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It is increasingly apparent that cancer cells, in addition to remodelling their metabolism to survive and proliferate, adapt and manipulate the metabolism of other cells. This property may be a telling sign that pre-clinical tumour metabolism studies exclusively utilising in-vitro mono-culture models could prove to be limited for uncovering novel metabolic targets able to translate into clinical therapies. Although this is increasingly recognised, and work towards addressing the issue is becoming routinary much remains poorly understood. For instance, knowledge regarding the biochemical mechanisms through which cancer cells manipulate non-cancerous cell metabolism, and the subsequent impact on their survival and proliferation remains limited. Additionally, the variations in these processes across different cancer types and progression stages, and their implications for therapy, also remain largely unexplored. This study employs an interdisciplinary approach that leverages the predictive power of mathematical modelling to enrich experimental findings. We develop a functional multicellular in-silico model that facilitates the qualitative and quantitative analysis of the metabolic network spawned by an in-vitro co-culture model of bone marrow mesenchymal stem- and myeloma cell lines. To procure this model, we devised a bespoke human genome constraint-based reconstruction workflow that combines aspects from the legacy mCADRE & Metabotools algorithms, the novel redHuman algorithm, along with 13C-metabolic flux analysis. Our workflow transforms the latest human metabolic network matrix (Recon3D) into two cell-specific models coupled with a metabolic network spanning a shared growth medium. When cross-validating our in-silico model against the in-vitro model, we found that the in-silico model successfully reproduces vital metabolic behaviours of its in-vitro counterpart; results include cell growth predictions, respiration rates, as well as support for observations which suggest cross-shuttling of redox-active metabolites between cells.
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Vacinas Anticâncer , Mieloma Múltiplo , Humanos , Redes e Vias Metabólicas , Algoritmos , Ciclo CelularRESUMO
PURPOSE: To present the clinical and imaging results of a series of patients undergoing anterior cruciate ligament reconstruction with vancomycin presoaking of the hamstring autograft compared with patients in the immediate period prior, when no vancomycin was used. METHODS: This was a retrospective sequential series of patients with anterior cruciate ligament reconstruction using either a graft protocol with no vancomycin presoaking (group 1, January 2013 to October 2015) or a graft protocol with vancomycin presoaking (group 2, November 2015 to December 2018). Lysholm and International Knee Documentation Committee scores were obtained at a minimum 24-month follow-up. Graft ruptures were recorded. Between 6 and 12 months' follow-up, magnetic resonance imaging (MRI) was obtained to evaluate graft healing and integration. RESULTS: There were 102 patients (72% male patients), with 40 in group 1 (mean age, 32.2 years) and 62 in group 2 (mean age, 32.3 years). A graft rupture occurred in 5 patients (13%) in group 1 and 6 patients (10%) in group 2 (P = .65). The median Lysholm score was 95 points (interquartile range [IQR], 86-100 points) in group 1 and 95 points (IQR, 90-100 points) in group 2 (P = .37). The median International Knee Documentation Committee score was 93 points (IQR, 82-99 points) in group 1 and 94 points (IQR, 86-99 points) in group 2 (P = .22). MRI evaluation of integration showed that 87 patients (90%) had no synovial fluid at the tunnel-graft interface, without a difference between groups (P = .24). On the basis of graft signal appearance, hyperintense grafts were found in 45 patients (46%); isointense, 45 (46%); and hypointense, 7 (7%). Group 1 had a higher prevalence of hypointense grafts, whereas group 2 had a higher prevalence of hyperintense and isointense grafts (P = .003). CONCLUSIONS: Vancomycin presoaking of hamstring grafts increased the number of hyperintense and isointense grafts on MRI. Additionally, more hypointense grafts were noted when vancomycin was not used, suggesting the presence of more mature grafts in the non-vancomycin group. LEVEL OF EVIDENCE: Level III, retrospective comparative study.
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Lesões do Ligamento Cruzado Anterior , Reconstrução do Ligamento Cruzado Anterior , Tendões dos Músculos Isquiotibiais , Adulto , Ligamento Cruzado Anterior/diagnóstico por imagem , Ligamento Cruzado Anterior/cirurgia , Lesões do Ligamento Cruzado Anterior/diagnóstico por imagem , Lesões do Ligamento Cruzado Anterior/cirurgia , Reconstrução do Ligamento Cruzado Anterior/métodos , Autoenxertos , Feminino , Tendões dos Músculos Isquiotibiais/transplante , Humanos , Imageamento por Ressonância Magnética , Masculino , Estudos Retrospectivos , Ruptura/cirurgia , Transplante Autólogo , Resultado do Tratamento , Vancomicina/uso terapêuticoRESUMO
OBJECTIVE: An analysis of the SARS-CoV-2 pandemic impact in the Spanish Gaucher Disease (GD) community is presented here. PATIENTS & METHODS: The Spanish GD foundation (FEETEF) surveyed 113 GD patients from March 30 to April 27; all patients provided a verbal consent. RESULTS: 110 surveys were analyzed. The median age was 47 years old (y.o.), 31 patients were ≥ 60 y.o.; and 34% of patients reported comorbidities. 46% (51/110) of patients were treated by enzyme replacement therapy (ERT), 48 of them at hospitals; 45.1% (45/110) were on substrate reduction therapy (SRT) and 9% (10/110) receive no therapy. 25% (11/48) of ERT-hospital-based patients reported therapy interruptions, while SRT-patients did not report missing doses. No bone crises were reported. However, 50% (55/110) of patients reported being worried about their predisposition to a severe SARS-COV-2 infection and 29% (16/55) of them took anxiolytics or antidepressants for this. While 6 patients reported to have contact with an infected person, another two confirmed SARS-CoV-2 infections were reported in splenectomyzed patients, one of them (a 79-year-old diabetic) died. CONCLUSIONS: One quarter of the patients treated at hospitals reported dose interruptions. Home-based therapy may need to be considered in order to minimize the impact of the COVID-19 pandemic.
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Betacoronavirus , Continuidade da Assistência ao Paciente , Infecções por Coronavirus , Terapia de Reposição de Enzimas , Doença de Gaucher/tratamento farmacológico , Glucosilceramidase/uso terapêutico , Serviços Hospitalares de Assistência Domiciliar , Pandemias , Pneumonia Viral , Adulto , Idoso , Ansiolíticos/uso terapêutico , Antidepressivos/uso terapêutico , Ansiedade/tratamento farmacológico , Ansiedade/etiologia , COVID-19 , Terapia Combinada , Comorbidade , Depressão/tratamento farmacológico , Depressão/etiologia , Diabetes Mellitus/epidemiologia , Suscetibilidade a Doenças , Terapia de Reposição de Enzimas/métodos , Feminino , Doença de Gaucher/psicologia , Doença de Gaucher/cirurgia , Glucosilceramidase/provisão & distribuição , Humanos , Hospedeiro Imunocomprometido , Masculino , Pessoa de Meia-Idade , SARS-CoV-2 , Espanha/epidemiologia , Esplenectomia/efeitos adversos , Adulto JovemRESUMO
Increasing the overall carbon and energy efficiency by integration of thermal processes with biological ones has gained considerable attention lately, especially within biorefining. A technology that is capable of processing wet feedstock with good energy efficiency is advantageous. Such a technology, exploiting the special properties of hot compressed water is called hydrothermal liquefaction. The reaction traditionally considered to take place at moderate temperatures (200-350 °C) and high pressures (10-25 MPa) although recent findings show the benefits of increased pressure at higher temperature regions. Hydrothermal liquefaction is quite robust, and in theory, all wet feedstock, including residues and waste streams, can be processed. The main product is a so-called bio-crude or bio-oil, which is then further upgraded to fuels or chemicals. Hydrothermal liquefaction is currently at pilot/demo stage with several lab reactors and a few pilots already available as well as there are a few demonstration plants under construction. The applied conditions are quite severe for the processing equipment and materials, and several challenges remain before the technology is commercial. In this review, a description is given about the influence of the feedstock, relevant for integration with biological processing, as well as the processing conditions on the hydrothermal process and products composition. In addition, the relevant upgrading methods are presented.
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Biocombustíveis , Biotecnologia/métodos , Temperatura Alta , Pressão Hidrostática , Plantas/química , Água , Biotecnologia/tendências , Plantas/efeitos da radiaçãoRESUMO
Thirthy three patients (mean age 32 years) undergoing OA were retrospectively evaluated. All patients had MRI at mean 6.6 months. Lysholm, International Knee Documentation Committee (IKDC), and Tegner scores. The aim is to evaluate Magnetic Resonance Imaging (MRI) in patients who underwent an Osteochondal Autograft (OA) and correlate them with their clinical results-evaluated at mean followup of 28 months (12-88). Tegner Pre-operatively: 6.6, Post-operative: 7.4 (p<0.001). Mean Lysholm: 87, mean IKDC: 86. MRI: complete filling of the lesion in 25 (75.7%) patients, complete integration of the graft in 5 (15.1%) and intact repair tissue in 22 (66.6%. Positive correlation between the degree of repair and filling of the defect and higher Lysholm and IKDC (p<0.05). There is a minor association between short-term MRI and mid-term clinical results after an OA being the degree of repair and filling of the chondral defect the only parameters correlated with patient´s evolution.
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Cartilagem Articular/cirurgia , Cartilagem Hialina/transplante , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/fisiopatologia , Imageamento por Ressonância Magnética , Adolescente , Adulto , Autoenxertos/diagnóstico por imagem , Cartilagem Articular/diagnóstico por imagem , Cartilagem Articular/lesões , Criança , Feminino , Seguimentos , Humanos , Escore de Lysholm para Joelho , Masculino , Pessoa de Meia-Idade , Amplitude de Movimento Articular , Estudos Retrospectivos , Fatores de Tempo , Adulto JovemRESUMO
Obstructive uropathy is defined as the structural or functional interruption of urinary outflow at any level in the urinary tract. It is regarded as one of the most prevalent causes of acute kidney injury (AKI), accounting for 5%-10% of cases. Acute severe obstruction of the urinary tract is a potentially threatening situation for the kidneys and therefore requires prompt identification and management to relieve obstruction. The aim of the present article is to review and synthesize available evidence on obstructive uropathy, providing a clinical guideline for clinicians. A literature review on obstructive uropathy in the context of AKI was performed, focusing on the least clarified aspects regarding diagnosis and management. Recent literature searching was conducted in English and top-level evidence articles including systematic reviews, metanalyses and large series were prioritized. Acute obstruction of the urinary tract is a diagnostic and therapeutical challenge that may lead to important clinical complications together with direct structural and hemodynamic damage to the kidney. Early recognition of the leading cause and its exact location is essential to ensure prompt urinary drainage together with the most suitable drainage technique selection. A multidisciplinary approach, including urologists, nephrologists, and other medical specialties, is best suited to correctly manage concomitant hemodynamic changes, fluid and electrolyte imbalances, and other related issues. Obstructive uropathy is one of the leading causes of AKI. Recognition of patients suitable for early diversion and feasibility or adequate selection of the indicated technique is sometimes challenging. A thorough understanding of the physiopathology behind the development of urinary obstruction is vital for correct diagnosis and management.
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Introduction: Learning laparoscopy (LAP) is challenging and requires different skills to conventional open surgery. There is a recognized need for a standardized laparoscopic training framework within urology to overcome these difficulties and to shift learning curve from patient to skills laboratory. Simulation-based training has been widely commented, but implementation in real day practice is lacking. We present our "LAP training program for residents". Material: Between 2017 and 2022, 11 residents participated in our self-designed program: Theoretical: (Moodle platform) basic knowledge and multimedia content for initiation into LAP. Evaluated through online exam. Practical: exercises for LAP skills acquisition were proposed and encouraged residents' practice in a box trainer available and experimental surgery sessions on a porcine model. On-site E-BLUS (European Basic Laparoscopic Urologic Skills) examination was performed annually. Feedback was obtained through an anonymous online survey. Results: All residents positively evaluated the program. Theoretical: 82% passed the online exam. The most valued topics: LAP in special clinical situations, complications, instruments, and configuration of the operating room (OR). Practical: all residents increased dry-lab box practices. A total of 23 experimental surgical sessions were carried out. For 64%, simulation in the experimental OR was a necessary complement to achieve laparoscopic skills and allowed them to feel more confident. Forty-five percent considered it essential to improve their surgical technique. E-BLUS evaluation was valued as a means to achieve dexterity and safer surgery by 90%. Reduction in time and errors were observed through time, although only 2 passed the E-BLUS. Conclusion: Our program for learning LAP includes the acquisition of knowledge, training of basic skills and surgical technique in a safe environment, as well as an objective evaluation. Encouraged practice of basic skills and surgical technique simulation and improved objective evaluation. It is structured, reproducible, systematic and has been positively valued, although it requires commitment for success.
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Epidemiologic studies demonstrate an association between early-life respiratory illnesses (RIs) and the development of childhood asthma. However, it remains uncertain whether these children are predisposed to both conditions or if early-life RIs induce alterations in airway function, immune responses, or other human biology that contribute to the development of asthma. Puerto Rican children experience a disproportionate burden of early-life RIs and asthma, making them an important population for investigating this complex interplay. PRIMERO, the Puerto Rican Infant Metagenomics and Epidemiologic Study of Respiratory Outcomes , recruited pregnant women and their newborns to investigate how the airways develop in early life among infants exposed to different viral RIs, and will thus provide a critical understanding of childhood asthma development. As the first asthma birth cohort in Puerto Rico, PRIMERO will prospectively follow 2,100 term healthy infants. Collected samples include post-term maternal peripheral blood, infant cord blood, the child's peripheral blood at the year two visit, and the child's nasal airway epithelium, collected using minimally invasive nasal swabs, at birth, during RIs over the first two years of life, and at annual healthy visits until age five. Herein, we describe the study's design, population, recruitment strategy, study visits and procedures, and primary outcomes.
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BACKGROUND: Sebelipase alfa (Kanuma®) is approved for patients with Wolman disease (WD) at a dosage of 3-5 mg/kg once weekly. Survival rates in the second of two clinical trials was greater, despite recruiting more severely ill patients, probably related to higher initial and maximal doses. We aimed to evaluate the effective pharmacokinetics and pharmacodynamics of Sebelipase alfa when administered to patients with severe WD at 5 mg/kg twice weekly, an intensive regimen which was not assessed in the trials. METHODS: We recruited 3 patients receiving Sebelipase alfa 5 mg/kg twice weekly. We measured LAL activity in leukocytes and plasma oxysterol concentration in two patients and LAL activity in fibroblasts in one patient. Clinical follow up was also assessed. RESULTS: Analyses of LAL activity and oxysterols demonstrate that there is short-lived enzyme activity post-dosing which is associated with the release of stored lipids. Clinical data demonstrate that 5 mg/kg twice weekly dosing is well tolerated and effective. CONCLUSION: 5 mg/kg twice weekly dosing with Sebelipase alfa rescues severely ill infants with WD by increasing substrate clearance. There is biologically relevant lipid accumulation in the 'trough' periods before the next dosing, even with this intensive regimen.
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Esterol Esterase , Doença de Wolman , Humanos , Lactente , Esterol Esterase/administração & dosagem , Esterol Esterase/uso terapêutico , Doença de Wolman/tratamento farmacológicoRESUMO
BACKGROUND: Renal colic is characterized by sharp, intense flank pain. Nonsteroidal anti-inflammatory drugs are the treatment of choice, although extracorporeal shock wave lithotripsy (SWL) is a noninvasive alternative for pain management. The objective of our study is to present results obtained using rapid SWL to treat renal colic in our center. METHODS: We analyzed 214 patients undergoing rapid shockwave extracorporeal lithotripsy between October 2014 and June 2018: 69.63% were male, and 30.37% female, with a mean age of 47.35 years (range, 16-84). The average stone size was 6.71 mm (3-16). Stone locations were as follows: The pelviureteric junction (PUJ) (10.75%), proximal ureter (45.79%), midureter (24.77%), and distal ureter (18.69%). RESULTS: Pain relief was achieved in 81.31% of the patients. The rates of successful pain control according to stone location were 65.22% when the stone was located in the PUJ, 79.59% in the proximal ureter, 88.68% in the midureter, and 85.00% in the distal ureter. Complete or partial stone resolution was achieved 4 weeks postoperatively in 78.50% of cases (64.95% and 13.55%, respectively). According to the stone location, the overall rate of resolution (complete + partial) was 90.00% for distal ureteral stones, 86.80% in the midureter, 73.47% in the proximal ureter, and 60.86% in the PUJ. 44 patients (20.56%) demonstrated complications. The most common complications were persistent pain, acute renal failure and fever. CONCLUSIONS: Immediate SWL was found to be a safe and effective treatment option for pain related to renal colic in 81% of the patients studied.
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Litotripsia , Cólica Renal , Ureter , Cálculos Ureterais , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Cólica Renal/etiologia , Cólica Renal/terapia , Litotripsia/métodos , Cálculos Ureterais/complicações , Cálculos Ureterais/terapia , Resultado do Tratamento , DorRESUMO
Urolithiasis is a disease characterized by the presence of stones in the urinary tract, whether in the kidneys, ureters, or bladder. Its origin is multiple, and causes can be cited as hereditary, environmental, dietary, anatomical, metabolic, or infectious factors. A kidney stone is a biomaterial that originates inside the urinary tract, following the principles of crystalline growth, and in most cases, it cannot be eliminated naturally. In this work, 40 calculi from the Don Benito, Badajoz University Hospital are studied and compared with those collected in Madrid to establish differences between both populations with the same pathology and located in very different geographical areas. Analysis by cathodoluminescence offers information on the low crystallinity of the phases and their hydration states, as well as the importance of the bonds with the Ca cation in all of the structures, which, in turn, is related to environmental and social factors of different population groups such as a high intake of proteins, medications, bacterial factors, or possible contamination with greenhouse gases, among other factors.
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Cálculos Renais , Humanos , Cálculos Renais/epidemiologia , Cálculos Renais/etiologia , Materiais Biocompatíveis , CristalizaçãoRESUMO
BACKGROUND: The availability of multiple treatments for type 1 Gaucher disease increases the need for real-life studies to evaluate treatment efficacy and safety and provide clinicians with more information to choose the best personalized therapy for their patients. AIMS: To determine whether treatment with eliglustat produces, in adult GD1 patients, ans optimal response in daily clinical practice. METHODS: We designed a real-life study with 2 years of follow-up (TRAZELGA [GEE-ELI-2017-01]) to uniformly evaluate the response and adverse events to eliglustat treatment. This study, conducted in 30 patients across Spain and previously treated with other therapies, included the evaluation of safety and efficacy by assessing visceral enlargement, bone disease (DEXA and T and Z scores), concomitant treatments and adverse events, as well as a quality of life evaluation (SF-36). In addition, the quantification of classical biomarkers (chitotriosidase activity, CCL18/PARC and glucosylsphingosine (GluSph)) and new candidates for GD biomarkers (YKL-40, cathepsin S, hepcidin and lipocalin-2 determined by immunoassay) were also assessed. Non-parametric statistical analysis was performed and p < 0.05 was considered statistically significant. MAIN RESULTS: Thirty patients were enrolled in the study. The median age was 41.5 years and the male-female ratio was 1.1:1. 84% of the patients had received ERT and 16% SRT as previous treatment. The most common symptoms at baseline were fatigue (42%) and bone pain (38%), no patient had a bone crisis during the study, and two years after switching, 37% had reduced their use of analgesics. Patient-reported outcomes showed a significant increase in physical function scores (p = 0.027) and physical pain scores (p = 0.010). None of the enrolled patients discontinued treatment due to adverse events, which were mild and transient in nature, mainly gastrointestinal and skin dryness. None of the biomarkers show a significant increase or decompensation after switching. CCL18/PARC (p = 0.0012), YKL-40 (p = 0.00004) and lipocalin-2 (p = 0.0155) improved after two years and GluSph after one year (p = 0.0008) and two years (p = 0.0245) of oral therapy. CONCLUSION: In summary, this real-life study, showed that eliglustat maintains stability and can improve quality of life with few side effects. Significant reductions in classic and other novel biomarkers were observed after two years of therapy.
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Doenças Ósseas , Doença de Gaucher , Adulto , Humanos , Masculino , Feminino , Doença de Gaucher/tratamento farmacológico , Doença de Gaucher/diagnóstico , Proteína 1 Semelhante à Quitinase-3 , Lipocalina-2 , Seguimentos , Qualidade de Vida , Biomarcadores , DorRESUMO
OBJECTIVES: To compare the efficacy of 4 different analgesic regimens that include music and nitrous oxide during the treatment of renal lithiasis with ambulatory extracorporeal shock wave lithotripsy (ESWL). MATERIALS AND METHODS: A single-centre, longitudinal, prospective, randomized, open and parallel group study was conducted. Patients with renal lithiasis were included and were randomized to Group A (basal analgesia: midazolam (1 mg), fentanyl (0.05 mg) and dexketoprofen (50 mg)), Group B (basal analgesia and nitrous oxide), Group C (basal analgesia and music) and Group D (basal analgesia, nitrous oxide and music). For the measurement of pain, a visual analogue scale ranging from 0 (no pain) to 100 (maximum pain imaginable) was used. Patient satisfaction was assessed using a Likert questionnaire. The epidemiological data of the patients in terms of lithiasis, previous clinical and ESWL sessions, and pain measured with the VAS before, during (maximum) at the end of the session and at discharge were recorded. Data on complications were also collected, as was the patients' subjective evaluation of the treatment and their satisfaction. The ESWL procedure was performed with a Storz Modulith SLX-F2® lithotripter. A maximum of 4000 waves were applied at a frequency of 1.5 Hz. RESULTS: Eighty patients were included (20 per group). None of the analgesia guidelines proved to be superior to the others for pain control during the ESWL session. Patients younger than 50 years had significantly higher values for the maximum VAS. Only 13.75% of patients required rescue analgesia. A total of 77.5% described their experience as good, very good or excellent, regardless of the assigned group. CONCLUSIONS: The addition of nitrous oxide and/or music did not result in a statistically significant improvement over the basal analgesia regimen of midazolam, fentanyl and dexketoprofen; however, the degree of patient satisfaction was very high.
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Litíase , Litotripsia , Música , Analgésicos , Fentanila/uso terapêutico , Humanos , Cetoprofeno/análogos & derivados , Litíase/complicações , Litíase/tratamento farmacológico , Litotripsia/métodos , Midazolam/uso terapêutico , Óxido Nitroso/uso terapêutico , Dor/etiologia , Dor/prevenção & controle , Estudos Prospectivos , TrometaminaRESUMO
Acidifying treatment and control of urinary pH may be an effective strategy to address recurrent lithiasic disease secondary to infective calculi. We present the case of a 39-year-old man with bilateral urolithiasis that led to episodes of complicated Reno ureteral colic.After undergoing multiple treatments by retrograde endourological surgery, he presented recurrence and progression of lithiasis disease, finally requiring percutaneous approach for treatment of a coralliform stone, after which he was free of lithiasis. It was then decided to start treatment with an acidifying oral supplement and home pH control by means of an electronic medical device as a complement to the surgeries he underwent, thus achieving stability of the disease, with absence of urinary tract infection or lithiasis recurrence.The patient, with poor adherence to previous treatments, presented in this case a correct follow-up of the treatment, as well as a high level of satisfaction with it.
El tratamiento acidificante y el control del pH urinario pueden constituir una estrategia eficaz para abordar la enfermedad litiásica recurrente secundaria a cálculos infectivos. Presentamos el caso de un varón de 39 años con urolitiasis bilaterales que le condicionaron episodios de cólicos renoureterales complicados.Tras ser sometido a múltiples tratamientos mediante cirugía endourológica retrógrada, presentó recidiva y progresión de enfermedad litiásica, precisando finalmente abordaje percutáneo para tratamiento de un cálculo coraliforme, tras lo cual queda libre de litiasis. Se decide entonces iniciar tratamiento con suplemento oral acidificante y control domiciliario de pH mediante dispositivo médico electrónico como complemento a las cirugías a las que fue sometido, logrando así estabilidad de enfermedad, con ausencia de cuadros de infección urinaria ni recidiva litiásica.El paciente, con mala adherencia a tratamientos previos, presentó en este caso un correcto seguimiento del tratamiento, así como elevado nivel de satisfacción con el mismo.
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Cálculos Renais , Litíase , Litotripsia , Infecções Urinárias , Urolitíase , Adulto , Humanos , Rim , Cálculos Renais/terapia , Litíase/cirurgia , Masculino , Urolitíase/terapiaRESUMO
BACKGROUND: Since enzyme replacement therapy for Gaucher disease (MIM#230800) has become available, both awareness of and the natural history of the disease have changed. However, there remain unmet needs such as the identification of patients at risk of developing bone crisis during therapy and late complications such as cancer or parkinsonism. The Spanish Gaucher Disease Registry has worked since 1993 to compile demographic, clinical, genetic, analytical, imaging and follow-up data from more than 400 patients. The aims of this study were to discover correlations between patients' characteristics at diagnosis and to identify risk features for the development of late complications; for this a machine learning approach involving correlation networks and decision trees analyses was applied. RESULTS: A total of 358 patients, 340 type 1 Gaucher disease and 18 type 3 cases were selected. 18% were splenectomyzed and 39% had advanced bone disease. 81% of cases carried heterozygous genotype. 47% of them were diagnosed before the year 2000. Mean age at diagnosis and therapy were 28 and 31.5 years old (y.o.) respectively. 4% developed monoclonal gammopathy undetermined significance or Parkinson Disease, 6% cancer, and 10% died before this study. Previous splenectomy correlates with the development of skeletal complications and severe bone disease (p = 0.005); serum levels of IgA, delayed age at start therapy (> 9.5 y.o. since diagnosis) also correlates with severe bone disease at diagnosis and with the incidence of bone crisis during therapy. High IgG (> 1750 mg/dL) levels and age over 60 y.o. at diagnosis were found to be related with the development of cancer. When modelling the decision tree, patients with a delayed diagnosis and therapy were the most severe and with higher risk of complications. CONCLUSIONS: Our work confirms previous observations, highlights the importance of early diagnosis and therapy and identifies new risk features such as high IgA and IgG levels for long-term complications.
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Doença de Gaucher , Aprendizado de Máquina , Fatores de Risco , Adulto , Terapia de Reposição de Enzimas , Feminino , Doença de Gaucher/complicações , Doença de Gaucher/tratamento farmacológico , Doença de Gaucher/genética , Glucosilceramidase/uso terapêutico , Humanos , Incidência , Masculino , Sistema de RegistrosRESUMO
OBJECTIVE: Review this pathology nowadays. METHODS: We search in Medline/PubMed database for reviews about cystic dysplasia of the testis. We review and discuss the relevant literature about it. RESULTS: Cystic dysplasia of the testis (CDT) is a rare benign disease, associated with upper urinary tract malformations. Its most frequent clinical manifestation is the increase of testicular size; the presence of cysts is demonstrated by ultrasound. No consensus exists in its treatment, it oftenly requires histological confirmation, performing testicle-sparing surgery. CONCLUSION: CDT needs to be taken into account in the differential diagnosis of childhood testicular tumors.
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Doenças Testiculares , Humanos , Masculino , Doenças Testiculares/diagnóstico , Doenças Testiculares/terapiaRESUMO
INTRODUCTION: Urology is a medicalsurgical specialty that deals with the study, diagnosis and treatment of medical and surgical conditions of the urinary tract and retroperitoneum in both sexes and of the male genital tract without age limit. The traditional method of training is based on the imitation of the skills and behaviors of the tutors, creating variability in the training between different centers and giving a passive role to resident internal physicians (MIR). LEGISLATIVE FRAMEWORK: The 2006 BOE establishes the specific formative content in its theoretical, practical and scientific facets. At the beginning of the MIR training period, the first year focuses on general surgical training and the remaining four on specific urological training. The current legislative framework that regulates our specialty is one of the oldest, with no prospect of renewal, since this would be carried out with the development of the trunk project, currently paralyzed after the judgment of the Supreme Court. Therefore, we are in a situation of uncertainty with a legal framework in renewal plans. CURRENT STATE OF TRAINING: a National survey shows the degree of surgical participation of the MIR is low, as well as training on models and course attendance. In addition, the self-confidence they feel for interventions that could be considered of low complexity is high, for activities such as consultation is moderate and for interventions of moderate-high complexity is low. CONCLUSION: The current training program is upgradeable. New studies and efforts should aim to standardize the acquisition of surgical and non-surgical skills, guarantee access to surgical training courses, establish a minimum of required interventions per year and at the end of residency, foster academic training, participation in research of residents and achieve an objective assessment of the specialty.
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Urologia/educação , Currículo , Internato e Residência , EspanhaRESUMO
Climate impacts of forest bioenergy result from a multitude of warming and cooling effects and vary by location and technology. While past bioenergy studies have analysed a limited number of climate-altering pollutants and activities, no studies have jointly addressed supply chain greenhouse gas emissions, biogenic CO2 fluxes, aerosols and albedo changes at high spatial and process detail. Here, we present a national-level climate impact analysis of stationary bioenergy systems in Norway based on wood-burning stoves and wood biomass-based district heating. We find that cooling aerosols and albedo offset 60-70% of total warming, leaving a net warming of 340 or 69 kg CO2e MWh-1 for stoves or district heating, respectively. Large variations are observed over locations for albedo, and over technology alternatives for aerosols. By demonstrating both notable magnitudes and complexities of different climate warming and cooling effects of forest bioenergy in Norway, our study emphasizes the need to consider multiple forcing agents in climate impact analysis of forest bioenergy.
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Waste-to-Energy (WtE) plants constitute one of the most common waste management options to deal with municipal solid waste. WtE plants have the dual objective to reduce the amount of waste sent to landfills and simultaneously to produce useful energy (heat and/or power). Energy from WtE is gaining steadily increasing importance in the energy mix of several countries. Norway is no exception, as energy recovered from waste currently represents the main energy source of the Norwegian district heating system. Life-cycle assessments (LCA) of WtE systems in a Norwegian context are quasi-nonexistent, and this study assesses the environmental performance of a WtE plant located in central Norway by combining detailed LCA methodology with primary data from plant operations. Mass transfer coefficients and leaching coefficients are used to trace emissions over the various life-cycle stages from waste logistics to final disposal of the ashes. We consider different fractions of input waste (current waste mix, insertion of 10% car fluff, 5% clinical waste and 10% and 50% wood waste), and find a total contribution to Climate Change Impact Potential ranging from 265 to 637gCO2eq/kg of waste and 25 to 61gCO2eq/MJ of heat. The key drivers of the environmental performances of the WtE system being assessed are the carbon biogenic fraction and the lower heating value of the incoming waste, the direct emissions at the WtE plant, the leaching of the heavy metals at the landfill sites and to a lesser extent the use of consumables. We benchmark the environmental performances of our WtE systems against those of fossil energy systems, and we find better performance for the majority of environmental impact categories, including Climate Change Impact Potential, although some trade-offs exist (e.g. higher impacts on Human Toxicity Potential than natural gas, but lower than coal). Also, the insertion of challenging new waste fractions is demonstrated to be an option both to cope with the excess capacity of the Norwegian WtE sector and to reach Norway's ambitious political goals for environmentally friendly energy systems.
Assuntos
Fontes Geradoras de Energia , Meio Ambiente , Resíduos Sólidos/análise , Gerenciamento de Resíduos/métodos , Dióxido de Carbono/análise , Mudança Climática , Eutrofização , Água Doce , Humanos , Óxidos de Nitrogênio/análise , Noruega , Ozônio , Material Particulado/análise , Dióxido de Enxofre/análise , Madeira/químicaRESUMO
Background: Renal colic is characterized by sharp, intense flank pain. Nonsteroidal anti-inflammatory drugs are the treatment of choice, although extracorporeal shock wave lithotripsy (SWL) is a noninvasive alternative for pain management. The objective of our study is to present results obtained using rapid SWL to treat renal colic in our center. Methods: We analyzed 214 patients undergoing rapid shockwave extracorporeal lithotripsy between October 2014 and June 2018: 69.63% were male, and 30.37% female, with a mean age of 47.35 years (range, 1684). The average stone size was 6.71 mm (316). Stone locations were as follows: The pelviureteric junction (PUJ) (10.75%), proximal ureter (45.79%), midureter (24.77%), and distal ureter (18.69%). Results: Pain relief was achieved in 81.31% of the patients. The rates of successful pain control according to stone location were 65.22% when the stone was located in the PUJ, 79.59% in the proximal ureter, 88.68% in the midureter, and 85.00% in the distal ureter. Complete or partial stone resolution was achieved 4 weeks postoperatively in 78.50% of cases (64.95% and 13.55%, respectively). According to the stone location, the overall rate of resolution (complete + partial) was 90.00% for distal ureteral stones, 86.80% in the midureter, 73.47% in the proximal ureter, and 60.86% in the PUJ. 44 patients (20.56%) demonstrated complications. The most common complications were persistent pain, acute renal failure and fever. Conclusions: Immediate SWL was found to be a safe and effective treatment option for pain related to renal colic in 81% of the patients studied (AU)