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Chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating condition associated with a number of chemotherapeutic agents. Drugs commonly implicated in the development of CIPN include platinum agents, taxanes, vinca alkaloids, bortezomib, and thalidomide analogues. As a drug response can vary between individuals, it is hypothesized that an individual's specific genetic variants could impact the regulation of genes involved in drug pharmacokinetics, ion channel functioning, neurotoxicity, and DNA repair, which in turn affect CIPN development and severity. Variations of other molecular markers may also affect the incidence and severity of CIPN. Hence, the objective of this review was to summarize the known biological (molecular and genomic) predictors of CIPN and discuss the means to facilitate progress in this field.
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Antineoplásicos/efeitos adversos , Síndromes Neurotóxicas/tratamento farmacológico , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/genética , Bortezomib/efeitos adversos , Predisposição Genética para Doença/genética , Humanos , Taxoides/efeitos adversos , Alcaloides de Vinca/efeitos adversosRESUMO
The present review explores the underlying mechanisms of phytophotodermatitis, a non-immunologic skin reaction triggered by certain plants followed by exposure to ultraviolet radiation emitted by sunlight. Recent research has advanced our understanding of the pathophysiology of phytophotodermatitis, highlighting the interaction between plant-derived photosensitizing compounds (e.g., furanocoumarins and psoralens) and ultraviolet light leading to skin damage (e.g., erythema, fluid blisters, edema, and hyperpigmentation), identifying these compounds as key contributors to the phototoxic reactions causing phytophotodermatitis. Progress in understanding the molecular pathways involved in the skin's response to these compounds has opened avenues for identifying potential therapeutic targets suitable for the management and prevention of this condition. The review emphasizes the importance of identifying the most common phototoxic plant families (e.g., Apiaceae, Rutaceae, and Moraceae) and plant species (e.g., Heracleum mantegazzianum, Ruta graveolens, Ficus carica, and Pastinaca sativa), as well as the specific phytochemical compounds responsible for inducing phytophototoxicity (e.g., limes containing furocoumarin have been linked to lime-induced photodermatitis), underscoring the significance of recognizing the dangerous plant sources. Moreover, the most used approaches and tests for accurate diagnosis such as patch testing, Wood's lamp examination, or skin biopsy are presented. Additionally, preventive measures such as adequate clothing (e.g., long-sleeved garments and gloves) and treatment strategies based on the current knowledge of phytophotodermatitis including topical and systemic therapies are discussed. Overall, the review consolidates recent findings in the field, covering a diverse array of phototoxic compounds in plants, the mechanisms by which they trigger skin reactions, and the implications for clinical management. By synthesizing these insights, we provide a comprehensive understanding of phytophotodermatitis, providing valuable information for both healthcare professionals and researchers working to address this condition.
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In this research, Hydroxyapatite-Potassium, Sodium Niobate-Chitosan (HA-KNN-CSL) biocomposites were synthesized, both as hydrogel and ultra-porous scaffolds, to offer two commonly used alternatives to biomaterials in dental clinical practice. The biocomposites were obtained by varying the content of low deacetylated chitosan as matrix phase, mesoporous hydroxyapatite nano-powder, and potassium-sodium niobate (K0.47Na0.53NbO3) sub-micron-sized powder. The resulting materials were characterized from physical, morpho-structural, and in vitro biological points of view. The porous scaffolds were obtained by freeze-drying the composite hydrogels and had a specific surface area of 18.4-24 m2/g and a strong ability to retain fluid. Chitosan degradation was studied for 7 and 28 days of immersion in simulated body fluid without enzymatic presence. All synthesized compositions proved to be biocompatible in contact with osteoblast-like MG-63 cells and showed antibacterial effects. The best antibacterial effect was shown by the 10HA-90KNN-CSL hydrogel composition against Staphylococcus aureus and the fungal strain Candida albicans, while a weaker effect was observed for the dry scaffold.
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For more than five decades, alkali niobate-based materials (KxNa1-xNbO3) have been one of the most promising lead-free piezoelectric materials researched to be used in electronics, photocatalysis, energy storage/conversion and medical applications, due to their important health and environmentally friendly nature. In this paper, our strategy was to synthetize the nearest reproductible composition to KxNa1-xNbO3 (KNN) with x = 0.5, placed at the limit of the morphotropic phase boundary (MPB) with the presence of both polymorphic phases, orthorhombic and tetragonal. The wet synthesis route was chosen to make the mix crystal powders, starting with the suspension preparation of Nb2O5 powder and KOH and NaOH alkaline solutions. Hydrothermal microwave-assisted maturation (HTMW), following the parameter variation T = 200-250 °C, p = 47-60 bar and dwelling time of 30-90 min, was performed. All powders therefore synthesized were entirely KxN1-xNbO3 solid solutions with x = 0.06-0.69, and the compositional, elemental, structural and morphological characterization highlighted polycrystalline particle assemblage with cubic and prismatic morphology, with sizes between 0.28 nm and 2.95 µm and polymorphic O-T phase coexistence, and a d33 piezoelectric constant under 1 pC/N of the compacted unsintered and unpoled discs were found.
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Objective: The International Cooperative Growth Study, NutropinAq® European Registry (iNCGS) (NCT00455728) monitored long-term safety and effectiveness of recombinant human growth hormone (rhGH; NutropinAq® [somatropin]) in paediatric growth disorders. Methods: Open-label, non-interventional, post-marketing surveillance study recruiting children with growth disorders. Endpoints included gain in height standard deviation score (SDS), adult height, and occurrence of adverse events (AEs). Results: 2792 patients were enrolled. 2082 patients (74.6%) had growth hormone deficiency (GHD), which was isolated idiopathic in 1825 patients (87.7%). Non-GHD diagnoses included Turner syndrome (TS) (n=199), chronic renal insufficiency (CRI) (n=10), other non-GHD (n=498), and missing data for three participants. Improvements from baseline height SDS occurred at all time points to Month 132, and in all subgroups by disease aetiology. At Month 12, mean (95% CI) change in height SDS by aetiology was: idiopathic GHD 0.63 (0.61;0.66), organic GHD 0.71 (0.62;0.80), TS 0.59 (0.53; 0.65), CRI 0.54 (-0.49;1.56), and other non-GHD 0.64 (0.59;0.69). Mean height ( ± SD) at the last visit among the 235 patients with adult or near-adult height recorded was 154.0 cm ( ± 8.0) for girls and 166.7 cm ( ± 8.0) for boys. The most frequent biological and clinical non-serious drug-related AEs were increased insulin-like growth factor concentrations (314 events) and injection site haematoma (99 events). Serious AEs related to rhGH according to investigators were reported (n=30); the most frequent were scoliosis (4 events), epiphysiolysis (3 events), and strabismus (2 events). Conclusions: There was an improvement in mean height SDS in all aetiology subgroups after rhGH treatment. No new safety concerns were identified.
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Transtornos do Crescimento/tratamento farmacológico , Hormônio do Crescimento Humano/uso terapêutico , Vigilância de Produtos Comercializados/estatística & dados numéricos , Proteínas Recombinantes/uso terapêutico , Sistema de Registros/estatística & dados numéricos , Insuficiência Renal Crônica/tratamento farmacológico , Síndrome de Turner/tratamento farmacológico , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Seguimentos , Transtornos do Crescimento/patologia , Hormônio do Crescimento Humano/deficiência , Humanos , Lactente , Agências Internacionais , Masculino , Prognóstico , Insuficiência Renal Crônica/patologia , Síndrome de Turner/patologiaRESUMO
This research focused on the synthesis of apatite, starting from a natural biogenic calcium source (egg-shells) and its chemical and morpho-structural characterization in comparison with two commercial xenografts used as a bone substitute in dentistry. The synthesis route for the hydroxyapatite powder was the microwave-assisted hydrothermal technique, starting from annealed egg-shells as the precursor for lime and di-base ammonium phosphate as the phosphate precursor. The powders were characterized by Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), energy-dispersive X-ray analysis (EDAX), transmission electron microscopy (TEM), X-ray fluorescence spectroscopy (XRF), and cytotoxicity assay in contact with amniotic fluid stem cell (AFSC) cultures. Compositional and structural similarities or differences between the powder synthesized from egg-shells (HA1) and the two commercial xenograft powders-Bio-Oss®, totally deproteinized cortical bovine bone, and Gen-Os®, partially deproteinized porcine bone-were revealed. The HA1 specimen presented a single mineral phase as polycrystalline apatite with a high crystallinity (Xc 0.92), a crystallite size of 43.73 nm, preferential growth under the c axes (002) direction, where it mineralizes in bone, a nano-rod particle morphology, and average lengths up to 77.29 nm and diameters up to 21.74 nm. The surface of the HA1 nanoparticles and internal mesopores (mean size of 3.3 ± 1.6 nm), acquired from high-pressure hydrothermal maturation, along with the precursor's nature, could be responsible for the improved biocompatibility, biomolecule adhesion, and osteoconductive abilities in bone substitute applications. The cytotoxicity assay showed a better AFSC cell viability for HA1 powder than the commercial xenografts did, similar oxidative stress to the control sample, and improved results compared with Gen-Os. The presented preliminary biocompatibility results are promising for bone tissue regeneration applications of HA1, and the study will continue with further tests on osteoblast differentiation and mineralization.
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PURPOSE OF REVIEW: To present recent developments in the treatment of breakthrough pain (BTP) in cancer, we reviewed the literature with a special focus on last publications using Medline. RECENT FINDINGS: BTP is distinguished from other pain syndromes because of its unique physiopathology, clinical and socio-economic importance and treatment considerations. Despite medical awareness, BTP remains underdiagnosed and therefore undertreated. Clinical information is essentially based on case series and expert opinion. Fentanyl, oral or nasal, remains the molecule of choice to treat BTP, but very important development is ongoing to improve tolerance, efficacy and pharmacokinetics. SUMMARY: Data from epidemiological and clinical studies show that breakthrough pain remains a challenge especially among cancer patients. An accurate diagnosis followed by a specific treatment is the key for an effective pain relief.
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Fentanila/uso terapêutico , Neoplasias/complicações , Dor/tratamento farmacológico , Administração Intranasal , Administração Oral , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/uso terapêutico , Fentanila/administração & dosagem , Humanos , Dor/etiologia , Dor/fisiopatologia , Medição da Dor , Resultado do TratamentoRESUMO
BACKGROUND: Patients with metastatic human epidermal growth factor receptor 2-positive breast cancer (HER2+ BC) frequently experience brain metastases (BM). We aimed to define risk factors for the development of BM in patients with HER2+ BC and to report on their outcome. METHODS: This is a retrospective analysis of patients diagnosed with HER2+ BC between January 2000 and December 2014 at Institut Jules Bordet, Belgium. Statistical analyses were conducted with SAS V.9.4 using Kaplan-Meier method and Cox regression analyses. RESULTS: A total of 483 patients were included of whom 108 (22.4%) developed metastases and 52 (10.8%) BM. Among 96 metastatic patients without BM at diagnosis, 40 (41.7%) developed BM in the course of their disease. In multivariate analysis, risk factors for the development of BM were age ≤40 years (HR 2.10, 95 % CI 1.02 to 4.36), tumour size >2 cm (HR 4.94, 95% CI 1.69 to 14.47), nodal involvement (HR 3.48, 95% CI 1.47 to 8.25), absence or late start (≥6 months after initial diagnosis) of adjuvant anti-HER2 treatment (HR 3.79, 95% CI 1.52 to 9.43 or HR 2.65, 95% CI 1.03 to 6.82) and the development of lung metastases as first site of relapse (HR 6.97, 95% CI 3.41 to 14.24). Twenty-two patients with HER2+ BC and BM sent to our institute for further treatment were included in the outcome analysis. Asymptomatic patients at the time of BM diagnosis showed a better overall survival than symptomatic patients (HR 0.49, 95% CI 0.25 to 0.94). CONCLUSION: A considerable number of patients with metastatic HER2+ BC will develop BM. Screening of patients with risk factors for BM might lead to early detection and better outcome. However, randomised controlled trials examining the use of MRI as a screening method for BM in patients with metastatic BC are warranted before such an approach can be recommended.
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We report the case of a 65-year-old woman, diagnosed with a breast cancer human epidermal growth factor receptor (HER2) previously negative, who developed leptomeningeal carcinomatosis and was treated with intrathecal (IT) trastuzumab (TST). After five doses of IT trastuzumab, at escalading doses, once weekly, the patient's neurological status stabilised, and that result was maintained for two months. There is evidence in the literature that breast cancer receptor status may change over time, and when it occurs, it may modify the therapeutical approach. We reviewed the pertinent literature and concluded that IT trastuzumab might be a promising treatment for patients with HER2-positive breast cancer leptomeningeal carcinomatosis.
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INTRODUCTION: Real time-sonoelastography (RTE) is a new developed technique that reveals the physical properties of the tissue by characterizing the difference in hardness between diseased tissue and surrounding tissue. Elasticity measurements have been already reported to be useful for the diagnosis and differentiation of many tumors: breast lesions, prostate cancer, lymph nodes and pancreatic masses but there are only few studies for the focal liver lesions. The aim of the study was to analyze whether computer enhanced dynamic analysis of elastography images is able to better characterize and differentiate benign and malignant liver lesions. MATERIAL AND METHODS: The study group included, in total thirty nine liver tumors. RTE was performed by EUS or transabdominal ultrasound. ROC analysis for the mean hue obtained through histogram analysis of the region of interest (liver lesion) after averaging individual pixels over a 10-second elastography movies was used to assess the color information inside the region of interest and to consequently differentiate benign and malignant liver lesions. Based on a cutoff of 170 for the mean hue histogram values recorded on the region of interest, the sensitivity, specificity, and accuracy of differentiation of benign and malignant masses were 92.5%, 88.8%, and 88.6%, respectively. The positive and negative predictive values were 86.7% and 92.3%, respectively. In conclusion, real time sonoelastography is a promising technique that might improve the characterization and differentiation between benign and malignant focal liver lesions visualized during transabdominal or endoscopic ultrasound.
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UNLABELLED: The aim of the study was to assess the costs of hospital admission for COPD patients in a high level unit ("Marius Nasta" Institute of Pulmonology) in order to appreciate the financial burden of the disease. We analyzed retrospectively the medical charts of patients admitted between January and September 2002. 181 charts were included. We extracted data regarding the patient (age, sex, smoking habits, income), disease (duration, severity) and hospital admittance (number of days, tests performed, medication received). Data were processed in EpiInfo 6. RESULTS: mean duration of admittance was 17, 18 days. Mean cost of admittance was 25,448,348 lei (727 Euro), divided in: mean costs of the lab tests - 5,936,812 lei (170 Euro), mean cost of medication--4,428,000 lei (126 Euro), with obvious dominance of COPD medication: 4,310,022 lei; mean cost of hospital stay (including hotel, food and personnel expenses) was 15,120,094 lei (432 Euro). COPD severity was judged on the spirometry at discharge. Mean FEV1 was 45.66% of predicted value. According to GOLD, 10 pts (5.52%) were in stage I, 44 pts (24.3%) in stage II, 69 (38.12%) in stage III and 58 pts (32.03%) in stage IV. Costs per patient were similar for stages I, II and III and significantly higher for stage IV CONCLUSIONS: admitted COPD patients are in severe stages, with a long duration of admittance. Overall costs are much smaller than in Europe, more than half of these costs are due to hospital stay.