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Plasmodium knowlesi has been reported as an emerging infection throughout the Southeast Asian region, especially in the Malaysian state of Sabah, where it accounts for the majority of the malaria cases reported. This is in contrast to Europe, where imported P. knowlesi is a rarely reported infection. We present a case of P. knowlesi infection in a Danish woman returning from a short trip to Malaysian Borneo. Microscopy of blood smears revealed 0.8% infected erythrocytes, but due to the atypical morphological presentation, a conclusive species identification was made by molecular methods. Plasmodium knowlesi is a potentially fatal infection and taking the increasing travel activity into consideration after the coronavirus disease 2019 (COVID-19) pandemic, P. knowlesi should be a differential diagnosis in patients with travel-associated illness returning from highly endemic Southeast Asian areas.
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COVID-19 , Malaria , Parásitos , Plasmodium knowlesi , Animales , Femenino , Humanos , Borneo , Plasmodium knowlesi/genética , Viaje , COVID-19/diagnóstico , Malaria/diagnóstico , Malaria/epidemiología , DinamarcaRESUMEN
PURPOSE: The Bone Metastases Ensemble Trees for Survival Decision Support Platform (BMETS-DSP) provides patient-specific survival predictions and evidence-based recommendations to guide multidisciplinary management for symptomatic bone metastases. We assessed the clinical utility of the BMETS-DSP through a pilot prepost design in a simulated clinical environment. METHODS: Ten Radiation Oncology physicians reviewed 55 patient cases at two time points: without and then with the use of BMETS-DSP. Assessment included 12-month survival estimate, confidence in and likelihood of sharing estimates with patients, and recommendations for open surgery, systemic therapy, hospice referral, and radiotherapy (RT) regimen. Paired statistics compared pre- versus post-DSP outcomes. Reported statistical significance is P < .05. RESULTS: Pre- versus post-DSP, overestimation of true minus estimated survival time was significantly reduced (mean difference -2.1 [standard deviation 4.1] v -1 month [standard deviation 3.5]). Prediction accuracy was significantly improved at cut points of < 3 (72 v 79%), ≤ 6 (64 v 71%), and ≥ 12 months (70 v 81%). Median ratings of confidence in and likelihood of sharing prognosis significantly increased. Significantly greater concordance was seen in matching use of 1-fraction RT with the true survival < 3 months (70 v 76%) and < 10-fraction RT with the true survival < 12 months (55 v 62%) and appropriate use of open surgery (47% v 53%), without significant changes in selection of hospice referral or systemic therapy. CONCLUSION: This pilot study demonstrates that BMETS-DSP significantly improved physician survival estimation accuracy, prognostic confidence, likelihood of sharing prognosis, and use of prognosis-appropriate RT regimens in the care of symptomatic bone metastases, supporting future multi-institutional validation of the platform.
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Neoplasias Óseas , Oncología por Radiación , Humanos , Proyectos Piloto , Neoplasias Óseas/terapia , Neoplasias Óseas/radioterapia , PronósticoRESUMEN
AIM: This study aimed to investigate various variables between maternal overweight and/or obesity versus normal-weight pregnant black South African women living with and without human immunodeficiency virus (HIV). METHODS: A cross-sectional study design was employed. A total of 200 pregnant women were enrolled in the study, categorized according to body mass index (BMI) (kg/m2 ) into two groups: (1) overweight/obese (≥25 kg/m2 ) (n = 97); and (2) nonoverweight/nonobese (<25 kg/m2 ) (n = 103), where 90 were HIV-infected and 110 were HIV-uninfected. The differences between the maternal BMI categories were assessed using Fisher's exact t-test and the χ2 test. Simple and multiple logistic regression analyses were used to determine factors associated with maternal overweight and obesity. RESULTS: Multiple logistic regression analysis showed that maternal age (odds ratio [OR]: 1.061; 95% confidence interval [CI] 1.008-1.117; p = 0.023) and gestational age (OR: 1.121; 95% CI 1.005-1.251; p = 0.041) were significantly associated with maternal overweight/obesity in both HIV-infected and HIV-uninfected. For maternal health outcomes, multiple logistic regression analysis showed that hypertensive disorders (OR: 0.273; 95% CI 0.124-0.601; p = 0.001) and anemia (OR: 2.420; 95% CI 1.283-4.563; p = 0.006) were significantly associated with maternal overweight/obesity in both HIV-infected and HIV-uninfected. The overweight/obese HIV-infected participants (OR: 0.233; 95% CI 0.075-0.717; p = 0.011) had increased odds for developing hypertensive disorders compared to HIV-uninfected overweight/obese participants (OR: 0.471; 95% CI 0.172-1.291; p = 0.143). CONCLUSIONS: Maternal overweight/obesity in both HIV-infected and HIV-uninfected pregnant black South African women was significantly associated with maternal age, gestational age, HPT disorders, and anemia. Maternal overweight/obesity decreased the odds for anemia, but increased the odds for the development of HPT disorders, especially in the HIV-infected pregnant women.
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Infecciones por VIH , Hipertensión Inducida en el Embarazo , Femenino , Embarazo , Humanos , Sobrepeso/complicaciones , Mujeres Embarazadas , Estudios Transversales , Sudáfrica , Obesidad/complicaciones , Índice de Masa Corporal , Infecciones por VIH/complicaciones , VIHRESUMEN
RATIONALE, AIMS AND OBJECTIVES: In the management of symptomatic bone metastases, current practice guidelines do not provide clear methodology for selecting palliative radiotherapy (RT) regimens based on specific patient and disease features. Decision support aids may offer an effective means for translating the complex data needed to render individualised treatment decisions, yet no such tools are available for use in this setting. Thus, we describe the development of the Bone Metastases Ensemble Trees for Survival-Decision Support Platform (BMETS-DSP), which aims to optimise selection of evidence-based, individualised palliative RT regimens. METHOD: The Ottawa Decision Support Framework was used as the theoretical basis for development of BMETS-DSP. First, we utilised stakeholder input and review of the literature to assess determinants underlying the provider decision. Based on this assessment and iterative stakeholder feedback, we developed the web-based, provider-facing BMETS-DSP. Consistent with the underlying theoretical framework, our design also included assessment of decision quality using the International Patient Decision Aids Standards (IPDAS) certification checklist. RESULTS: Stakeholder input and review of 54 evidence-based publications identified the following determinants of the provider decision: estimated prognosis, characteristics of the target symptomatic lesion and the primary cancer type, consideration of alternative interventions, access to patient-specific recommendations, and patient preferences. Based on these determinants, we developed the BMETS-DSP that (1) collects patient-specific data, (2) displays an individualised predicted survival curve, and (3) provides case-specific, evidence-based recommendations regarding RT, open surgery, systemic therapy, and hospice referral to aid in the decision-making process. The finalised tool met IPDAS quality requirements. Preliminary results of a pilot assessment suggest impact of clinical outcomes. CONCLUSIONS: We describe the successful development of a provider-facing decision support platform to aid in the provision of palliative RT in better alignment with patient and disease features. Impact of the BMETS-DSP on decision outcomes will be further assessed in a randomised, controlled study.
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Técnicas de Apoyo para la Decisión , Proyectos de Investigación , Humanos , PronósticoRESUMEN
PURPOSE: The Bone Metastases Ensemble Trees for Survival (BMETS) model uses a machine learning algorithm to estimate survival time following consultation for palliative radiation therapy for symptomatic bone metastases (SBM). BMETS was developed at a tertiary-care, academic medical center, but its validity and stability when applied to external data sets are unknown. PATIENTS AND METHODS: Patients treated with palliative radiation therapy for SBM from May 2013 to May 2016 at two hospital-based community radiation oncology clinics were included, and medical records were retrospectively reviewed to collect model covariates and survival time. The Kaplan-Meier method was used to estimate overall survival from consultation to death or last follow-up. Model discrimination was estimated using time-dependent area under the curve (tAUC), which was calculated using survival predictions from BMETS based on the initial training data set. RESULTS: A total of 216 sites of SBM were treated in 182 patients. Most common histologies were breast (27%), lung (23%), and prostate (23%). Compared with the BMETS training set, the external validation population was older (mean age, 67 v 62 years; P < .001), had more primary breast (27% v 19%; P = .03) and prostate cancer (20% v 12%; P = .01), and survived longer (median, 10.7 v 6.4 months). When the BMETS model was applied to the external data set, tAUC values at 3, 6, and 12 months were 0.82, 0.77, and 0.77, respectively. When refit with data from the combined training and external validation sets, tAUC remained > 0.79. CONCLUSION: BMETS maintained high discriminative ability when applied to an external validation set and when refit with new data, supporting its generalizability, stability, and the feasibility of dynamic modeling.
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Neoplasias Óseas , Aprendizaje Automático , Anciano , Neoplasias Óseas/mortalidad , Humanos , Cuidados Paliativos , Estudios RetrospectivosRESUMEN
INTRODUCTION: Angiotensin system inhibitors are associated with improved prognosis in patients with gastrointestinal and hepatobiliary cancers. Data suggest that renin-angiotensin system signaling stimulates the tumor's immune microenvironment to impact overall survival. The goal of this study is to investigate the role of angiotensin system inhibitor use on the overall survival and disease-free survival of esophageal cancer patients. METHODS: Retrospective review of esophagectomy patients with esophageal adenocarcinoma and squamous cell cancer at a single institution tertiary care center from 2007 to 2018 was performed. Outcomes include overall survival and disease-free survival. Patient characteristics were compared with t test and χ2 test. Survival was analyzed with Kaplan-Meier and Cox proportional-hazards regression. RESULTS: One hundred seventy-one patients were identified and 123 underwent esophagectomy for cancer. No significant differences in patient demographics were found between angiotensin system inhibitor users and non-angiotensin system inhibitor users except for the rates of hypertension (40% vs 94%, Pâ¯<â¯.01) and diabetes (16% vs 47%, Pâ¯<â¯.01). Distributions of tumor neoadjuvant therapy, adjuvant therapy, pathology, staging, margins, and surgical approach were similar. Postoperatively, there was no difference in major adverse cardiovascular events or infection rates. This study did not find any differences in overall survival and disease-free survival between angiotensin system inhibitor users and non-angiotensin system inhibitor users. CONCLUSION: Angiotensin system inhibitors have been shown to improve survival and decrease relative risk for several types of cancers; however, our data do not support the same effect on esophageal cancer patients undergoing curative intent surgery. Further research is needed to investigate potential nuances in angiotensin system inhibitor dose, chronicity of use, esophageal pathology, and applicability to nonsurgical candidates.
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BACKGROUND: Metastasectomy is standard of care for pediatric patients with metastatic sarcoma with limited disease. For patients with unresectable disease, stereotactic body radiotherapy (SBRT) may serve as an alternative. Herein, the authors report the results of a prospective, multi-institutional phase 2 trial of SBRT in children and young adults with metastatic sarcoma. METHODS: Patients aged >3 years and ≤40 years with unresected, osseous metastatic nonrhabdomyosarcoma sarcomas of soft tissue and bone were eligible. Patients received SBRT to a dose of 40 Gray (Gy) in 5 fractions. Local control (LC), progression-free survival (PFS), and overall survival (OS) were calculated using the Kaplan-Meier method. RESULTS: Fourteen patients with a median age of 17 years (range, 4-25 years) were treated to 37 distinct metastatic lesions. With a median follow-up of 6.8 months (30.5 months in surviving patients), the Kaplan-Meier patient-specific and lesion-specific LC rates at 6 months were 89% and 95%, respectively. The median PFS was 6 months and the median OS was 24 months. In a post hoc analysis, PFS (median, 9.3 months vs 3.7 months; log-rank P = .03) and OS (median not reached vs 12.7 months; log-rank P = .02) were improved when all known sites of metastatic disease were consolidated with SBRT compared with partial consolidation. SBRT was well tolerated, with 2 patients experiencing grade 3 toxicities. CONCLUSIONS: SBRT achieved high rates of LC in pediatric patients with inoperable metastatic nonrhabdomyosarcoma sarcomas of soft tissue and bone. These results suggest that the ability to achieve total consolidation of metastatic disease with SBRT is associated with improved PFS and OS.
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Neoplasias Óseas/radioterapia , Neoplasias Óseas/secundario , Radiocirugia/métodos , Sarcoma/patología , Adolescente , Adulto , Neoplasias Óseas/mortalidad , Niño , Preescolar , Femenino , Humanos , Masculino , Modelos de Riesgos Proporcionales , Adulto JovenRESUMEN
The use of brachytherapy for the treatment of gynecologic malignancies, particularly cervical cancer, has a long and rich history that is nearly as long as the history of radiation oncology itself. From the first gynecologic brachytherapy treatments in the early 20th century to the modern era, significant transformation has occurred driven largely by advancements in technology. The development of high-dose rate sources, remote afterloaders, novel applicators, and 3-dimensional image guidance has led to improved local control, and thus improved survival, solidifying the role of brachytherapy as an integral component in the treatment of locally advanced cervical cancer. Current research efforts examining novel magnetic resonance imaging sequences, active magnetic resonance tracking, and the application of hydrogel aim to further improve local control and reduce treatment toxicity.
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Braquiterapia/métodos , Imagen por Resonancia Magnética/métodos , Radioterapia Guiada por Imagen/métodos , Neoplasias del Cuello Uterino/diagnóstico por imagen , Neoplasias del Cuello Uterino/radioterapia , Femenino , Humanos , Imagenología Tridimensional , Neoplasias del Cuello Uterino/patologíaRESUMEN
OBJECTIVE: To develop expert consensus recommendations regarding radiation therapy for gynecologic malignancies during the COVID-19 pandemic. METHODS: An international committee of ten experts in gynecologic radiation oncology convened to provide consensus recommendations for patients with gynecologic malignancies referred for radiation therapy. Treatment priority groups were established. A review of the relevant literature was performed and different clinical scenarios were categorized into three priority groups. For each stage and clinical scenario in cervical, endometrial, vulvar, vaginal and ovarian cancer, specific recommendations regarding dose, technique, and timing were provided by the panel. RESULTS: Expert review and discussion generated consensus recommendations to guide radiation oncologists treating gynecologic malignancies during the COVID-19 pandemic. Priority scales for cervical, endometrial, vulvar, vaginal, and ovarian cancers are presented. Both radical and palliative treatments are discussed. Management of COVID-19 positive patients is considered. Hypofractionated radiation therapy should be used when feasible and recommendations regarding radiation dose, timing, and technique have been provided for external beam and brachytherapy treatments. Concurrent chemotherapy may be limited in some countries, and consideration of radiation alone is recommended. CONCLUSIONS: The expert consensus recommendations provide guidance for delivering radiation therapy during the COVID-19 pandemic. Specific recommendations have been provided for common clinical scenarios encountered in gynecologic radiation oncology with a focus on strategies to reduce patient and staff exposure to COVID-19.
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Infecciones por Coronavirus/prevención & control , Neoplasias de los Genitales Femeninos/radioterapia , Neoplasias de los Genitales Femeninos/virología , Pandemias/prevención & control , Neumonía Viral/prevención & control , Oncología por Radiación/métodos , Oncología por Radiación/normas , Betacoronavirus/aislamiento & purificación , COVID-19 , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/transmisión , Femenino , Humanos , Control de Infecciones/métodos , Control de Infecciones/normas , Neumonía Viral/epidemiología , Neumonía Viral/transmisión , SARS-CoV-2RESUMEN
PURPOSE: To determine whether a machine learning approach optimizes survival estimation for patients with symptomatic bone metastases (SBM), we developed the Bone Metastases Ensemble Trees for Survival (BMETS) to predict survival using 27 prognostic covariates. To establish its relative clinical utility, we compared BMETS with 2 simpler Cox regression models used in this setting. METHODS AND MATERIALS: For 492 bone sites in 397 patients evaluated for palliative radiation therapy (RT) for SBM from January 2007 to January 2013, data for 27 clinical variables were collected. These covariates and the primary outcome of time from consultation to death were used to build BMETS using random survival forests. We then performed Cox regressions as per 2 validated models: Chow's 3-item (C-3) and Westhoff's 2-item (W-2) tools. Model performance was assessed using cross-validation procedures and measured by time-dependent area under the curve (tAUC) for all 3 models. For temporal validation, a separate data set comprised of 104 bone sites treated in 85 patients in 2018 was used to estimate tAUC from BMETS. RESULTS: Median survival was 6.4 months. Variable importance was greatest for performance status, blood cell counts, recent systemic therapy type, and receipt of concurrent nonbone palliative RT. tAUC at 3, 6, and 12 months was 0.83, 0.81, and 0.81, respectively, suggesting excellent discrimination of BMETS across postconsultation time points. BMETS outperformed simpler models at each time, with respective tAUC at each time of 0.78, 0.76, and 0.74 for the C-3 model and 0.80, 0.78, and 0.77 for the W-2 model. For the temporal validation set, respective tAUC was similarly high at 0.86, 0.82, and 0.78. CONCLUSIONS: For patients with SBM, BMETS improved survival predictions versus simpler traditional models. Model performance was maintained when applied to a temporal validation set. To facilitate clinical use, we developed a web platform for data entry and display of BMETS-predicted survival probabilities.
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Algoritmos , Neoplasias Óseas/mortalidad , Neoplasias Óseas/secundario , Esperanza de Vida , Aprendizaje Automático , Analgésicos Opioides/uso terapéutico , Área Bajo la Curva , Recuento de Células Sanguíneas , Neoplasias Óseas/sangre , Neoplasias Óseas/radioterapia , Femenino , Humanos , Estimación de Kaplan-Meier , Estado de Ejecución de Karnofsky , Masculino , Persona de Mediana Edad , Cuidados Paliativos/métodos , Huesos Pélvicos , Pronóstico , Modelos de Riesgos Proporcionales , Reproducibilidad de los Resultados , Neoplasias de la Columna Vertebral/sangre , Neoplasias de la Columna Vertebral/mortalidad , Neoplasias de la Columna Vertebral/radioterapia , Neoplasias de la Columna Vertebral/secundario , Esteroides/uso terapéutico , Factores de TiempoRESUMEN
BACKGROUND: Assessment of psoriasis severity is strongly observer-dependent, and objective assessment tools are largely missing. The increasing number of patients receiving highly expensive therapies that are reimbursed only for moderate-to-severe psoriasis motivates the development of higher quality assessment tools. OBJECTIVE: To establish an accurate and objective psoriasis assessment method based on segmenting images by machine learning technology. METHODS: In this retrospective, non-interventional, single-centred, interdisciplinary study of diagnostic accuracy, 259 standardized photographs of Caucasian patients were assessed and typical psoriatic lesions were labelled. Two hundred and three of those were used to train and validate an assessment algorithm which was then tested on the remaining 56 photographs. The results of the algorithm assessment were compared with manually marked area, as well as with the affected area determined by trained dermatologists. RESULTS: Algorithm assessment achieved accuracy of more than 90% in 77% of the images and differed on average 5.9% from manually marked areas. The difference between algorithm-predicted and photograph-based estimated areas by physicians was 8.1% on average. CONCLUSION: The study shows the potential of the evaluated technology. In contrast to the Psoriasis Area and Severity Index (PASI), it allows for objective evaluation and should therefore be developed further as an alternative method to human assessment.
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Aprendizaje Automático , Psoriasis/diagnóstico por imagen , Índice de Severidad de la Enfermedad , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Humanos , Persona de Mediana Edad , Redes Neurales de la Computación , Variaciones Dependientes del Observador , Fotograbar , Psoriasis/patología , Reproducibilidad de los Resultados , Estudios Retrospectivos , Adulto JovenRESUMEN
PURPOSE: Numerous randomized trials have demonstrated noninferiority of single- versus multiple-fraction palliative radiation therapy (RT) in the management of uncomplicated bone metastases; yet there is neither a clear definition of what constitutes a complicated lesion, nor substantial data regarding the prevalence of such complicating features in clinical practice. Thus, we identify a range of evidence-based operational definitions of complicated symptomatic bone metastases and characterize the frequency of such complicating features at a high-volume, tertiary care center. METHODS AND MATERIALS: A retrospective review of patients seen in consultation for symptomatic bone metastases between March 1, 2007, and July 31, 2013, at Johns Hopkins Hospital identified patient and disease characteristics. Descriptive statistics characterized the frequency of the following complicating features: prior RT, prior surgery, neuraxis compromise, pathologic fracture, and soft tissue component at the symptomatic site. A range of definitions for complicated bone metastases was evaluated based on combinations of these features. Uni- and multivariable logistic regressions evaluated the odds of complicated bone metastases as a function of site of primary cancer and of the symptomatic target lesion. RESULTS: A total of 686 symptomatic bone metastases in 401 patients were evaluated. Percent of target sites complicated by prior RT was 4.4%, prior surgery was 8.9%, pathologic fracture was 20.6%, neuraxis compromise was 52.0% among spine and medial pelvis sites, and soft tissue component was 38.6%. More than 96 possible definitions of complicated bone metastases were identified. The presence of such complicated lesions ranged from 2.3% to 67.3%, depending on the operational definition used. Odds of a complicated lesion were significantly higher for spine sites and select nonbreast histologies. CONCLUSIONS: In this retrospective study, we found complicated symptomatic bone metastases may be present in up to two-thirds of patients. Literature review also demonstrates no clear standard definition of complicated bone metastases, potentially explaining underutilization of single-fraction palliative RT in this setting.
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Neoplasias Óseas/secundario , Neoplasias Óseas/diagnóstico , Neoplasias Óseas/radioterapia , Femenino , Humanos , Masculino , Análisis Multivariante , Cuidados Paliativos , Análisis de Regresión , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
We report human infection with simian Plasmodium cynomolgi in a tourist from Denmark who had visited forested areas in peninsular Malaysia and Thailand in August and September 2018. Because P. cynomolgi may go unnoticed by standard malaria diagnostics, this malaria species may be more common in humans than was previously thought.
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Malaria/parasitología , Plasmodium cynomolgi , Adulto , Dinamarca/etnología , Femenino , Humanos , Malaria/diagnóstico , Malaria/epidemiología , Malasia/epidemiología , Filogenia , Plasmodium cynomolgi/genética , Tailandia/epidemiología , ViajeRESUMEN
BACKGROUND: Emactuzumab is a monoclonal antibody against the colony-stimulating factor-1 receptor and targets tumor-associated macrophages (TAMs). This study assessed the safety, clinical activity, pharmacokinetics (PK) and pharmacodynamics (PD) of emactuzumab, as monotherapy and in combination with paclitaxel, in patients with advanced solid tumors. PATIENTS AND METHODS: This open-label, phase Ia/b study comprised two parts (dose escalation and dose expansion), each containing two arms (emactuzumab, every 2 or 3 weeks, as monotherapy or in combination with paclitaxel 80 mg/m2 weekly). The dose-escalation part explored the maximum tolerated dose and optimal biological dose (OBD). The dose-expansion part extended the safety assessment and investigated the objective response rate. A PK/PD analysis of serial blood, skin and tumor biopsies was used to explore proof of mechanism and confirm the OBD. RESULTS: No maximum tolerated dose was reached in either study arm, and the safety profile of emactuzumab alone and in combination does not appear to preclude its use. No patients receiving emactuzumab monotherapy showed an objective response; the objective response rate for emactuzumab in combination with paclitaxel was 7% across all doses. Skin macrophages rather than peripheral blood monocytes or circulating colony-stimulating factor-1 were identified as an optimal surrogate PD marker to select the OBD. Emactuzumab treatment alone and in combination with paclitaxel resulted in a plateau of immunosuppressive TAM reduction at the OBD of 1000 mg administered every 2 weeks. CONCLUSIONS: Emactuzumab showed specific reduction of immunosuppressive TAMs at the OBD in both treatment arms but did not result in clinically relevant antitumor activity alone or in combination with paclitaxel. (ClinicalTrials.gov Identifier: NCT01494688).
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Anticuerpos Monoclonales Humanizados/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Macrófagos/efectos de los fármacos , Neoplasias/tratamiento farmacológico , Paclitaxel/farmacología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales Humanizados/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Factor Estimulante de Colonias de Macrófagos/sangre , Factor Estimulante de Colonias de Macrófagos/metabolismo , Macrófagos/inmunología , Masculino , Dosis Máxima Tolerada , Persona de Mediana Edad , Neoplasias/sangre , Neoplasias/inmunología , Neoplasias/patología , Paclitaxel/uso terapéutico , Receptores de Factor Estimulante de Colonias de Granulocitos y Macrófagos/antagonistas & inhibidores , Receptores de Factor Estimulante de Colonias de Granulocitos y Macrófagos/metabolismo , Piel/citología , Piel/inmunología , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Gliomas with 1p/19q-codeletion as well as mutation of isocitrate dehydrogenase (IDH) 1 are typically characterized as oligodendrogliomas with comparatively good response to treatment with radiation and chemotherapy. CASE PRESENTATION: We present the case of a 28-year-old man with an IDH1 and TP53 mutant high grade glioma with abnormalities in chromosomes 1 and 19 suggestive of anaplastic oligodendroglioma that rapidly progressed to widespread metastatic disease. Biopsy of a liver lesion confirmed metastasis of the patient's known brain primary and chemotherapy with temozolomide was initiated. The patient's rapidly growing tumor burden with fulminant liver failure and tumor lysis led to multisystem failure of which the patient died. Further molecular testing illustrated features more consistent with glioblastoma: multiple large chromosomal aberrations including loss of whole chromosome 1 and 2q; gain/amplification of MYCN, MET, and CDK4; loss of CDKN2A/B; and an ATRX mutation. CONCLUSION: This case illustrates the importance of higher level molecular diagnostic testing for patients with particularly aggressive disease progression that is not concordant with standard prognoses. Additional data on cases with atypical alterations of 1p and 19q are needed to better understand the distinct biology of these cancers so that appropriate therapies can be developed.
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Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Glioblastoma/genética , Glioblastoma/patología , Isocitrato Deshidrogenasa/genética , Adulto , Aberraciones Cromosómicas , Resultado Fatal , Humanos , Masculino , MutaciónRESUMEN
Amoebae are single-celled parasites frequently colonizing human gut. However, few molecular tools are available for accurate identification. Here, we evaluated a panel of polymerase chain reactions (PCRs) targeting Entamoeba histolytica, Entamoeba dispar, Entamoeba coli, Entamoeba hartmanni, Entamoeba polecki, Endolimax nana and Iodamoeba bütschlii. Thirty-six faecal samples (18 containing at least one amoeba species by microscopy and 18 microscopy negative for amoebae) were tested. Real-time PCRs were used for detection and differentiation of E. histolytica and E. dispar. Conventional PCR with Sanger sequencing were applied for detection and differentiation of E. coli, E. hartmanni, E. polecki, E. nana and I. bütschlii. All microscopy results were confirmed by DNA-based methods. However, more samples were positive for single and mixed amoebic species by DNA-based assays than by microscopy (22 vs 18 and 7 vs 1, respectively). DNA sequencing allowed identification of E. coli subtypes (ST1 and ST2), showed low intra-specific variation within E. hartmanni, identified two phylogenetically distinct groups within E. nana, and identified Iodamoeba at the ribosomal lineage level. Taking into account the high intra-genetic diversity within some of the species at the small subunit (SSU) rRNA gene level, amplification of SSU rRNA genes with subsequent sequencing represents a useful method for detecting, differentiating and subtyping intestinal amoebae.
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Amebiasis/diagnóstico , Archamoebae/aislamiento & purificación , Endolimax/aislamiento & purificación , Entamoeba histolytica/aislamiento & purificación , Heces/parasitología , Técnicas de Diagnóstico Molecular/métodos , Archamoebae/clasificación , Archamoebae/genética , Enfermedades Asintomáticas , ADN Protozoario/química , ADN Protozoario/genética , ADN Ribosómico/química , ADN Ribosómico/genética , Endolimax/clasificación , Endolimax/genética , Entamoeba histolytica/clasificación , Entamoeba histolytica/genética , Humanos , Microscopía , Reacción en Cadena de la Polimerasa/métodos , ARN Ribosómico 18S/genética , Análisis de Secuencia de ADN/métodosRESUMEN
Blastocystis sp. is probably the most common enteric parasite in humans globally. Although the role of Blastocystis in human disease is still controversial, epidemiological and experimental evidence suggests that pathogenicity may be associated with certain subtypes of the protist. Since the life cycle of Blastocystis is maintained through still elusive pathways, companion animals have attracted the attention of researchers as potential reservoirs of human infections. In order to evaluate the risk of zoonotic transmission of Blastocystis, we investigated the occurrence and molecular diversity of this microorganism in human, canine and feline populations sharing temporal and spatial settings in the province of Álava, northern Spain. A total of 268 (including 179 human, 55 canine and 34 feline) faecal specimens were obtained from 63 family households during February-December 2014. Detection of Blastocystis was achieved by PCR amplification and sequencing of small subunit rRNA genes. Blastocystis was found in 35.2% (95% CI: 0.29%-0.42%) of the human stool samples analysed, but not in any of the canine or feline faecal specimens investigated. Out of the 63 PCR-positive human samples, 84.1% (53/63) were successfully subtyped, allowing the identification of the subtypes ST2 (62.3%), ST3 (17.0%), ST1 (13.2%) and ST4 (7.5%). No mixed subtype infections were identified. Blastocystis carriage was independent of the gender and region of origin of the affected individuals, but children in the age groups of >5-10 years and >10-15 years were significantly more affected by the protist. None of the risk factors considered (water-use practices, contact with livestock, contact with individual undergoing diarrhoeal episodes) were associated with increased prevalence of Blastocystis. Our data demonstrate that pet dogs and cats play a negligible role as natural reservoirs of human Blastocystis infection in this geographic region, although the applicability of these results should be corroborated in future molecular epidemiological studies.
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Infecciones por Blastocystis/veterinaria , Blastocystis/aislamiento & purificación , Reservorios de Enfermedades/veterinaria , Zoonosis/transmisión , Animales , Animales Domésticos/parasitología , Blastocystis/clasificación , Blastocystis/genética , Blastocystis/patogenicidad , Infecciones por Blastocystis/epidemiología , Infecciones por Blastocystis/parasitología , Infecciones por Blastocystis/transmisión , Enfermedades de los Gatos/epidemiología , Enfermedades de los Gatos/parasitología , Enfermedades de los Gatos/transmisión , Gatos , ADN Protozoario/genética , Reservorios de Enfermedades/parasitología , Enfermedades de los Perros/epidemiología , Enfermedades de los Perros/parasitología , Enfermedades de los Perros/transmisión , Perros , Composición Familiar , Heces/parasitología , Variación Genética , Humanos , Reacción en Cadena de la Polimerasa , Prevalencia , Factores de Riesgo , España/epidemiología , Zoonosis/epidemiología , Zoonosis/parasitologíaRESUMEN
PURPOSE: To compare the initial fixation stability, failure strength, and mode of failure of 5 different screw types and fixation methods commonly used for the classic Latarjet procedure. METHODS: Thirty-five fresh-frozen cadaveric shoulder specimens were allocated into 5 groups. A 25% anteroinferior glenoid defect was created, and a classic Latarjet coracoid transfer procedure was performed. All grafts were fixed with 2 screws, differing by screw type and/or fixation method. The groups included partially threaded solid 4.0-mm cancellous screws with bicortical fixation, partially threaded solid 4.0-mm cancellous screws with unicortical fixation, fully threaded solid 3.5-mm cortical screws with bicortical fixation, partially threaded cannulated 4.0-mm cancellous screws with bicortical fixation, and partially threaded cannulated 4.0-mm captured screws with bicortical fixation. All screws were stainless steel. Outcomes included cyclic creep and secant stiffness during cyclic loading, as well as load and work to failure during the failure test. Intergroup comparisons were made by a 1-way analysis of variance. RESULTS: There were no significant differences among different screw types or fixation methods in cyclic creep or secant stiffness after cyclic loading or in load to failure or work to failure during the failure test. Post-failure radiographs showed evidence of screw bending in only 1 specimen that underwent the Latarjet procedure with partially threaded solid cancellous screws with bicortical fixation. The mode of failure for all specimens analyzed was screw cutout. CONCLUSIONS: In this biomechanical study, screw type and fixation method did not significantly influence biomechanical performance in a classic Latarjet procedure. When performing this procedure, surgeons may continue to select the screw type and method of fixation (unicortical or bicortical) based on preference; however, further studies are required to determine the optimal method of treatment. CLINICAL RELEVANCE: Surgeons may choose the screw type and fixation method based on preference when performing the Latarjet procedure.
Asunto(s)
Tornillos Óseos , Inestabilidad de la Articulación/cirugía , Articulación del Hombro/cirugía , Adulto , Anciano , Fenómenos Biomecánicos , Cadáver , Apófisis Coracoides/trasplante , Diseño de Equipo , Falla de Equipo , Femenino , Humanos , Masculino , Ensayo de Materiales/métodos , Persona de Mediana Edad , Osteotomía/métodos , Radiografía , EscápulaRESUMEN
Dientamoeba fragilis is an intestinal protozoan of debated clinical significance. Here, we present cross-sectional and longitudinal observations on D. fragilis in children aged 0 to 6 years from a 1-year multi-day-care-center cohort study set in Copenhagen, Denmark. The inclusion period for the cohort was 2009 through 2012. Stool samples collected from the children were accompanied by questionnaires completed by the parents or guardians of the children. Using real-time PCR, D. fragilis was detected in the first stool sample from 97 of 142 (68.3%) children. We evaluated the associations between seven plausible risk factors (age, sex, having siblings, having domestic animals at home, having had infant colic, recent history of intake of antibiotics, and recent history of travel abroad) as well as six reported symptoms (lack of appetite, nausea, vomiting, abdominal pain, weight loss, and diarrhea) and testing positive for D. fragilis The final multivariable model identified being >3 years old and having a history of recent travel abroad as risk factors for testing positive for D. fragilis Moreover, univariable analyses indicated that having siblings was a risk factor. There was no statistical association between a recent history of gastrointestinal symptoms and testing positive for D. fragilis Among the 108 children who were represented by ≥2 samples and thus included in the longitudinal analysis, 32 tested negative on the first sample and positive later, and the last sample from each of the 108 children was positive. The results are in support of D. fragilis being a common enteric commensal in this population.