RESUMO
OBJECTIVES: This study aimed to explore the prevalence of macrolide resistance and the underlying resistance mechanisms in Haemophilus influenzae (nâ=â2556) and Haemophilus parainfluenzae (nâ=â510) collected between 2018 and 2021 from Bellvitge University Hospital, Spain. METHODS: Antimicrobial susceptibility was tested by microdilution. Whole-genome sequencing was performed using Illumina MiSeq and Oxford Nanopore technologies, and sequences were examined for macrolide resistance determinants and mobile genetic structures. RESULTS: Macrolide resistance was detected in 67 H. influenzae (2.6%) and 52 (10.2%) H. parainfluenzae strains and associated with resistance to other antimicrobials (co-trimoxazole, chloramphenicol, tetracycline). Differences in macrolide resistance existed between the two species. Acquired resistance genes were more prevalent in H. parainfluenzae (35/52; 67.3%) than in H. influenzae (12/67; 17.9%). Gene mutations and amino acid substitutions were more common in H. influenzae (57/67; 85%) than in H. parainfluenzae (16/52; 30.8%). Substitutions in L22 and in 23S rRNA were only detected in H. influenzae (34.3% and 29.0%, respectively), while substitutions in L4 and AcrAB/AcrR were observed in both species. The MEGA element was identified in 35 (67.3%) H. parainfluenzae strains, five located in an integrative and conjugative element (ICE); by contrast, 11 (16.4%) H. influenzae strains contained the MEGA element (all in an ICE). A new ICEHpaHUB8 was described in H. parainfluenzae. CONCLUSIONS: Macrolide resistance was higher in H. parainfluenzae than in H. influenzae, with differences in the underlying mechanisms. H. parainfluenzae exhibits co-resistance to other antimicrobials, often leading to an extensively drug-resistant phenotype. This highlights the importance of conducting antimicrobial resistance surveillance.
Assuntos
Antibacterianos , Farmacorresistência Bacteriana , Infecções por Haemophilus , Haemophilus influenzae , Haemophilus parainfluenzae , Macrolídeos , Testes de Sensibilidade Microbiana , Sequenciamento Completo do Genoma , Haemophilus parainfluenzae/genética , Haemophilus parainfluenzae/efeitos dos fármacos , Macrolídeos/farmacologia , Haemophilus influenzae/efeitos dos fármacos , Haemophilus influenzae/genética , Antibacterianos/farmacologia , Infecções por Haemophilus/microbiologia , Humanos , Farmacorresistência Bacteriana/genética , Espanha/epidemiologia , MutaçãoRESUMO
Interleukin (IL)-9 is present in atopic dermatitis (AD) lesions and is considered to be mainly produced by skin-homing T cells expressing the cutaneous lymphocyte-associated antigen (CLA). However, its induction by AD-associated triggers remains unexplored. Circulating skin-tropic CLA+ and extracutaneous/systemic CLA- memory T cells cocultured with autologous lesional epidermal cells from AD patients were activated with house dust mite (HDM) and staphylococcal enterotoxin B (SEB). Levels of AD-related mediators in response to both stimuli were measured in supernatants, and the cytokine response was associated with different clinical characteristics. Both HDM and SEB triggered heterogeneous IL-9 production by CLA+ and CLA- T cells in a clinically homogenous group of AD patients, which enabled patient stratification into IL-9 producers and non-producers, with the former group exhibiting heightened HDM-specific and total IgE levels. Upon allergen exposure, IL-9 production depended on the contribution of epidermal cells and class II-mediated presentation; it was the greatest cytokine produced and correlated with HDM-specific IgE levels, whereas SEB mildly induced its release. This study demonstrates that both skin-tropic and extracutaneous memory T cells produce IL-9 and suggests that the degree of allergen sensitization reflects the varied IL-9 responses in vitro, which may allow for patient stratification in a clinically homogenous population.
Assuntos
Dermatite Atópica , Enterotoxinas , Interleucina-9 , Células T de Memória , Dermatite Atópica/imunologia , Dermatite Atópica/metabolismo , Humanos , Interleucina-9/metabolismo , Feminino , Masculino , Adulto , Enterotoxinas/imunologia , Células T de Memória/imunologia , Células T de Memória/metabolismo , Pele/imunologia , Pele/metabolismo , Pyroglyphidae/imunologia , Animais , Imunoglobulina E/imunologia , Imunoglobulina E/sangue , Pessoa de Meia-Idade , Antígenos de Diferenciação de Linfócitos T/metabolismo , Adulto Jovem , Alérgenos/imunologia , Adolescente , Glicoproteínas de MembranaRESUMO
The PIK3CA and SOX2 genes map at 3q26, a chromosomal region frequently amplified in head and neck cancers, which is associated with poor prognosis. This study explores the clinical significance of PIK3CA and SOX2 gene amplification in early tumorigenesis. Gene copy number was analyzed by real-time PCR in 62 laryngeal precancerous lesions and correlated with histopathological grading and laryngeal cancer risk. Amplification of the SOX2 and PIK3CA genes was frequently detected in 19 (31%) and 32 (52%) laryngeal dysplasias, respectively, and co-amplification in 18 (29%) cases. The PIK3CA and SOX2 amplifications were predominant in high-grade dysplasias and significantly associated with laryngeal cancer risk beyond histological criteria. Multivariable Cox analysis further revealed PIK3CA gene amplification as an independent predictor of laryngeal cancer development. Interestingly, combined PIK3CA and SOX2 amplification allowed us to distinguish three cancer risk subgroups, and PIK3CA and SOX2 co-amplification was found the strongest predictor by ROC analysis. Our data demonstrate the clinical relevance of PIK3CA and SOX2 amplification in early laryngeal tumorigenesis. Remarkably, PIK3CA amplification was found to be an independent cancer predictor. Furthermore, combined PIK3CA and SOX2 amplification is emerging as a valuable and easy-to-implement tool for cancer risk assessment in patients with laryngeal precancerous lesions beyond current WHO histological grading.
Assuntos
Neoplasias Laríngeas , Lesões Pré-Cancerosas , Humanos , Amplificação de Genes , Neoplasias Laríngeas/genética , Lesões Pré-Cancerosas/genética , Classe I de Fosfatidilinositol 3-Quinases/genética , Carcinogênese/genética , Fatores de Transcrição SOXB1/genéticaRESUMO
BACKGROUND: Despite growing interest in treatment strategies that limit oxygen exposure in ICU patients, no studies have compared conservative oxygen with standard oxygen in postsurgical patients with sepsis/septic shock, although there are indications that it may improve outcomes. It has been proven that high partial pressure of oxygen in arterial blood (PaO2) reduces the rate of surgical-wound infections and mortality in patients under major surgery. The aim of this study is to examine whether PaO2 is associated with risk of death in adult patients with sepsis/septic shock after major surgery. METHODS: We performed a secondary analysis of a prospective observational study in 454 patients who underwent major surgery admitted into a single ICU. Patients were stratified in two groups whether they had hyperoxemia, defined as PaO2 > 100 mmHg (n = 216), or PaO2 ≤ 100 mmHg (n = 238) at the day of sepsis/septic shock onset according to SEPSIS-3 criteria maintained during 48 h. Primary end-point was 90-day mortality after diagnosis of sepsis. Secondary endpoints were ICU length of stay and time to extubation. RESULTS: In patients with PaO2 ≤ 100 mmHg, we found prolonged mechanical ventilation (2 [8] vs. 1 [4] days, p < 0.001), higher ICU stay (8 [13] vs. 5 [9] days, p < 0.001), higher organ dysfunction as assessed by SOFA score (9 [3] vs. 7 [5], p < 0.001), higher prevalence of septic shock (200/238, 84.0% vs 145/216) 67.1%, p < 0.001), and higher 90-day mortality (37.0% [88] vs. 25.5% [55], p = 0.008). Hyperoxemia was associated with higher probability of 90-day survival in a multivariate analysis (OR 0.61, 95%CI: 0.39-0.95, p = 0.029), independent of age, chronic renal failure, procalcitonin levels, and APACHE II score > 19. These findings were confirmed when patients with severe hypoxemia at the time of study inclusion were excluded. CONCLUSIONS: Oxygenation with a PaO2 above 100 mmHg was independently associated with lower 90-day mortality, shorter ICU stay and intubation time in critically ill postsurgical sepsis/septic shock patients. Our findings open a new venue for designing clinical trials to evaluate the boundaries of PaO2 in postsurgical patients with severe infections.
Assuntos
Sepse , Choque Séptico , Adulto , Humanos , Unidades de Terapia Intensiva , Pró-Calcitonina , Prognóstico , Estudos ProspectivosRESUMO
Antifungal susceptibility testing is an essential tool for guiding antifungal therapy. Reference methods are complex and usually only available in specialised laboratories. We have designed an expanded agar-based screening method for the detection of azole-resistant Aspergillus fumigatus isolates. Normally, identification of resistance mechanisms is obtained only after sequencing the cyp51A gene and promoter. However, our screening method provides azole resistance detection and presumptive resistance mechanisms identification. A previous agar-based method consisting of four wells containing voriconazole, itraconazole, posaconazole and a growth control, detected azole resistance to clinical azoles. Here, we have modified the concentrations of voriconazole and posaconazole to adapt to the updated EUCAST breakpoints against A. fumigatus. We have also expanded the method to include environmental azoles to assess azole resistance and the azole resistance mechanism involved. We used a collection of A. fumigatus including 54 azole-resistant isolates with Cyp51A modifications (G54, M220, G448S, TR53 , TR34 /L98H, TR46 /Y121F/T289A, TR34 /L98H/S297T/F495I), and 50 azole susceptible isolates with wild-type Cyp51A. The screening method detects azole-resistant A. fumigatus isolates when there is growth in any of the azole-containing wells after 48h. The growth pattern in the seven azoles tested helps determine the underlying azole resistance mechanism. This approach is designed for surveillance screening of A. fumigatus azole-resistant isolates and can be useful for the clinical management of patients prior to antifungal susceptibility testing confirmation.
Assuntos
Antifúngicos , Aspergillus fumigatus , Azóis , Farmacorresistência Fúngica , Ágar , Antifúngicos/farmacologia , Aspergillus fumigatus/efeitos dos fármacos , Aspergillus fumigatus/genética , Azóis/farmacologia , Farmacorresistência Fúngica/efeitos dos fármacos , Proteínas Fúngicas/genética , Testes de Sensibilidade Microbiana , Voriconazol/farmacologiaRESUMO
Drug resistance poses a serious threat to human health and agricultural production. Azole drugs are the largest group of 14-α sterol demethylation inhibitor fungicides that are used both in agriculture and in clinical practice. As plant pathogenic molds share their natural environment with fungi that cause opportunistic infections in humans, both are exposed to a strong and persistent pressure of demethylase inhibitor (DMI) fungicides, including imidazole and triazole drugs. As a result, a loss of efficacy has occurred for this drug class in several species. In the clinical setting, Aspergillus fumigatus azole resistance is a growing public health problem and finding the source of this resistance has gained much attention. It is urgent to determine if there is a direct link between the agricultural use of azole compounds and the different A. fumigatus resistance mechanisms described for clinical triazoles. In this work we have performed A. fumigatus susceptibility testing to clinical triazoles and crop protection DMIs using a collection of azole susceptible and resistant strains which harbor most of the described azole resistance mechanisms. Various DMI susceptibility profiles have been found in the different A. fumigatus populations groups based on their azole resistance mechanism and previous WGS analysis, which suggests that the different resistance mechanisms have different origins and are specifically associated to the local use of a particular DMI.Importance Due to the worldwide emergence of A. fumigatus azole resistance, this opportunistic pathogen poses a serious health threat and, therefore, it has been included in the Watch List of the CDC 2019 Antimicrobial Resistance Threats Report. Azoles play a critical role in the control and management of fungal diseases, not only in the clinical setting but also in agriculture. Thus, azole resistance leads to a limited therapeutic arsenal which reduces the treatment options for aspergillosis patients, increasing their mortality risk. Evidence is needed to understand whether A. fumigatus azole resistance is emerging from an agricultural source due to the extended use of demethylase inhibitors as fungicides, or whether it is coming from somewhere else such as the clinical setting. If the environmental route is demonstrated, the current use and management of azole antifungal compounds might be forced to change in the forthcoming years.
RESUMO
Hygienic measures are extremely important to avoid the transmission of contagious viruses and diseases. The use of an electronic faucet increases the hygiene, encourages hand washing, avoids touching the faucet for opening and closing, and it saves water, since the faucet is automatically closed. The microbial fuel cell (MFC) technology has the capability to convert environmental waste into energy. The implementation of low cost ceramic MFCs into electronic interfaces integrated in toilets, would offer a compact powering system as well as an environmentally friendly small-scale treatment plant. In this work, the use of low cost ceramic MFCs to power an L20-E electronic faucet is presented for the first time. A single MFC was capable of powering an electronic faucet with an open/close cycle of 8.5 min, with 200 ml of urine. With a footprint of 360 cm3, the MFC could easily be integrated in a toilet. The possibility to power e-toilet components with MFCs offers a sustainable energy generation system. Other electronic components including an automatic flush, could potentially be powered by MFCs and contribute to the maintenance efficiency and hygiene of the public toilets, leading to a new generation of self-sustained energy recovering e-toilets.
RESUMO
Candida albicans (CA) infections have been associated with psoriasis onset or disease flares. However, the integrated immune response against this fungus is still poorly characterized in psoriasis. We studied specific immunoglobulins in plasma and the CA response in cocultures of circulating memory CD45RA- cutaneous lymphocyte antigen (CLA)+/- T cell with autologous epidermal cells from plaque and guttate psoriasis patients (cohort 1, n = 52), and also healthy individuals (n = 17). A complete proteomic profile was also evaluated in plaque psoriasis patients (cohort 2, n = 114) regarding their anti-CA IgA levels. Increased anti-CA IgA and IgG levels are present in the plasma from plaque but not guttate psoriasis compared to healthy controls. CA cellular response is confined to CLA+ T cells and is primarily Th17. The levels of anti-CA IgA are directly associated with CLA+ Th17 response in plaque psoriasis. Proteomic analysis revealed distinct profiles in psoriasis patients with high anti-CA IgA. C-C motif chemokine ligand 18, chitinase-3-like protein 1 and azurocidin were significantly elevated in the plasma from plaque psoriasis patients with high anti-CA levels and severe disease. Our results indicate a mechanism by which Candida albicans exposure can trigger a clinically relevant IL-17 response in psoriasis. Assessing anti-CA IgA levels may be useful in order to evaluate chronic psoriasis patients.
Assuntos
Candidíase/imunologia , Imunidade Celular , Imunidade Humoral , Imunoglobulina A/sangue , Psoríase/imunologia , Adulto , Idoso , Anticorpos Antifúngicos/sangue , Candida albicans/imunologia , Candidíase/sangue , Candidíase/complicações , Feminino , Humanos , Interleucina-17 , Masculino , Pessoa de Meia-Idade , Oligossacarídeos , Proteômica , Psoríase/sangue , Psoríase/complicações , Antígeno Sialil Lewis X/análogos & derivados , Adulto JovemRESUMO
Invasive aspergillosis, mainly caused by Aspergillus fumigatus, can lead to severe clinical outcomes in immunocompromised individuals. Antifungal treatment, based on the use of azoles, is crucial to increase survival rates. However, the recent emergence of azole-resistant A. fumigatus isolates is affecting the efficacy of the clinical therapy and lowering the success rate of azole strategies against aspergillosis. Azole resistance mechanisms described to date are mainly associated with mutations in the azole target gene cyp51A that entail structural changes in Cyp51A or overexpression of the gene. However, strains lacking cyp51A modifications but resistant to clinical azoles have recently been detected. Some genes have been proposed as new players in azole resistance. In this study, the gene hmg1, recently related to azole resistance, and its paralogue hmg2 were studied in a collection of fifteen azole-resistant strains without cyp51A modifications. Both genes encode HMG-CoA reductases and are involved in the ergosterol biosynthesis. Several mutations located in the sterol sensing domain (SSD) of Hmg1 (D242Y, G307D/S, P309L, K319Q, Y368H, F390L and I412T) and Hmg2 (I235S, V303A, I312S, I360F and V397C) were detected. The role of these mutations in conferring azole resistance is discussed in this work.
Assuntos
Antifúngicos/farmacologia , Aspergillus fumigatus/efeitos dos fármacos , Farmacorresistência Fúngica/genética , Proteínas Fúngicas/genética , Hidroximetilglutaril-CoA Redutases/genética , Antifúngicos/química , Aspergilose/microbiologia , Aspergillus fumigatus/genética , Aspergillus fumigatus/isolamento & purificação , Azóis/química , Sistema Enzimático do Citocromo P-450/genética , Farmacorresistência Fúngica/efeitos dos fármacos , Proteínas Fúngicas/química , Regulação Fúngica da Expressão Gênica/efeitos dos fármacos , Humanos , Hidroximetilglutaril-CoA Redutases/química , Testes de Sensibilidade Microbiana , Mutação Puntual , Regiões Promotoras Genéticas , Sequenciamento Completo do GenomaRESUMO
INTRODUCTION: The objective of this work was to analyse the postoperative clinical results of patients surgically treated for colorectal cancer in relation to the results of the preoperative comprehensive geriatric evaluation. METHODS: Observational study in which postoperative morbidity and mortality at 30 and 90 days were analysed in a cohort of patients surgically treated for colorectal cancer according to age groups: group 1) between 75 and 79 years old; group 2) between 80 and 84 years old, and group 3) ≥85 years old. In addition to the anaesthetic risk assessment, patients were assessed with the Karnofsky, Barthel and Pfeiffer indexes. Mortality at 30 and 90 days after surgery was analysed in relation to the results of the comprehensive evaluation. RESULTS: A total of 227 patients with colorectal cancer were included in the study period: 91 in group 1, 89 in group 2 and 47 in group 3. There were statistically significant differences in mortality at 30 days (p=0,029) but not at 90 days after surgery, according to age groups. Mortality at 90 days was significantly higher in patients with worse scores on the Karnofsky and Barthel scales. CONCLUSIONS: Comprehensive geriatric assessment using different scales is a good tool to assess postoperative mortality in the mid-term postoperative period.
Assuntos
Neoplasias Colorretais/cirurgia , Avaliação Geriátrica/métodos , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Estudos Prospectivos , Resultado do TratamentoRESUMO
BACKGROUND: The long-term survival of germline retinoblastoma patients is decreased due to the risk of second primary tumors (SPTs) that occur years after the diagnosis of retinoblastoma. This risk is related to genetic predisposition and other factors, such as the treatment of retinoblastoma by external beam radiotherapy (EBRT). PROCEDURE: We studied the incidence, risk factors, and prognosis of specific craniofacial SPTs developed within the margins of radiation field in a cohort of 209 patients with germline retinoblastoma treated with EBRT at our institution between 1977 and 2010. Clinical characteristics, survival, incidence, and histology of craniofacial SPTs were recorded. RESULTS: Fifty-three of the 209 patients developed 60 distinct craniofacial SPTs in irradiated field with a median time from EBRT of 16.9 years (4-35) and a median follow-up of 24.8 years (5.3-40). Osteosarcoma (33.3%) and undifferentiated sarcoma (23.3%) were the more prevalent histological entities. Benign tumors (16.7%) also occurred. The cumulative incidence of craniofacial SPTs reached 32.6% at 35 years after EBRT, and the median survival after diagnosis was five years. In our series, irradiation under 12 months of age, bilateral EBRT, or previous treatment of retinoblastoma with chemotherapy did not significantly increase the risk of craniofacial SPTs. CONCLUSIONS: This work presents a strong argument to avoid EBRT in the management of retinoblastoma and emphasizes the high risk and poor prognosis of specific craniofacial SPTs. This study also points to the question of the need and benefits of special programs for early detection of craniofacial SPTs in survivors of irradiated germline retinoblastoma.
Assuntos
Predisposição Genética para Doença , Células Germinativas/patologia , Neoplasias Induzidas por Radiação/etiologia , Segunda Neoplasia Primária/etiologia , Radioterapia/efeitos adversos , Neoplasias da Retina/radioterapia , Retinoblastoma/radioterapia , Adolescente , Adulto , Sobreviventes de Câncer/estatística & dados numéricos , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Masculino , Neoplasias Induzidas por Radiação/patologia , Segunda Neoplasia Primária/patologia , Prognóstico , Neoplasias da Retina/genética , Neoplasias da Retina/patologia , Retinoblastoma/genética , Retinoblastoma/patologia , Estudos Retrospectivos , Taxa de Sobrevida , Adulto JovemRESUMO
Circulating tumor DNA (ctDNA) is a powerful tool for the molecular characterization of cancer. The most frequent pediatric kidney tumors (KT) are Wilms' tumors (WT), but other diagnoses may occur. According to the SIOP strategy, in most countries pediatric KT have a presumptive diagnosis of WT if they are clinically and radiologically compatible. The histologic confirmation is established after post-chemotherapy nephrectomy. Thus, there is a risk for a small fraction of patients to receive neoadjuvant chemotherapy that is not adapted to the disease. The aim of this work is to perform molecular diagnosis of pediatric KT by tumor genetic characterization based on the analysis of ctDNA. We analyzed ctDNA extracted from plasma samples of 18 pediatric patients with KT by whole-exome sequencing and compared the results to their matched tumor and germline DNA. Copy number alterations (CNAs) and single nucleotide variations (SNVs) were analyzed. We were able to detect tumor cell specific genetic alterations-CNAs, SNVs or both-in ctDNA in all patients except in one (for whom the plasma sample was obtained long after nephrectomy). These results open the door to new applications for the study of ctDNA with regards to the molecular diagnosis of KT, with a possibility of its usefulness for adapting the treatment early after diagnosis, but also for disease monitoring and follow up.
Assuntos
Biomarcadores Tumorais/genética , DNA Tumoral Circulante/genética , Neoplasias Renais/genética , Tumor de Wilms/genética , Biomarcadores Tumorais/sangue , Criança , Pré-Escolar , DNA Tumoral Circulante/sangue , Variações do Número de Cópias de DNA , Feminino , Humanos , Lactente , Neoplasias Renais/diagnóstico , Neoplasias Renais/terapia , Masculino , Terapia Neoadjuvante , Nefrectomia , Estudos Retrospectivos , Sensibilidade e Especificidade , Sequenciamento Completo do Genoma/métodos , Tumor de Wilms/diagnóstico , Tumor de Wilms/terapiaRESUMO
Ceramic membranes for MFCs offer a low cost alternative to the expensive ion exchange membranes, whilst promoting catholyte accumulation. However, their physicochemical properties need to be optimised, in order to increase the power output and the catholyte quality from MFCs. Two compositions of fine fire clay (FFC) cured under three firing cycles were manufactured, analysed and tested as ion-exchange and structural material for MFCs. The samples were characterised by scanning electron microscopy (SEM) and electrochemical impedance spectroscopy (EIS). The power and catholyte generated from the ceramic MFCs with different FFC types was also evaluated. The results show a direct correlation between the ohmic resistance, the MFC power generation and the water absorption of the ceramics, giving a maximum power of 1â¯mW from the MFC with the most absorptive FFC (16.37% water absorbance). A slightly more alkaline catholyte was synthesised from the MFCs with higher water absorption FFC.
RESUMO
The anode and cathode electrodes of a microbial fuel cell (MFC) stack, composed of 28 single MFCs, were used as the negative and positive electrodes, respectively of an internal self-charged supercapacitor. Particularly, carbon veil was used as the negative electrode and activated carbon with a Fe-based catalyst as the positive electrode. The red-ox reactions on the anode and cathode, self-charged these electrodes creating an internal electrochemical double layer capacitor. Galvanostatic discharges were performed at different current and time pulses. Supercapacitive-MFC (SC-MFC) was also tested at four different solution conductivities. SC-MFC had an equivalent series resistance (ESR) decreasing from 6.00â¯Ω to 3.42â¯Ω in four solutions with conductivity between 2.5 mScm-1 and 40 mScm-1. The ohmic resistance of the positive electrode corresponded to 75-80% of the overall ESR. The highest performance was achieved with a solution conductivity of 40â¯mSâ¯cm-1 and this was due to the positive electrode potential enhancement for the utilization of Fe-based catalysts. Maximum power was 36.9â¯mW (36.9â¯Wâ¯m-3) that decreased with increasing pulse time. SC-MFC was subjected to 4520 cycles (8 days) with a pulse time of 5â¯s (ipulse 55â¯mA) and a self-recharging time of 150â¯s showing robust reproducibility.
RESUMO
BACKGROUND: the aim of this study was to analyze the clinical results of the multidisciplinary management of elderly patients with colorectal cancer in a single center and to describe postoperative quality of life. METHODS: a comparative study was designed to compare the results and quality of life of patients treated in our center for colon cancer, aged from 80 to 84 years (study group) compared to a control group (aged form 75 to 79 years of age). Morbidity, mortality, oncological results and quality of life were analyzed. RESULTS: eighty-seven patients aged between 80 and 84 years of age (study group) were compared to a control group, which was formed by 91 patients aged from 75 to 79 years of age. There were no significant differences in technique and morbidity. Survival at 30 days, 90 days and at the end of follow-up (median 48 months) were similar in both groups. There were no differences in quality of life except for one item with regard to physical function (p = 0.0138). CONCLUSION: similar clinical results and quality of life were achieved after treating elderly patients with colon cancer with a multidisciplinary management approach.
Assuntos
Neoplasias do Colo/mortalidade , Neoplasias do Colo/cirurgia , Qualidade de Vida , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/cirurgia , Feminino , Humanos , Estimativa de Kaplan-Meier , Tempo de Internação/estatística & dados numéricos , Masculino , Reoperação/estatística & dados numéricos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Central nervous system (CNS) tumors are a leading cause of death in pediatric oncology. New drugs are desperately needed to improve survival. We evaluated the outcome of children and adolescents with CNS tumors participating in phase I trials within the Innovative Therapies for Children with Cancer (ITCC) consortium. Patients with solid tumors aged < 18 years at enrollment in their first dose-finding trial between 2000 and 2014 at eight ITCC centers were included retrospectively. Survival was evaluated using univariate/multivariate analyses. Overall, 114 patients were included (109 evaluable for efficacy). Median age was 10.2 years (range 1.0-17.9). Main diagnoses included: medulloblastoma/primitive neuroectodermal tumors (32.5%) and high-grade gliomas (23.7%). Complete/partial responses (CR/PR) were reported in 7.3% patients and stable disease (SD) in 23.9%. Performance status of 90-100%, school/work attendance, normal ALT/AST and CR/PR/SD correlated with better overall survival (OS) in the univariate analysis. No variables assessable at screening/enrollment were associated with OS in the multivariate analysis. Five patients (4.5%) were discontinued from study due to toxicity. No toxic deaths occurred. Median OS was 11.9 months with CR/PR, 14.5 months with SD and 3.7 months with progressive disease (p < 0.001). The enrollment of children and adolescents with CNS tumors in phase I trials is feasible, safe and offers potential benefit for the patients. Sustained disease stabilization has a promising role as a marker of anti-tumor activity in children with CNS tumors participating in phase I trials.
Assuntos
Neoplasias do Sistema Nervoso Central/terapia , Adolescente , Neoplasias do Sistema Nervoso Central/diagnóstico , Criança , Pré-Escolar , Ensaios Clínicos Fase I como Assunto , Progressão da Doença , Feminino , Humanos , Lactente , Estimativa de Kaplan-Meier , Masculino , Avaliação de Resultados em Cuidados de Saúde , Resultado do TratamentoRESUMO
BACKGROUND: The European Paediatric Regulation was introduced in 2007 to facilitate access to new medicines for children. Our study explored accessibility of early-phase trials in pediatric oncology, in line with the European Paediatric Regulation, to identify the reasons for not inviting patients to participate, parents' refusal, or inclusion failure. PROCEDURE: We conducted a retrospective chart review at Institut Curie, Paris, for all pediatric patients whose cancer progressed despite known effective treatments between July 2010 and December 2013. RESULTS: Out of 100 patients in the palliative phase, 52 received one or more invitations to participate in early-phase trials. Twenty parents declined the invitation, mainly prioritizing quality of life or fearing constraints. Fourteen inclusions failed despite parental approval, mostly due to rapid clinical deterioration. Five patients received no invitations because no early-phase trials were available. Major reasons for noninclusion in the 43 remaining patients were presence of exclusion criteria or other physical factors, preference for conventional treatment, constraints, psychological factors, and follow-up in another hospital after moving. CONCLUSIONS: The Paediatric Regulation has led to increased availability of early-phase trials. Better timing of the proposal, designing less constraining early-phase trials, reducing waiting lists, and improving information for parents and children would facilitate pediatric access to new medicines.
Assuntos
Antineoplásicos/uso terapêutico , Ensaios Clínicos como Assunto/normas , Tomada de Decisões , Neoplasias/terapia , Seleção de Pacientes , Adolescente , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Prognóstico , Estudos RetrospectivosRESUMO
A novel design of microbial fuel cells (MFC) fuelled with undiluted urine was demonstrated to be an efficient power source for decentralised areas, but had only been tested under controlled laboratory conditions. Hence, a field-trial was carried out to assess its feasibility for practical implementation: a bespoke stack of 12 MFC modules was implemented as a self-sufficient lit urinal system at UK's largest music festival. Laboratory investigation showed that with a hydraulic retention time (HRT) of 44â¯h, a cascade of 4 modules (19.2â¯L displacement volume) was continuously producing ≈150â¯mW. At the same HRT, the chemical oxygen demand (COD) was reduced from 5586â¯mg COD·L-1 to 625â¯mg COD·L-1. Field results of the system under uncontrolled usage indicate an optimal retention time for power production between 2h30 and ≈9â¯h. When measured (HRT of ≈11h40), the COD decreased by 48% and the total nitrogen content by 13%. Compared to the previous PEE POWER® field-trial (2015), the present system achieved a 37% higher COD removal with half the HRT. The 2016 set-up produced ≈30% more energy in a third of the total volumetric footprint (max 600â¯mW). This performance corresponds to ≈7-fold technological improvement.
Assuntos
Dermatite Atópica , Humanos , Interleucina-13 , Células T de Memória , Células Th2 , Enterotoxinas/farmacologia , Células Th1 , PeleRESUMO
The last few years have seen the identification of pharmacologic approaches to target bromodomain and extraterminal (BET) proteins for cancer treatment. These proteins have an essential role in gene transcription regulation by binding acetylated lysine residues on histone tails, activating gene transcription. BET inhibitors have been tested in preclinical models including pediatric malignancies and several adult clinical trials are ongoing. Since the development of new drugs in pediatric cancer has long lagged behind programs for adults, the aim of this review is to show the importance of these therapies in pediatric malignancies to support their development in pediatric oncology/hematology.