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AIMS: Sarcomas constitute a group of rare malignant neoplasms, commonly subcategorized into soft tissue sarcomas (STS) and bone sarcomas. This study aims to describe the treatment modalities and outcome of head and neck sarcoma (HNS) patients in western Denmark and to identify prognostic factors for overall survival and recurrence in HNS patients. MATERIALS AND METHODS: The Aarhus sarcoma registry, The National Danish Sarcoma Database, and the Danish National Pathology Registry were used to identify HNS adult patients diagnosed between 1979 and 2022. RESULTS: Altogether, 291 patients were included in this study. The prevalent histological subtypes were undifferentiated pleomorphic sarcoma (16%; 48/291) and leiomyosarcoma (15%; 44/291) for STS patients (n = 230) and chondrosarcoma (10%; 28/291) and osteosarcoma (7%; 19/291) for bone sarcoma patients (n = 61). Surgery with curative intent was performed in 71% (164/230) and 70% (43/61) of STS and bone sarcoma patients, respectively. Clear resection was achieved in 59% (97/164) of STS patients and 44% (19/43) of bone sarcoma patients. Eighty-nine patients relapsed (STS n = 66, bone sarcoma n = 23) after a median time of 2.7/5.5 years for STS/bone sarcoma patients. The five-year overall survival rates were 45% for STS patients and 66% for bone sarcoma patients. The following factors were significantly, negatively associated with overall survival in STS patients: Age (hazard ratio (HR)) = 1.02, p < 0.001), tumour size ≥5 cm (HR = 1.75, p = 0.003), metastatic disease (HR = 3.17, p < 0.001), high grade tumour (HR = 2.24, p = 0.004), previous cancer (HR = 2.84, p < 0.001), and high Aarhus composite biomarker score (ACBS) (HR = 4.56, p = 0.001). For relapse in STS patients, higher tumour grade (HR = 3.19, p = 0.014), intralesional margins (HR = 2.84, p < 0.001), ≥2 previous cancers (HR = 3.00, p = 0.004), and high ACBS (HR = 3.29, p = 0.047), were negatively associated. For bone sarcomas only higher age (HR = 1.02, p = 0.049) and intralesional margins (HR = 2.91, p = 0.042) were significant negative factors for overall survival. CONCLUSION: Multiple prognostic factors for overall survival and relapse were identified, especially for STS patients.
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Neoplasias de Cabeza y Cuello , Sarcoma , Humanos , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Sarcoma/terapia , Sarcoma/patología , Sarcoma/mortalidad , Pronóstico , Adulto , Neoplasias de Cabeza y Cuello/terapia , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/mortalidad , Anciano , Adulto Joven , Adolescente , Anciano de 80 o más Años , Dinamarca/epidemiología , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/patología , Resultado del Tratamiento , Tasa de SupervivenciaRESUMEN
INTRODUCTION: Percutaneous coronary intervention (PCI) has been increasingly performed to treat coronary artery disease. The performance of multiple PCI has also been increasing. Consequently, the percentage of patients presenting for coronary artery bypass graft (CABG) surgery is reported to vary from 13 to 40%. The influence of previous PCI on CABG outcomes has been studied in single center, regional studies, registries and meta-analyses. Some reports showed a negative effect on mortality and morbidity in early or long-term follow-up, but others did not find this influence. METHODS AND RESULTS: A cohort of 3007 patients consecutively operated for CABG, 261 of them with previous PCI, were included in this analysis. Comparison of the groups "previous PCI" and "primary CABG" was made in the original cohort and in a propensity score matched cohort of 261 patients. There were some differences in preoperative clinical characteristics in both types of cohort, even in the matched one. Outcomes were compared at 30 days, 1 year and 5 years of follow-up. There were no statistically significant differences in mortality in any period or cohort. There were some differences in other outcomes as readmission and composite events, including cardiovascular death at 1 and 5 years of follow-up. These differences, neverthless, were not confirmed in comparison with the matched cohort. CONCLUSION: Although there are some limitations in this study, it was not found consistent negative influence of previous PCI on CABG.
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Intervención Coronaria Percutánea , Anciano , Puente de Arteria Coronaria , Enfermedad de la Arteria Coronaria , Stents Liberadores de Fármacos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Puntaje de Propensión , Resultado del TratamientoRESUMEN
Abstract Introduction: Percutaneous coronary intervention (PCI) has been increasingly performed to treat coronary artery disease. The performance of multiple PCI has also been increasing. Consequently, the percentage of patients presenting for coronary artery bypass graft (CABG) surgery is reported to vary from 13 to 40%. The influence of previous PCI on CABG outcomes has been studied in single center, regional studies, registries and meta-analyses. Some reports showed a negative effect on mortality and morbidity in early or long-term follow-up, but others did not find this influence. Methods and Results: A cohort of 3007 patients consecutively operated for CABG, 261 of them with previous PCI, were included in this analysis. Comparison of the groups "previous PCI" and "primary CABG" was made in the original cohort and in a propensity score matched cohort of 261 patients. There were some differences in preoperative clinical characteristics in both types of cohort, even in the matched one. Outcomes were compared at 30 days, 1 year and 5 years of follow-up. There were no statistically significant differences in mortality in any period or cohort. There were some differences in other outcomes as readmission and composite events, including cardiovascular death at 1 and 5 years of follow-up. These differences, neverthless, were not confirmed in comparison with the matched cohort. Conclusion: Although there are some limitations in this study, it was not found consistent negative influence of previous PCI on CABG.
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Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Intervención Coronaria Percutánea , Enfermedad de la Arteria Coronaria , Puente de Arteria Coronaria , Resultado del Tratamiento , Stents Liberadores de Fármacos , Puntaje de PropensiónRESUMEN
BACKGROUND: Secreted protein acidic and rich in cysteine (SPARC) has been suggested as a new biomarker and therapeutic target in breast cancer, as well as other tumor types. PATIENTS AND METHODS: We evaluated the frequency of SPARC expression among different molecular breast cancer subtypes and its role for therapy response after neoadjuvant chemotherapy. In this study, pretherapeutic core biopsies of 667 patients from the neoadjuvant GeparTrio trial were evaluated for SPARC expression by immunohistochemistry using a standardized immunoreactive score (IRS). RESULTS: An increased SPARC expression (IRS ≥6) was observed in 26% of all tumors. In triple-negative tumors, SPARC expression was increased in 37% of tumors, compared with other molecular subtypes (23% HR+/HER2-, 29% HR+/HER2+ and 22% HR-/HER2+; P = 0.038). Increased SPARC expression was associated with an increased pathological complete response (pCR) rate of 27%, compared with 15% in tumors with low SPARC expression (P < 0.001). In the triple-negative subgroup, pCR rates were 47% in tumors with high SPARC expression, compared with 26% in tumors with low SPARC expression (P = 0.032). In multivariable analysis, SPARC was independently predictive in the overall population (P = 0.010) as well as the triple-negative subgroup (P = 0.036). CONCLUSIONS: SPARC is frequently expressed in breast cancer with triple-negative breast cancer revealing the highest expression rate. High SPARC expression of the primary tumor is associated with a higher chance of achieving a pathological complete remission after TAC or TAC-NX chemotherapy. As SPARC is an albumin-binding protein and might mediate intratumoral accumulation of albumin bound drugs, SPARC should be further evaluated as a predictive marker especially for response to albumin-bound drugs like nab-paclitaxel. CLINICAL TRIAL NUMBER: NCT00544765.
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Biomarcadores de Tumor/biosíntesis , Terapia Neoadyuvante , Osteonectina/biosíntesis , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/mortalidad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ciclofosfamida/uso terapéutico , Supervivencia sin Enfermedad , Doxorrubicina/uso terapéutico , Femenino , Humanos , Persona de Mediana Edad , Estudios Prospectivos , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Taxoides/uso terapéutico , Resultado del TratamientoRESUMEN
The use of adjuvant is of fundamental importance in vaccines formulations and antisera production. Currently selection and use of adjuvant systems in snake antivenom preparation has become a major issue in terms of animal welfare as well as economics. In order to minimize disadvantages associated with traditionally used Freund's adjuvant (FA) in equines and to produce potent polyvalent antivenom against four Indian snake venoms in minimum possible period, a comparison was made between various commercially available non-emulsion/emulsion based adjuvants like IMS 3012, ISA 206 and ISA 35 with Incomplete Freund's adjuvant (IFA) for their immunopotentiation capacity and safety in donor animals. The present study was conducted in 33 new horses, randomly divided into four groups and hyperimmunized using crude mixture of snake venoms, viz.; Cobra venom (CV), Russell's viper venom (RV), Krait venom (KV) and Saw-scaled viper (EV) along with four above mentioned adjuvants through subcutaneous (s.c.) route at intervals of two weeks. Periodic standard safety assessments were done. Immunopotentiation ability of each adjuvant group in terms of percent responders were estimated at 14th, 21st, 30th and 43rd week. The neutralization activity (ED(50)) of pooled sera samples by 43(rd) week, obtained with IMS 3012 group for CV, RV, KV and EV venoms were 0.133, 0.143, 0.070 and 0.270 mg venom/ml of serum respectively. The antivenom potency with IMS 3012 and overall responding horses (100%) even against weak immunogen like CV was significantly higher (p<0.05) than other three adjuvants studied. The horses of IMS 3012 group showed minimum local reactions at injection site, while horses from other three groups exhibited moderate (++) reactions; 66.7% in ISA 206, 12.5% in ISA 35 and 14.3% in IFA respectively, however these were transient and reabsorbed or healed subsequently. Finally, we conclude that, nanoparticle adjuvant IMS 3012 could be a possible alternative to the emulsion adjuvants for primary phase of immunization in antivenom preparation considering its better immunopotentiation capacity and safety in donor animals.
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Adyuvantes Inmunológicos/farmacología , Antivenenos/sangre , Emulsiones/farmacología , Adyuvante de Freund/farmacología , Lípidos/farmacología , Nanopartículas/química , Venenos de Serpiente/inmunología , Adyuvantes Inmunológicos/administración & dosificación , Adyuvantes Inmunológicos/efectos adversos , Animales , Emulsiones/administración & dosificación , Emulsiones/efectos adversos , Femenino , Adyuvante de Freund/administración & dosificación , Adyuvante de Freund/efectos adversos , Caballos , Inmunización Secundaria/métodos , Inyecciones Subcutáneas , Lípidos/administración & dosificación , Lípidos/efectos adversos , Estudios Longitudinales , Masculino , Nanopartículas/administración & dosificación , Nanopartículas/efectos adversos , Pruebas de NeutralizaciónRESUMEN
Serial measurements of three milkability traits from two commercial dairy farms in Germany were used to estimate heritabilities and breeding values (BVs). Overall, 6352 cows in first, second and third lactations supplied 2 188 810 records based on daily values recorded from 1998 to 2003. Only the records between day 8 and day 305 after calving were considered. The estimated genetic correlations between different parities within the three milkability traits ranged from rg = 0.88 to 0.98, i.e. they were sufficiently high to warrant a repeatability model. The resulting estimated heritability coefficients were h2 = 0.42 for average milk flow, h2 = 0.56 for maximum milk flow and h2 = 0.38 for milking time. We analysed the genetic correlation between milkability and somatic cell score (SCS) and between milkability and the liability to mastitis, respectively, as the optimum milk flow for udder health is not well defined. There were 66 146 records with information on somatic cell count. Furthermore, 23 488 days of medical treatment for udder diseases were available, resulting in 2 600 302 days of observation in total. Heritabilities for the liability to mastitis, estimated with a test-day threshold model, were h2 = 0.19 and h2 = 0.13, depending on the data-recording period (first 50 days of lactation and first 305 days of lactation, respectively). With respect to the relationship between milkability and udder health, the results indicated a slight and linear correlation insofar as one can assume: the higher the milk flow, the worse the udder health. For this reason, bulls and cows with high BVs for milk flow should be excluded from breeding to avoid a deterioration of udder health. The establishment of a special data-recording scheme for functional traits such as milkability and mastitis on commercial dairy farms may be possible according to these results.
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INTRODUCTION: Urogenital chlamydia is still common in the young. The late risks are well-documented. Most of the infections are diagnosed in general practice. The aim was to assess general practitioners' handling of urogenital chlamydial infections in young people aged 15-25 years. METHODS: Two groups of GPs were selected at random and were asked to complete a questionnaire before and after a "State-of-the-Art" was sent to all GPs from the National Board of Health. The questionnaire covered questions about 1) the test indication; 2) advice on the infection diagnosed; 3) contact tracing; and 4) first choice of treatment for uncomplicated infection in non-pregnant women. RESULTS: There was no difference between the two groups in the answers to questions 1) to 3), but an obvious change towards single-dose treatment in question 4), not because of the "State-of-the-Art", but rather because of the intensive marketing of the simple treatment regime. DISCUSSION: Implementation of new knowledge in general practice does not work only through national guidelines from the authorities to general practice, but is wholly dependent on central and local collaboration and GPs having the chance to discuss it between themselves.
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Infecciones por Chlamydia , Medicina Familiar y Comunitaria , Pautas de la Práctica en Medicina , Adolescente , Adulto , Infecciones por Chlamydia/diagnóstico , Infecciones por Chlamydia/tratamiento farmacológico , Infecciones por Chlamydia/transmisión , Trazado de Contacto , Femenino , Conocimientos, Actitudes y Práctica en Salud , Humanos , Masculino , Sexo Seguro , Encuestas y CuestionariosRESUMEN
The purpose of this study was to assess the effect of graphic feed-back of vaccination scores (VS) for vaccination against measles, mumps and rubella (MMR) at the age of 15 months among practices in a Danish county. The study was designed as an intervention study, comparing VS for each practice with VS for the other practices in the county. The feed-back was evaluated qualitatively by use of a postal questionnaire. A majority of the 73 responding practices welcomed the graphic feed-back, regarded it as easily understood and requested similar information on an annual basis in the future. In 13 (18%) of the practices, the calculated VS was lower than the doctors had expected. The most frequent explanation for this discrepancy, given by 4 practices, was incorrect registration of the vaccination. Twenty-one percent of the practices had taken action to improve their performance after receiving the feed-back, but there was no significant improvement in VS in this group. In practices with low VS (< 70%) before intervention, there was no significant change in VS. The total VS for all practices in the county was 89% before and 88% after intervention. In conclusion, the feed-back had no observable effect on VS. Registration errors may explain why some practices had low VS. Feed-back with performance indicators may have better quantitative effect if accompanied by qualitative measures.
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Vacuna Antisarampión/administración & dosificación , Vacuna contra la Parotiditis/administración & dosificación , Vacuna contra la Rubéola/administración & dosificación , Dinamarca , Estudios de Evaluación como Asunto , Medicina Familiar y Comunitaria/estadística & datos numéricos , Humanos , Lactante , Sistema de Registros , Encuestas y CuestionariosRESUMEN
Recombinant inbred (RI) mouse strains were developed primarily as a tool to detect and provisionally map major gene loci--those with effects large enough to cause a bimodal distribution in the trait of interest. This implied that progress toward gene mapping was possible only for gene loci accounting for at least half of the genetic variance. More recently, QTL (quantitative trait loci) approaches have been advanced that do not require bimodal distributions and are thus applicable to a much wider range of phenotypes. They offer the prospect of meaningful progress toward detecting and mapping minor as well as major gene loci affecting any trait of interest, provided there is a significant degree of genetic determination among the RI strains. This paper presents a review of RI gene mapping efforts concerning phenotypes related to drug abuse and presents new data for studies now in progress for nitrous oxide and acute ethanol withdrawal intensity. These two studies exemplify several strengths and limitations of the RI QTL approach.