ABSTRACT
Dogs are reservoir hosts for Leishmania infantum, a protozoan parasite transmitted by phlebotomine sand flies. The anti-feeding and fast-killing efficacy of Scalibor® deltamethrin collars against experimental Phlebotomus perniciosus challenges on dogs was determined over 1 year. Two groups of 8 dogs each were fitted with placebo (control) or deltamethrin collars (treated) on Day 0 and exposed to sand flies approximately every 28 days up to Day 364. After each exposure, anti-feeding and fast-killing efficacy rates were determined by comparing blood-fed or live insects, respectively, in the treated vs. the control group. Blood-fed and live sand flies were significantly less in treated dogs as compared to control dogs at each assessment. The anti-feeding efficacy rate exceeded 90% except on Day 337 (89%) but increased again (96%) on Day 364. Fast killing efficacy was <74% over the study when considering all flies. However, this value increased cumulatively to 98% when only blood-fed flies were compared between groups. Scalibor® collars are highly effective at preventing P. perniciosus blood-feeding and in fast-killing flies taking a blood meal for up to 1 year after application. These strong and long-lasting effects are an important strategic component for L. infantum transmission control.
Subject(s)
Dog Diseases , Leishmania infantum , Phlebotomus , Psychodidae , Pyrethrins , Animals , Dog Diseases/parasitology , Dog Diseases/prevention & control , Dogs , Nitriles/pharmacology , Phlebotomus/parasitology , Pyrethrins/pharmacologyABSTRACT
Dogs are reservoir hosts of leishmaniasis caused by Leishmania infantum and transmitted by phlebotomine vectors. The effect of dinotefuran, pyriproxyfen and permethrin spot-on solution (Vectra®3D, Ceva Santé Animale, Libourne, France) on Leishmania transmissibility by naturally infected dogs via reared Phlebotomus perniciosus, was assessed. Dogs affected by leishmaniasis were submitted to xenodiagnosis and 6 infecting >10% of insects were treated topically on day 0. Antifeeding, insecticidal and anti-transmissibility effects were evaluated through xenodiagnoses performed on days 1, 7 and 28, using individual pre-treatment parameters as control. Feeding and mortality rates were assessed at 24 h, whereas promastigote infection, maturation and burden were assessed up to 96 h post blood meal (potentially infectious rate). On day 1, the anti-feeding efficacy was >95% in 4 dogs, insecticidal efficacy 100% in 4 dogs, and anti-transmissibility effect 100% in 6 dogs. Efficacy rates recorded on day 7 were very similar to day 1. On day 28, anti-feeding and insecticidal efficacy values were much broader, ranging 32.6-100% and 7.7-94.4%, respectively. Potentially infectious insects were recorded from two dogs, with sharp decrease in transmissibility rate as compared with pre-treatment condition. Altogether, Vectra®3D abrogated by >98% the potential Leishmania transmissibility by the examined pool of infected dogs over 1 month.
Subject(s)
Dog Diseases , Insecticides , Leishmania infantum , Leishmaniasis, Visceral , Leishmaniasis , Phlebotomus , Animals , Dogs , Guanidines , Insecticides/pharmacology , Leishmaniasis/veterinary , Leishmaniasis, Visceral/veterinary , Neonicotinoids , Nitro Compounds , Permethrin/pharmacology , PyridinesABSTRACT
With the aim of improving phototherapy for neonatal jaundice (hyperbilirubinemia), this study investigates the degradation of unconjugated bilirubin under irradiance by conventional light and by white, red, green, and blue LED sources in vitro. The absorption spectra of bilirubin under these different light sources are compared. The results demonstrate that white LED phototherapy promotes more efficient bilirubin degradation than conventional blue-light therapy. This study provides a basis for the design of novel phototherapy devices for the treatment of hyperbilirubinemia.
Subject(s)
Jaundice, Neonatal , Phototherapy , Bilirubin , Humans , Infant, Newborn , LightABSTRACT
AIMS: Occupational Burnout (OB) is currently measured through several Patient-Reported Outcome Measures (PROMs) and some of them have become widely used in occupational health research and practice. We, therefore, aimed to review and grade the psychometric validity of the five OB PROMs considered as valid for OB measure in mental health professionals (the Maslach Burnout Inventory (MBI), the Pines' Burnout Measure (BM), the Psychologist Burnout Inventory (PBI), the OLdenburg Burnout Inventory (OLBI) and the Copenhagen Burnout Inventory (CBI)). METHODS: We conducted systematic literature searches in MEDLINE, PsycINFO and EMBASE databases. We reviewed studies published between January 1980 and September 2018 following a methodological framework, in which each step of PROM validation, the reference method, analytical technics and result interpretation criteria were assessed. Using the COnsensus-based Standards for the selection of health Measurement Instruments we evaluated the risk of bias in studies assessing content and criterion validity, structural validity, internal consistency, reliability, measurement error, hypotheses testing and responsiveness of each PROM. Finally, we assessed the level of evidence for the validity of each PROM using the GRADE approach. RESULTS: We identified 6541 studies, 19 of which were included for review. Fifteen studies dealt with MBI whereas BM, PBI, OLBI and CBI were each examined in only one study. OLBI had the most complete validation, followed by CBI, MBI, BM and PBI, respectively. When examining the result interpretation correctness, the strongest disagreement was observed for MBI (27% of results), BM (25%) and CBI (17%). There was no disagreement regarding PBI and OLBI. For OLBI and CBI, the quality of evidence for sufficient content validity, the crucial psychometric property, was moderate; for MBI, BM and PBI, it was very low. CONCLUSION: To be validly and reliably used in medical research and practice, PROM should exhibit robust psychometric properties. Among the five PROMs reviewed, CBI and, to a lesser extent, OLBI meet this prerequisite. The cross-cultural validity of these PROMs was beyond the scope of our work and should be addressed in the future. Moreover, the development of a diagnostic standard for OB would be helpful to assess the sensitivity and specificity of the PROMs and further reexamine their validity.The study protocol was registered in PROSPERO (CRD 42019124621).
Subject(s)
Burnout, Professional/diagnosis , Patient Reported Outcome Measures , Psychometrics/statistics & numerical data , Surveys and Questionnaires/standards , Burnout, Professional/psychology , Burnout, Psychological , Humans , Reproducibility of ResultsABSTRACT
PURPOSE: To develop a novel risk tool that allows the prediction of lymph node invasion (LNI) among patients with prostate cancer (PCa) treated with robot-assisted radical prostatectomy (RARP) and extended pelvic lymph node dissection (ePLND). METHODS: We retrospectively identified 742 patients treated with RARPâ¯+â¯ePLND at a single center between 2012 and 2018. All patients underwent multiparametric magnetic resonance imaging (mpMRI) and were diagnosed with targeted biopsies. First, the nomogram published by Briganti et al. was validated in our cohort. Second, three novel multivariable logistic regression models predicting LNI were developed: (1) a complete model fitted with PSA, ISUP grade groups, percentage of positive cores (PCP), extracapsular extension (ECE), and Prostate Imaging Reporting and Data System (PI-RADS) score; (2) a simplified model where ECE score was not included (model 1); and (3) a simplified model where PI-RADS score was not included (model 2). The predictive accuracy of the models was assessed with the receiver operating characteristic-derived area under the curve (AUC). Calibration plots and decision curve analyses were used. RESULTS: Overall, 149 patients (20%) had LNI. In multivariable logistic regression models, PSA (OR: 1.03; P= 0.001), ISUP grade groups (OR: 1.33; P= 0.001), PCP (OR: 1.01; P= 0.01), and ECE score (ECE 4 vs. 3 OR: 2.99; ECE 5 vs. 3 OR: 6.97; P< 0.001) were associated with higher rates of LNI. The AUC of the Briganti et al. model was 74%. Conversely, the AUC of model 1 vs. model 2 vs. complete model was, respectively, 78% vs. 81% vs. 81%. Simplified model 1 (ECE score only) was then chosen as the best performing model. A nomogram to calculate the individual probability of LNI, based on model 1 was created. Setting our cut-off at 5% we missed only 2.6% of LNI patients. CONCLUSIONS: We developed a novel nomogram that combines PSA, ISUP grade groups, PCP, and mpMRI-derived ECE score to predict the probability of LNI at final pathology in RARP candidates. The application of a nomogram derived cut-off of 5% allows to avoid a consistent number of ePLND procedures, missing only 2.6% of LNI patients. External validation of our model is needed.
Subject(s)
Extranodal Extension/diagnostic imaging , Multiparametric Magnetic Resonance Imaging , Nomograms , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/pathology , Adult , Aged , Humans , Lymph Node Excision , Male , Middle Aged , Prostatectomy , Prostatic Neoplasms/surgery , Retrospective StudiesABSTRACT
Dogs are the reservoir host of zoonotic visceral leishmaniasis (VL) caused by Leishmania infantum (Kinetoplastida: Trypanosomatidae). Both subclinically-infected and sick animals can be infectious to competent phlebotomine vectors. The degree and duration of insecticidal efficacy of an oral dose of fluralaner (Bravecto®; Merck Animal Health) was determined in dogs exposed to bites of Phlebotomus perniciosus (Diptera: Psychodidae), a main Mediterranean vector of VL. Twelve dogs allocated to two groups of six animals each were included in a parallel-group designed, negative-controlled, randomized, blinded, single-centre efficacy study. Group 2 was treated with fluralaner on day 0, and sand-fly exposure of both groups was performed on days 1, 28 and 84. Viability of blood-fed females was assessed up to 96 h after exposure and efficacy was measured as the survival rate of specimens fed on Group 2 versus those fed on Group 1. A mortality of 100% was recorded at 24 h in females fed on Group 2 at both days 1 and 28. Significant insecticidal efficacy was still observed on day 84, with > 50% mortality recorded by 48 h post blood meal in Group 2. Fluralaner treatment of dogs represents a promising and affordable method for reducing the pool of infected vectors in endemic settings of zoonotic VL.
Subject(s)
Dog Diseases/prevention & control , Insect Control , Insect Vectors , Insecticides , Isoxazoles , Leishmaniasis, Visceral/veterinary , Phlebotomus , Administration, Oral , Animals , Dog Diseases/parasitology , Dogs , Female , Leishmania infantum/physiology , Leishmaniasis, Visceral/parasitology , Leishmaniasis, Visceral/prevention & control , Male , Time FactorsABSTRACT
Feline injection site sarcoma (FISS) is a mesenchymal neoplasm with highly malignant characteristics. These tumours originate in anatomical sites where there has been previous parenteral administration of medicinal substances or implantation of medical devices. The aim of this study was to investigate the epidemiological and pathological features associated with FISS in the southern region of Brazil. The database of the Department of Veterinary Pathology of the Federal University of Rio Grande do Sul was searched for excisional and incisional biopsy samples compatible with FISS submitted between 2007 and 2017. Biopsy reports were reviewed and epidemiological information, including breed, age and sex of affected cats, as well as gross findings including anatomical location and size of the tumour and the presence of tissue invasion, were extracted. Eighty-nine samples were selected based on the established criteria. Most animals were of undefined breed and were female cats with a median age of 10 years. Grossly, 84.8% of the tumours were >2 cm in diameter. Regarding anatomical location, 34.9% of the tumours were located in the subcutaneous tissue of the thoracic wall, 29.2% in the flank, 21.3% in the interscapular region and 14.6% in the limbs. Histologically, the tumours originated in the subcutaneous tissue and were diagnosed as malignant mesenchymal neoplasms. Most were compatible with fibrosarcomas, but variants with features of pleomorphic sarcoma or chondrosarcoma were recognized. All tumours exhibited areas of necrosis and peripheral inflammatory infiltrate, composed predominantly of lymphocytes, plasma cells and macrophages. The results of this study suggest the need for dissemination of information on FISS epidemiology and guidelines for management of this tumour to veterinarians in the region.
Subject(s)
Fibrosarcoma/veterinary , Injection Site Reaction/veterinary , Soft Tissue Neoplasms/veterinary , Animals , Brazil , Cat Diseases/epidemiology , Cat Diseases/pathology , Cats , Female , Fibrosarcoma/pathology , Injection Site Reaction/epidemiology , Injection Site Reaction/pathology , Mesenchymoma/pathology , Mesenchymoma/veterinary , Retrospective Studies , Soft Tissue Neoplasms/pathology , Vaccination/veterinaryABSTRACT
Abstract Host infection by parasites is influenced by an array of factors, including host and environmental features. We investigated the relationship between host sex, body size and age, as well as seasonality on infection patterns by acanthocephalan in coatis (Procyonidae: Nasua nasua) and in crab-eating foxes (Canidae: Cerdocyon thous ) from the Brazilian Pantanal wetlands. Between 2006 and 2009, we collected faecal samples from these hosts and analyzed for the presence of acanthocephalan eggs. Prevalence, abundance and intensity of eggs of acanthocephalans were calculated. Egg abundance was analyzed using generalized linear models (GLM) with a negative binomial distribution and models were compared by Akaike criteria to verify the effect of biotic and abiotic factors. Prevalence of acanthocephalans was higher in the wet season in both host species but did not differ between host sexes; however, adult crab-eating foxes showed higher prevalence of acanthocephalan eggs than juveniles. In contrast, prevalence of acanthocephalan eggs found in coatis was higher in coati juveniles than in adults. Host age, season and maximum temperature were the top predictors of abundance of acanthocephalan eggs in crab-eating foxes whereas season and host sex were predictors of egg abundance in coatis. The importance of seasonality for abundance of acanthocephalan was clear for both host species. The influence of host-related attributes, however, varied by host species, with host gender and host age being important factors associated with prevalence and parasite loads.
Resumo A infecção de hospedeiro por parasitos é influenciada por uma série de fatores, incluindo características do hospedeiro e ambientais. Nós investigamos a relação entre sexo do hospedeiro, tamanho corporal e idade, bem como sazonalidade nos padrões de infecção por acantocéfalos em coatis (Procyonidae: Nasua nasua) e em cachorro-do-mato (Canidae: Cerdocyon thous ) do Pantanal brasileiro e quais fatores explicaram melhor a prevalência e a intensidade desses parasitos. Entre 2006 e 2009, coletamos amostras fecais desses hospedeiros e analisamos a presença de ovos de acantocéfalos. Prevalência, abundância e intensidade de ovos de acantócefálios foram calculados. A abundância de ovos foi analisada utilizando modelos lineares generalizados (GLM) com distribuição binomial negativa e os modelos foram comparados pelo critério de Akaike para verificar o efeito de fatores bióticos e abióticos. A prevalência de acantocéfalos foi maior na estação úmida em ambas as espécies de hospedeiros, mas não diferiu entre os sexos do hospedeiro; no entanto, os cachorros-do-mato adultos apresentaram maior prevalência de ovos de acantocéfalos do que em juvenis. Em contraste, a prevalência de ovos de acantocéfalos encontrados em coatis foi maior em juvenis do que em adultos. A idade do hospedeiro, a estação e a temperatura máxima foram os preditores de abundância de ovos de acantocéfalos em cachorro-do-mato, enquanto a estação e o sexo do hospedeiro foram preditores da abundância dos ovos do parasito em coatis. A importância da sazonalidade para a abundância do acantocéfalo foi clara para ambas as espécies hospedeiras. A influência dos atributos relacionados ao hospedeiro, no entanto, variou entre as espécies de hospedeiros, sendo o sexo e idade do hospedeiro fatores importantes associados à prevalência e às cargas parasitárias.
Subject(s)
Animals , Male , Female , Procyonidae , Acanthocephala/physiology , Foxes , Helminthiasis, Animal/epidemiology , Seasons , Brazil/epidemiology , Prevalence , Population Density , Helminthiasis, Animal/parasitologyABSTRACT
Host infection by parasites is influenced by an array of factors, including host and environmental features. We investigated the relationship between host sex, body size and age, as well as seasonality on infection patterns by acanthocephalan in coatis (Procyonidae: Nasua nasua) and in crab-eating foxes (Canidae: Cerdocyon thous ) from the Brazilian Pantanal wetlands. Between 2006 and 2009, we collected faecal samples from these hosts and analyzed for the presence of acanthocephalan eggs. Prevalence, abundance and intensity of eggs of acanthocephalans were calculated. Egg abundance was analyzed using generalized linear models (GLM) with a negative binomial distribution and models were compared by Akaike criteria to verify the effect of biotic and abiotic factors. Prevalence of acanthocephalans was higher in the wet season in both host species but did not differ between host sexes; however, adult crab-eating foxes showed higher prevalence of acanthocephalan eggs than juveniles. In contrast, prevalence of acanthocephalan eggs found in coatis was higher in coati juveniles than in adults. Host age, season and maximum temperature were the top predictors of abundance of acanthocephalan eggs in crab-eating foxes whereas season and host sex were predictors of egg abundance in coatis. The importance of seasonality for abundance of acanthocephalan was clear for both host species. The influence of host-related attributes, however, varied by host species, with host gender and host age being important factors associated with prevalence and parasite loads.
Subject(s)
Acanthocephala/physiology , Canidae/parasitology , Helminthiasis, Animal/epidemiology , Procyonidae , Animals , Brazil/epidemiology , Female , Helminthiasis, Animal/parasitology , Male , Population Density , Prevalence , Procyonidae/parasitology , SeasonsABSTRACT
Inclusion of legume in grass pastures optimizes protein values of the forage and promotes improved digestibility. Therefore, we hypothesized that finishing steers on a novel combination of legumes and grass pasture would produce carcasses with acceptable traits when compared to carcasses from steers finished in feedlot systems. In this study, we evaluated the effects of finishing steers on three systems including: grazing legume-grass pasture containing oats, ryegrass, white and red clover (PAST), grazing PAST plus supplementation with whole corn grain (14 g/kg BW (SUPP)), and on a feedlot-confined system with concentrate only (28 g/kg BW, consisting of 850 g/kg of whole corn grain and 150 g/kg of protein-mineral-vitamin supplement (GRAIN)) on growth performance of steers, carcass traits and digestive disorders. Eighteen steers were randomly assigned to one of three dietary treatments and finished for 91 days. Data regarding pasture and growth performance were collected during three different periods (0 to 28, 29 to 56 and 57 to 91 days). Subsequently, steers were harvested to evaluate carcass traits, presence of rumenitis, abomasitis and liver abscesses. The legume-grass pasture provided more than 19% dry matter of protein. In addition, pasture of paddocks where steers were assigned to SUPP and PAST treatments showed similar nutritional quality. When compared to PAST, finishing on SUPP increased total weight gain per hectare, stocking rate, daily and total weight gains. The increase of weight gain was high to GRAIN than SUPP and PAST. Steers finished on GRAIN had high hot carcass weight, fat thickness and marbling score when compared to PAST. However, these attributes did not differ between GRAIN and SUPP. Abomasum lesions were more prevalent in steers finished on GRAIN when compared to PAST. Results of this research showed that it is possible to produce carcasses with desirable market weight and fat thickness by finishing steers on legume-grass pasture containing oats, ryegrass, white and red clover. Moreover, supplementing steers with corn when grazing on legume-grass pasture produced similar carcass traits when compared to beef fed corn only.
Subject(s)
Animal Husbandry/methods , Cattle/physiology , Diet/veterinary , Fabaceae/chemistry , Meat/analysis , Poaceae/chemistry , Animals , Brazil/epidemiology , Cattle/growth & development , Cattle Diseases/epidemiology , Cattle Diseases/etiology , Female , Gastrointestinal Diseases/epidemiology , Gastrointestinal Diseases/etiology , Gastrointestinal Diseases/veterinaryABSTRACT
BACKGROUND: A link between burnout and paranoid ideation has long been suspected. However, systematic research on the association has been scarce. AIMS: We investigated the relationship between burnout and paranoid ideation. Because burnout overlaps with depression, depression was also examined. METHODS: A total of 218 Swiss schoolteachers participated in the study (58% female; mean age: 47). Burnout symptoms were assessed with the emotional exhaustion (EE) and depersonalization (DP) subscales of the Maslach Burnout Inventory-Educators Survey, depressive symptoms with the PHQ-9 and paranoid ideation with the Green et al. Paranoid Thought Scales. RESULTS: Burnout, depression and their subdimensions showed raw correlations ranging from 0.42 to 0.55 with paranoid ideation. Burnout, depression and paranoid thoughts were found to cluster together. Lower levels of burnout and depression coexisted with lower levels of paranoid ideation and higher levels of burnout and depression coexisted with higher levels of paranoid ideation. When corrected for measurement error, the correlations of EE with depression and DP were 0.96 and 0.57, respectively. A principal component analysis confirmed that EE was indistinguishable from depression. CONCLUSIONS: Burnout is substantially associated with paranoid ideation. Interestingly, EE correlated as strongly with paranoid ideation as it correlated with DP. Moreover, if burnout is a syndrome of EE and DP that excludes depression, then the EE-depression correlation should not be close to 1 and EE should not correlate more strongly with depression than with DP. These basic requirements for construct distinctiveness and syndromal unity were not satisfied.
Subject(s)
Burnout, Professional/epidemiology , Depression/epidemiology , Paranoid Disorders/epidemiology , Adult , Burnout, Professional/psychology , Female , Humans , Male , Middle Aged , School Teachers/psychology , Surveys and Questionnaires , SwitzerlandABSTRACT
Indoleamine 2,3 dioxygenase 1 (IDO1) is a metabolic enzyme that catalyzes the conversion of the essential amino acid tryptophan (Trp) into a series of immunoactive catabolites, collectively known as kynurenines. Through the depletion of Trp and the generation of kynurenines, IDO1 represents a key regulator of the immune responses involved in physiologic homeostasis as well as in neoplastic and autoimmune pathologies. The IDO1 enzyme has been described as an important immune checkpoint to be targeted by catalytic inhibitors in the treatment of cancer. In contrast, a defective expression/activity of the enzyme has been demonstrated in autoimmune diseases. Beside its catalytic activity, the IDO1 protein is endowed with an additional function associated with the presence of two immunoreceptor tyrosine-based inhibitory motifs (ITIMs), which, once phosphorylated, bind SHP phosphatases and mediate a long-term immunoregulatory activity of IDO1. Herein, we report the screening of a focused library of molecules bearing a propanol core by a protocol combining microscale thermophoresis (MST) analysis and a cellular assay. As a result, the combined screening identified a 2-propanolol analogue, VIS351, as the first potent activator of the ITIM-mediated function of the IDO1 enzyme. VIS351 displayed a good dissociation constant (Kdâ¯=â¯1.90⯵M) for IDO1 and a moderate cellular inhibitor activity (IC50â¯=â¯11.463⯵M), although it did not show any catalytic inhibition of the recombinant IDO1 enzyme. Because we previously demonstrated that the enzymatic and non-enzymatic (i.e., ITIM-mediated) functions of IDO1 reside in different conformations of the protein, we hypothesized that in the cellular system VIS351 may shift the dynamic conformational balance towards the ITIM-favoring folding of IDO1, resulting in the activation of the signaling rather than catalytic activity of IDO1. We demonstrated that VIS351 activated the ITIM-mediated signaling of IDO1 also in mouse plasmacytoid dendritic cells, conferring those cells an immunosuppressive phenotype detectable in vivo. Thus the manuscript describes for the first time a small molecule as a positive modulator of IDO1 signaling function, paving the basis for an innovative approach to develop first-in-class drugs acting on the IDO1 target.
Subject(s)
2-Propanol/chemistry , 2-Propanol/metabolism , Indoleamine-Pyrrole 2,3,-Dioxygenase/chemistry , Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism , Animals , Cell Survival/drug effects , Cell Survival/physiology , Dose-Response Relationship, Drug , Female , Mice , Mice, Inbred C57BL , Molecular Docking Simulation/methods , Protein Structure, SecondaryABSTRACT
A 1-year-old male American pit bull terrier was presented with a history of proprioceptive deficits and mild lameness of the right hindlimb, which progressed after 5 months to paraparesis, culminating in tetraparesis after 2 weeks. Necropsy findings were limited to the spinal cord and consisted of multiple, intradural, extramedullary, slightly red masses which produced segmental areas of medullary swelling located in the cervical intumescence, thoracolumbar column, sacral segment and cauda equina. Histological evaluation revealed a tumour, composed of epithelial, stromal and blastemal cells, with structures resembling tubules, acini and embryonic glomeruli. Immunohistochemical labelling for vimentin, cytokeratin and S100 was positive for the stromal, epithelial and blastemal cells, respectively. A final diagnosis of multifocal spinal cord nephroblastoma was established. This is the first report of such a tumour showing concomitant involvement of the cervicothoracic, thoracolumbar, sacral and cauda equina areas of the spinal cord.
Subject(s)
Dog Diseases/pathology , Spinal Cord Neoplasms/veterinary , Wilms Tumor/veterinary , Animals , Dogs , MaleABSTRACT
Background: To investigate the activity and safety of afatinib in the preoperative treatment of squamous cell carcinoma of the head and neck (SCCHN). Patients and methods: This study was an open-label, randomized, multicenter, phase II window of opportunity trial. Treatment-naïve SCCHN patients selected for primary curative surgery were randomized (5 : 1 ratio) to receive afatinib during 14 days (day -15 until day -1) before surgery (day 0) or no treatment. Tumor biopsies, 2-[fluorine-18]-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET), and magnetic resonance imaging (MRI) were carried out at diagnosis and just before surgery. The primary end point was metabolic FDG-PET response (according to EORTC guidelines). Other end points included response assessment based on the Response Evaluation Criteria In Solid Tumors (RECIST) v1.1, dynamic contrast-enhanced (DCE)-MRI, diffusion weighted (DW)-MRI, safety, and translational research (TR). Results: Thirty patients were randomized: 25 to afatinib and 5 to control arm. Of the 23 eligible patients randomized to afatinib, 16 (70%; 95% CI: 47% to 87%) patients had a partial metabolic FDG-PET response (PMR). Five patients (22%; 95% CI: 8% to 44%) showed a partial response by RECISTv1.1. Responses assessed via DCE-MRI and DWI-MRI did not show a strong association with PMR or RECIST. One patient discontinued afatinib after 11 days for grade 3 diarrhea with subsequent renal failure and 24 days delay in surgery. No grade 4 toxicities or surgical comorbidities related to afatinib were reported. TR results indicated that PMR was more frequent in the tumors with high Cluster3-hypoxia score expression and with TP53 wild type. Conclusion: Afatinib given for 2 weeks to newly diagnosed SCCHN patients induces a high rate of FDG-PET partial metabolic response and partial response according to RECISTv1.1. Afatinib can be safely administered before surgery. Although exploratory, the hypoxic gene signature needs further investigations as a predictive biomarker of afatinib activity. Clinical trial registration: ClinicalTrials.gov: NCT01538381.
Subject(s)
Afatinib/therapeutic use , Antineoplastic Agents/therapeutic use , Head and Neck Neoplasms/drug therapy , Squamous Cell Carcinoma of Head and Neck/drug therapy , Adult , Afatinib/adverse effects , Aged , Antineoplastic Agents/adverse effects , Biomarkers/metabolism , Female , Fluorodeoxyglucose F18/administration & dosage , Head and Neck Neoplasms/diagnostic imaging , Head and Neck Neoplasms/metabolism , Head and Neck Neoplasms/surgery , Humans , Male , Middle Aged , Positron-Emission Tomography , Preoperative Care , Squamous Cell Carcinoma of Head and Neck/diagnostic imaging , Squamous Cell Carcinoma of Head and Neck/metabolism , Squamous Cell Carcinoma of Head and Neck/surgeryABSTRACT
Abstract Host infection by parasites is influenced by an array of factors, including host and environmental features. We investigated the relationship between host sex, body size and age, as well as seasonality on infection patterns by acanthocephalan in coatis (Procyonidae: Nasua nasua) and in crab-eating foxes (Canidae: Cerdocyon thous ) from the Brazilian Pantanal wetlands. Between 2006 and 2009, we collected faecal samples from these hosts and analyzed for the presence of acanthocephalan eggs. Prevalence, abundance and intensity of eggs of acanthocephalans were calculated. Egg abundance was analyzed using generalized linear models (GLM) with a negative binomial distribution and models were compared by Akaike criteria to verify the effect of biotic and abiotic factors. Prevalence of acanthocephalans was higher in the wet season in both host species but did not differ between host sexes; however, adult crab-eating foxes showed higher prevalence of acanthocephalan eggs than juveniles. In contrast, prevalence of acanthocephalan eggs found in coatis was higher in coati juveniles than in adults. Host age, season and maximum temperature were the top predictors of abundance of acanthocephalan eggs in crab-eating foxes whereas season and host sex were predictors of egg abundance in coatis. The importance of seasonality for abundance of acanthocephalan was clear for both host species. The influence of host-related attributes, however, varied by host species, with host gender and host age being important factors associated with prevalence and parasite loads.
Resumo A infecção de hospedeiro por parasitos é influenciada por uma série de fatores, incluindo características do hospedeiro e ambientais. Nós investigamos a relação entre sexo do hospedeiro, tamanho corporal e idade, bem como sazonalidade nos padrões de infecção por acantocéfalos em coatis (Procyonidae: Nasua nasua) e em cachorro-do-mato (Canidae: Cerdocyon thous ) do Pantanal brasileiro e quais fatores explicaram melhor a prevalência e a intensidade desses parasitos. Entre 2006 e 2009, coletamos amostras fecais desses hospedeiros e analisamos a presença de ovos de acantocéfalos. Prevalência, abundância e intensidade de ovos de acantócefálios foram calculados. A abundância de ovos foi analisada utilizando modelos lineares generalizados (GLM) com distribuição binomial negativa e os modelos foram comparados pelo critério de Akaike para verificar o efeito de fatores bióticos e abióticos. A prevalência de acantocéfalos foi maior na estação úmida em ambas as espécies de hospedeiros, mas não diferiu entre os sexos do hospedeiro; no entanto, os cachorros-do-mato adultos apresentaram maior prevalência de ovos de acantocéfalos do que em juvenis. Em contraste, a prevalência de ovos de acantocéfalos encontrados em coatis foi maior em juvenis do que em adultos. A idade do hospedeiro, a estação e a temperatura máxima foram os preditores de abundância de ovos de acantocéfalos em cachorro-do-mato, enquanto a estação e o sexo do hospedeiro foram preditores da abundância dos ovos do parasito em coatis. A importância da sazonalidade para a abundância do acantocéfalo foi clara para ambas as espécies hospedeiras. A influência dos atributos relacionados ao hospedeiro, no entanto, variou entre as espécies de hospedeiros, sendo o sexo e idade do hospedeiro fatores importantes associados à prevalência e às cargas parasitárias.
ABSTRACT
BACKGROUND: The Study Group on Accreditation and Quality Improvement of the Italian Society of Pediatrics has developed an observational study about the hospital management of pediatric patients affected by severe asthma, in order to evaluate how the Guidelines for severe asthma in childhood are applied in the daily practice. METHODS: This study included patients between 2 and 17 years, hospitalized or under short intensive observation for acute asthma. The data collection was carried out through the compilation of on-line forms. The statistical technique used was the Chi Square test. RESULTS: 409 forms were filled in by 32 Italian Centers. 17% of the patients showed severe asthma, 59% moderate and 24% mild. On arrival at the Emergency Room the oximetry was measured in 95% of the patients, the respiratory rate in 64% while the heart rate in 88% of them. 48% of the children were exposed to chest X-ray. More than half of the children received oxygen therapy, 98.5% received short-acting beta-2 agonists and systemic steroid therapy was given to 82% of children, mainly orally. At discharge only half of the children were provided with written instructions for the management of any subsequent asthmatic episode. The analysis of the collected data highlights that not all the children had their oxygen saturation measured, although this parameter is one of the main indicators of disease severity, as well as the respiratory rate, which was detected in a minimal percentage of cases. The frequency of chest X-ray was extremely high, even though it does not have any indication in the majority of asthma cases. The evaluation of the therapeutic treatment denotes an adequate use of the oxygen therapy according to the oximetry values found on arrival, but an abuse of steroid therapy. Critical issues emerge at discharge: children are not always educated about the home management of the disease and the self-evaluation of the illness seriousness. CONCLUSION: The pediatric network has become an excellent system of monitoring of the clinical management of asthmatic children, highlighting strengths and weaknesses on which to focus actions of improvement.