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1.
Philos Trans A Math Phys Eng Sci ; 382(2273): 20230197, 2024 Jun 09.
Artículo en Inglés | MEDLINE | ID: mdl-38736334

RESUMEN

The origin of micrometeorites (MMs) from asteroids and comets is well-established, but the relative contribution from these two classes remains poorly resolved. Likewise, determining the precise origin of individual MMs is an open challenge. Here, cosmic-ray exposure ages are used to resolve the spatial origins of 12 MMs collected from urban areas and Antarctica. Their 26Al and 10Be concentration, produced during cosmic-ray irradiation in space, were measured by accelerator mass spectrometry. These data are compared to results from a model simulating the transport and irradiation of the MM precursors in space. This model, for the first time, considers a variety of orbits, precursor particle sizes, compositions and densities and incorporates non-isotropic solar and galactic cosmic-ray flux profiles, depth-dependent production rates, as well as spherical evaporation during atmospheric entry. While the origin for six MMs remains ambiguous, two MMs show a preferential tendency towards an origin in the Inner Solar System (Near Earth Objects to the Asteroid Belt) and four towards an origin in the Outer Solar System (Jupiter Family Comets to the Kuiper Belt). These findings challenge the notion that dust originating from the Outer Solar System is unlikely to survive long-term transport and delivery to the terrestrial planets. This article is part of the theme issue 'Dust in the Solar System and beyond'.

2.
J Cyst Fibros ; 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38658252

RESUMEN

BACKGROUND: Newborn bloodspot screening (NBS) for cystic fibrosis (CF) is important for early diagnosis and treatment. However, screening can lead to false-positive results leading to unnecessary follow-up tests and distress. This study evaluated the 11-year performance of the Swiss CF-NBS programme, estimated optimal cut-offs for immunoreactive trypsinogen (IRT), and examined how simulated algorithms would change performance. METHODS: The Swiss CF-NBS is based on an IRT-DNA algorithm with a second IRT (IRT-2) as safety net. We analysed data from 2011 to 2021, covering 959,006 IRT-1 analyses and 282 children with CF. We studied performance based on European Cystic Fibrosis Society (ECFS) standards including sensitivity, specificity, positive predictive value (PPV), false negative rate, and second heel-prick tests; identified optimal IRT cut-offs using receiver operating characteristics (ROC) curves; and calculated performance for simulated algorithms with different cut-offs for IRT-1, IRT-2, and safety net. RESULTS: The Swiss CF-NBS showed excellent sensitivity (96 %, 10 false negative cases) but moderate PPV (25 %). Optimal IRT-1 and IRT-2 cut-offs were identified at 2.7 (>99th percentile) and 5.9 (>99.8th percentile) z-scores, respectively. Analysis of simulated algorithms showed that removing the safety net from the current algorithm could increase PPV to 30 % and eliminate >200 second heel-prick tests per year, while keeping sensitivity at 95 %. CONCLUSION: The Swiss CF-NBS program performed well over 11 years but did not achieve the ECFS standards for PPV (≥30 %). Modifying or removing the safety net could improve PPV and reduce unnecessary follow-up tests while maintaining the ECFS standards for sensitivity.

3.
PLoS Biol ; 21(8): e3002239, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37651504

RESUMEN

Understanding central auditory processing critically depends on defining underlying auditory cortical networks and their relationship to the rest of the brain. We addressed these questions using resting state functional connectivity derived from human intracranial electroencephalography. Mapping recording sites into a low-dimensional space where proximity represents functional similarity revealed a hierarchical organization. At a fine scale, a group of auditory cortical regions excluded several higher-order auditory areas and segregated maximally from the prefrontal cortex. On mesoscale, the proximity of limbic structures to the auditory cortex suggested a limbic stream that parallels the classically described ventral and dorsal auditory processing streams. Identities of global hubs in anterior temporal and cingulate cortex depended on frequency band, consistent with diverse roles in semantic and cognitive processing. On a macroscale, observed hemispheric asymmetries were not specific for speech and language networks. This approach can be applied to multivariate brain data with respect to development, behavior, and disorders.


Asunto(s)
Corteza Auditiva , Humanos , Percepción Auditiva , Encéfalo , Electrocorticografía , Electrofisiología
5.
Clin Oncol (R Coll Radiol) ; 35(8): e453-e468, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37217434

RESUMEN

This review aims to showcase the brachytherapy tools and technologies that have emerged during the last 10 years. Soft-tissue contrast using magnetic resonance and ultrasound imaging has seen enormous growth in use to plan all forms of brachytherapy. The era of image-guided brachytherapy has encouraged the development of advanced applicators and given rise to the growth of individualised 3D printing to achieve reproducible and predictable implants. These advances increase the quality of implants to better direct radiation to target volumes while sparing normal tissue. Applicator reconstruction has moved beyond manual digitising, to drag and drop of three-dimensional applicator models with embedded pre-defined source pathways, ready for auto-recognition and automation. The simplified TG-43 dose calculation formalism directly linked to reference air kerma rate of high-energy sources in the medium water remains clinically robust. Model-based dose calculation algorithms accounting for tissue heterogeneity and applicator material will advance the field of brachytherapy dosimetry to become more clinically accurate. Improved dose-optimising toolkits contribute to the real-time and adaptive planning portfolio that harmonises and expedites the entire image-guided brachytherapy process. Traditional planning strategies remain relevant to validate emerging technologies and should continue to be incorporated in practice, particularly for cervical cancer. Overall, technological developments need commissioning and validation to make the best use of the advanced features by understanding their strengths and limitations. Brachytherapy has become high-tech and modern by respecting tradition and remaining accessible to all.


Asunto(s)
Braquiterapia , Neoplasias del Cuello Uterino , Femenino , Humanos , Braquiterapia/métodos , Radiometría , Imagen por Resonancia Magnética , Algoritmos , Planificación de la Radioterapia Asistida por Computador/métodos , Dosificación Radioterapéutica
6.
Persoonia ; 49: 261-350, 2022 Dec 20.
Artículo en Inglés | MEDLINE | ID: mdl-38234383

RESUMEN

Novel species of fungi described in this study include those from various countries as follows: Argentina, Colletotrichum araujiae on leaves, stems and fruits of Araujia hortorum. Australia, Agaricus pateritonsus on soil, Curvularia fraserae on dying leaf of Bothriochloa insculpta, Curvularia millisiae from yellowing leaf tips of Cyperus aromaticus, Marasmius brunneolorobustus on well-rotted wood, Nigrospora cooperae from necrotic leaf of Heteropogon contortus, Penicillium tealii from the body of a dead spider, Pseudocercospora robertsiorum from leaf spots of Senna tora, Talaromyces atkinsoniae from gills of Marasmius crinis-equi and Zasmidium pearceae from leaf spots of Smilaxglyciphylla. Brazil, Preussia bezerrensis from air. Chile, Paraconiothyrium kelleni from the rhizosphere of Fragaria chiloensis subsp. chiloensis f. chiloensis. Finland, Inocybe udicola on soil in mixed forest with Betula pendula, Populus tremula, Picea abies and Alnus incana. France, Myrmecridium normannianum on dead culm of unidentified Poaceae. Germany, Vexillomyces fraxinicola from symptomless stem wood of Fraxinus excelsior. India, Diaporthe limoniae on infected fruit of Limonia acidissima, Didymella naikii on leaves of Cajanus cajan, and Fulvifomes mangroviensis on basal trunk of Aegiceras corniculatum. Indonesia, Penicillium ezekielii from Zea mays kernels. Namibia, Neocamarosporium calicoremae and Neocladosporium calicoremae on stems of Calicorema capitata, and Pleiochaeta adenolobi on symptomatic leaves of Adenolobus pechuelii. Netherlands, Chalara pteridii on stems of Pteridium aquilinum, Neomackenziella juncicola (incl. Neomackenziella gen. nov.) and Sporidesmiella junci from dead culms of Juncus effusus. Pakistan, Inocybe longistipitata on soil in a Quercus forest. Poland, Phytophthora viadrina from rhizosphere soil of Quercus robur, and Septoria krystynae on leaf spots of Viscum album. Portugal (Azores), Acrogenospora stellata on dead wood or bark. South Africa, Phyllactinia greyiae on leaves of Greyia sutherlandii and Punctelia anae on bark of Vachellia karroo. Spain, Anteaglonium lusitanicum on decaying wood of Prunus lusitanica subsp. lusitanica, Hawksworthiomyces riparius from fluvial sediments, Lophiostoma carabassense endophytic in roots of Limbarda crithmoides, and Tuber mohedanoi from calcareus soils. Spain (Canary Islands), Mycena laurisilvae on stumps and woody debris. Sweden, Elaphomyces geminus from soil under Quercus robur. Thailand, Lactifluus chiangraiensis on soil under Pinus merkusii, Lactifluus nakhonphanomensis and Xerocomus sisongkhramensis on soil under Dipterocarpus trees. Ukraine, Valsonectria robiniae on dead twigs of Robinia hispida. USA, Spiralomyces americanus (incl. Spiralomyces gen. nov.) from office air. Morphological and culture characteristics are supported by DNA barcodes. Citation: Tan YP, Bishop-Hurley SL, Shivas RG, et al. 2022. Fungal Planet description sheets: 1436-1477. Persoonia 49: 261-350. https://doi.org/10.3767/persoonia.2022.49.08.

7.
Sci Rep ; 9(1): 15858, 2019 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-31676810

RESUMEN

Stroke is one of the main causes of human disabilities. Experimental observations indicate that several mechanisms are activated during the recovery of functional activity after a stroke. Here we unveil how the brain recovers by explaining the role played by three mechanisms: Plastic adaptation, hyperexcitability and synaptogenesis. We consider two different damages in a neural network: A diffuse damage that simply causes the reduction of the effective system size and a localized damage, a stroke, that strongly alters the spontaneous activity of the system. Recovery mechanisms observed experimentally are implemented both separately and in a combined way. Interestingly, each mechanism contributes to the recovery to a limited extent. Only the combined application of all three together is able to recover the spontaneous activity of the undamaged system. This explains why the brain triggers independent mechanisms, whose cooperation is the fundamental ingredient for the system's recovery.


Asunto(s)
Lesiones Encefálicas/fisiopatología , Encéfalo/fisiopatología , Modelos Neurológicos , Plasticidad Neuronal , Recuperación de la Función , Accidente Cerebrovascular/fisiopatología , Humanos
8.
Ultramicroscopy ; 207: 112844, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31542566

RESUMEN

In specimens with an inhomogeneous displacement field in electron beam direction dynamical diffraction effects lead to complex non-linear properties of the diffracted electron wave. Consequently, the diffracted beam's phase contains information about the inhomogeneous displacement field. These phases are experimentally and theoretically investigated under different excitation errors and specimen thicknesses as well as for different depths of the displacement field. An inclined InGaAs layer with a larger lattice constant than the surrounding GaAs matrix serves as controlled displacement field, which is inhomogeneous in electron beam direction with a continuously changing depth. The phase and amplitude of the diffracted beam are measured by dark-field electron holography. The measurements agree with calculations performed by numerical propagation of the electron wave using the Darwin-Howie-Whelan equations. A strong dependency on the excitation conditions is found showing that the interplay between dynamical effects and the strain field must be considered in the interpretation of the geometric phase.

9.
Andrology ; 7(4): 498-506, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-30903744

RESUMEN

BACKGROUND: Type II testicular germ cell tumors (GCTs) arise from a common precursor lesion (germ cell neoplasia in situ) and are stratified into seminomas and non-seminomas, which differ considerably in morphology, gene expression, and epigenetic landscape. The N6-methyladenosine (6mA) epigenetic modification is the most abundant modification in mRNA and is also detectable in eukaryotic DNA. The functional role of 6mA is not fully understood, but 6mA residues may influence transcription by affecting splicing, miRNA processing, and mRNA stability. Additionally, the methyl group of 6mA destabilizes Watson-Crick base-pairing affecting RNA structure and protein binding. OBJECTIVES: Here, we analyzed the presence of the 6mA epigenetic modification in germ cells and GCT tissues and cell lines. MATERIALS AND METHODS: We screened for the presence of 6mA in DNA and RNA by immunohistochemistry, mass spectrometry or ELISA-based quantification assays. Additionally, expression of 6mA writer-, eraser- and reader-factors was analyzed by microarrays, qRT-PCR, western blotting and screening of public databases. RESULTS: We demonstrate that 6mA is detectable in RNA, but not DNA, of GCT cell lines and tissues, fibroblasts, and Sertoli cells as well as germ cells of different developmental stages. Based on expression analyses, our results suggest METTL3, ALKBH5, YTHDC1, YTHDF1, YTHDF2 and HNRNPC as main writers, erasers, and readers of the 6mA modification in GCTs. DISCUSSION: Owing to the lack of 6mA in DNA of GCTs, a functional role in regulating DNA transcription can be excluded. Interestingly, expression levels of 6mA regulators are comparable between tumor and normal tissues/cells, suggesting a similar mechanism of 6mA regulation in RNA. Finally, we demonstrate that 6mA levels in RNA increase upon differentiation of GCT cell lines, suggesting a role of 6mA in cell fate decisions. CONCLUSION: In summary, our data provide the starting point for further experiments deciphering the role of 6mA in the RNA of GCTs.


Asunto(s)
Adenosina/análogos & derivados , Desmetilasa de ARN, Homólogo 5 de AlkB/metabolismo , Metiltransferasas/metabolismo , Neoplasias de Células Germinales y Embrionarias/metabolismo , ARN/metabolismo , Neoplasias Testiculares/metabolismo , Adenosina/metabolismo , Animales , Línea Celular Tumoral , Ribonucleoproteína Heterogénea-Nuclear Grupo C/metabolismo , Humanos , Masculino , Ratones , Proteínas del Tejido Nervioso/metabolismo , Factores de Empalme de ARN/metabolismo , Proteínas de Unión al ARN/metabolismo
10.
Bone Joint Res ; 8(1): 32-40, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30800297

RESUMEN

OBJECTIVES: Platelet-rich plasma (PRP) is being used increasingly often in the clinical setting to treat tendon-related pathologies. Yet the optimal PRP preparations to promote tendon healing in different patient populations are poorly defined. Here, we sought to determine whether increasing the concentration of platelet-derived proteins within a derivative of PRP, platelet lysate (PL), enhances tenocyte proliferation and migration in vitro, and whether the mitogenic properties of PL change with donor age. METHODS: Concentrated PLs from both young (< 50 years) and aged (> 50 years) donors were prepared by exposing pooled PRP to a series of freeze-thaw cycles followed by dilution in plasma, and the levels of several platelet-derived proteins were measured using multiplex immunoassay technology. Human tenocytes were cultured with PLs to simulate a clinically relevant PRP treatment range, and cell growth and migration were assessed using DNA quantitation and gap closure assays, respectively. RESULTS: Platelet-derived protein levels increased alongside higher PL concentrations, and PLs from both age groups improved tenocyte proliferation relative to control conditions. However, PLs from aged donors yielded a dose-response relationship in tenocyte behaviour, with higher PL concentrations resulting in increased tenocyte proliferation and migration. Conversely, no significant differences in tenocyte behaviour were detected when increasing the concentration of PLs from younger donors. CONCLUSION: Higher PL concentrations, when prepared from the PRP of aged but not young donors, were more effective than lower PL concentrations at promoting tenocyte proliferation and migration in vitro.Cite this article: D. R. Berger, C. J. Centeno, N. J. Steinmetz. Platelet lysates from aged donors promote human tenocyte proliferation and migration in a concentration-dependent manner. Bone Joint Res 2019;8:32-40. DOI: 10.1302/2046-3758.81.BJR-2018-0164.R1.

11.
Phys Rev E ; 99(1-1): 010302, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30780306

RESUMEN

Pattern recognition is a fundamental neuronal process which enables a cortical system to interpret visual stimuli. How the brain learns to recognize patterns is, however, an unsolved problem. The frequently employed method of back propagation excels at this task but has been found to be unbiological in many aspects. In this Rapid Communication we achieve pattern recognition tasks in a biologically, fully consistent framework. We consider a neuronal network exhibiting avalanche dynamics, as observed experimentally, and implement negative feedback signals. These are chemical signals, such as dopamine, which mediate synaptic plasticity and sculpt the network to achieve certain tasks. The system is able to distinguish horizontal and vertical lines with high accuracy, as well as to perform well at the more complicated task of handwritten digit recognition. Resulting from the learning mechanism, spatially separate activity regions emerge, as observed in the primary visual cortex using functional magnetic resonance imaging techniques. The results therefore suggest that negative feedback signals offer an explanation for the emergence of distinct activity areas in the visual cortex.

12.
J Small Anim Pract ; 60(1): 27-31, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29998573

RESUMEN

OBJECTIVES: To determine the potency and reproducibility of milbemycin oxime when compounded as an aqueous suspension (20 mg/mL). MATERIALS AND METHODS: Preparation choice reflected current prescribing practices. Samples were acquired by prescription from two national veterinary compounding pharmacies at three time points. Two different storage conditions were evaluated and sampled at four time points from the order date (day 7, 14, 21 and 28). Milbemycin oxime recovery was performed by solid-phase extraction and concentration strength measured via high-performance liquid chromatography. RESULTS: The average concentration on day 7 for Pharmacy A samples was 16.29 mg/mL [confidence interval (CI): 15.66 to 16.92] with a coefficient of variation (CV) = 11%, while for Pharmacy B it was 20.46 mg/mL (CI: 19.83 to 21.08) with CV = 22%. The mean decrease in concentration over 28 days for Pharmacy A was 22% (CI: 9% to 34%) while Pharmacy B was 18% (CI: 2% to 35%). CLINICAL SIGNIFICANCE: The compounded milbemycin oxime suspensions evaluated in this study deviated by more than 10% from their labelled strength in five of the six lots. Clinical efficacy of compounded milbemycin oxime suspensions remains unknown and the use of these products should be discouraged at this time.


Asunto(s)
Composición de Medicamentos/veterinaria , Macrólidos , Administración Oral , Animales , Macrólidos/análisis , Medicamentos bajo Prescripción/análisis , Reproducibilidad de los Resultados
13.
Hernia ; 22(5): 739-741, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-30159771
14.
Int J Colorectal Dis ; 33(6): 709-717, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29541894

RESUMEN

PURPOSE: Proximal and distal colon cancers differ in terms of epidemiology, clinical presentation, and pathologic features. The aim of our study was to evaluate the impact of right-sided (RC), transverse (TC), and left-sided (LC) colon cancer on morbidity rates and oncological outcomes. METHODS: A retrospective analysis of patients with resected colon cancer between 2004 and 2014 was conducted. Cox proportional hazard models were used to assess predictors of overall (OS), and disease-specific survival (DSS), as well as disease-free survival (DFS). RESULTS: A total of 1189 patients were included. RC patients (n = 618) were older, predominantly women, and had a higher comorbidity rate. LC (n = 454) was associated with symptomatic presentation and increased rates of laparoscopic surgery. Multivisceral resections were more frequently performed in TC tumors (n = 117). This group was admitted 1 day longer and had a higher complication rate (RC 35.6% vs. TC 43.6% vs. LC 31.1%, P0.032). Although the incidence of abscess/leak was similar between the groups, the necessity of readmission and subsequent reoperation for a leak was significantly higher in LC patients. Pathology revealed more poorly differentiated tumors and microsatellite instability in RC. Kaplan-Meier curves demonstrated worse 5-year OS for right-sided tumors (RC 73.0%; TC 76.2%. LC 80.8%, P0.023). However, after adjustment, no differences were found in OS, DSS, and DFS between tumor location. Only pathological features were independently correlated with prognosis, as were baseline characteristics for OS. CONCLUSION: Tumor location in colon cancer was not associated with survival or disease recurrence. Pathological differences beyond tumor stage were significantly more important.


Asunto(s)
Neoplasias del Colon/patología , Anciano , Anciano de 80 o más Años , Neoplasias del Colon/cirugía , Comorbilidad , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Modelos de Riesgos Proporcionales , Análisis de Supervivencia , Factores de Tiempo , Resultado del Tratamiento
15.
J Gastrointest Surg ; 22(6): 1052-1058, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29427228

RESUMEN

BACKGROUND: Screening for colorectal cancer has resulted in declining incidence rates of both colon and rectal cancer and it may influence stage at presentation and improve survival. The aim of this study was to assess the impact of screening on patients diagnosed with locally advanced rectal cancer. METHODS: A retrospective analysis of a consecutive series of patients who underwent neoadjuvant therapy and had an R0-resection for clinical AJCC stage II or stage III disease. All patients received surgery at a single center between 2004 and 2015. Patients diagnosed through screening were compared to patients diagnosed through symptomatic presentation. RESULTS: Three hundred nine patients were included, of whom 43 (13.9%) were diagnosed through screening. Screened patients had more often a white ethnicity, while there were no other differences in baseline characteristics or median household income. Screened patients had a lower rate of disease recurrence in addition to a longer disease free survival and overall survival. CONCLUSIONS: Patients with locally advanced rectal cancer diagnosed through screening demonstrated more favorable short and long-term outcomes than patients diagnosed through symptoms. Findings of this study reinforce the need for screening programs in addition to the need for research regarding optimization of screening adherence.


Asunto(s)
Detección Precoz del Cáncer , Recurrencia Local de Neoplasia , Neoplasias del Recto/diagnóstico , Neoplasias del Recto/terapia , Anciano , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Neoplasias del Recto/patología , Estudios Retrospectivos , Tasa de Supervivencia
16.
Leukemia ; 32(4): 1016-1022, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-29249817

RESUMEN

Systemic mastocytosis (SM) is a mast cell (MC) neoplasm with complex pathology and a variable clinical course. In aggressive SM (ASM) and MC leukemia (MCL), responses to conventional drugs are poor and the prognosis is dismal. R763 is a multi-kinase inhibitor that blocks the activity of Aurora-kinase-A/B, ABL1, AKT and FLT3. We examined the effects of R763 on proliferation and survival of neoplastic MC. R763 produced dose-dependent inhibition of proliferation in the human MC lines HMC-1.1 (IC50 5-50 nM), HMC-1.2 (IC50 1-10 nM), ROSAKIT WT (IC50 1-10 nM), ROSAKIT D816V (IC50 50-500 nM) and MCPV-1.1 (IC50 100-1000 nM). Moreover, R763 induced growth inhibition in primary neoplastic MC in patients with ASM and MCL. Growth-inhibitory effects of R763 were accompanied by signs of apoptosis and a G2/M cell cycle arrest. R763 also inhibited phosphorylation of KIT, BTK, AKT and STAT5 in neoplastic MC. The most sensitive target appeared to be STAT5. In fact, tyrosine phosphorylation of STAT5 was inhibited by R763 at 10 nM. At this low concentration, R763 produced synergistic growth-inhibitory effects on neoplastic MC when combined with midostaurin or dasatinib. Together, R763 is a novel promising multi-kinase inhibitor that blocks STAT5 activation and thereby overrides drug-resistance in neoplastic MC.


Asunto(s)
Resistencia a Antineoplásicos/efectos de los fármacos , Mastocitos/efectos de los fármacos , Fosforilación/efectos de los fármacos , Factor de Transcripción STAT5/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Animales , Apoptosis/efectos de los fármacos , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Dasatinib/farmacología , Perros , Sinergismo Farmacológico , Femenino , Puntos de Control de la Fase G2 del Ciclo Celular/efectos de los fármacos , Humanos , Leucemia de Mastocitos/tratamiento farmacológico , Leucemia de Mastocitos/metabolismo , Masculino , Mastocitos/metabolismo , Mastocitosis Sistémica/tratamiento farmacológico , Mastocitosis Sistémica/metabolismo , Persona de Mediana Edad , Norbornanos/farmacología , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Proto-Oncogénicas c-kit/metabolismo , Pirimidinas/farmacología , Estaurosporina/análogos & derivados , Estaurosporina/farmacología , Adulto Joven
17.
Am J Surg ; 216(1): 93-98, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-29174165

RESUMEN

BACKGROUND: Neo-adjuvant chemoradiation followed by surgery and adjuvant therapy is standard treatment of clinical node positive rectal cancer. Understaging leads to delay in treatment with possible detrimental results. This study analyses effects of understaging stage III rectal cancer on long-term outcomes. METHODS: A consecutive series of patients, operated on in MGH between 2004 and 2015 was included. Outcomes of non-neoadjuvantly treated clinical stage I patients who turned out to have pathological stage III disease and neoadjuvantly treated clinical stage III patients were retrospectively reviewed. The latter group was subdivided into patients who had persistent nodal disease (ypN+) and patients without positive lymph nodes after neoadjuvant treatment (ypN0). RESULTS: Of the 204 included patients, 30 had unexpected nodal disease on pathology. Clinical stage I-patients had higher rates of local recurrence, and rectal cancer and overall mortality than ypN0-patients. CONCLUSION: Understaging stage III rectal cancer led to poorer oncologic outcomes, when compared to patients without positive lymph nodes on pathology after neoadjuvant. Future research should focus on identifying patients with treatment susceptible lymph node involvement.


Asunto(s)
Adenocarcinoma/diagnóstico , Estadificación de Neoplasias/métodos , Educación del Paciente como Asunto , Neoplasias del Recto/diagnóstico , Adenocarcinoma/terapia , Adulto , Anciano , Terapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias del Recto/terapia , Estudios Retrospectivos , Resultado del Tratamiento
18.
Hernia ; 22(1): 183-198, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-29134456

RESUMEN

BACKGROUND: International guidelines on the prevention and treatment of parastomal hernias are lacking. The European Hernia Society therefore implemented a Clinical Practice Guideline development project. METHODS: The guidelines development group consisted of general, hernia and colorectal surgeons, a biostatistician and a biologist, from 14 European countries. These guidelines conformed to the AGREE II standards and the GRADE methodology. The databases of MEDLINE, CINAHL, CENTRAL and the gray literature through OpenGrey were searched. Quality assessment was performed using Scottish Intercollegiate Guidelines Network checklists. The guidelines were presented at the 38th European Hernia Society Congress and each key question was evaluated in a consensus voting of congress participants. RESULTS: End colostomy is associated with a higher incidence of parastomal hernia, compared to other types of stomas. Clinical examination is necessary for the diagnosis of parastomal hernia, whereas computed tomography scan or ultrasonography may be performed in cases of diagnostic uncertainty. Currently available classifications are not validated; however, we suggest the use of the European Hernia Society classification for uniform research reporting. There is insufficient evidence on the policy of watchful waiting, the route and location of stoma construction, and the size of the aperture. The use of a prophylactic synthetic non-absorbable mesh upon construction of an end colostomy is strongly recommended. No such recommendation can be made for other types of stomas at present. It is strongly recommended to avoid performing a suture repair for elective parastomal hernia. So far, there is no sufficient comparative evidence on specific techniques, open or laparoscopic surgery and specific mesh types. However, a mesh without a hole is suggested in preference to a keyhole mesh when laparoscopic repair is performed. CONCLUSION: An evidence-based approach to the diagnosis and management of parastomal hernias reveals the lack of evidence on several topics, which need to be addressed by multicenter trials. Parastomal hernia prevention using a prophylactic mesh for end colostomies reduces parastomal herniation. Clinical outcomes should be audited and adverse events must be reported.


Asunto(s)
Hernia Ventral/terapia , Herniorrafia/métodos , Estomía/efectos adversos , Estomas Quirúrgicos/efectos adversos , Hernia Ventral/diagnóstico , Hernia Ventral/etiología , Humanos , Laparoscopía , Mallas Quirúrgicas
19.
Br J Anaesth ; 119(4): 595-605, 2017 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-29121289

RESUMEN

BACKGROUND: We hypothesised that intraoperative non-depolarising neuromuscular blocking agent (NMBA) dose is associated with 30-day hospital readmission. METHODS: Data from 13,122 adult patients who underwent abdominal surgery under general anaesthesia at a tertiary care hospital were analysed by multivariable regression, to examine the effects of intraoperatively administered NMBA dose on 30-day readmission (primary endpoint), hospital length of stay, and hospital costs. RESULTS: Clinicians used cisatracurium (mean dose [SD] 0.19 mg kg-1 [0.12]), rocuronium (0.83 mg kg-1 [0.53]) and vecuronium (0.14 mg kg-1 [0.07]). Intraoperative administration of NMBAs was dose-dependently associated with higher risk of 30-day hospital readmission (adjusted odds ratio 1.89 [95% Confidence Interval (CI) 1.26-2.84] for 5th quintile vs 1st quintile; P for trend: P<0.001), prolonged hospital length of stay (adjusted incidence rate ratio [aIRR] 1.20 [95% CI 1.11-1.29]; P for trend: P<0.001) and increased hospital costs (aIRR 1.18 [95% CI 1.13-1.24]; P for trend: P<0.001). Admission type (same-day vs inpatient surgery) significantly modified the risk (interaction term: aOR 1.31 [95% CI 1.05-1.63], P=0.02), and the adjusted odds of readmission in patients undergoing ambulatory surgical procedures who received high-dose NMBAs vs low-dose NMBAs amounted to 2.61 [95% CI 1.11-6.17], P for trend: P<0.001. Total intraoperative neostigmine dose increased the risk of 30-day readmission (aOR 1.04 [1.0-1.08], P=0.048). CONCLUSIONS: In a retrospective analysis, high doses of NMBAs given during abdominal surgery was associated with an increased risk of 30-day readmission, particularly in patients undergoing ambulatory surgery.


Asunto(s)
Abdomen/cirugía , Cuidados Intraoperatorios/métodos , Bloqueo Neuromuscular/efectos adversos , Bloqueantes Neuromusculares/efectos adversos , Readmisión del Paciente/estadística & datos numéricos , Complicaciones Posoperatorias/epidemiología , Adulto , Anciano , Procedimientos Quirúrgicos Ambulatorios , Boston/epidemiología , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
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