimates of RR for tinnitus risk factors.
RESULTS
From 2389 records identified, a total of 374 articles were read as full text (24 reviews, 301 cross-sectional studies, 42 cohort studies, and 7 case-control studies). However, from 49 case-control and cohort studies, only 25 adequately reported risk ratios. Using the findings from these studies, positive causal associations were found for various hearing-related factors (i.e., unspecified hearing loss, sensorineural hearing loss, occupational noise exposure, ototoxic platinum therapy, and otitis media). Evidence was also found for a number of non-otological risk factors including temporo-mandibular joint disorder, depression, chronic obstructive pulmonary disease, and hyperlipidemia. Negative associations indicating preventative effects were found for diabetes and high alcohol consumption. No associations were found for low alcohol consumption, body mass index, head injury, heart failure, hypertension, leisure noise exposure, migraine, rheumatoid arthritis, sex, smoking, stroke, and whiplash. However, with the exception of unspecified hearing loss, these findings resulted from pooling no more than 4 studies, illustrating that the vast majority of the associations still remain inconclusive.
CONCLUSIONS
These systematic review and meta-analysis confirm a number of otological and non-otological risk factors for tinnitus. By highlighting major gaps in knowledge, our synthesis can help provide direction for future research that will shed light on the pathophysiology, improve management strategies, and inform more effective preventions.
Topics: Humans; Tinnitus; Cross-Sectional Studies; Hearing Loss; Risk Factors; Hearing Loss, Sensorineural; Observational Studies as Topic
PubMed: 36380120
DOI: 10.1007/s10162-022-00874-y -
European Journal of Hospital Pharmacy :... Jul 2023Updated European Committee on Antimicrobial Susceptibility Testing (EUCAST) amikacin breakpoints for Enterobacterales and included revised dosing recommendations of... (Review)
Review
BACKGROUND
Updated European Committee on Antimicrobial Susceptibility Testing (EUCAST) amikacin breakpoints for Enterobacterales and included revised dosing recommendations of 25-30 mg/kg to achieve key pharmacokinetic/pharmacodynamic parameters, higher than recommended in the British National Formulary. The objectives of this review were to identify clinical evidence for high-dose amikacin regimens and to determine drug exposures that are related to adverse events and toxicity.
METHODS
The literature search was conducted in October 2021 and updated in May 2022 using electronic databases for any study reporting adult participants treated with amikacin at doses ≥20 mg/kg/day. Reference lists of included papers were also screened for potential papers. Data were extracted for pharmacokinetic parameters and clinical outcomes, presented in a summary table and consolidated narratively. Meta-analysis was not possible. Each study was assessed for bias before, during and after the intervention using the ROBINS-I tool.
RESULTS
Nine studies (total 501 participants in 10 reports) were identified and included, eight of which were observational studies. Assessment of bias showed substantial flaws. Dosing regimens ranged from 25 to 30 mg/kg/day. Six studies adjusted the dose in obesity when participants had a body mass index of ≥30 kg/m. Target peak serum concentrations ranged from 60 mg/L to 80 mg/L and 59.6-81.8% of patients achieved these targets, but there was no information on clinical outcomes. Two studies reported the impact of high-dose amikacin on renal function. No studies reporting auditory or vestibular toxicity were identified.
CONCLUSION
All included papers were limited by a significant risk of bias, while methodological and reporting heterogeneity made drawing conclusions challenging. Lack of information on the impact on renal function or ototoxicity means high-dose regimens should be used cautiously in older people. There is a need for a consensus guideline for high-dose amikacin to be written.
TRIAL REGISTRATION NUMBER
PROSPERO (CRD42021250022).
Topics: Adult; Aged; Humans; Amikacin; Clinical Protocols
PubMed: 36344247
DOI: 10.1136/ejhpharm-2022-003421 -
Iranian Journal of Otorhinolaryngology Sep 2022Noise-induced hearing loss (NIHL) is defined as the sensorineural hearing loss caused by acute acoustic trauma or chronic exposure to high-intensity noises. Exposure to...
INTRODUCTION
Noise-induced hearing loss (NIHL) is defined as the sensorineural hearing loss caused by acute acoustic trauma or chronic exposure to high-intensity noises. Exposure to noises can lead to irreversible damage to the inner ear and, consequently, to a permanent shift of the hearing threshold. Police officers are particularly at risk of acute or chronic hearing damages. The aim of this study is to evaluate the hearing loss of police officers in relation to the occupational risk factors and clinical-anamnestic characteristics by collecting and analyzing existing data and evidence available in public databases.
MATERIALS AND METHODS
A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses group (PRISMA). Studies were included if they met inclusion and exclusion criteria. Study selection, data extraction, and quality assessment were conducted independently by two researchers.
RESULTS
Our initial literature search yielded 29 peer-reviewed articles. Out of 29 papers, only 10 were included in the review, after inclusion and exclusion criteria were applied the.
CONCLUSIONS
Hypertension, smoking and alcohol intake significantly affect hearing performance. In addition, a history of acoustic trauma, use of ototoxic drugs, exposure to noise in leisure-time activities and failure to use ear protectors are often found in a fair number of subjects. NIHL is also related to the age of the subjects as well as the extent and duration of noise exposure. Furthermore, NIHL is also influenced by shooting practice sessions police officers are required to undertake as well as by the chronic exposure to traffic noise, especially in motorcycle police officers.
PubMed: 36246192
DOI: 10.22038/IJORL.2022.64036.3198 -
Audiology Research Jul 2022This systematic review investigates ear cooling and cryotherapy in the prevention and treatment of inner ear damage and disease, within the context of animal models and... (Review)
Review
This systematic review investigates ear cooling and cryotherapy in the prevention and treatment of inner ear damage and disease, within the context of animal models and clinical studies. A literature search was carried out in the databases Pubmed and Cochrane Library. Ten studies were identified concerning the otoprotective properties of cryotherapy. Nine of these were rodent in vivo studies (mice, rats, gerbils, guinea pigs). One study involved human subjects and investigated cryotherapy in idiopathic sensorineural hearing loss. The studies were heterogeneous in their goals, methods, and the models used. Disorder models included ischemia and noise damage, ototoxicity (cisplatin and aminoglycoside), and CI-electrode insertion. All ten studies demonstrated significant cryotherapeutic otoprotection for their respective endpoints. No study revealed or expressly investigated otodestructive effects. While limited in number, all of the studies within the scope of the review demonstrated some degree of cryotherapeutic, otoprotective effect. These promising results support the conducting of further work to explore and refine the clinical applicability and impact of cryotherpeutics in otolaryngology.
PubMed: 35892664
DOI: 10.3390/audiolres12040038 -
Antimicrobial Agents and Chemotherapy Aug 2022To systematically evaluate the relationships between vancomycin trough serum concentrations and clinical outcomes in children using meta-analysis. Several databases,... (Meta-Analysis)
Meta-Analysis
To systematically evaluate the relationships between vancomycin trough serum concentrations and clinical outcomes in children using meta-analysis. Several databases, including PubMed, Elsevier, Web of Science, EMBASE, Medline, clinicaltrials.gov, the Cochrane Library, and three Chinese databases (Wanfang Data, China National Knowledge Infrastructure, and SINOMED), were comprehensively searched to obtain research articles on vancomycin use in children from inception through December 2021. All studies were screened and evaluated using the Cochrane systematic review method. Then, the feature information was extracted for meta-analysis. The evaluated results included clinical efficacy, vancomycin-associated nephrotoxicity, hepatotoxicity, ototoxicity, mortality, and microbial clearance. A total of 35 studies involving 4820 children were included in the analysis. The meta-analysis showed that compared with children with vancomycin trough concentrations <10 μg/mL, those with vancomycin trough concentrations ≥10 μg/mL had a higher clinical efficacy rate [OR: 2.23, 95% CI: 1.29 to 3.84, = 0.004] and higher incidences of nephrotoxicity [OR: 2.76, 95% CI: 1.51 to 5.07, = 0.001], ototoxicity [OR: 1.87, 95% CI: 1.08 to 3.23, = 0.02] and microbial clearance [OR: 2.36, 95% CI: 1.53 to 3.64, = 0.0001]. All-cause mortality [OR: 1.07, 95% CI: 0.45 to 2.53, = 0.88] and hepatotoxicity [OR: 0.84, 95% CI: 0.46 to 1.53, = 0.57] were similar between the two groups. Subgroup analysis showed that compared with children with vancomycin trough concentrations of 10 to 15 μg/mL, those with vancomycin trough concentrations >15 μg/mL had a higher incidence of nephrotoxicity [OR: 2.64, 95% CI: 1.28 to 5.43, = 0.008], but there was no significant difference in clinical efficacy [OR: 0.85, 95% CI: 0.30 to 2.44, = 0.76]. A vancomycin trough concentration of 10 to 15 μg/mL can improve clinical efficacy in children. Additionally, avoidance of trough concentrations >15 μg/mL can reduce the incidence of adverse reactions.
Topics: Anti-Bacterial Agents; Chemical and Drug Induced Liver Injury; Child; Humans; Ototoxicity; Renal Insufficiency; Retrospective Studies; Vancomycin
PubMed: 35862741
DOI: 10.1128/aac.00138-22