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BACKGROUND: Among patients with resectable early-stage non-small-cell lung cancer (NSCLC), a perioperative approach that includes both neoadjuvant and adjuvant immune checkpoint inhibition may provide benefit beyond either approach alone. METHODS: We conducted a randomized, double-blind, phase 3 trial to evaluate perioperative pembrolizumab in patients with early-stage NSCLC. Participants with resectable stage II, IIIA, or IIIB (N2 stage) NSCLC were assigned in a 1:1 ratio to receive neoadjuvant pembrolizumab (200 mg) or placebo once every 3 weeks, each of which was given with cisplatin-based chemotherapy for 4 cycles, followed by surgery and adjuvant pembrolizumab (200 mg) or placebo once every 3 weeks for up to 13 cycles. The dual primary end points were event-free survival (the time from randomization to the first occurrence of local progression that precluded the planned surgery, unresectable tumor, progression or recurrence, or death) and overall survival. Secondary end points included major pathological response, pathological complete response, and safety. RESULTS: A total of 397 participants were assigned to the pembrolizumab group, and 400 to the placebo group. At the prespecified first interim analysis, the median follow-up was 25.2 months. Event-free survival at 24 months was 62.4% in the pembrolizumab group and 40.6% in the placebo group (hazard ratio for progression, recurrence, or death, 0.58; 95% confidence interval [CI], 0.46 to 0.72; P<0.001). The estimated 24-month overall survival was 80.9% in the pembrolizumab group and 77.6% in the placebo group (P = 0.02, which did not meet the significance criterion). A major pathological response occurred in 30.2% of the participants in the pembrolizumab group and in 11.0% of those in the placebo group (difference, 19.2 percentage points; 95% CI, 13.9 to 24.7; P<0.0001; threshold, P = 0.0001), and a pathological complete response occurred in 18.1% and 4.0%, respectively (difference, 14.2 percentage points; 95% CI, 10.1 to 18.7; P<0.0001; threshold, P = 0.0001). Across all treatment phases, 44.9% of the participants in the pembrolizumab group and 37.3% of those in the placebo group had treatment-related adverse events of grade 3 or higher, including 1.0% and 0.8%, respectively, who had grade 5 events. CONCLUSIONS: Among patients with resectable, early-stage NSCLC, neoadjuvant pembrolizumab plus chemotherapy followed by resection and adjuvant pembrolizumab significantly improved event-free survival, major pathological response, and pathological complete response as compared with neoadjuvant chemotherapy alone followed by surgery. Overall survival did not differ significantly between the groups in this analysis. (Funded by Merck Sharp and Dohme; KEYNOTE-671 ClinicalTrials.gov number, NCT03425643.).
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Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma de Pulmón de Células no Pequeñas , Cisplatino , Neoplasias Pulmonares , Humanos , Adyuvantes Inmunológicos/administración & dosificación , Adyuvantes Inmunológicos/efectos adversos , Adyuvantes Inmunológicos/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/cirugía , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Cisplatino/uso terapéutico , Terapia CombinadaRESUMEN
BACKGROUND: At the first interim analysis of the KEYNOTE-671 trial, adding perioperative pembrolizumab to neoadjuvant chemotherapy significantly improved event-free survival in participants with early-stage non-small-cell lung cancer (NSCLC). We report overall survival and health-related quality of life outcomes from the second interim analysis. METHODS: KEYNOTE-671 was a global phase 3 trial done at 189 medical centres. Eligible participants (aged ≥18 years) with resectable stage II, IIIA, or IIIB (N2) NSCLC were randomly assigned (1:1) to four cycles of neoadjuvant pembrolizumab (200 mg administered intravenously every 3 weeks) plus cisplatin-based chemotherapy followed by surgery and 13 cycles of adjuvant pembrolizumab (200 mg administered intravenously every 3 weeks) or to four cycles of neoadjuvant placebo (administered intravenously every 3 weeks) plus cisplatin-based chemotherapy followed by surgery and 13 cycles of adjuvant placebo (administered intravenously every 3 weeks). Randomisation was done centrally using an interactive response technology system and was stratified by disease stage, PD-L1 expression, histology, and geographical region in blocks of four. Participants, investigators, and sponsor personnel were masked to treatment assignments; local pharmacists were unmasked to support treatment preparation. The dual primary endpoints were overall survival and event-free survival evaluated in the intention-to-treat population. This study is registered at ClinicalTrials.gov, NCT03425643, and is ongoing but closed to enrolment. FINDINGS: Between May 11, 2018, and Dec 15, 2021, 797 participants were randomly assigned to the pembrolizumab group (n=397) or the placebo group (n=400). Median study follow-up at the second interim analysis was 36·6 months (IQR 27·6-47·8). 36-month overall survival estimates were 71% (95% CI 66-76) in the pembrolizumab group and 64% (58-69) in the placebo group (hazard ratio 0·72 [95% CI 0·56-0·93]; one-sided p=0·0052; threshold, one-sided p=0·0054). Median event-free survival was 47·2 months (95% CI 32·9 to not reached) in the pembrolizumab group and 18·3 months (14·8-22·1) in the placebo group (hazard ratio 0·59 [95% CI 0·48-0·72]). In the as-treated population, grade 3-5 treatment-related adverse events occurred in 179 (45%) of 396 participants in the pembrolizumab group and in 151 (38%) of 399 participants in the placebo group. Treatment-related adverse events led to death in four (1%) participants in the pembrolizumab group and three (1%) participants in the placebo group. INTERPRETATION: The significant overall survival benefit of neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab compared with neoadjuvant chemotherapy alone coupled with a manageable safety profile support the use of perioperative pembrolizumab in patients with resectable, early-stage NSCLC. FUNDING: Merck Sharp & Dohme, a subsidiary of Merck & Co, Rahway, NJ, USA.
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Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Terapia Neoadyuvante , Humanos , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/mortalidad , Masculino , Femenino , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Persona de Mediana Edad , Terapia Neoadyuvante/métodos , Método Doble Ciego , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioterapia Adyuvante , Cisplatino/administración & dosificación , Estadificación de Neoplasias , Calidad de Vida , Antineoplásicos Inmunológicos/uso terapéutico , Antineoplásicos Inmunológicos/administración & dosificación , Antineoplásicos Inmunológicos/efectos adversos , AdultoRESUMEN
This review aims to describe and compare porcine models of metabolic syndrome. This syndrome and its associated secondary comorbidities are set to become the greatest challenge to healthcare providers and policy makers in the coming century. However, an incomplete understanding of the pathogenesis has left significant knowledge gaps in terms of efficacious therapeutics. To further our comprehension and, in turn, management of metabolic syndrome, appropriate high-fidelity models of the disease complex are of great importance. In this context, our review aims to assess the most promising porcine models of metabolic syndrome currently available for their similarity to the human phenotype. In addition, we aim to highlight the strengths and shortcomings of each model in an attempt to identify the most appropriate application of each. Although no porcine model perfectly recapitulates the human metabolic syndrome, several pose satisfactory approximations. The Ossabaw miniature swine in particular represents a highly translatable model that develops each of the core parameters of the syndrome with many of the associated secondary comorbidities. Future high-fidelity porcine models of metabolic syndrome need to focus on secondary sequelae replication, which may require extended induction period to reveal.
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Síndrome Metabólico , Animales , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Síndrome Metabólico/etiología , Porcinos , Porcinos EnanosRESUMEN
Collective cell migration drives the formation of complex organ systems as well as certain tumour invasions and wound healing processes. A characteristic feature of many migrating collectives is tissue-scale polarity, whereby 'leader' cells at the tissue edge guide 'followers' cells that become assembled into polarized epithelial tissues. In this study, we employed particle image velocimetry (PIV) as a tool to quantitate local dynamics underlying the migration of the posterior lateral line primordium (pLLP) in zebrafish at a short time scale. Epithelial cadherin-EGFP was the fluorescent tracer in time-lapse images for PIV analysis. At the tissue level, global speed and directionality of the primordium were extracted from spatially averaged velocity fields. Interestingly, fluctuating velocity patterns evolve at the mesoscale level, which distinguishes the pseudo-mesenchymal leading front from the epithelialized trailing edge, and superimpose to the global deceleration of the whole primordium during the separation of a protoneuromast. Local velocity fields obtained by PIV proved sensitive to estimate the migration speed and directionality of the pLLP in zebrafish, predicting protoneuromast separation at short time scales. Finally, the PIV approach may be suitable for analysing the dynamics of otherin vivomodels of collective migration.
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Sistema de la Línea Lateral , Pez Cebra , Animales , Movimiento Celular , Reología , Análisis Espacio-TemporalRESUMEN
BACKGROUND: Malaria the first causes of death from parasitic infection worldwide. Interventions to reduce the burden of malaria have produced a tremendous drop in malaria morbidity and mortality. However, progress is slower in DRC, which shares with Nigeria 39% of deaths related to malaria globally. Inappropriate use of drugs may be one of the factors of this below-average performance. The aim of this study was to describe the use of drugs in the management of uncomplicated malaria in public health facilities in DRC. METHODS: A drug use study was carried out in DRC from January to March 2014. In each of the former 11 provinces of DRC, one Rural Health Centre, one Urban Health Centre and one General Hospital were selected. In each of them, 100 patient's files containing prescription of anti-malarials from January to December 2013 were randomly selected. Among them, all of the files with diagnosis of uncomplicated malaria were included in this study. Prescribed anti-malarials, co-prescribed drugs and their indications were collected. Descriptive analyses were performed. RESULTS: A total of 2300 files out of 3300 (69.7%) concerned uncomplicated malaria and were included in analysis. Malaria treatment was initiated after a positive RDT or microscopy in 51.5% of cases, upon suspicion without requesting biological confirmation in 37% and despite negative results in 11%. Twenty-nine (29) different treatment regimens were used. The drugs recommended by the National Malaria Control Programme were used in 54.3% of cases (artesunate-amodiaquine 37.4% or artemether-lumefantrine 16.9%). The second most used anti-malarial was quinine (32.4%). Apart from anti-malarials, an average of 3.1 drugs per patient were prescribed, among which antibiotics (67.9%), analgesics and non-steroidal anti-inflammatory (NSAIDs) (all abbreviations to be explicated on first use) (70.6%), vitamins (29.1%), anaemia drugs, including blood transfusion (9.1%) and corticosteroids (5.7%), In 51.4% of cases there was no indication for the concomitant medication. CONCLUSION: Management of uncomplicated malaria in DRC is characterized by a low adherence to treatment policy, numerous treatment regimens, and abundant concomitant medication potentially harmful to the patient. This may contribute to the low performance of DRC in malaria control. Determinant of this irrational use of drugs need to be assessed in order to formulate and implement efficient corrective measures.
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Antimaláricos/uso terapéutico , Instituciones de Salud , Malaria/tratamiento farmacológico , Servicios de Salud Rural , Adolescente , Adulto , Anciano , Niño , Preescolar , República Democrática del Congo , Instituciones de Salud/estadística & datos numéricos , Humanos , Lactante , Recién Nacido , Malaria/prevención & control , Persona de Mediana Edad , Servicios de Salud Rural/estadística & datos numéricos , Adulto JovenRESUMEN
(1) Background: Malaria heavily affects the Democratic Republic of the Congo (DRC) despite the use of effective drugs. Poor adherence to malaria treatment may contribute to this problem. (2) Methods: In one rural and one urban health area in each of the 11 former provinces of the DRC, all households with a case of malaria in the 15 days preceding the survey were selected and the patients or caregivers were interviewed. Adherence to malaria treatment was assessed by self-declaration about its completion. Logistic regression was used to assess predictors. (3) Results: 1732 households participated. Quinine was the most used drug; adherence to artesunate-amodiaquine was the lowest and the main reason for treatment discontinuation was adverse reactions. Predictors of adherence were residence in an urban area, university education, catholic religion, and adoption of recommended behaviour towards a malaria case. Adherence was significantly lower for responders who obtained information on antimalarials from Community Health Workers (CHW). (4) Conclusions: Usage of recommended drugs and adherence to malaria treatment need to be promoted, especially in rural areas, and CHW involvement needs to be improved. Awareness messages need to be made accessible and comprehensible to poorly educated populations and churches need to be involved.
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(1) Background: The Democratic Republic of the Congo (DRC) is heavily affected by malaria despite availability of effective treatments. Ignorance and unrecommended behaviour toward a suspected malaria case in households may contribute to this problem. (2) Method: In communities of one rural and one urban Health Centres in each of the 11 previous provinces of DRC, all households with a case of malaria in the 15 days prior to the survey were selected. The patient or caregiver (responder) were interviewed. Logistic regression was used to assess predictors of knowledge of recommended antimalarials and adequate behaviour in case of suspected malaria. (3) Results: 1732 households participated; about 62% (1060/1721) of the responders were informed about antimalarials, 70.1% (742/1059) knew the recommended antimalarials and 58.6% (995/1699) resorted to self-medication. Predictors of knowledge of antimalarials were education to secondary school or university, information from media and smaller households. Predictors of good behaviour were Catholic religion and smaller households. Receiving information from Community Health Workers (CHWs) failed to be determinants of knowledge or adequate behaviour. (4) Conclusion: malaria control in DRC is hampered by ignorance and non-adherence to national recommendations. These aspects are influenced by unsuccessful communication, size of households and level of education.
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PURPOSE: To compare the results for patients treated with intercalary endoprosthetic replacement (EPR) or intercalary allograft reconstruction for diaphyseal tumours of the femur in terms of: (1) reconstruction failure rates; (2) cause of failure; (3) risk of amputation of the limb; and (4) functional result. METHODS: Patients with bone sarcomas of the femoral diaphysis, treated with en bloc resection and reconstructed with an intercalary EPR or allograft, were reviewed. A total of 107 patients were included in the study (36 EPR and 71 intercalary allograft reconstruction). No differences were found between the two groups in terms of follow-up, age, gender and the use of adjuvant chemotherapy. RESULTS: The probability of failure for intercalary EPR was 36% at 5 years and 22% for allograft at 5 years (p = 0.26). Mechanical failures were the most prevalent in both types of reconstruction. Aseptic loosening and implant fracture are the main cause in the EPR group. For intercalary allograft reconstructions, fracture followed by nonunion was the most common complication. Ten-year risk of amputation after failure for both reconstructions was 3%. There were no differences between the groups in terms of the mean Musculoskeletal Tumor Society score (27.4, range 16-30 vs. 27.6, range 17-30). CONCLUSIONS: We have demonstrated similar failure rates for both reconstructions. In both techniques, mechanical failure was the most common complication with a low rate of limb amputation and good functional results. LEVEL OF EVIDENCE: Level III, therapeutic study.
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Amputación Quirúrgica/estadística & datos numéricos , Trasplante Óseo , Neoplasias Femorales/cirugía , Osteosarcoma/cirugía , Implantación de Prótesis , Insuficiencia del Tratamiento , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Diáfisis , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Medición de Riesgo , Resultado del Tratamiento , Adulto JovenRESUMEN
The colonization of surfaces by bacteria is a widespread phenomenon with consequences on environmental processes and human health. While much is known about the molecular mechanisms of surface colonization, the influence of the physical environment remains poorly understood. Here we show that the colonization of non-planar surfaces by motile bacteria is largely controlled by flow. Using microfluidic experiments with Pseudomonas aeruginosa and Escherichia coli, we demonstrate that the velocity gradients created by a curved surface drive preferential attachment to specific regions of the collecting surface, namely the leeward side of cylinders and immediately downstream of apexes on corrugated surfaces, in stark contrast to where nonmotile cells attach. Attachment location and rate depend on the local hydrodynamics and, as revealed by a mathematical model benchmarked on the observations, on cell morphology and swimming traits. These results highlight the importance of flow on the magnitude and location of bacterial colonization of surfaces.
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Adhesión Bacteriana , Biopelículas/crecimiento & desarrollo , Escherichia coli/fisiología , Modelos Biológicos , Pseudomonas aeruginosa/fisiología , Fenómenos Biomecánicos , Hidrodinámica , Técnicas Analíticas Microfluídicas , Movimiento/fisiología , Propiedades de SuperficieRESUMEN
Infertility is a common medical condition encountered by health systems throughout the world. Despite the development of complex in vitro fertilization techniques, only one-third of these procedures are successful. New lab-on-a-chip systems that focus on spermatozoa selection require a better understanding of sperm behavior under ultra-confined conditions in order to improve outcomes. Experimental studies combined with models and simulations allow the evaluation of the efficiency of different lab-on-a-chip devices during the design process. In this work, we provide experimental evidence of the dynamics of sperm interacting with a lateral wall in a shallow chamber. We observe a decrease in average sperm velocity during initial wall interaction and partial recovery after the alignment of the trajectory of the cell. To describe this phenomenon, we propose a simple model for the sperm alignment process with a single free parameter. By incorporating experimental motility characterization into the model, we achieve an accurate description of the average velocity behavior of the sperm population close to walls. These results will contribute to the design of more efficient lab-on-a-chip devices for the treatment of human infertility.
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The behavioral function of a pheromone released by males of the army-worm moth Pseudaletia unipuncta was investigated both in laboratory wind-tunnel experiments and in experiments with moth-baited traps in the field. Such male moth scents have been thought to act at close range as sexual stimulants for females of the same species. However, the only obvious effect of the P. unipuncta male pheromone was upon other males, decreasing their tendency to approach sexually receptive, pheromone-releasing females and to exhibit copulatory behavior when near those females. The adaptive significance of the male pheromone may be related to the increased reproductive efficiency that results if multiple males are prevented from competing for a single female.
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Pheromone-releasing females of the closely related noctuid moths Trichoplusia ni and Autographa californica attract mainly males of their own species. Sex-pheromone-concentration specificity appears to be an important reproductive isolating mechanism for these two species. Apparently, both species utilize the same pheromone, cis-7-dodecenyl acetate, for mating communication, but T. ni utilizes a higher level than does A. californica. Traps releasing amounts of cis-7-dodecenyl acetate that are highly attractive for males of one of the species catch very few males of the other species.
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The synthetic sex pheromone (gossyplure) of the pink bollworm was evaporated into the atmosphere of three cotton fields during an entire growing season. The resulting disruption of premating pheromone communication between male and female moths led to a reduction in the population of larvae infesting cotton bolls. This larval control was comparable, in terms of both effectiveness and expense of materials used, to the control achieved in ten comparison fields by growers using conventional insecticide applications.
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Control de Insectos/métodos , Lepidópteros/efectos de los fármacos , Mariposas Nocturnas/efectos de los fármacos , Feromonas/farmacología , Atractivos Sexuales/farmacología , Animales , Reproducción/efectos de los fármacosRESUMEN
Propylure, 10-n-propyl-trans-5,9-tridecadienyl acetate, and deet, N,N,-diethyl-m-tolumide, were previously reported as the sex pheromone and a sex pheromone activator, respectively, of the pink bollworm. Neither chemical in three extracts of female moth abdomen tips could be detected by gas-liquid chromatographic analysis. These compounds, alone or in combination, exhibited little or no biological activity in the laboratory or in the field. Hexalure, cis-7-hexadecenyl acetate, a synthetic attractant for pink bollworm males, could not be detected in female moth abdomen tip extracts. The pink bollworm sex pheromone was identified as a mixture of cis,cis and cis,trans isomers of 7,11-hexadecadienyl acetate.
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This research was conducted to determine the effects of feeding different P levels with and without phytase supplementation on broiler growth performance, bone-breaking strength (BBS), and litter P concentration. An experiment with 4 trials was conducted with 7,840 Ross x Ross straight-run broilers. For each trial, 1,960 broilers were allotted on d 0 to treatments, with 7 replications each and with 70 broilers per replication. The broilers were fed a 4-period feeding program consisting of starter (0 to 14 d), grower (14 to 32 d), finisher (32 to 41 d), and withdrawal (41 to 50 d) periods. For each trial, the same pen was used continuously for each treatment-replication combination, and the litter was not removed between trials. Broilers were fed a control diet [0.43, 0.40, 0.36, or 0.32% nonphytate P (nPP)] in the starter, grower, finisher, and withdrawal periods, respectively, a low Ca and P (LCaP) diet with a 0.05% reduction in nPP in each period, and these 2 diets supplemented with phytase at 600 phytase units/kg (nPP and Ca were reduced by 0.094% in diets with phytase). Diet did not affect (P > 0.10) broiler performance in the starter or withdrawal periods. Generally, both phytase addition and the LCaP diet decreased some aspects of growth performance during the grower and finisher periods. There was no main effect of phytase on BBS, but BBS was decreased in the broilers fed the LCaP diet with phytase addition (nPP x phytase, P < 0.01) in the grower period, and BBS was decreased in the finisher (P < 0.02) and withdrawal (P < 0.01) periods for broilers fed the LCaP diet. Total P, soluble P (SP), and reactive soluble P (RSP) were decreased (P < 0.04) in the litter of broilers fed the LCaP diets. Total P, SP, and RSP were decreased (P < 0.01) in the litter of broilers fed phytase. These data indicate that phytase supplementation at 600 phytase units/kg reduces growth in some periods, has no effect on BBS, and reduces total P, SP, and RSP in the litter.
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6-Fitasa/administración & dosificación , Densidad Ósea/efectos de los fármacos , Pollos/crecimiento & desarrollo , Pisos y Cubiertas de Piso , Fósforo Dietético/administración & dosificación , Fósforo/análisis , 6-Fitasa/farmacología , Animales , Suplementos Dietéticos , Femenino , Vivienda para Animales , Masculino , Fósforo Dietético/farmacologíaRESUMEN
A patient with classical hemophilia (factor VIII deficiency) was found to have a new abnormal fibrinogen (fibrinogen St. Louis). Other family members exhibited either defect alone. Fibrinogen St. Louis was inherited as an autosomal dominant and was not associated with clinical bleeding. When compared with normal fibrinogen, fibrinogen St. Louis was found to have defective fibrin polymerization and possibly a slower release of fibrinopeptides. The prolonged thrombin times were partially corrected by calcium chloride and protamine sulfate. Ultracentrifugal sedimentation, electrophoretic mobility, DEAE chromatographic pattern, carbohydrate content, N-terminal amino acids, immunodiffusion, and immunoelectrophoretic patterns and electrophoresis of reduced and alkylated fragments were all normal. In contrast to fibrinogen St. Louis, the most similar other fibrinogen variant (fibrinogen Zurich) was found to be heterogeneous by several criteria and to have reduced hexose content.
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Fibrinógeno/análisis , Hemofilia A/sangre , Adulto , Aminoácidos/análisis , Coagulación Sanguínea/efectos de los fármacos , Factores de Coagulación Sanguínea/análisis , Pruebas de Coagulación Sanguínea , Electroforesis de las Proteínas Sanguíneas , Cloruro de Calcio/farmacología , Carbohidratos/análisis , Cromatografía DEAE-Celulosa , Retracción del Coagulo , Factor VIII , Femenino , Fibrina/análisis , Hemofilia A/complicaciones , Hemofilia A/genética , Humanos , Concentración de Iones de Hidrógeno , Inmunodifusión , Inmunoelectroforesis , Masculino , Persona de Mediana Edad , Linaje , Péptidos/análisis , Adhesividad Plaquetaria , Protaminas/farmacología , Tiempo de Protrombina , UltracentrifugaciónRESUMEN
We reviewed the oncological and functional outcomes of patients treated for a primary sarcoma possibly involving the knee joint and present an algorithm to guide treatment. The records of 76 patients who had a primary bone or soft tissue sarcoma possibly invading the knee between 1996 and 2012 were identified. Mean age and follow-up was 32 years (9-74) and 64 months (12-195), respectively. Patients were grouped according to the resection (Intra-articular [IAR] vs. Extra-articular [EAR] vs. Amputation/rotationplasty) for survival and functional outcomes. Overall 5 and 10 year survival was 61% and 53%, respectively. No differences in survival were found between the 3 groups (p = 0.55). Sixteen patients developed local recurrence with no difference between the groups. Mean MSTS score was 24.5 (12-30). Mean flexion at final follow-up was 106° (70-130°). We conclude that EAR of the knee allows for good oncologic and functional outcomes but with an increased risk of complications compared to IAR. Intra-operative assessment of joint involvement can be done in patients where joint infiltration by the tumour is not clear to avoid an unnecessary EAR. For chondrosarcoma patients with joint involvement, an EAR should be carefully considered because they present a significantly higher local recurrence risk.
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Articulación de la Rodilla/cirugía , Sarcoma/cirugía , Adolescente , Adulto , Anciano , Algoritmos , Niño , Femenino , Estudios de Seguimiento , Humanos , Recuperación del Miembro , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
AIMS: The aim of this study was to identify any progression between benign osteofibrous dysplasia (OFD), OFD-like adamantinoma and malignant adamantinoma, and to investigate the rates of local recurrence, metastases and survival, in order to develop treatment algorithms for each. PATIENTS AND METHODS: A single institution retrospective review of all patients presenting with OFD, OFD-like adamantinoma and adamantinoma between 1973 and 2012 was undertaken. Complete data were available for 73 patients (42 with OFD; ten with an OFD-like adamantinoma and 21 with an adamantinoma). The mean follow-up was 10.3 years (3 to 25) for OFD, 9.2 years (3.0 to 26.3) for OFD-like and 11.6 years (0.25 to 33) for adamantinoma. RESULTS: The mean age at diagnosis for OFD was 13.5 years (1 to 49), 10.5 years (6 to 28) for OFD-like and 34 years (14 to 86) for adamantinoma. A total of 24 of the 42 patients with OFD (57%) have not required any treatment and have been managed with observation. A total of 18 of the 42 patients with OFD underwent surgery, 13 with curettage and five with resection. In all, three patients developed recurrence following curettage (23%) but none following resection. All these patients were cured with further limited surgery. A total of six patients initially diagnosed with OFD were subsequently found to have OFD-like adamantinoma. Of the ten patients initially diagnosed with OFD-like adamantinoma, three (30%) were managed with observation alone and seven underwent surgery, two with curettage and five with resection. Local recurrence arose in two patients, one each after curettage and resection. No patients with either OFD or an OFD-like adamantinoma developed metastases or had progression to adamantinoma. All patients with an adamantinoma were treated by surgery, three with curettage, six with amputation and 12 with excision. In all, two of the three treated with curettage developed local recurrence, requiring further surgery. Late development of both local recurrence and metastases led to a ten year disease specific survival of 93% which had dropped to 39% by 20 years. CONCLUSION: We found no evidence of progression from OFD to adamantinoma. Conservative management with observation or curettage is often successful for patients with OFD and OFD-like adamantinoma. Resection with clear margins is required for patients with adamantinoma. Late tumour recurrence is not uncommon in adamantinoma and prolonged follow-up should be considered. Cite this article: Bone Joint J 2017;99-B:409-16.
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Adamantinoma/diagnóstico , Enfermedades del Desarrollo Óseo/diagnóstico , Adamantinoma/secundario , Adamantinoma/terapia , Adolescente , Enfermedades del Desarrollo Óseo/terapia , Transformación Celular Neoplásica , Niño , Preescolar , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Lactante , Estimación de Kaplan-Meier , Masculino , Recurrencia Local de Neoplasia , Radiografía , Estudios Retrospectivos , Adulto JovenRESUMEN
Improvements in survival for patients with renal cell carcinoma have resulted in an increase in the burden of disease due to skeletal metastases, which are often solitary and resistant to radiotherapy. Surgical intervention remains a valid treatment to improve function and relieve pain, and replacement is able to achieve this and improve disease free implant survival. The aim of this study was identify prognostic factors for reconstruction survival of skeletal metastases in renal cell carcinoma and to characterise the nature of the reconstruction related complications. A retrospective analysis of all patients treated for metastatic renal cell carcinoma in three international bone tumour units between 2000 and 2014 identified 268 surgical interventions suitable for inclusion. Reconstruction survivorship was calculated using the Kaplan-Meier method whilst factors affecting reconstruction survival were assessed using Cox-regression multivariate analysis. Differences in proportions were assessed using Fisher's exact test. The overall rate of complications was 17%, which were classified as structural failure (7.1%), infection (4.9%) and tumour progression (3.7%). Endoprosthetic replacement when performed as the primary procedure demonstrate the best survivorship whilst factors associated with compromised reconstruction survival included previous surgical intervention and pre operative radiotherapy, and intralesional resection margins. We conclude that endoprosthetic replacement be considered as the index surgical intervention for skeletal metastases from renal cell carcinoma in certain locations as this carries the lowest incidence of complications. Revision of previous skeletal stabilisation, especially when combined with radiotherapy carries a high risk of complication, including infection, which often necessitates amputation.
Asunto(s)
Neoplasias Óseas/mortalidad , Neoplasias Óseas/cirugía , Carcinoma de Células Renales/mortalidad , Carcinoma de Células Renales/cirugía , Neoplasias Renales/patología , Procedimientos de Cirugía Plástica/efectos adversos , Procedimientos de Cirugía Plástica/métodos , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Óseas/secundario , Carcinoma de Células Renales/secundario , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Fijadores Internos , Estimación de Kaplan-Meier , Neoplasias Renales/mortalidad , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Calidad de Vida , Procedimientos de Cirugía Plástica/estadística & datos numéricos , Reoperación/efectos adversos , Estudios RetrospectivosRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Malaria is the most prevalent parasitic disease and the foremost cause of morbidity and mortality in the Democratic Republic of Congo. For the management of this disease, a large Congolese population recourses to traditional medicinal plants. To date the efficacy and safety of many of these plants have been validated scientifically in rodent malaria models. In order to generate scientific evidence of traditional remedies used in the Democratic Republic of Congo for the management of malaria, and show the potential of Congolese plants as a major source of antimalarial drugs, this review highlights the antiplasmodial and toxicological properties of the Congolese antimalarial plants investigated during the period of 1999-2014. In doing so, a useful resource for further complementary investigations is presented. Furthermore, this review may pave the way for the research and development of several available and affordable antimalarial phytomedicines. MATERIALS AND METHODS: In order to get information on the different studies, a Google Scholar and PubMed literature search was performed using keywords (malaria, Congolese, medicinal plants, antiplasmodial/antimalarial activity, and toxicity). Data from non-indexed journals, Master and Doctoral dissertations were also collected. RESULTS: Approximately 120 extracts and fractions obtained from Congolese medicinal plants showed pronounced or good antiplasmodial activity. A number of compounds with interesting antiplasmodial properties were also isolated and identified. Some of these compounds constituted new scaffolds for the synthesis of promising antimalarial drugs. Interestingly, most of these extracts and compounds possessed high selective activity against Plasmodium parasites compared to mammalian cells. The efficacy and safety of several plant-derived products was confirmed in mice, and a good correlation was observed between in vitro and in vivo antimalarial activity. The formulation of several plant-derived products also led to some clinical trials and license of three plant-derived drugs (Manalaria(®), Nsansiphos(®), and Quinine Pharmakina(®)). CONCLUSION: The obtained results partly justify and support the use of various medicinal plants to treat malaria in folk medicine in the Democratic Republic of Congo. Antimalarial plants used in Congolese traditional medicine represent an important source for the discovery and development of new antimalarial agents. However, in order to ensure the integration of a larger number of plant-derived products in the Congolese healthcare system, some parameters and trends should be considered in further researches, in agreement with the objectives of the "Traditional Medicine Strategy" proposed by the World Health Organization in 2013. These include evaluation of geographical and seasonal variation, investigation of reproductive biology, assessment of prophylactic antimalarial activity, evaluation of natural products as adjuvant antioxidant therapy for malaria, development of plant-based combination therapies and monitoring of herbal medicines in pharmacovigilance systems.