RESUMO
Nanoparticle-mediated mRNA delivery has emerged as a promising therapeutic modality, but its growth is still limited by the discovery and optimization of effective and well-tolerated delivery strategies. Lipid nanoparticles containing charged or ionizable lipids are an emerging standard for in vivo mRNA delivery, so creating facile, tunable strategies to synthesize these key lipid-like molecules is essential to advance the field. Here, we generate a library of N-substituted glycine oligomers, peptoids, and undertake a multistage down-selection process to identify lead candidate peptoids as the ionizable component in our Nutshell nanoparticle platform. First, we identify a promising peptoid structural motif by clustering a library of >200 molecules based on predicted physical properties and evaluate members of each cluster for reporter gene expression in vivo. Then, the lead peptoid motif is optimized using design of experiments methodology to explore variations on the charged and lipophilic portions of the peptoid, facilitating the discovery of trends between structural elements and nanoparticle properties. We further demonstrate that peptoid-based Nutshells leads to expression of therapeutically relevant levels of an anti-respiratory syncytial virus antibody in mice with minimal tolerability concerns or induced immune responses compared to benchmark ionizable lipid, DLin-MC3-DMA. Through this work, we present peptoid-based nanoparticles as a tunable delivery platform that can be optimized toward a range of therapeutic programs.
Assuntos
Nanopartículas , Peptoides , RNA Mensageiro , Peptoides/química , Nanopartículas/química , Animais , Camundongos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Humanos , Vírus Sinciciais Respiratórios , Lipídeos/químicaRESUMO
Pre-existing (chronic) atrial fibrillation (AF) has been identified as a risk factor for cardiovascular complications and mortality in patients with COVID-19; however, evidence in Latin America (LATAM) is scarce. This prospective and multicenter study from the CARDIO COVID 19-20 database includes hospitalized adults with COVID-19 from 14 countries in LATAM. A parsimonious logistic regression model was used to identify the main factors associated with mortality in a simulated case-control setting comparing patients with a history of AF to those without. In total, 3260 patients were included, of which 115 had AF. The AF group was older, had a higher prevalence of comorbidities, and had greater use of cardiovascular medications. In the model, AF, chronic kidney disease, and a respiratory rate > 25 at admission were associated with higher in-hospital mortality. The use of corticosteroids did not reach statistical significance; however, an effect was seen through the confidence interval. Thus, pre-existing AF increases mortality risk irrespective of other concomitant factors. Chronic kidney disease and a high respiratory rate at admission are also key factors for in-hospital mortality. These findings highlight the importance of comorbidities and regional characteristics in COVID-19 outcomes, in this instance, enhancing the evidence for patients from LATAM.
RESUMO
Cross-linking mass spectrometry (XL-MS) has evolved into a pivotal technique for probing protein interactions. This study describes the implementation of Parallel Accumulation-Serial Fragmentation (PASEF) on timsTOF instruments, enhancing the detection and analysis of protein interactions by XL-MS. Addressing the challenges in XL-MS, such as the interpretation of complex spectra, low abundant cross-linked peptides, and a data acquisition bias, our current study integrates a peptide-centric approach for the analysis of XL-MS data and presents the foundation for integrating data-independent acquisition (DIA) in XL-MS with a vendor-neutral and open-source platform. A novel workflow is described for processing data-dependent acquisition (DDA) of PASEF-derived information. For this, software by Bruker Daltonics is used, enabling the conversion of these data into a format that is compatible with MeroX and Skyline software tools. Our approach significantly improves the identification of cross-linked products from complex mixtures, allowing the XL-MS community to overcome current analytical limitations.
Assuntos
Reagentes de Ligações Cruzadas , Espectrometria de Massas , Software , Fluxo de Trabalho , Reagentes de Ligações Cruzadas/química , Peptídeos/química , Peptídeos/análise , HumanosRESUMO
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can infect human cells by first attaching to the ACE-2 receptor via its receptor-binding domain (RBD) in the spike protein. Here, we report the influence of N-glycosylation sites of the RBD and the membrane (M) protein on IgG antibody binding in serum samples from patients infected with the original SARS-CoV-2 strain in Germany. The RBDs of the wildtype, alpha, beta, gamma, and kappa variants expressed in HEK293S GnTI- cells were all N-glycosylated at Asn331, Asn334, Asn343, and Asn360 or Asn370, whereas the M-protein was glycosylated at Asn5. An ELISA using a coated RBD and probed with anti-RBD IgG antibodies gave a sensitivity of 96.3% and a specificity of 100% for the wildtype RBD, while the sensitivity decreased by 5% to 10% for the variants of concern, essentially in the order of appearance. Deglycosylation of the wildtype RBD strongly reduced antibody recognition by ~20%, considering the mean of the absorbances recorded for the ELISA. This effect was even stronger for the unglycosylated RBD expressed in Escherichia coli, suggesting structural changes affecting epitope recognition. Interestingly, the N-glycosylated M-protein expressed in HEK293S GnTI- cells gave good sensitivity (95%), which also decreased to 65% after deglycosylation, and selectivity (100%). In conclusion, N-glycosylation of the M-protein, the RBD, and most likely the spike protein are important for proper antibody binding and immunological assays, whereas the type of N-glycosylation is less relevant.
RESUMO
INTRODUCTION: Because of the obesity epidemic, more obese patients are on liver transplant (LT) waiting lists. The diseases associated with obesity may increase complications and limit survival after LT. However, there is no established measure or cut-off point to determine this impact and aid decision making. The aim of the present study is to evaluate obesity in patients undergoing LT via BMI and CT-based measurement of adipose tissue (AAT). These parameters will be used to predict the risk of postoperative complications and 5-year survival. METHODS: A retrospective, single-center study was carried out at a tertiary Spanish hospital, including all patients who received LT between January 2012 and July 2019 (n = 164). The patients were adults who underwent LT using the 'piggyback' technique, preserving the recipient vena cava. Visceral adipose tissue (VAT) and BMI were calculated to examine correlations with postoperative complications and 5-year survival. RESULTS: No significant association was found between postoperative complications by Comprehensive Complication Index, BMI, AAT/height, subcutaneous fat/height and VAT/height. Kaplan-Meier curves for 5-year survival compared LT recipients with BMI < 30.45 versus ≥30.45, with an estimated survival of 58.97 months versus 43.11 months, respectively (P < .001) (Fig. 3) and for LT recipients with an AAT/height <27.35 mm versus ≥27.35 mm, with an estimated survival of 57.69 months versus 46.34 months (P = .001). CONCLUSIONS: This study does not show a higher rate of postoperative complications in obese patients. There is a significantly lower long-term survival in patients with AAT/height ≥27.35 mm and BMI ≥ 30.45. BMI is a valid estimate of obesity and is predictive of survival.
Assuntos
Índice de Massa Corporal , Transplante de Fígado , Complicações Pós-Operatórias , Humanos , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Transplante de Fígado/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/mortalidade , Obesidade/complicações , Gordura Abdominal/transplante , Gordura Abdominal/diagnóstico por imagem , Adulto , Taxa de Sobrevida , Idoso , Tomografia Computadorizada por Raios X , Estimativa de Kaplan-Meier , Gordura Intra-Abdominal/diagnóstico por imagemRESUMO
Liver transplantation (LT) is a curative treatment for early-stage hepatocellular carcinoma (HCC) unsuitable for surgical resection. However, tumor recurrence (TR) rates range from 8% to 20% despite strict selection criteria. The validation of new prognostic tools, such as pre-MORAL or RETREAT risks, is necessary to improve recurrence prediction. A retrospective study was conducted at Marqués de Valdecilla University Hospital in Cantabria, Spain, between 2010 and 2019 to determine the rate of TR in LT patients and identify associated factors. Patients with liver-kidney transplantation, re-transplantation, HIV infection, survival less than 90 days, or incidental HCC were excluded. Data on demographic, liver disease-related, LT, and tumor-related variables, as well as follow-up records, including TR and death, were collected. TR was analyzed using the Log-Rank test, and a multivariate Cox regression analysis was performed. The study was approved by the IRB of Cantabria. TR occurred in 13.6% of LT patients (95% CI = 7.3-23.9), primarily as extrahepatic recurrence (67%) within the first 5 years (75%). Increased TR was significantly associated with higher Body Mass Index (BMI) (HR = 1.3 [95% CI = 1.1-1.5]), vascular micro-invasion (HR = 8.8 [1.6-48.0]), and medium (HR = 20.4 [3.0-140.4]) and high pre-MORAL risk (HR = 30.2 [1.6-568.6]). TR also showed a significant correlation with increased mortality. Conclusions: LT for HCC results in a 13.6% rate of tumor recurrence. Factors such as BMI, vascular micro-invasion, and medium/high pre-MORAL risk are strongly associated with TR following LT.
RESUMO
STUDY OBJECTIVE: To determine whether a postoperative 5-day treatment schedule with vaginal metronidazole added to conventional antibiotic prophylaxis with 2 g cefazolin modifies the risk of pelvic cellulitis (PC) and pelvic abscess (PA) after total laparoscopic hysterectomy (TLH). DESIGN: A randomized, controlled, triple-blind, multicenter clinical trial. SETTING: Two centers dedicated to minimally invasive gynecologic surgery in Colombia. PATIENTS: A total of 574 patients were taken to TLH because of benign diseases. INTERVENTION: Patients taken to TLH were divided into 2 groups (treatment group, cefazolin 2 g intravenous single dose before surgery + metronidazole vaginal ovules for 5 days postoperatively, control group: cefazolin 2 g intravenous single dose + placebo vaginal ovules for 5 days postoperatively). MEASUREMENTS AND MAIN RESULTS: The absolute frequency (AF) of PC and PA and their relationship with the presence of bacterial vaginosis (BV) were measured. There was no difference in AF of PC (AF, 2/285 [0.7%] vs 5/284 [1.7%] in the treatment and placebo groups, respectively; risk ratio, 1.75; 95% confidence interval, 0.54-5.65; p = .261), nor for PA (AF, 0/285 [0%] vs 2/289 [0.7%]; p = .159, in the treatment and placebo groups, respectively). The incidence of BV was higher in the metronidazole group than the placebo group (42.5% vs 33.4%, p = .026). CONCLUSION: The use of vaginal metronidazole ovules during the first 5 days in postoperative TLH added to conventional cefazolin prophylaxis does not prevent the development of PC or PA, regardless of the patient's diagnosis of BV.
Assuntos
Laparoscopia , Parametrite , Vaginose Bacteriana , Humanos , Feminino , Metronidazol/uso terapêutico , Abscesso/etiologia , Abscesso/prevenção & controle , Cefazolina/uso terapêutico , Parametrite/tratamento farmacológico , Histerectomia/efeitos adversos , Vaginose Bacteriana/diagnóstico , Vaginose Bacteriana/tratamento farmacológico , Laparoscopia/efeitos adversos , Método Duplo-Cego , Antibacterianos/uso terapêuticoRESUMO
Endometriosis is a common condition associated with chronic pelvic pain and infertility. Its pathogenesis is poorly understood, diagnosis relies on laparoscopy, and staging is based on extent of disease. Unfortunately, the current staging systems do not correlate well with pain severity and impact, nor do they predict prognosis, i.e., treatment success and recurrence of disease. In this article, we discuss the strengths and limitations of current staging systems and propose modifications that will enable better classification systems to be developed in the future.
Assuntos
Endometriose , Infertilidade Feminina , Laparoscopia , Feminino , Humanos , Endometriose/diagnóstico , Endometriose/cirurgia , Endometriose/complicações , Dor Pélvica/etiologia , Infertilidade Feminina/complicações , Prognóstico , Resultado do Tratamento , Laparoscopia/efeitos adversosRESUMO
BACKGROUND & AIMS: Complex portal vein thrombosis (PVT) is a challenge in liver transplantation (LT). Extra-anatomical approaches to portal revascularization, including renoportal (RPA), left gastric vein (LGA), pericholedochal vein (PCA), and cavoportal (CPA) anastomoses, have been described in case reports and series. The RP4LT Collaborative was created to record cases of alternative portal revascularization performed for complex PVT. METHODS: An international, observational web registry was launched in 2020. Cases of complex PVT undergoing first LT performed with RPA, LGA, PCA, or CPA were recorded and updated through 12/2021. RESULTS: A total of 140 cases were available for analysis: 74 RPA, 18 LGA, 20 PCA, and 28 CPA. Transplants were primarily performed with whole livers (98%) in recipients with median (IQR) age 58 (49-63) years, model for end-stage liver disease score 17 (14-24), and cold ischemia 431 (360-505) minutes. Post-operatively, 49% of recipients developed acute kidney injury, 16% diuretic-responsive ascites, 9% refractory ascites (29% with CPA, p <0.001), and 10% variceal hemorrhage (25% with CPA, p = 0.002). After a median follow-up of 22 (4-67) months, patient and graft 1-/3-/5-year survival rates were 71/67/61% and 69/63/57%, respectively. On multivariate Cox proportional hazards analysis, the only factor significantly and independently associated with all-cause graft loss was non-physiological portal vein reconstruction in which all graft portal inflow arose from recipient systemic circulation (hazard ratio 6.639, 95% CI 2.159-20.422, p = 0.001). CONCLUSIONS: Alternative forms of portal vein anastomosis achieving physiological portal inflow (i.e., at least some recipient splanchnic blood flow reaching transplant graft) offer acceptable post-transplant results in LT candidates with complex PVT. On the contrary, non-physiological portal vein anastomoses fail to resolve portal hypertension and should not be performed. IMPACT AND IMPLICATIONS: Complex portal vein thrombosis (PVT) is a challenge in liver transplantation. Results of this international, multicenter analysis may be used to guide clinical decisions in transplant candidates with complex PVT. Extra-anatomical portal vein anastomoses that allow for at least some recipient splanchnic blood flow to the transplant allograft offer acceptable results. On the other hand, anastomoses that deliver only systemic blood flow to the allograft fail to resolve portal hypertension and should not be performed.
Assuntos
Doença Hepática Terminal , Varizes Esofágicas e Gástricas , Hipertensão Portal , Transplante de Fígado , Trombose Venosa , Humanos , Pessoa de Meia-Idade , Veia Porta/cirurgia , Transplante de Fígado/métodos , Doença Hepática Terminal/complicações , Varizes Esofágicas e Gástricas/complicações , Ascite/complicações , Hemorragia Gastrointestinal , Índice de Gravidade de Doença , Hipertensão Portal/complicações , Hipertensão Portal/cirurgia , Trombose Venosa/etiologia , Trombose Venosa/cirurgiaRESUMO
Persistent organic pollutants (POPs) are widely distributed along the world and their levels in surface waters may pose a risk to human health due to consumption of contaminated water or fish long-term exposure to contaminated water. The occurrence of polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) in the Piedras river (Colombia) is a problem of serious concern since freshwater is conducted to a drinking water supply system that provides more than 3 million users. In this research, we deployed silicone rubber membranes as passive samplers in two sampling campaigns at seven sampling stations selected along the river, to assess sources and spatial variation of POPs. The measurements confirmed freely dissolved concentration of the EPA prioritized PAHs (excluding naphthalene), PCBs, heptachlor isomers, dieldrin, endosulfan isomers, among other POPs at trace levels in the water source. The Risk Quotient (RQ) method was applied to prioritize POPs with the highest potential toxicity over aquatic ecosystems. The OCP Heptachlor overcome RQ, while Dieldrin and Endosulfan, and some PAHs congeners such as Perylene, Pyrene, Benzo[a]pyrene, and Fluoranthene displayed medium-risk RQ. Significant differences between sampling stations assessed by One-way ANOVA suggested that the main PAHs and PCBs sources to the river were the punctual discharge from the WWTP and a leachate discharge form a landfill located in the study area. Additionally, nonpoint sources of OCPs were identified. Our results showed that the origin of PAHs and PCBs are associated with urban activities, while the contribution of OCPs is related to the presence of legacy pesticides from past usage in agricultural activities in the basin.
Assuntos
Água Potável , Poluentes Ambientais , Hidrocarbonetos Clorados , Praguicidas , Bifenilos Policlorados , Hidrocarbonetos Policíclicos Aromáticos , Poluentes Químicos da Água , Animais , Humanos , Bifenilos Policlorados/análise , Monitoramento Ambiental/métodos , Dieldrin , Endossulfano , Ecossistema , Poluentes Químicos da Água/análise , Hidrocarbonetos Clorados/análise , Hidrocarbonetos Policíclicos Aromáticos/análise , Praguicidas/análise , HeptacloroRESUMO
BACKGROUND: This research aimed to determine the porosity and particle size distribution in canned Vienna-type sausages using digital image analysis (DIA) on photographs captured with a digital camera and applying a Monte Carlo simulation. The methodology determined morphometric parameters (area and Feret diameter) by DIA of transverse and longitudinal sections of canned sausages. Those images were previously contrast enhanced, color threshold adjusted, and binarized. Subsequently, the estimation of the pore volume was carried out from the inverse Gaussian distributions of Feret diameter and area, as well as the porosity, using Monte Carlo simulation. RESULTS: The pores had an average Feret diameter of 0.335 mm and an average area of 0.085 mm2 . The highest estimated bivariate kernel density was presented for the smallest pores (around 0.02 mm2 in area and 0.25 mm in diameter). Simulation average values of pore volume, assumed as a cylinder, and porosity were 1.455 mm3 and 0.737 respectively. The average porosity value was consistent with the value experimentally estimated by the indirect method, in concordance with the definition of porosity, which was 0.715, presenting a mean relative percentage error of 3.08% concerning the estimated experimental value as well. CONCLUSION: This research presents interesting perspectives for the quantitative analysis of the microstructure of food and biological materials through a novel, low-cost, reliable, and fast proposal. Moreover, this is the first study to report the porosity determination in canned sausages by DIA. © 2022 Society of Chemical Industry.
Assuntos
Porosidade , Método de Monte Carlo , Simulação por ComputadorRESUMO
Traditional ecological knowledge of indigenous groups in the southeastern Colombian Amazon coincides in identifying the two main hydrological transition periods (wet-dry: August-November; dry-wet: March-April) as those with greater susceptibility to disease in humans. Here we analyze the association between indigenous knowledge about these two periods and the incidence of two vector-borne diseases: malaria and dengue. We researched seven "ecological calendars" from three regions in the Colombian Amazon, malaria and dengue cases reported from 2007 to 2019 by the Colombian National Institute of Health, and daily temperature and precipitation data from eight meteorological stations in the region from 1990-2019 (a climatological normal). Malaria and dengue follow a seasonal pattern: malaria has a peak from August to November, corresponding with the wet-dry transition (the "season of the worms" in the indigenous calendars), and dengue has a peak in March and April, coinciding with the dry-wet transition. Previous studies have shown a positive correlation between rainfall and dengue and a negative correlation between rainfall and malaria. However, as the indigenous ecological knowledge codified in the calendars suggests, disease prediction cannot be reduced to a linear correlation with a single environmental variable. Our data show that two major aspects of the indigenous calendars (the time of friaje as a critical marker of the year and the hydrological transition periods as periods of greater susceptibility to diseases) are supported by meteorological data and by the available information about the incidence of malaria and dengue.(AU)
Los conocimientos ecológicos tradicionales de grupos indígenas del sureste de la Amazonia colombiana coinciden en identificar dos principales periodos de transición hidrológica (seco-húmedo: agosto-noviembre; húmedo-seco: marzo-abril) como los de mayor susceptibilidad a enfermedades en humanos. Aquí analizamos la asociación entre el conocimiento indígena sobre estos dos periodos y la incidencia de dos enfermedades transmitidas por vectores: malaria y dengue. Investigamos siete calendarios ecológicos de tres regiones en la Amazonia colombiana, casos de dengue y malaria reportados de 2007 hasta 2019 por el Instituto Nacional de Salud de Colombia y datos diarios de temperatura y precipitación de ocho estaciones meteorológicas en la región, de 1990 a 2019 (una normal climatológica). Malaria y dengue siguen un patrón estacional, la malaria tiene un pico de agosto a noviembre, correspondiendo con la transición húmedo-seco (el "tiempo de gusano" según los calendarios indígenas), mientras que dengue tiene un pico de marzo a abril, coincidiendo con la transición seco-húmedo. Estudios previos mostraron una correlación positiva entre precipitación y dengue, y una correlación negativa entre precipitación y malaria. Sin embargo, como lo sugiere el conocimiento ecológico codificado en los calendarios indígenas, la predicción de enfermedades no puede reducirse a una correlación lineal con una sola variable medioambiental. Nuestros datos muestran que dos aspectos principales de los calendarios indígenas (el tiempo de friaje como un marcador crítico anual y los periodos de transición hidrológica como épocas de mayor susceptibilidad a enfermedades) están soportados por datos meteorológicos e información disponible acerca de la incidencia de malaria y dengue.(AU)
Assuntos
Humanos , Povos Indígenas , Doenças Transmitidas por Vetores , Ecossistema Amazônico , Dengue , Calendários como Assunto , MaláriaRESUMO
The inherent poor sampling of fragment ions in time-of-flight mass analyzers was recently improved for data-dependent acquisition (DDA) by considering their drift times in traveling wave ion mobility spectrometry (TWIMS). Here, we extend this TWIMS-DDA approach to the data-independent acquisition (DIA) mode MSE to improve the signal intensities of fragment ions by providing improved ion beam sampling efficiency, which we termed therefore signal-enhanced MSE (SEMSE). The theoretical expectation that SEMSE improves the number of identified peptides, the number of quantifiable peptides, and the lower limit of quantitation in wideband DIA was evaluated on an electrospray ionisation-ion mobility spectrometry-quadrupole-time-of-flight-MS (ESI-IMS-Q-TOF-MS) (Synapt G2-Si) in comparison to five established TWIMS-DDA and TWIMS-MSE methods with respect to the number of peptide identifications, the spectral quality of supporting peptide spectra matches, and (most importantly) fragment ion signal sensitivity. A comparison of the fragment signals clearly indicated that SEMSE provides 6.8- to 11.5-fold larger peak areas than established MSE techniques. While this clearly shows the advantages of SEMSE, the inherent limitations of the current software tools do not allow using all benefits in routine analyses. As the simultaneous fragmentation of co-eluting peptides limited peptide identification, DDA and MSE data sets were integrated using Skyline.
Assuntos
Espectrometria de Mobilidade Iônica , Peptídeos , Espectrometria de Mobilidade Iônica/métodos , Íons , Fragmentos de Peptídeos , Peptídeos/química , Espectrometria de Massas em Tandem/métodosAssuntos
Vacina de mRNA-1273 contra 2019-nCoV , COVID-19 , Transplante de Fígado , Vacinas Virais , Vacina de mRNA-1273 contra 2019-nCoV/efeitos adversos , Anticorpos Antivirais , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Humanos , Imunidade , Transplante de Fígado/efeitos adversos , SARS-CoV-2 , TransplantadosRESUMO
Different reports have shown the clinical and serologic response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger RNA (mRNA) vaccines in preventing coronavirus disease 2019 (COVID-19) in the general population, but few studies have examined these responses in transplant recipients. We assessed the vaccine immunogenicity of two doses (100 µg) of the mRNA-1273 vaccine (Moderna) administered with a 28-day interval in liver transplant recipients (LTRs) at follow-up at the Marques de Valdecilla University Hospital. LTRs without a history of COVID-19 infection were tested for SARS-CoV-2 immunoglobulin G (IgG) antibodies directed against the spike protein (S) a median of 43 days after receiving the second Moderna vaccine dose. Clinical data, including immunosuppressive regimen and routine laboratory data, were obtained from the medical record of each patient up to 3 months before the date of the first vaccination. Factors associated with serologic response were evaluated through logistic regression. In total, 129 LTRs who had anti-S results were included. Most patients were men (n = 99; 76.7%) with a median age of 63 years (interquartile range, 56-68). Alcohol (43.4%) and chronic hepatitis C (18.6%) were the most frequent causes of liver transplantation. A positive anti-S IgG response was observed in 113 LTRs (87.6%; 95% confidence interval [CI], 80.8-92.2). A strong inverse relationship between mycophenolate mofetil use and serologic response was found (odds ratio, 0.07; 95% CI, 0.02-0.26; p = 0.001). Conclusion: Most LTRs develop an immunological response to the Moderna SARS-CoV-2 mRNA-based vaccine. An immunosuppressive regimen that includes mycophenolate predicts a weak serologic response.
Assuntos
COVID-19 , Transplante de Fígado , Vacinas Virais , Vacina de mRNA-1273 contra 2019-nCoV , Anticorpos Antivirais , Formação de Anticorpos , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Feminino , Humanos , Imunoglobulina G , Transplante de Fígado/efeitos adversos , Masculino , Pessoa de Meia-Idade , RNA Mensageiro , SARS-CoV-2RESUMO
Merkel-cell-carcinoma of the hand is rare. The Pathological and Immunohistochemical diagnosis helps us to focus the treatment. Immunotherapy has shown beneficial effects in unresectable/advanced/metastatic stages. The quantification of antibodies against Merkel-cell-polyomavirus (MCPyV) can be a useful for prognosis and follow-up. A wide margin in surgery and the sentinel node are the first option with Radiotherapy.
RESUMO
OBJECTIVE: To contribute to the training of specialists by describing in a systematic and detailed way the ten steps to perform a safe and feasible Total Laparoscopic Hysterectomy (HTL). METHOD: The detailed description of the steps of the HTL intends that this procedure can be safely and effectively reproduced. RESULTS: By clearly knowing the steps of HTL, it is possible to favor minimally invasive routes so that patients benefit from its multiple proven benefits. CONCLUSIONS: The benefits of minimally invasive routes for performing a hysterectomy have already been demonstrated in the literature. It is particularly important that specialists are familiar with these techniques and that groups standardize the procedure so that more patients can safely undergo and benefit from the laparoscopic approach.
OBJETIVO: Contribuir a la formación de los especialistas describiendo de manera sistemática y pormenorizada los diez pasos para realizar una histerectomía total por laparoscopia (HTL) segura y reproducible. MÉTODO: La descripción detallada de los pasos de la HTL pretende que este procedimiento pueda ser reproducido de manera segura y efectiva. RESULTADOS: Al conocer claramente los pasos de la HTL es posible favorecer las rutas de mínima invasión para que las pacientes se beneficien de sus múltiples beneficios demostrados. CONCLUSIONES: Los beneficios de las rutas mínimamente invasivas para la realización de una histerectomía ya han sido demostrados en la literatura. En muy importante que los especialistas estén familiarizados con estas técnicas y que los grupos estandaricen el procedimiento para que más pacientes puedan ser intervenidas de manera segura y se beneficien de la vía laparoscópica.