Impacto de los sistemas de nefrometría renal en la valoración de las complicaciones en el tratamiento percutáneo guiado por imagen de las masas renales de pequeño tamaño / Usefulness of renal nephrometry scoring systems in the prediction of complications associated to percutaneous image-guided treatment for small renal masses

Introducción Los tumores renales son un desafío para los profesionales de la salud debido a su creciente prevalencia y complejidad de manejo. El estudio investiga la utilidad de los sistemas de nefrometría renal R.E.N.A.L. score y Padua en la predicción de complicaciones de la crioablación percutánea (CA). Material y métodos El estudio analiza de forma prospectiva a 90 pacientes con carcinoma de células renales (CCR) estadio T1a tratados con crioablación, totalizando 101 tumores. Resultados Se estudiaron 90 pacientes con 101 tumores renales de pequeño tamaño que recibieron terapia crioablativa. Los pacientes tenían una edad media de 68 años y mayoría eran hombres (74,4%). La mayoría de los tumores eran menores a 4 cm (89,1%) y la puntuación media del Padua y R.E.N.A.L. scores fue de 8,65 y 7,35, respectivamente. Se observaron complicaciones en 12 casos. El PADUA y R.E.N.A.L. scores demostraron un poder predictivo moderado (área bajo la curva [AUC] = 0,58 y AUC = 0,63, respectivamente) para las complicaciones poscrioablación. Conclusiones La CA es un tratamiento seguro y efectivo para los tumores renales de pequeño tamaño. Los sistemas de nefrometría renal R.E.N.A.L. y Padua scores tienen un poder predictivo moderado para las complicaciones asociadas a la CA de tumores renales. (AU)

Introduction Due to their increasing prevalence and complex management, renal tumors are challenging for health professionals. The study aims to evaluate the usefulness of R.E.N.A.L. and PADUA nephrometry scores in the prediction of complications after percutaneous cryoablation. Material and methods The study prospectively analyzed 90 patients with 101 stage T1a renal cell carcinoma (RCC) tumors treated with cryoablation. Results Ninety patients with 101 small renal tumors who received cryoablative therapy were investigated. The mean age of the patients was 68 years and 74.4% were male. Most tumors were smaller than 4 cm (89.1%) and the mean PADUA and R.E.N.A.L. scores were 8.65 and 7.35, respectively. Complications were observed in 12 cases. PADUA and R.E.N.A.L. scores demonstrated moderate predictive power (AUC = 0.58 and AUC = 0.63, respectively) for post-cryoablation complications. Conclusions Percutaneous cryoablation is a safe and effective treatment for small renal tumors. The R.E.N.A.L. and PADUA renal nephrometry scores have moderate predictive power for complications associated with percutaneous cryoablation of renal tumors. (AU)

Innovaciones tecnológicas en la litotricia de ondas de choque / Technological innovations in shock wave lithotripsy

Introducción Desde 1980, la litotricia extracorpórea por ondas de choque (SWL) ha sido empleada en el tratamiento de las litiasis urinarias, ofreciendo alternativas no invasivas a las técnicas quirúrgicas. Aunque limitada por tamaño y ubicación de las piedras, su efectividad se ve afectada por varios factores. A pesar de la evolución de técnicas quirúrgicas, la SWL podría mantener su relevancia con nuevos avances. Nuestro objetivo es revisar la bibliografía existente para recopilar los mayores avances hasta la fecha en el tratamiento extracorpóreo de la litiasis. Material y métodos Se ha realizado una revisión bibliográfica no sistemática, entre los años 2017 a 2023 para obtener 26 artículos sobre 3 tipos de innovación tecnológica en litotricia extracorpórea: Burst Wave Lithotripsy (BWL), Histotripsy y Microbubble Lithotripsy (ML). Resultados La BWL emplea ondas sinusoidales ultrasónicas de menor y mayor frecuencia que la SWL tradicional. Su mecanismo de acción genera una fragmentación de mayor calidad (finos fragmentos) en lugar de generar fuerzas tensionales como en la SWL tradicional que generan líneas de fractura que dan lugar a fragmentos de mayor tamaño. Resultados en cerdos y humanos han mostrado fragmentación efectiva con buen perfil de seguridad. Basada en la tecnología de ultrasonido focalizado de alta intensidad (HIFU), la histotricia fragmenta tejido empleando fenómenos de cavitación. Han mostrado buenos resultados in vitro, aunque la formación de microburbujas que se interponen entre la litiasis y las ondas de ultrasonido son un impedimento para el progreso de esta técnica. La ML combina microburbujas y ultrasonido para fragmentar litiasis con seguridad y eficacia. Resultados in vitro y en cerdos son prometedores. Puede optimizar tratamientos y reducir niveles energéticos. Conclusiones La innovación tecnológica no solo se está aplicando a técnicas endourológicas, sino también a la ESWL. ... (AU)

Introduction Since 1980, extracorporeal Shock Wave Lithotripsy (SWL) has been employed in the treatment of urolithiasis, offering noninvasive alternatives to surgical techniques. In addition to being limited by the size and location of the stones, its efficacy is influenced by several factors. Despite the advancement of other surgical techniques, SWL could maintain its position with new improvements. Our objective is to review the existing literature on the latest advances in the extracorporeal treatment of lithiasis. Material and methods A non-systematic literature review was carried out from 2017 to 2023 to obtain 26 articles on three different emerging technologies in extracorporeal lithotripsy: Burst Wave Lithotripsy (BWL), Histotripsy, and Microbubble Lithotripsy (ML). Results The BWL uses sinusoidal bursts of US waves delivered at lower and higher frequencies than conventional SWL. Its mechanism of action generates a higher quality fragmentation (fine fragments) instead of generating tensile stresses for stone fracture resulting in larger fragments, as in traditional SWL. Studies in pigs and humans have shown effective fragmentation with a good safety profile. Based on High Intensity Focused Ultrasound (HIFU) technology, histotripsy fragments tissue through cavitation. Good in vitro results have been shown, but the formation of microbubbles between the stone and ultrasound waves hinders the progress of this technique. Microbubble Lithotripsy (ML) combines microbubbles and ultrasound for safe and effective stone fragmentation. In vitro and pig results are promising. This technique can help optimize treatments and reduce energy levels. Conclusions Technological innovation is not only being applied to endourological techniques, but also to ESWL. New techniques such as BWL, histotripsy and ML are promising, with good results in the research phase. (AU)

Usefulness of renal nephrometry scoring systems in the prediction of complications associated to percutaneous image-guided treatment for small renal masses.

INTRODUCTION: Due to their increasing prevalence and complex management, renal tumors are challenging for health professionals. The study aims to evaluate the usefulness of R.E.N.A.L. and PADUA nephrometry scores in the prediction of complications after percutaneous cryoablation. MATERIAL AND METHODS: The study prospectively analyzed 90 patients with 101 stage T1a renal cell carcinoma (RCC) tumors treated with cryoablation. RESULTS: Ninety patients with 101 small renal tumors who received cryoablative therapy were investigated. The mean age of the patients was 68 years and 74.4% were male. Most tumors were smaller than 4 cm (89.1%) and the mean PADUA and R.E.N.A.L. scores were 8.65 and 7.35, respectively. Complications were observed in 12 cases. PADUA and R.E.N.A.L. scores demonstrated moderate predictive power (AUC = 0.58 and AUC = 0.63, respectively) for post-cryoablation complications. CONCLUSIONS: Percutaneous cryoablation is a safe and effective treatment for small renal tumors. The R.E.N.A.L. and PADUA renal nephrometry scores have moderate predictive power for complications associated with percutaneous cryoablation of renal tumors.

Technological innovations in shock wave lithotripsy.

INTRODUCTION: Since 1980, extracorporeal shock wave lithotripsy (SWL) has been employed in the treatment of urolithiasis, offering noninvasive alternatives to surgical techniques. In addition to being limited by the size and location of the stones, its efficacy is influenced by several factors. Despite the advancement of other surgical techniques, SWL could maintain its position with new improvements. Our objective is to review the existing literature on the latest advances in the extracorporeal treatment of lithiasis. MATERIAL AND METHODS: A non-systematic literature review was carried out from 2017 to 2023 to obtain 26 articles on three different emerging technologies in extracorporeal lithotripsy: Burst Wave Lithotripsy (BWL), Histotripsy, and Microbubble Lithotripsy (ML). RESULTS: The BWL uses sinusoidal bursts of US waves delivered at lower and higher frequencies than conventional SWL. Its mechanism of action generates a higher quality fragmentation (fine fragments) instead of generating tensile stresses for stone fracture resulting in larger fragments, as in traditional SWL. Studies in pigs and humans have shown effective fragmentation with a good safety profile. Based on High Intensity Focused Ultrasound (HIFU) technology, histotripsy fragments tissue through cavitation. Good in vitro results have been shown, but the formation of microbubbles between the stone and ultrasound waves hinders the progress of this technique. Microbubble Lithotripsy (ML) combines microbubbles and ultrasound for safe and effective stone fragmentation. In vitro and pig results are promising. This technique can help optimize treatments and reduce energy levels. CONCLUSIONS: Technological innovation is not only being applied to endourological techniques, but also to ESWL. New techniques such as BWL, histotripsy and ML are promising, with good results in the research phase.

Gastric GDF15 levels are regulated by age, sex, and nutritional status in rodents and humans.

AIM: Growth differentiation factor 15 (GDF15) is a stress response cytokine that has been proposed as a relevant metabolic hormone. Descriptive studies have shown that plasma GDF15 levels are regulated by short term changes in nutritional status, such as fasting, or in obesity. However, few data exist regarding how GDF15 levels are regulated in peripheral tissues. The aim of the present work was to study the variations on gastric levels of GDF15 and its precursor under different physiological conditions, such as short-term changes in nutritional status or overfeeding achieved by HFD. Moreover, we also address the sex- and age-dependent alterations in GDF15 physiology. METHODS: The levels of gastric and plasma GDF15 and its precursor were measured in lean and obese mice, rats and humans by western blot, RT-PCR, ELISA, immunohistochemistry and by an in vitro organ culture system. RESULTS: Our results show a robust regulation of gastric GDF15 production by fasting in rodents. In obesity an increase in GDF15 secretion from the stomach is reflected with an increase in circulating levels of GDF15 in rats and humans. Moreover, gastric GDF15 levels increase with age in both rats and humans. Finally, gastric GDF15 levels display sexual dimorphism, which could explain the difference in circulating GFD15 levels between males and females, observed in both humans and rodents. CONCLUSIONS: Our results provide clear evidence that gastric GDF15 is a critical contributor of circulating GDF15 levels and can explain some of the metabolic effects induced by GDF15.

Uroguanylin: a new actor in the energy balance movie.

Uroguanylin (UGN) is a potential target in the fight against obesity. The mature protein is released after enzymatic cleavage from its natural precursor, proUGN. UGN is mostly produced in the gut, and its production is regulated by nutritional status. However, UGN is also produced in other tissues such as the kidneys. In the past, UGN has been widely studied as a natriuretic peptide owing to its involvement in several different pathologies such as heart failure, cancer and gastrointestinal diseases. However, recent studies have suggested that UGN also acts as a regulator of body weight homeostasis because it modulates both food intake and energy expenditure. This ultimately results in a decrease in body weight. This action is mediated by the sympathetic nervous system. Future studies should be directed at the potential effects of UGN agonists in regulating body weight in human obesity.

Eritema ab igne, un peculiar efecto secundario del ordenador portátil / Erythema ab igne, a peculiar side effect of laptops

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Analysis of pulmonary non-tuberculous mycobacterial infections after lung transplantation.

PURPOSE: Non-tuberculous mycobacteria (NTM) are important pathogens in lung transplant recipients. This study describes the spectrum of NTM respiratory tract infections and examines the association of NTM infections with lung transplant complications. METHODS: Data from 208 recipients transplanted from November 1990 to November 2005 were analyzed. Follow-up data were available to November 2010. Lung infection was defined by bronchoalveolar lavage, sputum, or blood cultures in the appropriate clinical setting. All identified NTM respiratory tract infections were tabulated. The cohort of patients with NTM lung infections (NTM+) were compared to the cohort without infection (NTM-). Univariate and multivariate analysis was performed to determine characteristics associated with NTM infection. Survival analyses for overall survival and development of bronchiolitis obliterans syndrome (BOS) were also performed. RESULTS: In total, 52 isolates of NTM lung infection were identified in 30 patients. The isolates included Mycobacterium abscessus (46%), Mycobacterium avium complex (MAC) (36%), Mycobacterium gordonae (9%), Mycobacterium chelonae (7%), and Mycobacterium fortuitum (2%), with multiple NTM isolates seen on 3 different occasions. The overall incidence was 14%, whereas cumulative incidences at 1, 3, and 5 years after lung transplantation were 11%, 15%, and 20%, respectively. Comparisons between the NTM+ and NTM- cohorts revealed that NTM+ patients were more likely to be African-American and have cytomegalovirus mismatch. Although no difference was seen in survival, the NTM+ cohort was more likely to develop BOS (80% vs. 58%, P = 0.02). NTM+ infection, however, was not independently associated with development of BOS by multivariate analysis. CONCLUSION: With nearly 20 years of follow-up, 14% of lung recipients develop NTM respiratory tract infections, with M. abscessus and MAC more commonly identified. M. gordonae was considered responsible for nearly 10% of NTM infections. Although survival of patients with NTM infections is similar, a striking difference in BOS rates is present in the NTM+ and NTM- groups.

FNDC5 is produced in the stomach and associated to body composition.

The fibronectin type III domain-containing protein 5 (FNDC5) discovered in 2002 has recently gained attention due to its potential role in protecting against obesity. In rat, no data exist regarding FNDC5 production and regulation in the stomach. The aim of the present work was to determine the expression of FNDC5 in the rat stomach and its potential regulation by body composition. The present data shows FNDC5 gene expression in the gastric mucosa. Immunohistochemical studies found FNDC5 immunopositivity in chief cells of gastric tissue. By the use of three different antibodies FNDC5 was found expressed in gastric mucosa and secreted by the stomach. The rate of gastric FNDC5 secretion parallels the circulating levels of FNDC5. The body fat mass increase after intervention with high fat diet coincided with a decrease in the secretion of FNDC5 from the stomach and a diminution in the FNDC5 circulating levels. In summary, the present data shows, for the first time, the expression of FNDC5 in the stomach of rats and its regulation by body composition, suggesting a potential role of gastric FNDC5 in energy homeostasis.

Secreted factors derived from obese visceral adipose tissue regulate the expression of breast malignant transformation genes.

BACKGROUND/OBJECTIVES: Obese adipose tissue, especially the visceral depot, exhibits altered production of several molecules that could have a role on the initiation/promotion of breast cancer development. The aim of this work was to evaluate the effect of excess adipose tissue and its secreted factors on the expression of genes involved in the early steps of tumor promotion on the mammary gland. SUBJECTS AND METHODS: Carcinogenesis-related gene expression was evaluated in mammary gland tissue from female diet-induced obese (DIO) Sprague-Dawley rats and circulating leukocytes isolated from a group of breast cancer diagnosed and non-diagnosed obese women and compared with their normal weight counterparts. In addition, the human non-tumoral mammary epithelial cell line MCF10A was treated in vitro with the visceral (retroperitoneal adipose tissue (RPAT)) or subcutaneous adipose tissue (SAT) secretome and with rising concentrations of the lipid peroxidation by-product 4-hydroxynonenal (4-HNE). RESULTS: DIO rats were classified as susceptible to DIO (DIO-S) or partially resistant to DIO (DIO-R) according to the maximum fat mass gain of the lean group as a cut-off. As compared with lean and DIO-R, the DIO-S group showed a higher fat mass and lower lean mass. The anatomical characteristic of DIO-S was correlated with differential expression of cellular proliferation (ALDH3A1 and MYC) and antioxidant and DNA protection (GSTM2, SIRT1), and tumor suppression (TP53, PTEN, TGFB1) genes. Remarkably, this carcinogenesis-related gene expression pattern was reproduced in MCF10A treated with the RPAT secretome from DIO-S rats and with the lipid peroxidation by-product 4-HNE. Moreover, this pattern was also detected in leukocytes from obese women compared with normal weight women without evidence of breast cancer. CONCLUSIONS: Lipid peroxides secreted by the obese visceral adipose tissue could be among the relevant factors that promote changes involved in the early steps of tumor development in mammary gland. These changes can be detected even before histological alterations and in circulating leukocytes.

Uroguanylin levels in intestine and plasma are regulated by nutritional status in a leptin-dependent manner.

PURPOSE: Uroguanylin (UGN) is a 16 amino acid peptide produced mainly by intestinal epithelial cells. Nutrients intake increases circulating levels of prouroguanylin that is processed and converted to UGN to activate the guanylyl cyclase 2C receptor (GUCY2C). Given that the UGN-GUCY2C system has been proposed as a novel gut-brain endocrine axis regulating energy balance, the aim of the present study was to investigate the regulation of UGN protein levels in duodenum and circulating levels in lean and obese mice under different nutritional conditions and its potential interaction with leptin. METHODS: Swiss, C57BL/6 wild-type and ob/ob male adult mice under different nutritional conditions were used: fed ad libitum standard diet (control); 48 h fasting (fasted); 48 h fasting followed by 24 h of feeding (refed); and fed high-fat diet (45 %) during 10 weeks. In addition, peripheral leptin administration was performed. Intestinal uroguanylin expression was studied by Western blot analysis; plasma levels were measured by ELISA. RESULTS: Food deprivation significantly reduced plasma UGN levels, which were correlated with the lower protein levels of UGN in duodenum. These effects were reverted after refeeding and leptin challenge. Consistently, in ob/ob mice UGN expression was decreased, whereas leptin treatment up-regulated UGN levels in duodenum in these genetically modified mice compared to WT. Diet-induced obese mice displayed increased UGN levels in intestine and plasma in comparison with lean mice. CONCLUSIONS: Our findings suggest that UGN levels are correlated with energy balance status and that the regulation of UGN by nutritional status is leptin-dependent.

Drug development strategies for the treatment of obesity: how to ensure efficacy, safety, and sustainable weight loss.

The prevalence of obesity has increased worldwide, and approximately 25%-35% of the adult population is obese in some countries. The excess of body fat is associated with adverse health consequences. Considering the limited efficacy of diet and exercise in the current obese population and the use of bariatric surgery only for morbid obesity, it appears that drug therapy is the only available method to address the problem on a large scale. Currently, pharmacological obesity treatment options are limited. However, new antiobesity drugs acting through central nervous system pathways or the peripheral adiposity signals and gastrointestinal tract are under clinical development. One of the most promising approaches is the use of peptides that influence the peripheral satiety signals and brain-gut axis such as GLP-1 analogs. However, considering that any antiobesity drug may affect one or several of the systems that control food intake and energy expenditure, it is unlikely that a single pharmacological agent will be effective as a striking obesity treatment. Thus, future strategies to treat obesity will need to be directed at sustainable weight loss to ensure maximal safety. This strategy will probably require the coadministration of medications that act through different mechanisms.

The brain-stomach connection.

The stomach-brain connection has been revealed to be one of the most promising targets in treating obesity. The stomach plays a key role in the homeostatic mechanism implicating stomach-brain communication regulated under neural and hormonal control. The present review explores specific topics related to gut-brain interactions focus on the stomach-brain connection through the different known systems implied in energy balance control as ghrelin, and nesfatin. Moreover, novel mechanisms for energy balance regulation involving gastric-brain communication are described including the role of the gastric intracellular mTOR/S6K1 pathway mediating the interaction among ghrelin, nesfatin and endocannabinoid gastric systems to modulate metabolism.

The vagus nerve as a regulator of growth hormone secretion.

The growth hormone (GH) axis is mainly regulated by the growth hormone releasing hormone (GHRH) and somatostatin (SS) hypothalamic peptides. Nevertheless, since ghrelin peptide was discovered as the natural ligand for growth hormone secretagogue receptor (GHS-R), the mechanism of GH regulation has acquired a new dimension. It was described that ghrelin possesses a relevant effect inducing GH secretion when it is administered peripherally. A role of the vagus nerve mediating ghrelin action has been described although this effect is not understood. Under this context the main objective of this work was to determine the possible involvement of the vagus in the somatotroph axis regulation. The results in this manuscript show that animals with a disruption of the vagus connection presented lower basal IGF-1 and GH levels, a decreased GH response to peripheral GHRH administration and a marked diminution in the GH response to peripheral and central ghrelin treatments. In addition, vagotomized animals showed a down-regulation of GHRH mRNA in the arcuate nucleus of the hypothalamus and a down-regulation in both GHRH and GHS receptors' mRNA at the pituitary level. In conclusion, the present work reveals that the vagus nerve is crucial in growth hormone regulation and essential for the full GH-releasing effect of ghrelin.

Macronutrients act directly on the stomach to regulate gastric ghrelin release.

BACKGROUND: Ghrelin is a gastric secreted hormone deeply implicated in meal initiation and body weight regulation. This peptide is a peripheral orexigenic hormone with a nutritional status-dependent regulation showing a pre-pandrial rise and post-prandial fall pattern. A wide variety of studies have tested the effect of meal different nutrient composition over stomach mucosa ghrelin content and plasmatic ghrelin levels; nevertheless, few and non-conclusive data exist about the direct action of macronutrients on the stomach in order to regulate ghrelin secretion. The recent identification of taste receptors or chemoreceptors in the stomach mucosa would reinforce this paradigm. AIMS: To investigate the individual effect of different macronutrients (l-glutamine, lipids, and glucose) over gastric ghrelin secretion by using an in vitro gastric explants model. RESULTS: L-glutamine and intralipid emulsion act locally in the stomach decreasing ghrelin secretion, while no effect was found after glucose exposure. CONCLUSIONS: These results show for the first time that macronutrients, and specially amino acids and lipids, act directly in the stomach in order to regulate gastric ghrelin release. Consequently, the chemosensory capacity of the stomach, until now restricted to the oral cavity or intestine, is demonstrated.