A metabolomics pipeline for the mechanistic interrogation of the gut microbiome.

Gut microorganisms modulate host phenotypes and are associated with numerous health effects in humans, ranging from host responses to cancer immunotherapy to metabolic disease and obesity. However, difficulty in accurate and high-throughput functional analysis of human gut microorganisms has hindered efforts to define mechanistic connections between individual microbial strains and host phenotypes. One key way in which the gut microbiome influences host physiology is through the production of small molecules1-3, yet progress in elucidating this chemical interplay has been hindered by limited tools calibrated to detect the products of anaerobic biochemistry in the gut. Here we construct a microbiome-focused, integrated mass-spectrometry pipeline to accelerate the identification of microbiota-dependent metabolites in diverse sample types. We report the metabolic profiles of 178 gut microorganism strains using our library of 833 metabolites. Using this metabolomics resource, we establish deviations in the relationships between phylogeny and metabolism, use machine learning to discover a previously undescribed type of metabolism in Bacteroides, and reveal candidate biochemical pathways using comparative genomics. Microbiota-dependent metabolites can be detected in diverse biological fluids from gnotobiotic and conventionally colonized mice and traced back to the corresponding metabolomic profiles of cultured bacteria. Collectively, our microbiome-focused metabolomics pipeline and interactive metabolomics profile explorer are a powerful tool for characterizing microorganisms and interactions between microorganisms and their host.

The effect of pregnancy on the course of uveitis in single and multiple pregnancies.

PURPOSE: To explore the effect of pregnancy on the clinical course, outcome, and treatment in multiparous women with non-infectious uveitis. METHODS: Retrospective study of women with a history of non-infectious uveitis and pregnancies prior to and during disease course. Disease activity and severity 1-year prior pregnancy, during pregnancy, and 1-year postpartum were recorded as well as patients' and diseases' characteristics. The main outcome measures included the rate and severity of uveitis attacks and the effect on ocular complications and therapies. RESULTS: Included were 32 women (70 pregnancies, mean of 2.6 pregnancies/patient), with a mean follow-up time of 6.5 years. The most common uveitis types were anterior (31%) and pan-uveitis (31%). Flare-ups were more frequent in the year prior to pregnancy, in the first trimester, and in the postpartum period and decreased markedly during pregnancy. Women who experienced a flare-up during pregnancy had a higher rate of flare-ups in the year prior pregnancy than those who did not experience a flare-up during pregnancy (p-0.047). The rate of flare-ups 12 months' postpartum was also higher compared to women without any flare-up during pregnancy (p = 0.01). Severity of flare-ups in the postpartum period was worse in women who experienced a flare-up during pregnancy compared to women without flare-ups (p = 0.001). The severity of flare-ups was higher in the first pregnancy compared to subsequent pregnancies. CONCLUSIONS: Women who had active or non-controlled uveitis prior to pregnancy have higher disease activity and severity during pregnancy as well. The first pregnancy seems to behave differently from subsequent pregnancies, in terms of disease severity.

Multi-Annual Evaluation of Time Series of Sentinel-1 Interferometric Coherence as a Tool for Crop Monitoring.

Interferometric coherence from SAR data is a tool used in a variety of Earth observation applications. In the context of crop monitoring, vegetation indices are commonly used to describe crop dynamics. The most frequently used vegetation indices based on radar data are constructed using the backscattered intensity at different polarimetric channels. As coherence is sensitive to the changes in the scene caused by vegetation and its evolution, it may potentially be used as an alternative tool in this context. The objective of this work is to evaluate the potential of using Sentinel-1 interferometric coherence for this purpose. The study area is an agricultural region in Sevilla, Spain, mainly covered by 18 different crops. Time series of different backscatter-based radar vegetation indices and the coherence amplitude for both VV and VH channels from Sentinel-1 were compared to the NDVI derived from Sentinel-2 imagery for a 5-year period, from 2017 to 2021. The correlations between the series were studied both during and outside the growing season of the crops. Additionally, the use of the ratio of the two coherences measured at both polarimetric channels was explored. The results show that the coherence is generally well correlated with the NDVI across all seasons. The ratio between coherences at each channel is a potential alternative to the separate channels when the analysis is not restricted to the growing season of the crop, as its year-long temporal evolution more closely resembles that of the NDVI. Coherence and backscatter can be used as complementary sources of information, as backscatter-based indices describe the evolution of certain crops better than coherence.

Range Spectral Filtering in SAR Interferometry: Methods and Limitations.

A geometrical decorrelation constitutes one of the sources of noise present in Synthetic Aperture Radar (SAR) interferograms. It comes from the different incidence angles of the two images used to form the interferograms, which cause a spectral (frequency) shift between them. A geometrical decorrelation must be compensated by a specific filtering technique known as range filtering, the goal of which is to estimate this spectral displacement and retain only the common parts of the images' spectra, reducing the noise and improving the quality of the interferograms. Multiple range filters have been proposed in the literature. The most widely used methods are an adaptive filter approach, which estimates the spectral shift directly from the data; a method based on orbital information, which assumes a constant-slope (or flat) terrain; and slope-adaptive algorithms, which consider both orbital information and auxiliary topographic data. Their advantages and limitations are analyzed in this manuscript and, additionally, a new, more refined approach is proposed. Its goal is to enhance the filtering process by automatically adapting the filter to all types of surface variations using a multi-scale strategy. A pair of RADARSAT-2 images that mapped the mountainous area around the Etna volcano (Italy) are used for the study. The results show that filtering accuracy is improved with the new method including the steepest areas and vegetation-covered regions in which the performance of the original methods is limited.

The inadequate use of the determination coefficient in analytical calibrations: How other parameters can assess the goodness-of-fit more adequately.

Simple linear regression using ordinary least-squares is the most common function applied in laboratories for analytical calibrations. The determination and/or the correlation coefficients are usually the parameters applied for assessing the goodness-of-fit of a simple linear calibration. However, these parameters are unable to detect the highly biased results at low calibration levels that are obtained with ordinary least-squares. In this study, the use of other parameters based on the relative standard errors of the calculated contents is evaluated. It has been found that these alternative parameters can detect the biased results obtained at low calibration levels with ordinary least-squares, being the relative standard error the one that seems to provide the most adequate results. Ordinary least-squares should only be applied if the lower limit of quantification is set to at least five times above the conventional limit of quantification. For trace analysis, where the lowest possible limit of quantification is required, weighted least-squares should be applied to obtain accurate estimates, especially at low concentrations. One of the greatest advantages of the relative standard error is that this parameter can be determined for all types of regression functions and is not limited to calibrations with linear relationships between the variables.

Linear calibrations in chromatography: The incorrect use of ordinary least squares for determinations at low levels, and the need to redefine the limit of quantification with this regression model.

Ordinary least squares is widely applied as the standard regression method for analytical calibrations, and it is usually accepted that this regression method can be used for quantification starting at the limit of quantification. However, it requires calibration being homoscedastic and this is not common. Different calibrations have been evaluated to assess whether ordinary least squares is adequate to quantify estimates at low levels. All calibrations evaluated were linear and heteroscedastic. Despite acceptable values for precision at limit of quantification levels were obtained, ordinary least squares fitting resulted in significant and unacceptable bias at low levels. When weighted least squares regression was applied, bias at low levels was solved and accurate estimates were obtained. With heteroscedastic calibrations, limit values determined by conventional methods are only appropriate if weighted least squares are used. A "practical limit of quantification" can be determined with ordinary least squares in heteroscedastic calibrations, which should be fixed at a minimum of 20 times the value calculated with conventional methods. Biases obtained above this "practical limit" were acceptable applying ordinary least squares and no significant differences were obtained between the estimates measured using weighted and ordinary least squares when analyzing real-world samples.

Evaluation and optimization of the derivatization reaction conditions of glyphosate and aminomethylphosphonic acid with 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate using reversed-phase liquid chromatography.

Due to the polar and ionic characteristics of glyphosate and its main metabolite, aminomethylphosphonic acid, a derivatization reaction is required before performing liquid chromatographic determination of these compounds. In this study, reaction conditions using 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate as the derivatization reagent are assessed. A two-level full-factorial design is applied here to optimize the derivatization time (ranging from 0.5 to 20 min) and temperature (from 24 to 55°C). It is found that neither of these two variables have a significant effect on the derivatization process and that the reaction is quantitatively achieved in a few seconds at room temperature (24°C). The results obtained indicate that derivatization reaction with 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate is achieved in milder conditions, with a faster kinetic reaction, than those required with the most conventional derivatization reagents used today, and the derivatives are more stable. It has been found that the most important parameter affecting the chromatographic separation is the pH of the mobile phase, as it has a significant effect on the retention time of the hydrolyzed excess of reagent. When ammonium acetate is used in the mobile phase, buffered solutions at pH around 5.0 are required.

Inclusion of limited amounts of extruded legumes plus cereal mixes in normocaloric or obesogenic diets for rats: effects on intestinal microbiota composition.

BACKGROUND: Differences in the composition of the intestinal microbiota and energetic metabolism between lean and obese populations have been described. Legume consumption has been reported to modulate intestinal microbiota composition. However, to the best of our knowledge, no information can be found in the literature on the effects of consumption of diets containing extruded legume plus cereal mixes on the intestinal microbiota composition of rats. Our purpose was to evaluate the effects on lipids profile (see the accompanying paper) and intestinal microbiota composition (current paper) of incorporating this new food ingredient in normocaloric and obesogenic diets. RESULTS: Intestinal and fecal qPCR-based microbial composition of rats fed the extruded legumes plus cereal mixes differed (P < 0.05) from controls. Obesogenic diets did not affect bacterial counts. However, the inclusion of the extruded mixes reduced (P < 0.05) log10 counts in some bacterial groups and increased (P < 0.05) counts of Lactobacilli, while others remained unaffected. PCoA at the genus level grouped together Lactobacillus reuteri, Akkermansia miciniphila and species from Parabacteroides, Prevotella, Rikenellaceae, and Lactobacillus with extruded legume plus cereal diets. Feeding on extruded legumes plus cereal mixes was associated with increased mRNA expression of the cytokines IL6 and TNF-α and decreased expression of TLR4. CONCLUSIONS: Our results show that the inclusion in the feed of limited amounts of extruded legumes plus cereal mix, providing a diet that is closer to a normal human one, did modulate the intestinal microbiota composition. Taken together, these results point to the protective, health-promoting properties of extruded legume plus cereal mixes.

2,5-Dimethylfuran as a Validated Biomarker of Smoking Status.

INTRODUCTION: Exposure biomarkers are required in tobacco use studies to accurately assess smoking status since self-reporting usually results in misclassification estimates. This study uses breath analysis and assesses some volatile organic compounds (VOCs) as potential biomarkers of tobacco smoke exposure. METHODS: Forced-expiratory breath samples were obtained from 377 volunteers (174 smokers and 203 nonsmokers). Exhaled breath levels of different VOCs previously related to tobacco smoke were evaluated. The toluene-to-benzene ratio was evaluated as this ratio has been found to be different in atmospheric samples and tobacco smoke emissions. Finally, breath analyses from 64 patients attending a clinical practice were evaluated and the results were compared to their self-reporting status. RESULTS: Univariate analysis shows that all compounds evaluated gave significant differences (p < .001). Receiver operating characteristic (ROC) curves suggest that xylenes and toluene are not able to accurately determine smoking status, and benzene and the T/B ratio present potential utility in certain conditions. The highest discriminant capacity was obtained for 2,5-dimethylfuran (AUC = 0.982, 95% confidence interval [CI]: 0.969-0.995), with a cut-off value of 0.016 ppbv (sensibility = 0.965, specificity = 0.896). Drinking coffee was the only confounding parameter that can give low breath levels for this compound. The evaluation of the results obtained from the patients attending a clinical practice showed that 8% of people who claim to be nonsmokers hid their real smoking status. CONCLUSIONS: The results obtained confirm that the determination of 2,5-dimethylfuran in breath samples is a good and simpler alternative to conventional blood or urine tests for assessing smoking status. IMPLICATIONS: Analysis of 2,5-dimethylfuran in breath samples results in a simple and fast method for the determination of the smoking status of a person. This methodology presents multiple advantages as it is neither invasive nor embarrassing for patients attending clinical practices. Moreover, analysis of biomarkers in breath samples is simpler and faster than using conventional methods based on urine or blood analysis.

Biomarker and Histopathology Evaluation of Patients with Recurrent Glioblastoma Treated with Galunisertib, Lomustine, or the Combination of Galunisertib and Lomustine.

Galunisertib, a Transforming growth factor-ßRI (TGF-ßRI) kinase inhibitor, blocks TGF-ß-mediated tumor growth in glioblastoma. In a three-arm study of galunisertib (300 mg/day) monotherapy (intermittent dosing; each cycle =14 days on/14 days off), lomustine monotherapy, and galunisertib plus lomustine therapy, baseline tumor tissue was evaluated to identify markers associated with tumor stage (e.g., histopathology, Ki67, glial fibrillary acidic protein) and TGF-ß-related signaling (e.g., pSMAD2). Other pharmacodynamic assessments included chemokine, cytokine, and T cell subsets alterations. 158 patients were randomized to galunisertib plus lomustine (n = 79), galunisertib (n = 39) and placebo+lomustine (n = 40). In 127 of these patients, tissue was adequate for central pathology review and biomarker work. Isocitrate dehydrogenase (IDH1) negative glioblastoma patients with baseline pSMAD2⁺ in cytoplasm had median overall survival (OS) 9.5 months vs. 6.9 months for patients with no tumor pSMAD2 expression (p = 0.4574). Eight patients were IDH1 R132H⁺ and had a median OS of 10.4 months compared to 6.9 months for patients with negative IDH1 R132H (p = 0.5452). IDH1 status was associated with numerically higher plasma macrophage-derived chemokine (MDC/CCL22), higher whole blood FOXP3, and reduced tumor CD3⁺ T cell counts. Compared to the baseline, treatment with galunisertib monotherapy preserved CD4⁺ T cell counts, eosinophils, lymphocytes, and the CD4/CD8 ratio. The T-regulatory cell compartment was associated with better OS with MDC/CCL22 as a prominent prognostic marker.

Pharmacokinetic, pharmacodynamic and biomarker evaluation of transforming growth factor-ß receptor I kinase inhibitor, galunisertib, in phase 1 study in patients with advanced cancer.

Purpose Transforming growth factor-beta (TGF-ß) signaling plays a key role in epithelial-mesenchymal transition (EMT) of tumors, including malignant glioma. Small molecule inhibitors (SMI) blocking TGF-ß signaling reverse EMT and arrest tumor progression. Several SMIs were developed, but currently only LY2157299 monohydrate (galunisertib) was advanced to clinical investigation. Design The first-in-human dose study had three parts (Part A, dose escalation, n = 39; Part B, safety combination with lomustine, n = 26; Part C, relative bioavailability study, n = 14). Results A preclinical pharmacokinetic/pharmacodynamic (PK/PD) model predicted a therapeutic window up to 300 mg/day and was confirmed in Part A after continuous PK/PD. PK was not affected by co-medications such as enzyme-inducing anti-epileptic drugs or proton pump inhibitors. Changes in pSMAD2 levels in peripheral blood mononuclear cells were associated with exposure indicating target-related pharmacological activity of galunisertib. Twelve (12/79; 15%) patients with refractory/relapsed malignant glioma had durable stable disease (SD) for 6 or more cycles, partial responses (PR), or complete responses (CR). These patients with clinical benefit had high plasma baseline levels of MDC/CCL22 and low protein expression of pSMAD2 in their tumors. Of the 5 patients with IDH1/2 mutation, 4 patients had a clinical benefit as defined by CR/PR and SD ≥6 cycles. Galunisertib had a favorable toxicity profile and no cardiac adverse events. Conclusion Based on the PK, PD, and biomarker evaluations, the intermittent administration of galunisertib at 300 mg/day is safe for future clinical investigation.

Integrated satellite data fusion and mining for monitoring lake water quality status of the Albufera de Valencia in Spain.

Lake eutrophication is a critical issue in the interplay of water supply, environmental management, and ecosystem conservation. Integrated sensing, monitoring, and modeling for a holistic lake water quality assessment with respect to multiple constituents is in acute need. The aim of this paper is to develop an integrated algorithm for data fusion and mining of satellite remote sensing images to generate daily estimates of some water quality parameters of interest, such as chlorophyll a concentrations and water transparency, to be applied for the assessment of the hypertrophic Albufera de Valencia. The Albufera de Valencia is the largest freshwater lake in Spain, which can often present values of chlorophyll a concentration over 200 mg m(-3) and values of transparency (Secchi Disk, SD) as low as 20 cm. Remote sensing data from Moderate Resolution Imaging Spectroradiometer (MODIS) and Landsat Thematic Mapper (TM) and Enhance Thematic Mapper (ETM+) images were fused to carry out an integrative near-real time water quality assessment on a daily basis. Landsat images are useful to study the spatial variability of the water quality parameters, due to its spatial resolution of 30 m, in comparison to the low spatial resolution (250/500 m) of MODIS. While Landsat offers a high spatial resolution, the low temporal resolution of 16 days is a significant drawback to achieve a near real-time monitoring system. This gap may be bridged by using MODIS images that have a high temporal resolution of 1 day, in spite of its low spatial resolution. Synthetic Landsat images were fused for dates with no Landsat overpass over the study area. Finally, with a suite of ground truth data, a few genetic programming (GP) models were derived to estimate the water quality using the fused surface reflectance data as inputs. The GP model for chlorophyll a estimation yielded a R(2) of 0.94, with a Root Mean Square Error (RMSE) = 8 mg m(-3), and the GP model for water transparency estimation using Secchi disk showed a R(2) of 0.89, with an RMSE = 4 cm. With this effort, the spatiotemporal variations of water transparency and chlorophyll a concentrations may be assessed simultaneously on a daily basis throughout the lake for environmental management.

Genetics of dizziness: cerebellar and vestibular disorders.

PURPOSE OF REVIEW: Recent advances in next generation sequencing techniques (NGS) are increasing the number of novel genes associated with cerebellar and vestibular disorders. We have summarized clinical and molecular genetics findings in neuro-otolology during the last 2 years. RECENT FINDINGS: Whole-exome and targeted sequencing have defined the genetic basis of dizziness including new genes causing ataxia: GBA2, TGM6, ANO10 and SYT14. Novel mutations in KCNA1 and CACNA1A genes are associated with episodic ataxia type 1 and type 2, respectively. Moreover, new variants in genes such as COCH, MYO7A and POU4F3 are associated with nonsyndromic deafness and vestibular dysfunction. Several susceptibility loci have been linked to familial vestibular migraine, suggesting genetic heterogeneity, but no specific gene has been identified. Finally, loci for complex and heterogeneous diseases such as bilateral vestibular hypofunction or familial Ménière disease have not been identified yet, despite their strong familial aggregation. SUMMARY: Cerebellar and vestibular disorders leading to dizziness or episodic vertigo may show overlapping clinical features. A deep phenotyping including a complete familial history is a key step in performing a reliable molecular genetic diagnosis using NGS. Personalized molecular medicine will be essential to understand disease mechanisms as well as to improve their diagnosis and treatment.

Environmental factors shape the community of symbionts in the hoopoe uropygial gland more than genetic factors.

Exploring processes of coevolution of microorganisms and their hosts is a new imperative for life sciences. If bacteria protect hosts against pathogens, mechanisms facilitating the intergenerational transmission of such bacteria will be strongly selected by evolution. By disentangling the diversity of bacterial strains from the uropygium of hoopoes (Upupa epops) due to genetic relatedness or to a common environment, we explored the importance of horizontal (from the environment) and vertical (from parents) acquisition of antimicrobial-producing symbionts in this species. For this purpose, we compared bacterial communities among individuals in nonmanipulated nests; we also performed a cross-fostering experiment using recently hatched nestlings before uropygial gland development and some nestlings that were reared outside hoopoe nests. The capacity of individuals to acquire microbial symbionts horizontally during their development was supported by our results, since cross-fostered nestlings share bacterial strains with foster siblings and nestlings that were not in contact with hoopoe adults or nests also developed the symbiosis. Moreover, nestlings could change some bacterial strains over the course of their stay in the nest, and adult females changed their bacterial community in different years. However, a low rate of vertical transmission was inferred, since genetic siblings reared in different nests shared more bacterial strains than they shared with unrelated nestlings raised in different nests. In conclusion, hoopoes are able to incorporate new symbionts from the environment during the development of the uropygium, which could be a selective advantage if strains with higher antimicrobial capacity are incorporated into the gland and could aid hosts in fighting against pathogenic and disease-causing microbes.

Special structures of hoopoe eggshells enhance the adhesion of symbiont-carrying uropygial secretion that increase hatching success.

Animals live in a bacterial world, and detecting and exploring adaptations favouring mutualistic relationships with antibiotic-producing bacteria as a strategy to fight pathogens are of prime importance for evolutionary ecologists. Uropygial secretion of European hoopoes (Upupa epops, Linnaeus) contains antimicrobials from mutualistic bacteria that may be used to prevent embryo infection. Here, we investigated the microscopic structure of hoopoe eggshells looking for special features favouring the adhesion of antimicrobial uropygial secretions. We impeded female access to the uropygial gland and compared microscopic characteristics of eggshells, bacterial loads of eggs and of uropygial secretion, and hatching success of experimental and control females. Then, we explored the link between microbiological characteristics of uropygial secretion and these of eggs of hoopoes, as well as possible fitness benefits. The microscopic study revealed special structures in hoopoes' eggshells (crypts). The experimental prevention of females' gland access demonstrated that crypts are filled with uropygial secretion and that symbiotic enterococci bacteria on the eggshells come, at least partially, from those in the female's uropygial gland. Moreover, the experiment resulted in a higher permeability of eggshells by several groups of bacteria and in elimination of the positive relationships detected for control nests between hatching success and density of symbiotic bacteria, either in the uropygial secretion of females or on the eggshell. The findings of specialized crypts on the eggshells of hoopoes, and of video-recorded females smearing secretion containing symbiotic bacteria at a high density onto the eggshells strongly support a link between secretion and bacteria on eggs. Moreover, the detected associations between bacteria and hatching success suggest that crypts enhancing the adhesion of symbiont-carrying uropygial secretion likely protect embryos against infections.

The importance of a good evaluation in order to prevent oral nerve injuries: a review.

OBJECTIVE: Oral nerve injuries are a less frequent complication but they involve a decrease in the patient life quality. The purpose of the current review is to know the described risk factors to prevent injuries and to know the therapies against an established injury. MATERIALS AND METHODS: A Pubmed search of the English and Spanish language literature from 2000-2012 using the keywords 'oral surgery' or 'trigeminal nerve injuries' or 'lingual nerve injuries' or 'mandibular nerve injuries' was performed. Review articles were included and important articles from the references were added. RESULTS: A total of 662 were obtained from the search, from which 25 were selected accomplishing the inclusion criteria. Moreover, seven important articles were selected from the references of the ones mentioned, obtaining a total of 32 articles for the review. CONCLUSIONS: There is a relationship between the position of the extracted tooth and the incidence of the inferior alveolar nerve and lingual nerve injuries; as well as the age of the patient, the intra-operatory exposition of the nerve, the technique access for the lower third molar extraction and the surgeon's inexperience. The radiological examination is useful to evaluate the nerve damage and to decide on the surgical technique.

Resource competition predicts assembly of gut bacterial communities in vitro.

Microbial community dynamics arise through interspecies interactions, including resource competition, cross-feeding and pH modulation. The individual contributions of these mechanisms to community structure are challenging to untangle. Here we develop a framework to estimate multispecies niche overlaps by combining metabolomics data of individual species, growth measurements in spent media and mathematical models. We applied our framework to an in vitro model system comprising 15 human gut commensals in complex media and showed that a simple model of resource competition accounted for most pairwise interactions. Next, we built a coarse-grained consumer-resource model by grouping metabolomic features depleted by the same set of species and showed that this model predicted the composition of 2-member to 15-member communities with reasonable accuracy. Furthermore, we found that incorporation of cross-feeding and pH-mediated interactions improved model predictions of species coexistence. Our theoretical model and experimental framework can be applied to characterize interspecies interactions in bacterial communities in vitro.

[The current state of renal sympathetic denervation in hypertension]. / Estado actual de la denervación renal simpática en el tratamiento de la hipertensión.

This review provides an overview of the efficacy and safety of renal sympathetic denervation as a therapeutic approach for resistant hypertension. While the initial enthusiasm was sparked by the results of early clinical trials, it was dampened by the findings of the Symplicity HTN-3 study. However, recent advances in catheter technology and more refined patient selection criteria have yielded more promising results. Subsequent studies, such as SPYRAL HTN-OFF MED and RADIANCE II, demonstrated significant reductions in blood pressure, even in patients with mild to moderate hypertension. Despite the lack of robust data on major clinical outcomes, investigations into the time in therapeutic range for patients undergoing renal sympathetic denervation suggested potential cardiovascular benefits. Nevertheless, further research is needed to thoroughly understand the long-term impact, assess cost-effectiveness, and accurately identify which patient subgroups may derive the greatest benefits from this therapy.

Esta revisión brinda una síntesis de la eficacia y la seguridad de la denervación simpática renal como enfoque terapéutico para la hipertensión resistente. A pesar del entusiasmo inicial generado por los resultados de los primeros ensayos clínicos, la eficacia de esta terapia se vio comprometida por los hallazgos negativos del estudio Symplicity HTN-3. Sin embargo, recientes avances en la tecnología de catéteres y una refinada selección de los pacientes han proporcionado resultados más prometedores. Estudios posteriores, como SPYRAL HTN-OFF MED y RADIANCE II, demostraron reducciones significativas en la presión arterial, incluso en pacientes con hipertensión de leve a moderada. A pesar de la falta de datos sólidos sobre desenlaces clínicos importantes, las investigaciones sobre el tiempo en rango terapéutico de los pacientes sometidos a denervación simpática renal sugirieron posibles beneficios cardiovasculares. No obstante, se requiere una mayor investigación para comprender a fondo el impacto a largo plazo, evaluar la relación costo-efectividad y determinar con precisión qué subgrupos de pacientes podrían obtener los mayores beneficios de esta terapia.