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1.
J Phys Chem A ; 128(10): 1958-1971, 2024 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-38427974

RESUMEN

We assess the capability of machine-learned potentials to compute rate coefficients by training a neural network (NN) model and applying it to describe the chemical landscape on the C5H5 potential energy surface, which is relevant to molecular weight growth in combustion and interstellar media. We coupled the resulting NN with an automated kinetics workflow code, KinBot, to perform all necessary calculations to compute the rate coefficients. The NN is benchmarked exhaustively by evaluating its performance at the various stages of the kinetics calculations: from the electronic energy through the computation of zero point energy, barrier heights, entropic contributions, the portion of the PES explored, and finally the overall rate coefficients as formulated by transition state theory.

2.
Ann Med Surg (Lond) ; 85(8): 3816-3826, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37554920

RESUMEN

This study aimed to examine the differences in epidemiologic and disease aspects among patients with coronavirus disease-19 (COVID-19). Methods: The authors reviewed the hospital records between April 2020 and September 2021 and followed up on the patients for post-COVID complications. Findings: Older adult patients were predominantly affected during the third wave, and middle-aged patients were predominantly affected during the first and second waves. Men were predominantly admitted, considering the three waves, although more women were admitted in the second wave. Cough was more common in the second and third waves than in the first wave 522 (59.7%). Respiratory distress was the most common in the third wave, 251(67.1%), and least common in the first wave, 403 (46.1%). Anosmia was more common in the third wave 116 (31.2%). In the third wave, patients presenting in a critical state 23 (6.2%) and with severe disease 152 (40.8%) were more common. The hospital admission median (IQR) was longer in the first wave, 12 (8-20), than in other waves. More patients were admitted in the first wave (52%) than in the other waves, and patients received more oxygen in the third wave (75%) than in the other waves. Death occurred more commonly in the first wave (51%) than in the other waves. The positivity rate was higher in the third wave (22.8%) than in the other waves. In the third wave, the positivity rate was higher in women (24.3%) than in men. Post-COVID cough increased in the second wave, and fatigue was higher in the third wave than in the other waves. Tiredness and memory loss were greater during the second wave than in other waves. Conclusion: The authors found differences in the presentation, outcomes, and hospital epidemiologic trend of COVID-19 among the three waves.

3.
J Chem Inf Model ; 63(16): 5153-5168, 2023 08 28.
Artículo en Inglés | MEDLINE | ID: mdl-37559203

RESUMEN

Many important industrial processes rely on heterogeneous catalytic systems. However, given all possible catalysts and conditions of interest, it is impractical to optimize most systems experimentally. Automatically generated microkinetic models can be used to efficiently consider many catalysts and conditions. However, these microkinetic models require accurate estimation of many thermochemical and kinetic parameters. Manually calculating these parameters is tedious and error prone, involving many interconnected computations. We present Pynta, a workflow software for automating the calculation of surface and gas-surface reactions. Pynta takes the reactants, products, and atom maps for the reactions of interest, generates sets of initial guesses for all species and saddle points, runs all optimizations, frequency, and IRC calculations, and computes the associated thermochemistry and rate coefficients. It is able to consider all unique adsorption configurations for both adsorbates and saddle points, allowing it to handle high index surfaces and bidentate species. Pynta implements a new saddle point guess generation method called harmonically forced saddle point searching (HFSP). HFSP defines harmonic potentials based on the optimized adsorbate geometries and which bonds are breaking and forming that allow initial placements to be optimized using the GFN1-xTB semiempirical method to create reliable saddle point guesses. This method is reaction class agnostic and fast, allowing Pynta to consider all possible adsorbate site placements efficiently. We demonstrate Pynta on 11 diverse reactions involving monodenate, bidentate, and gas-phase species, many distinct reaction classes, and both a low and a high index facet of Cu. Our results suggest that it is very important to consider reactions between adsorbates adsorbed in all unique configurations for interadsorbate group transfers and reactions on high index surfaces.


Asunto(s)
Física , Cinética , Flujo de Trabajo
4.
J Phys Chem A ; 127(3): 565-588, 2023 Jan 26.
Artículo en Inglés | MEDLINE | ID: mdl-36607817

RESUMEN

Automation of rate-coefficient calculations for gas-phase organic species became possible in recent years and has transformed how we explore these complicated systems computationally. Kinetics workflow tools bring rigor and speed and eliminate a large fraction of manual labor and related error sources. In this paper we give an overview of this quickly evolving field and illustrate, through five detailed examples, the capabilities of our own automated tool, KinBot. We bring examples from combustion and atmospheric chemistry of C-, H-, O-, and N-atom-containing species that are relevant to molecular weight growth and autoxidation processes. The examples shed light on the capabilities of automation and also highlight particular challenges associated with the various chemical systems that need to be addressed in future work.

5.
Facts Views Vis Obgyn ; 13(1): 3-7, 2021 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-33889855

RESUMEN

The preoperative work-up and optimal surgical approach to colorectal endometriosis is a highly studied topic lacking definitive recommendations. Synthesis of the available data can be extremely challenging for surgeons due to the heterogeneity of existing comparisons, a variety of studied surgical outcomes, and a predominant focus on operative complications. While these considerations are extremely important for surgeons performing such complex gynaecologic surgery there is still much to be desired with regards to evidence based guidelines for the preoperative assessment and surgical technique for colorectal endometriosis. Having an established guideline stating in which clinical situations endometriosis surgeons should performing rectovaginal shaving, versus discoid excision, versus segmental resection would be extremely important for all pelvic surgeons, even those operating in high-volume centres dedicated to the surgical management of complex endometriosis. This perspective highlights the shortcomings of the available data and attempts to create an algorithm surgeons can follow when performing surgery for colorectal endometriosis. This algorithm is based on our expert opinion after synthesising available data.

6.
Braz. j. biol ; Braz. j. biol;81(1): 83-91, Feb. 2021. tab, graf
Artículo en Inglés | LILACS | ID: biblio-1153327

RESUMEN

Abstract Current study assessed the impact of Lantana camara invasion on native plant diversity in Pothohar region of Pakistan. The approach used for study was random samplings and comparisons of diversity indices [number of species (S), abundance (N), species richness (R), evenness (Jꞌ), Shannon diversity index (Hꞌ) and Simpson index of dominance (λ)] with two categorical factors i.e., invaded and non-invaded (control). Control plots harboured by an average of 1.74 more species/10m2. The control category was diverse (Hꞌ=2.56) than invaded category (Hꞌ=1.56). The higher value of species richness in control plots shows heterogeneous nature of communities and vice versa in invaded plots. At multivariate scale, ordination (nMDS) and ANOSIM showed significant magnitude of differences between invaded and control plots at all sites. The decrease in studied diversity indices in invaded over control sites indicated that plant communities become less productive due to Lantana invasion.


Resumo O presente estudo avaliou o impacto da invasão de Lantana camara na diversidade de plantas nativas na região de Pothohar, no Paquistão. A abordagem utilizada para o estudo foram a amostragem aleatória e a comparação de índices de diversidade, como número de espécies (S), abundância (N), riqueza de espécies (R), equitabilidade (Jꞌ), índice de diversidade de Shannon (Hꞌ) e índice de dominância de Simpson (λ), com dois fatores categóricos, ou seja, invadidos e não invadidos (controle). As parcelas não invadidas tinham, em média, 1,74 espécie a mais / 10 m2 que parcelas invadidas. A categoria controle foi mais diversa (Hꞌ = 2,56) do que a categoria invadida (Hꞌ = 1,56). O maior valor da riqueza de espécies em parcelas de controle mostra a natureza heterogênea das comunidades, e vice-versa, em parcelas invadidas. Na escala multivariada, ordenação (nMDS) e ANOSIM mostraram magnitude significativa das diferenças entre as parcelas invadidas e controle em todos os locais. A diminuição nos índices de diversidade estudados em locais invadidos por controle indicou que as comunidades de plantas se tornam menos produtivas por causa da invasão de Lantana.


Asunto(s)
Lantana , Pakistán , Plantas
7.
J Cancer Res Clin Oncol ; 146(11): 2897-2911, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32748119

RESUMEN

Advances in surgery, peri-operative care and systemic chemotherapy have not significantly improved the prognosis of pancreatic cancer for several decades. Early clinical trials of immunotherapy have yielded disappointing results proposing other means by which the tumour microenvironment serves to decrease the immune response. Additionally, the emergence of various subtypes of pancreatic cancer has emerged as a factor for treatment responses with immunogenic subtypes carrying a better prognosis. Herein we discuss the reasons for the poor response to checkpoint inhibitors and outline a rationale why combination treatments are likely to be most effective. We review the therapies which could provide optimal synergistic effects to immunotherapy including chemotherapy, agents targeting the stroma, co-stimulatory molecules, vaccinations and methods of immunogenic tumour priming including radiofrequency ablation. Finally, we discuss reasons why peri-operative and in particular neoadjuvant combination treatments are likely to be most effective and should be considered for early clinical trials.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma Ductal Pancreático/terapia , Terapia Combinada/métodos , Inmunoterapia/métodos , Neoplasias Pancreáticas/terapia , Animales , Humanos
8.
J Cancer ; 9(4): 629-637, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29556320

RESUMEN

Background: Malignant biliary and/or pancreatic obstruction has often encountered in the advanced stages of periampullary and cholangicarcinomas. HabibTM Radiofrequency (RF) ablation has been successfully used in the management of various cancers of liver and pancreas. Percutaneous HPB probe (EMcision Ltd, London, UK) is a new addition to this class of tools. It is an endoluminal Radiofrequency (RF) catheter which works on the principle of ablation and induces coagulative necrosis to recanalize the obstructed duct. The aim of this study is to address the technical details of canalization, feasibilities and outcomes of percutaneous endo-luminal Radiofrequency (RF) catheter in patients with unresectable malignancy with obstructed bile and pancreatic duct (PD). Material and Method: A total of 134 patients with inoperable malignant obstruction of biliary and PD underwent RF based percutaneous endoluminal RF ablation in a tertiary referral centre between December 15th, 2010 to August 7th, 2015. This device was used in a sequential manner with an intent to recanalize the obstructed. Following the initial catheter drainage of the duct, subsequent percutaneous endobiliary RF ablation, the metallic stent was placed to recanalize the obstructed bile and PD secondary to unresectable malignancy under real-time fluoroscopic guidance. Results: The percutaneous RF based ablation of obstructed bile duct and PD with metallic stent placement was successfully achieved in 130 (97.01%) cases. The three failures were noted in cases of biliary obstruction whilst, one with PD obstruction. The patency restored in 124 and patients, where the procedure was successfully completed and revealed clinical improvement reported. Conclusion: The percutaneous endoluminal RF based ablation of obstructed duct with metallic stent placement appeared to be a safe, effective procedure and may improve survival in patients with advanced stage cancer presenting with biliary and PD obstruction. Considering the above mentioned evidence, this modality may stand ahead of stenting alone. This could be considered as viable modality in management of such patients where very limited treatment options are available.

9.
J Healthc Eng ; 2017: 4574172, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-29065604

RESUMEN

INTRODUCTION: The development augmented reality devices allow physicians to incorporate data visualization into diagnostic and treatment procedures to improve work efficiency, safety, and cost and to enhance surgical training. However, the awareness of possibilities of augmented reality is generally low. This review evaluates whether augmented reality can presently improve the results of surgical procedures. METHODS: We performed a review of available literature dating from 2010 to November 2016 by searching PubMed and Scopus using the terms "augmented reality" and "surgery." Results. The initial search yielded 808 studies. After removing duplicates and including only journal articles, a total of 417 studies were identified. By reading of abstracts, 91 relevant studies were chosen to be included. 11 references were gathered by cross-referencing. A total of 102 studies were included in this review. CONCLUSIONS: The present literature suggest an increasing interest of surgeons regarding employing augmented reality into surgery leading to improved safety and efficacy of surgical procedures. Many studies showed that the performance of newly devised augmented reality systems is comparable to traditional techniques. However, several problems need to be addressed before augmented reality is implemented into the routine practice.


Asunto(s)
Competencia Clínica , Enseñanza Mediante Simulación de Alta Fidelidad , Laparoscopía/educación , Cirugía Asistida por Computador/educación , Realidad Virtual , Humanos , Imagenología Tridimensional
10.
Cardiovasc Intervent Radiol ; 40(12): 1911-1920, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-28681224

RESUMEN

PURPOSE: The aim of this study is to provide a technical detail and feasibility of percutaneous image-guided pancreatic duct (PD) drainage and to discuss its subtleties in a series of patients with obstructed PD. MATERIALS AND METHODS: Thirty patients presenting with PD obstruction from pancreatic head tumour or pancreatitis were subjected to percutaneous image-guided PD drainage under a guidance of ultrasound or computed tomography. Following the successful puncture of PD, a locking loop drainage catheter was placed using conventional guidewire techniques under real-time fluoroscopy guidance. RESULTS: The percutaneous drainage of obstructed PD was completed in 29 (96.7%) patients as an independent therapeutic intent or as a bridge to further percutaneous procedures. Clinical improvement following drainage was documented by the gradual reduction in clinical symptoms, including pain, nausea and fever and improved blood test results, showing the significant decrease of amylase concentration. The amount of pancreatic fluid drained post procedure was between 300 and 900 mL/day. No major procedure-related complications were observed. Subsequently, 14 of 29 patients underwent further procedures, including endoluminal placement of metal stent with or without radiofrequency ablation, balloon assisted percutaneous descending litholapaxy (BAPDL), endoluminal biopsy and balloon dilatation using the same drainage tract. CONCLUSION: The percutaneous PD drainage appears to be a safe and effective procedure. It should be considered in patients with obstructed PD secondary to malignancy, pancreatitis etc., where endoscopic retrograde cannulation has been failed or impracticable. The procedure can also be contemplated either as an independent treatment option or as an initial step for the subsequent therapeutic endoluminal procedures.


Asunto(s)
Drenaje/métodos , Enfermedades Pancreáticas/diagnóstico por imagen , Enfermedades Pancreáticas/terapia , Conductos Pancreáticos/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Ultrasonografía Intervencional/métodos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas , Estudios Prospectivos , Radiografía Intervencional/métodos , Resultado del Tratamiento
11.
Oncogene ; 36(36): 5189-5198, 2017 09 07.
Artículo en Inglés | MEDLINE | ID: mdl-28481870

RESUMEN

TGF-ß is a multifunctional cytokine affecting many cell types and implicated in tissue remodeling processes. Due to its many functions and cell-specific effects, the consequences of TGF-ß signaling are process-and stage-dependent, and it is not uncommon that TGF-ß exerts distinct and sometimes opposing effects on a disease progression depending on the stage and on the pathological changes associated with the stage. The mechanisms underlying cell- and process-specific effects of TGF-ß are poorly understood. We are describing a novel pathway that mediates induction of angiogenesis in response to TGF-ß1. We found that in endothelial cells (EC) thrombospondin-4 (TSP-4), a secreted extracellular matrix (ECM) protein, is upregulated in response to TGF-ß1 and mediates the effects of TGF-ß1 on angiogenesis. Upregulation of TSP-4 does not require the synthesis of new protein, is not caused by decreased secretion of TSP-4, and is mediated by activation of SMAD3. Using Thbs4-/- mice and TSP-4 shRNA, we found that TSP-4 mediated pro-angiogenic functions in cultured EC and angiogenesis in vivo in response to TGF-ß1. We observed~3-fold increases in tumor mass and levels of angiogenesis markers in animals injected with TGF-ß1, and these effects did not occur in Thbs4-/- animals. Injections of an inhibitor of TGF-ß1 signaling SB-431542 also decreased the weights of tumors and cancer angiogenesis. Our results from in vivo angiogenesis models and cultured EC document that TSP-4 mediates upregulation of angiogenesis by TGF-ß1. Upregulation of pro-angiogenic TSP-4 and selective effects of TSP-4 on EC may contribute to stimulation of tumor growth by TGF-ß despite the inhibition of cancer cell proliferation.


Asunto(s)
Inductores de la Angiogénesis/metabolismo , Endotelio Vascular/patología , Músculo Liso Vascular/patología , Neovascularización Patológica/patología , Trombospondinas/fisiología , Factor de Crecimiento Transformador beta/farmacología , Animales , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Embrión de Pollo , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/metabolismo , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Músculo Liso Vascular/efectos de los fármacos , Músculo Liso Vascular/metabolismo , Neovascularización Patológica/tratamiento farmacológico , Neovascularización Patológica/metabolismo , Transducción de Señal/efectos de los fármacos
12.
Braz. j. biol ; Braz. j. biol;2017.
Artículo en Inglés | LILACS-Express | LILACS, VETINDEX | ID: biblio-1467404

RESUMEN

Abstract Current study assessed the impact of Lantana camara invasion on native plant diversity in Pothohar region of Pakistan. The approach used for study was random samplings and comparisons of diversity indices [number of species (S), abundance (N), species richness (R), evenness (J), Shannon diversity index (H) and Simpson index of dominance ()] with two categorical factors i.e., invaded and non-invaded (control). Control plots harboured by an average of 1.74 more species/10m2. The control category was diverse (H=2.56) than invaded category (H=1.56). The higher value of species richness in control plots shows heterogeneous nature of communities and vice versa in invaded plots. At multivariate scale, ordination (nMDS) and ANOSIM showed significant magnitude of differences between invaded and control plots at all sites. The decrease in studied diversity indices in invaded over control sites indicated that plant communities become less productive due to Lantana invasion.


Resumo O presente estudo avaliou o impacto da invasão de Lantana camara na diversidade de plantas nativas na região de Pothohar, no Paquistão. A abordagem utilizada para o estudo foram a amostragem aleatória e a comparação de índices de diversidade, como número de espécies (S), abundância (N), riqueza de espécies (R), equitabilidade (J), índice de diversidade de Shannon (H) e índice de dominância de Simpson (), com dois fatores categóricos, ou seja, invadidos e não invadidos (controle). As parcelas não invadidas tinham, em média, 1,74 espécie a mais / 10 m2 que parcelas invadidas. A categoria controle foi mais diversa (H = 2,56) do que a categoria invadida (H = 1,56). O maior valor da riqueza de espécies em parcelas de controle mostra a natureza heterogênea das comunidades, e vice-versa, em parcelas invadidas. Na escala multivariada, ordenação (nMDS) e ANOSIM mostraram magnitude significativa das diferenças entre as parcelas invadidas e controle em todos os locais. A diminuição nos índices de diversidade estudados em locais invadidos por controle indicou que as comunidades de plantas se tornam menos produtivas por causa da invasão de Lantana.

13.
Br J Surg ; 103(4): 328-36, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26791838

RESUMEN

BACKGROUND: Drain amylase content in the days immediately after major pancreatic resection has been investigated previously as a predictor of postoperative pancreatic fistula (POPF). Its accuracy, however, has not been determined conclusively. The purpose of this study was to evaluate the accuracy of drain amylase content on the first day after major pancreatic resection in predicting the occurrence of POPF. METHODS: A literature search of the MEDLINE, Embase and Scopus(®) databases to 13 May 2015 was performed to identify studies evaluating the accuracy of drain amylase values on day 1 after surgery in predicting the occurrence of POPF. The area under the hierarchical summary receiver operating characteristic (ROC) curve (AUChSROC ) was calculated as an index of accuracy, and pooled estimates of accuracy indices (sensitivity and specificity) were calculated at different cut-off levels. Subgroup and meta-regression analyses were performed to test the robustness of the results. RESULTS: Thirteen studies involving 4416 patients were included. The AUChSROC was 0·89 (95 per cent c.i. 0·86 to 0·92) for clinically significant POPF and 0·88 (0·85 to 0·90) for POPF of any grade. Pooled estimates of sensitivity and specificity were calculated for the different cut-offs: 90-100 units/l (0·96 and 0·54 respectively), 350 units/l (0·91 and 0·84) and 5000 units/l (0·59 and 0·91). Accuracy was independent of the type of operation, type of anastomosis performed and octreotide administration. CONCLUSION: Evaluation of drain amylase content on the first day after surgery is highly accurate in predicting POPF following major pancreatic resection. It may allow early drain removal and institution of an enhanced recovery pathway.


Asunto(s)
Pancreatectomía/efectos adversos , Fístula Pancreática , alfa-Amilasas Pancreáticas/metabolismo , Complicaciones Posoperatorias/diagnóstico , Salud Global , Humanos , Incidencia , Fístula Pancreática/enzimología , Fístula Pancreática/epidemiología , Fístula Pancreática/etiología , Complicaciones Posoperatorias/enzimología , Valor Predictivo de las Pruebas
14.
Appl Radiat Isot ; 107: 98-102, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26474209

RESUMEN

Filtered neutron techniques were applied to produce quasi-mono-energetic neutron beams in the energy range of 1.5-7.5 keV at the accelerator port using the generated neutron spectrum from a Li (p, n) Be reaction. A simulation study was performed to characterize the filter components and transmitted beam lines. The feature of the filtered beams is detailed in terms of optimal thickness of the primary and additive components. A computer code named "QMNB-AS" was developed to carry out the required calculations. The filtered neutron beams had high purity and intensity with low contamination from the accompanying thermal, fast neutrons and γ-rays.


Asunto(s)
Terapia por Captura de Neutrón de Boro/métodos , Terapia por Captura de Neutrón de Boro/instrumentación , Terapia por Captura de Neutrón de Boro/estadística & datos numéricos , Simulación por Computador , Neutrones Rápidos/uso terapéutico , Filtración , Rayos gamma , Humanos , Modelos Teóricos , Neoplasias/radioterapia
16.
Technol Cancer Res Treat ; 14(5): 573-82, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24945372

RESUMEN

The incidence of colorectal carcinoma is still growing in the Czech Republic and also all around the world. With success of oncological treatment is also growing a number of potential patients with liver metastases, who can profit from surgical therapy. The aim of this study was to confirm on porcine models that this method by using new surgical device is effective and safe for patients who have to undergo liver resection. The primary hypothesis of the study was to evaluate whether this new device is able to consistently produce homogeneous and predictable areas of coagulation necrosis without the Pringle maneuver of vascular inflow occlusion. The secondary hypothesis of the study was to compare the standard linear radiofrequency device and a new semi-spherical bipolar device for liver ablation and resection in a hepatic porcine model. Twelve pigs were randomly divided into two groups. Each pig underwent liver resection from both liver lobes in the marginal, thinner part of liver parenchyma. The pigs in first group were operated with standard using device and in the second group we used new developed semi-spherical device. We followed blood count in 0(th), 14(th) and 30(th) day from operation. 14(th) day from resection pigs underwent diagnostic laparoscopy to evaluate of their state, and 30(th) day after operation were all pigs euthanized and subjected to histopathological examination. Histopathological evaluation of thermal changes at the resection margin showed strong thermal alteration in both groups. Statistical analysis of collected dates did not prove any significant (p < 0.05) differences between standard using device and our new surgical tool. We proved safety of new designed semi-spherical surgical. This device can offer the possibility of shortening the ablation time and operating time, which is benefit for patients undergoing the liver resection.


Asunto(s)
Ablación por Catéter/métodos , Neoplasias Colorrectales/radioterapia , Hepatectomía/métodos , Neoplasias Hepáticas/radioterapia , Animales , Neoplasias Colorrectales/cirugía , República Checa , Modelos Animales de Enfermedad , Femenino , Laparoscopía , Hígado/patología , Hígado/cirugía , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/cirugía , Masculino , Sus scrofa
17.
Colorectal Dis ; 16(6): O197-205, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24344746

RESUMEN

AIM: Up to a quarter of patients with rectal cancer have synchronous liver metastases at the time of diagnosis. This is a predictor of poor outcome. There are no standardized guidelines for treatment. We reviewed the outcomes of our patients with synchronous rectal liver metastases treated with a curative intent by neoadjuvant chemotherapy with or without chemoradiotherapy followed by resection of the primary tumour and then liver metastases. METHOD: Between 2004 and 2012, patients who presented with rectal cancer and synchronous liver metastasis were treated with curative intent with peri-operative systemic chemotherapy as the first line of treatment. Responders to chemotherapy underwent resection of the primary tumour with or without preoperative chemoradiotherapy followed by hepatic resection. RESULTS: Fifty-three rectal cancer patients with 152 synchronous liver lesions were identified. After a median follow-up of 29.6 months, the median survival was 41.4 months. Overall survival was 59.0% at 3 years and 39.0% at 5 years. CONCLUSION: Rectal resection before hepatic resection combined with neoadjuvant chemotherapy is associated with promising clinical outcome. It allows downstaging of liver lesions and removal of the primary tumour before the progression of further micrometastases. Furthermore, patients who do not respond to chemotherapy can be identified and may avoid major surgical intervention.


Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias Hepáticas/terapia , Cuidados Preoperatorios/métodos , Neoplasias del Recto/terapia , Adulto , Anciano , Colectomía , Diagnóstico por Imagen , Femenino , Estudios de Seguimiento , Hepatectomía , Humanos , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante/métodos , Estadificación de Neoplasias , Neoplasias del Recto/diagnóstico , Neoplasias del Recto/secundario , Estudios Retrospectivos , Tasa de Supervivencia/tendencias , Resultado del Tratamiento , Reino Unido/epidemiología
18.
Anaesthesia ; 68(11): 1114-9, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-24006919

RESUMEN

In 2008, the UK National Patient Safety Agency (NPSA) made recommendations for safe arterial line management. Following a patient safety incident in our intensive care unit (ICU), we surveyed current practice in arterial line management and determined whether these recommendations had been adopted. We contacted all 241 adult ICUs in the UK; 228 (94.6%) completed the survey. Some NPSA recommendations have been widely implemented - use of sodium chloride 0.9% as flush fluid, two-person checking of fluids before use - and their practice was consistent. Others have been incompletely implemented and many areas of practice (prescription of fluids, two-person checking at shift changes, use of opaque pressure bags, arterial sampling technique) were highly variable. More importantly, the use of the wrong fluid as an arterial flush was reported by 30% of respondents for ICU practice, and a further 30% for practice elsewhere in the hospital. Our survey provides evidence of continuing risk to patients.


Asunto(s)
Recolección de Muestras de Sangre/métodos , Recolección de Muestras de Sangre/normas , Cuidados Críticos/normas , Encuestas de Atención de la Salud/métodos , Seguridad del Paciente/estadística & datos numéricos , Dispositivos de Acceso Vascular/normas , Adulto , Recolección de Muestras de Sangre/estadística & datos numéricos , Cuidados Críticos/métodos , Cuidados Críticos/estadística & datos numéricos , Encuestas de Atención de la Salud/estadística & datos numéricos , Humanos , Unidades de Cuidados Intensivos/normas , Unidades de Cuidados Intensivos/estadística & datos numéricos , Errores Médicos/estadística & datos numéricos , Seguridad del Paciente/normas , Guías de Práctica Clínica como Asunto , Reino Unido , Dispositivos de Acceso Vascular/estadística & datos numéricos
19.
Cancer Gene Ther ; 20(2): 65-9, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23238593

RESUMEN

A vaccine platform has been created by attaching the target-associated antigen (TAA) for the vaccine to the extracellular domain (ecd) of the potent immunostimulatory signal CD40 ligand (CD40L). Attachment of the TAA to the CD40L promotes uptake of the TAA into dendritic cells (DCs), binding to Class I as well as Class II MHC leading to presentation of the TAA on the DCs, expansion of the TAA-specific B cell and CD8 effector T-cell lymphocytes, and induction of a memory response. In addition, the TAA/ecdCD40L vaccine can overcome anergy, induce regressions of pre-existing subcutaneous (SC) nodules of cancer cells, and induce high titers of neutralizing antibodies against viral antigens. This vaccine, which can be administered SC as a TAA/ecdCD40L fusion protein, or as expression vectors (viral or plasmid) or as a vector prime-protein boost strategy, is applicable to the development of vaccine for a wide range of cancers and infectious agents.


Asunto(s)
Antígenos de Neoplasias/inmunología , Ligando de CD40/inmunología , Vacunas contra el Cáncer/inmunología , Enfermedades Transmisibles/tratamiento farmacológico , Neoplasias/tratamiento farmacológico , Adenoviridae/genética , Adyuvantes Inmunológicos/administración & dosificación , Antígenos de Neoplasias/genética , Ligando de CD40/administración & dosificación , Ligando de CD40/genética , Linfocitos T CD8-positivos/citología , Linfocitos T CD8-positivos/inmunología , Vacunas contra el Cáncer/administración & dosificación , Vacunas contra el Cáncer/genética , Enfermedades Transmisibles/inmunología , Células Dendríticas/citología , Células Dendríticas/inmunología , Vectores Genéticos , Humanos , Neoplasias/inmunología
20.
Eur J Nucl Med Mol Imaging ; 39(9): 1391-9, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22644713

RESUMEN

PURPOSE: This study evaluated the ability of (18)F-FDG PET/CT imaging to predict early response to (90)Y-radioembolization in comparison with contrast-enhanced CT (CECT) using RECIST and lesion density (Choi) criteria. Progression-free survival (PFS) in patients with liver metastases at 2 years and decline in tumour markers were the primary end-points of the study. METHODS: A total of 121 liver lesions were evaluated in 25 patients (14 men, 11 women) with liver-dominant metastatic colorectal cancer who underwent (18)F-FDG PET/CT and CECT before and 6-8 weeks after treatment. Changes in SUV(max), tumour density measured in terms of Hounsfield units and the sum of the longest diameters (LD) were calculated for the target liver lesions in each patient. The patient responses to treatment were categorized using EORTC PET criteria, tumour density criteria (Hounsfield units) and RECIST, and were correlated with the responses of tumour markers and 2-year PFS using Kaplan-Meier plots and the log-rank test for comparison. Multivariate proportional hazards (Cox) regression analysis was performed to assess the effect of relevant prognostic factors on PFS. RESULTS: Using (18)F-FDG PET/CT response criteria, 15 patients had a partial response (PR) and 10 patients had stable disease (SD), while using RECIST only 2 patients had a PR and 23 had SD. Two patients had a PR, 21 SD and 2 progressive disease using tumour density criteria. The mean changes in SUV(max), sum of the LDs and tumour density after treatment were 2.9 ± 2.6, 7.3 ± 14.4 mm and 1.9 ± 13.18 HU, respectively. Patients who had a PR on (18)F-FDG PET/CT had a mean decrease of 44.5 % in SUV(max) compared to those with SD who had a decrease of only 10.3 %. The decreases in SUV(max) and sum of the LDs were significant (p < 0.0001, p < 0.05, respectively) while the decrease in tumour density was not (p > 0.1065). The responses on the (18)F-FDG PET/CT studies were highly correlated with the responses of tumour markers (p < 0.0001 for LDH, p = 0.01 for CEA and p = 0.02 for Ca19-9), while the responses on the CECT studies using both RECIST and tumour density criteria were not significantly correlated with the responses of tumour markers. The responses on (18)F-FDG PET/CT studies also significantly predicted PFS (the median PFS in those with a PR was 12.0 months and in those with SD was 5 months, p < 0.0001), while RECIST and tumour density did not significantly predict PFS. Multivariate analysis demonstrated that responses on (18)F-FDG PET/CT studies and decreases in SUV(max) of ≤ 2.0 were the strongest predictors of PFS. CONCLUSION: Early response assessment to (90)Y-radioembolization using (18)F-FDG PET/CT is superior to RECIST and tumour density, demonstrating a correlation with tumour markers and significantly predicting PFS in patients with liver metastases. This could enable early response-adapted treatment strategies to be employed.


Asunto(s)
Neoplasias Colorrectales/diagnóstico por imagen , Neoplasias Colorrectales/radioterapia , Medios de Contraste , Embolización Terapéutica , Fluorodesoxiglucosa F18 , Imagen Multimodal/métodos , Tomografía de Emisión de Positrones , Tomografía Computarizada por Rayos X , Adulto , Anciano , Biomarcadores de Tumor/sangre , Neoplasias Colorrectales/sangre , Neoplasias Colorrectales/patología , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento , Carga Tumoral , Radioisótopos de Itrio/uso terapéutico
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