RESUMEN
PURPOSE OF REVIEW: Artificial intelligence (AI) is transforming electrocardiography (ECG) interpretation. AI diagnostics can reach beyond human capabilities, facilitate automated access to nuanced ECG interpretation, and expand the scope of cardiovascular screening in the population. AI can be applied to the standard 12-lead resting ECG and single-lead ECGs in external monitors, implantable devices, and direct-to-consumer smart devices. We summarize the current state of the literature on AI-ECG. RECENT FINDINGS: Rhythm classification was the first application of AI-ECG. Subsequently, AI-ECG models have been developed for screening structural heart disease including hypertrophic cardiomyopathy, cardiac amyloidosis, aortic stenosis, pulmonary hypertension, and left ventricular systolic dysfunction. Further, AI models can predict future events like development of systolic heart failure and atrial fibrillation. AI-ECG exhibits potential in acute cardiac events and non-cardiac applications, including acute pulmonary embolism, electrolyte abnormalities, monitoring drugs therapy, sleep apnea, and predicting all-cause mortality. Many AI models in the domain of cardiac monitors and smart watches have received Food and Drug Administration (FDA) clearance for rhythm classification, while others for identification of cardiac amyloidosis, pulmonary hypertension and left ventricular dysfunction have received breakthrough device designation. As AI-ECG models continue to be developed, in addition to regulatory oversight and monetization challenges, thoughtful clinical implementation to streamline workflows, avoiding information overload and overwhelming of healthcare systems with false positive results is necessary. Research to demonstrate and validate improvement in healthcare efficiency and improved patient outcomes would be required before widespread adoption of any AI-ECG model.
Asunto(s)
Inteligencia Artificial , Electrocardiografía , Humanos , Electrocardiografía/métodos , Cardiopatías/diagnóstico , Cardiopatías/fisiopatologíaRESUMEN
Projecting the future distributions of commercially and ecologically important species has become a critical approach for ecosystem managers to strategically anticipate change, but large uncertainties in projections limit climate adaptation planning. Although distribution projections are primarily used to understand the scope of potential change-rather than accurately predict specific outcomes-it is nonetheless essential to understand where and why projections can give implausible results and to identify which processes contribute to uncertainty. Here, we use a series of simulated species distributions, an ensemble of 252 species distribution models, and an ensemble of three regional ocean climate projections, to isolate the influences of uncertainty from earth system model spread and from ecological modeling. The simulations encompass marine species with different functional traits and ecological preferences to more broadly address resource manager and fishery stakeholder needs, and provide a simulated true state with which to evaluate projections. We present our results relative to the degree of environmental extrapolation from historical conditions, which helps facilitate interpretation by ecological modelers working in diverse systems. We found uncertainty associated with species distribution models can exceed uncertainty generated from diverging earth system models (up to 70% of total uncertainty by 2100), and that this result was consistent across species traits. Species distribution model uncertainty increased through time and was primarily related to the degree to which models extrapolated into novel environmental conditions but moderated by how well models captured the underlying dynamics driving species distributions. The predictive power of simulated species distribution models remained relatively high in the first 30 years of projections, in alignment with the time period in which stakeholders make strategic decisions based on climate information. By understanding sources of uncertainty, and how they change at different forecast horizons, we provide recommendations for projecting species distribution models under global climate change.
Asunto(s)
Cambio Climático , Ecosistema , Explotaciones Pesqueras , Predicción , IncertidumbreRESUMEN
Primary hyperparathyroidism (PHPT) is a disorder characterized by hypercalcemia and an elevated or inappropriately normal parathyroid hormone level. Classic features include bone pain, fractures, renal impairment, nephrolithiasis, and mental disturbance. However, most cases of PHPT are now asymptomatic at diagnosis or associated with nonspecific neurocognitive changes. The most frequent cause of PHPT is a solitary adenoma that secretes parathyroid hormone without the normal suppressive effect of serum calcium. A smaller number of cases can be attributed to multigland disease. Parathyroidectomy is curative and is considered for nearly all affected patients. Although PHPT is primarily a clinical and biochemical diagnosis, imaging is key to the localization of adenomas, which can lie in conventional locations adjacent to the thyroid gland or less commonly at ectopic sites in the neck and mediastinum. In addition, accurate localization facilitates the use of a minimally invasive or targeted surgical approach. Frequently used localization techniques include US, parathyroid scintigraphy, and four-dimensional CT. Second- and third-line modalities such as MRI, PET/CT, and selective venous sampling with or without parathyroid arteriography can increase confidence before surgery. These localization techniques, along with the associated technical aspects, relative advantages, and drawbacks, are described. Local expertise, patient factors, and surgeon preference are important considerations when determining the type and sequence of investigation. A multimodality approach is ultimately desirable, particularly in challenging scenarios such as multigland disease, localization of ectopic adenomas, and persistent or recurrent PHPT. Online supplemental material is available for this article. ©RSNA, 2022.
Asunto(s)
Adenoma , Hiperparatiroidismo Primario , Neoplasias de las Paratiroides , Adenoma/complicaciones , Adenoma/diagnóstico por imagen , Humanos , Hiperparatiroidismo Primario/complicaciones , Hiperparatiroidismo Primario/diagnóstico por imagen , Hormona Paratiroidea , Neoplasias de las Paratiroides/complicaciones , Neoplasias de las Paratiroides/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de PositronesRESUMEN
INTRODUCTION: The Crescent® is a recently introduced dual lumen cannula by which veno-venous extracorporeal membrane oxygenation (VV ECMO) is delivered. It has a number of features that enhance its ease of placement, pressure-flow dynamics and may reduce catheter-related complication rates. METHODS: We present the first case series of its kind analysing this device by means of a retrospective observational study of prospectively collected data from the first year of its use in a high volume severe acute respiratory failure centre (Glenfield, UK). We compare complication rates of the Crescent®, with data from the international ELSO database and our own historic centre data and discuss subjective clinician experience of introducing this device. RESULTS: Over the first 12 months of its use (23/09/2019-23/09/2020), 54 patients were cannulated using a Crescent® catheter. There were no serious/life-threatening adverse events and a low number of minor cannula-related complications. Subjectively users found it has a number of advantages over other devices and configurations, not captured within current data collection frameworks. CONCLUSION: The Crescent® is a safe and effective device by which to deliver VV ECMO support to patients with severe acute respiratory failure.
Asunto(s)
Oxigenación por Membrana Extracorpórea , Síndrome de Dificultad Respiratoria , Insuficiencia Respiratoria , Adulto , Humanos , Oxigenación por Membrana Extracorpórea/efectos adversos , Cánula , Síndrome de Dificultad Respiratoria/terapia , Catéteres , Insuficiencia Respiratoria/terapia , Insuficiencia Respiratoria/etiologíaRESUMEN
OBJECTIVES: The authors evaluated the outcome of adult patients with coronavirus disease 2019 (COVID-19)-related acute respiratory distress syndrome (ARDS) requiring the use of extracorporeal membrane oxygenation (ECMO). DESIGN: Multicenter retrospective, observational study. SETTING: Ten tertiary referral university and community hospitals. PARTICIPANTS: Patients with confirmed severe COVID-19-related ARDS. INTERVENTIONS: Venovenous or venoarterial ECMO. MEASUREMENTS AND MAIN RESULTS: One hundred thirty-two patients (mean age 51.1 ± 9.7 years, female 17.4%) were treated with ECMO for confirmed severe COVID-19-related ARDS. Before ECMO, the mean Sequential Organ Failure Assessment score was 10.1 ± 4.4, mean pH was 7.23 ± 0.09, and mean PaO2/fraction of inspired oxygen ratio was 77 ± 50 mmHg. Venovenous ECMO was adopted in 122 patients (92.4%) and venoarterial ECMO in ten patients (7.6%) (mean duration, 14.6 ± 11.0 days). Sixty-three (47.7%) patients died on ECMO and 70 (53.0%) during the index hospitalization. Six-month all-cause mortality was 53.0%. Advanced age (per year, hazard ratio [HR] 1.026, 95% CI 1.000-1-052) and low arterial pH (per unit, HR 0.006, 95% CI 0.000-0.083) before ECMO were the only baseline variables associated with increased risk of six-month mortality. CONCLUSIONS: The present findings suggested that about half of adult patients with severe COVID-19-related ARDS can be managed successfully with ECMO with sustained results at six months. Decreased arterial pH before ECMO was associated significantly with early mortality. Therefore, the authors hypothesized that initiation of ECMO therapy before severe metabolic derangements subset may improve survival rates significantly in these patients. These results should be viewed in the light of a strict patient selection policy and may not be replicated in patients with advanced age or multiple comorbidities. CLINICAL TRIAL REGISTRATION: identifier, NCT04383678.
Asunto(s)
COVID-19 , Oxigenación por Membrana Extracorpórea , Síndrome de Dificultad Respiratoria , Adulto , Femenino , Humanos , Persona de Mediana Edad , Síndrome de Dificultad Respiratoria/terapia , Estudios Retrospectivos , SARS-CoV-2RESUMEN
BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is increasingly used to support adults with severe respiratory failure refractory to conventional measures. In 2011, NHS England commissioned a national service to provide ECMO to adults with refractory acute respiratory failure. Our aims were to characterise the patients admitted to the service, report their outcomes, and highlight characteristics potentially associated with survival. METHODS: An observational cohort study was conducted of all patients treated by the NHS England commissioned ECMO service between December 1, 2011 and December 31, 2017. Analysis was conducted according to a prespecified protocol (NCT: 03979222). Data are presented as median [inter-quartile range, IQR]. RESULTS: A total of 1205 patients were supported with ECMO during the study period; the majority (n=1150; 95%) had veno-venous ECMO alone. The survival rate at ECMO ICU discharge was 74% (n=887). Survivors had a lower median age (43 yr [32-52]), compared with non-survivors (49 y [39-60]). Increased severity of hypoxaemia at time of decision-to-cannulate was associated with a lower probability of survival: survivors had a median Sao2 of 90% (84-93%; median Pao2/Fio2, 9.4 kPa [7.7-12.6]), compared with non-survivors (Sao2 88% [80-92%]; Pao2/Fio2 ratio: 8.5 kPa [7.1-11.5]). Patients requiring ECMO because of asthma were more likely to survive (95% survival rate (95% CI, 91-99%), compared with a survival of 71% (95% CI, 69-74%) in patients with respiratory failure attributable to other diagnoses. CONCLUSION: A national ECMO service can achieve good short-term outcomes for patients with undifferentiated respiratory failure refractory to conventional management. CLINICAL TRIAL REGISTRATION: NCT03979222.
Asunto(s)
Oxigenación por Membrana Extracorpórea/métodos , Insuficiencia Respiratoria/terapia , Medicina Estatal , Adulto , Estudios de Cohortes , Inglaterra , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Resultado del TratamientoRESUMEN
Gene-by-environment (GxE) interactions determine common disease risk factors and biomedically relevant complex traits. However, quantifying how the environment modulates genetic effects on human quantitative phenotypes presents unique challenges. Environmental covariates are complex and difficult to measure and control at the organismal level, as found in GWAS and epidemiological studies. An alternative approach focuses on the cellular environment using in vitro treatments as a proxy for the organismal environment. These cellular environments simplify the organism-level environmental exposures to provide a tractable influence on subcellular phenotypes, such as gene expression. Expression quantitative trait loci (eQTL) mapping studies identified GxE interactions in response to drug treatment and pathogen exposure. However, eQTL mapping approaches are infeasible for large-scale analysis of multiple cellular environments. Recently, allele-specific expression (ASE) analysis emerged as a powerful tool to identify GxE interactions in gene expression patterns by exploiting naturally occurring environmental exposures. Here we characterized genetic effects on the transcriptional response to 50 treatments in five cell types. We discovered 1455 genes with ASE (FDR < 10%) and 215 genes with GxE interactions. We demonstrated a major role for GxE interactions in complex traits. Genes with a transcriptional response to environmental perturbations showed sevenfold higher odds of being found in GWAS. Additionally, 105 genes that indicated GxE interactions (49%) were identified by GWAS as associated with complex traits. Examples include GIPR-caffeine interaction and obesity and include LAMP3-selenium interaction and Parkinson disease. Our results demonstrate that comprehensive catalogs of GxE interactions are indispensable to thoroughly annotate genes and bridge epidemiological and genome-wide association studies.
Asunto(s)
Perfilación de la Expresión Génica/métodos , Estudio de Asociación del Genoma Completo/métodos , Sitios de Carácter Cuantitativo/efectos de los fármacos , Alelos , Cafeína/farmacología , Línea Celular , Regulación de la Expresión Génica/efectos de los fármacos , Interacción Gen-Ambiente , Células Endoteliales de la Vena Umbilical Humana , Humanos , Melanocitos/citología , Melanocitos/efectos de los fármacos , Selenio/farmacología , Tunicamicina/farmacologíaRESUMEN
Large experimental efforts are characterizing the regulatory genome, yet we are still missing a systematic definition of functional and silent genetic variants in non-coding regions. Here, we integrated DNaseI footprinting data with sequence-based transcription factor (TF) motif models to predict the impact of a genetic variant on TF binding across 153 tissues and 1,372 TF motifs. Each annotation we derived is specific for a cell-type condition or assay and is locally motif-driven. We found 5.8 million genetic variants in footprints, 66% of which are predicted by our model to affect TF binding. Comprehensive examination using allele-specific hypersensitivity (ASH) reveals that only the latter group consistently shows evidence for ASH (3,217 SNPs at 20% FDR), suggesting that most (97%) genetic variants in footprinted regulatory regions are indeed silent. Combining this information with GWAS data reveals that our annotation helps in computationally fine-mapping 86 SNPs in GWAS hit regions with at least a 2-fold increase in the posterior odds of picking the causal SNP. The rich meta information provided by the tissue-specificity and the identity of the putative TF binding site being affected also helps in identifying the underlying mechanism supporting the association. As an example, the enrichment for LDL level-associated SNPs is 9.1-fold higher among SNPs predicted to affect HNF4 binding sites than in a background model already including tissue-specific annotation.
Asunto(s)
Huella de ADN , Desoxirribonucleasas/metabolismo , Polimorfismo de Nucleótido Simple/genética , Alelos , Sitios de Unión , Biología Computacional , Genes Reporteros , Estudio de Asociación del Genoma Completo , Humanos , Anotación de Secuencia Molecular , Motivos de Nucleótidos/genética , Unión Proteica , Secuencias Reguladoras de Ácidos Nucleicos/genética , Reproducibilidad de los Resultados , Factores de TranscripciónRESUMEN
The recovery of predators has the potential to restore ecosystems and fundamentally alter the services they provide. One iconic example of this is keystone predation by sea otters in the Northeast Pacific. Here, we combine spatial time series of sea otter abundance, canopy kelp area, and benthic invertebrate abundance from Washington State, USA, to examine the shifting consequences of sea otter reintroduction for kelp and kelp forest communities. We leverage the spatial variation in sea otter recovery to understand connections between sea otters and the kelp forest community. Sea otter increases created a pronounced decline in sea otter prey-particularly kelp-grazing sea urchins-and led to an expansion of canopy kelps from the late 1980s until roughly 2000. However, while sea otter and kelp population growth rates were positively correlated prior to 2002, this association disappeared over the last two decades. This disconnect occurred despite surveys showing that sea otter prey have continued to decline. Kelp area trends are decoupled from both sea otter and benthic invertebrate abundance at current densities. Variability in kelp abundance has declined in the most recent 15 years, as it has the synchrony in kelp abundance among sites. Together, these findings suggest that initial nearshore community responses to sea otter population expansion follow predictably from trophic cascade theory, but now, other factors may be as or more important in influencing community dynamics. Thus, the utility of sea otter predation in ecosystem restoration must be considered within the context of complex and shifting environmental conditions.
Asunto(s)
Kelp , Nutrias , Animales , Ecosistema , Cadena Alimentaria , Bosques , WashingtónRESUMEN
Veno-venous extracorporeal membrane oxygenation can be performed either by two cannulae or by a single dual-lumen cannula. The dual-lumen cannulation configuration offers multiple advantages: it avoids the femoral site which may be at greater risk of infection, it improves patient mobility, eases prone positioning and greatly reduces recirculation. The Avalon was the first commercially available dual-lumen cannula for adults. It has gained much popularity, but, for more than a year now, the adult vascular access kit with the 30Fr dilator has been discontinued in the United Kingdom. In this article, we share our experience with an alternative insertion method, using a percutaneous dilatational tracheostomy kit. This off-label use of the tracheostomy dilator appears to be safe. It may allow the continuing use of Avalon dual-lumen cannulae while waiting for a more permanent solution to be provided by the manufacturer.
Asunto(s)
Cateterismo/métodos , Tráquea/cirugía , Traqueostomía/métodos , Adulto , Oxigenación por Membrana Extracorpórea/métodos , HumanosRESUMEN
The benefits and ecosystem services that humans derive from the oceans are threatened by numerous global change stressors, one of which is ocean acidification. Here, we describe the effects of ocean acidification on an upwelling system that already experiences inherently low pH conditions, the California Current. We used an end-to-end ecosystem model (Atlantis), forced by downscaled global climate models and informed by a meta-analysis of the pH sensitivities of local taxa, to investigate the direct and indirect effects of future pH on biomass and fisheries revenues. Our model projects a 0.2-unit drop in pH during the summer upwelling season from 2013 to 2063, which results in wide-ranging magnitudes of effects across guilds and functional groups. The most dramatic direct effects of future pH may be expected on epibenthic invertebrates (crabs, shrimps, benthic grazers, benthic detritivores, bivalves), and strong indirect effects expected on some demersal fish, sharks, and epibenthic invertebrates (Dungeness crab) because they consume species known to be sensitive to changing pH. The model's pelagic community, including marine mammals and seabirds, was much less influenced by future pH. Some functional groups were less affected to changing pH in the model than might be expected from experimental studies in the empirical literature due to high population productivity (e.g., copepods, pteropods). Model results suggest strong effects of reduced pH on nearshore state-managed invertebrate fisheries, but modest effects on the groundfish fishery because individual groundfish species exhibited diverse responses to changing pH. Our results provide a set of projections that generally support and build upon previous findings and set the stage for hypotheses to guide future modeling and experimental analysis on the effects of OA on marine ecosystems and fisheries.
Asunto(s)
Explotaciones Pesqueras , Cadena Alimentaria , Animales , California , Ecosistema , Concentración de Iones de Hidrógeno , Invertebrados , Mamíferos , Océanos y MaresRESUMEN
Stable isotopes are used to address a wide range of ecological questions and can help researchers and managers better understand the movement and trophic ecology of sharks. Here, we review how shark studies from the Northeast Pacific Ocean (NEP) have employed stable isotopes to estimate trophic level and diet composition and infer movement and habitat-use patterns. To date, the number of NEP shark studies that have used stable isotopes is limited, suggesting that the approach is underutilized. To aid shark researchers in understanding the strengths and limitations of the approach, we provide a brief overview of carbon and nitrogen stable isotope trophic discrimination properties (e.g., change in δ15N between predator and prey), tissue sample preparation methods specific to elasmobranchs, and methodological considerations for the estimation of trophic level and diet composition. We suggest that stable isotopes are a potentially powerful tool for addressing basic questions about shark ecology and are perhaps most valuable when combined and analysed with other data types (e.g., stomach contents, tagging data, or other intrinsic biogeochemical markers).
Asunto(s)
Distribución Animal/fisiología , Cadena Alimentaria , Isótopos/metabolismo , Tiburones/fisiología , Animales , Dieta/veterinaria , Océano PacíficoRESUMEN
MOTIVATION: Expression quantitative trait loci (eQTL) studies have discovered thousands of genetic variants that regulate gene expression, enabling a better understanding of the functional role of non-coding sequences. However, eQTL studies are costly, requiring large sample sizes and genome-wide genotyping of each sample. In contrast, analysis of allele-specific expression (ASE) is becoming a popular approach to detect the effect of genetic variation on gene expression, even within a single individual. This is typically achieved by counting the number of RNA-seq reads matching each allele at heterozygous sites and testing the null hypothesis of a 1:1 allelic ratio. In principle, when genotype information is not readily available, it could be inferred from the RNA-seq reads directly. However, there are currently no existing methods that jointly infer genotypes and conduct ASE inference, while considering uncertainty in the genotype calls. RESULTS: We present QuASAR, quantitative allele-specific analysis of reads, a novel statistical learning method for jointly detecting heterozygous genotypes and inferring ASE. The proposed ASE inference step takes into consideration the uncertainty in the genotype calls, while including parameters that model base-call errors in sequencing and allelic over-dispersion. We validated our method with experimental data for which high-quality genotypes are available. Results for an additional dataset with multiple replicates at different sequencing depths demonstrate that QuASAR is a powerful tool for ASE analysis when genotypes are not available. AVAILABILITY AND IMPLEMENTATION: http://github.com/piquelab/QuASAR. CONTACT: fluca@wayne.edu or rpique@wayne.edu SUPPLEMENTARY INFORMATION: Supplementary Material is available at Bioinformatics online.
Asunto(s)
Linfocitos B/metabolismo , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Células Endoteliales de la Vena Umbilical Humana/metabolismo , ARN/genética , Análisis de Secuencia de ARN/métodos , Programas Informáticos , Alelos , Linfocitos B/citología , Células Cultivadas , Genoma Humano , Genotipo , Células Endoteliales de la Vena Umbilical Humana/citología , HumanosRESUMEN
We investigate quantum radiation reaction in laser-electron interactions across different energy and intensity regimes. Using a fully quantum approach which also accounts exactly for the effect of the strong laser pulse on the electron motion, we identify in particular a regime in which radiation reaction is dominated by quantum interference. We find signatures of quantum radiation reaction in the electron spectra which have no classical analogue and which cannot be captured by the incoherent approximations typically used in the high-intensity regime. These signatures are measurable with presently available laser and accelerator technology.
RESUMEN
Ultrasonography (US) is often the initial imaging modality employed in the evaluation of renal diseases. Despite improvements in B-mode and Doppler imaging, US still faces limitations in the assessment of focal renal masses and complex cysts as well as the microcirculation. The applications of contrast-enhanced US (CEUS) in the kidneys have dramatically increased to overcome these shortcomings with guidelines underlining their importance. This article describes microbubble contrast agents and their role in renal imaging. Microbubble contrast agents consist of a low solubility complex gas surrounded by a phospholipid shell. Microbubbles are extremely safe and well-tolerated pure intravascular agents that can be used in renal failure and obstruction, where computed tomographic (CT) and magnetic resonance (MR) imaging contrast agents may have deleterious effects. Their intravascular distribution allows for quantitative perfusion analysis of the microcirculation, diagnosis of vascular problems, and qualitative assessment of tumor vascularity and enhancement patterns. Low acoustic power real-time prolonged imaging can be performed without exposure to ionizing radiation and at lower cost than CT or MR imaging. CEUS can accurately distinguish pseudotumors from true tumors. CEUS has been shown to be more accurate than unenhanced US and rivals contrast material-enhanced CT in the diagnosis of malignancy in complex cystic renal lesions and can upstage the Bosniak category. CEUS can demonstrate specific enhancement patterns allowing the differentiation of benign and malignant solid tumors as well as focal inflammatory lesions. In conclusion, CEUS is useful in the characterization of indeterminate renal masses and cysts.
Asunto(s)
Medios de Contraste , Enfermedades Renales/diagnóstico por imagen , Trasplante de Riñón , Riñón/diagnóstico por imagen , Microburbujas , Sistemas de Computación , Medios de Contraste/administración & dosificación , Medios de Contraste/efectos adversos , Humanos , Riñón/irrigación sanguínea , Enfermedades Renales Quísticas/diagnóstico por imagen , Microburbujas/efectos adversos , Enfermedades Renales Poliquísticas/diagnóstico por imagen , UltrasonografíaRESUMEN
The 50th year of the European Federation of Societies in Ultrasound in Medicine and Biology (EFSUMB) has been celebrated 2022 publishing articles on the history of US. Contrast enhanced ultrasound (CEUS) allows to visualize blood flow and tissue perfusion. CEUS has proven to be safe without risk of nephrotoxicity. The availability of a contrast agent (tracer) for ultrasound imaging allows for the first time a dynamic assessment of tissue perfusion (blood flow and wash-in/wash-out pattern) which is an essential part for the detection and characterisation of pathological tissue and abnormal organ function. It was an outstanding achievement of academic centers in close cooperation with EFSUMB to investigate and validate the clinical potential of this new technology for the diagnosis and monitoring of various diseases and to develop clinical guidelines based on an in-depth assessment of the existing scientific publications. An important part of the implementation of CEUS in clinical practice was the development of contrast-specific imaging modes on the ultrasound scanners (in close cooperation with the machine manufacturers), the optimization of the machine setups for contrast imaging and the education provided to clinical users in form of workshops, webinars, textbooks and scientific congresses.
RESUMEN
BACKGROUND: Resistance to chemotherapy represents a significant obstacle in prostate cancer therapeutics. Novel mechanistic understandings in cancer cell chemotherapeutic sensitivity and resistance can optimize treatment and improve patient outcome. Molecular alterations in the metabolic pathways are associated with cancer development; however, the role of these alterations in chemotherapy efficacy is largely unknown. METHODS: In a bed-side to bench-side reverse translational approach, we used cDNA microarray and qRT-PCR to identify genes that are associated with biochemical relapse after chemotherapy. Further, we tested the function of these genes in cell proliferation, metabolism, and chemosensitivity in prostate cancer cell lines. RESULTS: We report that the gene encoding mitochondrial malate dehydrogenase 2 (MDH2) is overexpressed in clinical prostate cancer specimens. Patients with MDH2 overexpression had a significantly shorter period of relapse-free survival (RFS) after undergoing neoadjuvant chemotherapy. To understand the molecular mechanism underlying this clinical observation, we observed that MDH2 expression was elevated in prostate cancer cell lines compared to benign prostate epithelial cells. Stable knockdown of MDH2 via shRNA in prostate cancer cell lines decreased cell proliferation and increased docetaxel sensitivity. Further, MDH2 shRNA enhanced docetaxel-induced activations of JNK signaling and induced metabolic inefficiency. CONCLUSION: Taken together, these data suggest a novel function for MDH2 in prostate cancer development and chemotherapy resistance, in which MDH2 regulates chemotherapy-induced signal transduction and oxidative metabolism.
Asunto(s)
Antineoplásicos/uso terapéutico , Resistencia a Medicamentos/genética , Metabolismo Energético/genética , Sistema de Señalización de MAP Quinasas/genética , Malato Deshidrogenasa/metabolismo , Neoplasias de la Próstata/metabolismo , Taxoides/uso terapéutico , Línea Celular Tumoral , Proliferación Celular , Supervivencia sin Enfermedad , Docetaxel , Humanos , Malato Deshidrogenasa/genética , Masculino , Consumo de Oxígeno/genética , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/genética , Especies Reactivas de Oxígeno/metabolismoRESUMEN
OBJECTIVE: This article aims to illustrate the spectrum of sonographic findings in perforation of the small bowel due to a variety of causes and discusses the potential role of sonography in the diagnosis. CONCLUSION: Although sonography is not the first-line investigation of choice in suspected small intestinal perforation, an understanding of the characteristic appearances seen during general abdominal sonography may aid the radiologist in the early diagnosis. Recognition of small bowel perforation on general abdominal sonography will shorten the time to diagnosis and ultimate surgical management.
Asunto(s)
Perforación Intestinal/diagnóstico por imagen , Perforación Intestinal/etiología , Intestino Delgado/diagnóstico por imagen , Ultrasonografía/métodos , HumanosRESUMEN
BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has become an integral part of paediatric cardiac surgery. We report the experience of a well-established ECMO service over 5 years. METHODS: This retrospective study analysed all paediatric patients who required ECMO support following cardiac surgery from April 2015 to March 2020. Inclusion criteria were age less than 18 years and post-operative ECMO support. Patients were analysed dividing into groups according to the urgency for ECMO support (extracorporeal cardiopulmonary resuscitation (ECPR) and cardiac ECMO) and according to age (neonatal and paediatric ECMO groups). They were followed for 30-day, 6-month mortality, long-term survival, postoperative morbidity and the need for reintervention. RESULTS: Forty-six patients were included who had a total of venoarterial (VA) 8 ECMO runs. The 5-year incidence of the need for VA ECMO after cardiac surgery was 3.3% (48 of the overall 1441 cases recorded). The median follow-up period was 3.5 (interquartile ranges, 0.8-4.7) years. Thirty-day, 6-month and follow-up survival rate was 85%, 65% and 52% respectively. At the 6-month follow-up, the ECPR group showed a trend towards worse survival compared with the cardiac ECMO group (47% vs. 55%) but with no statistical significance (p = 0.35). Furthermore, the survival rates between paediatric (60%) and neonatal (46%) ECMO groups were similar, with no statistical significance (p = 0.45). The rate of acute neurological events was 27% (13/48). CONCLUSION: ECPR and neonatal ECMO groups had higher mortality. VA ECMO 30-day and 6-month survival rates were 85% and 65% respectively. Major neurological injury resulting in ECMO termination occurred in 3 patients. Accumulated experiences and protocols in ECMO management can improve mortality and morbidity.
Asunto(s)
Procedimientos Quirúrgicos Cardíacos , Reanimación Cardiopulmonar , Oxigenación por Membrana Extracorpórea , Paro Cardíaco , Recién Nacido , Humanos , Niño , Adolescente , Oxigenación por Membrana Extracorpórea/métodos , Estudios RetrospectivosRESUMEN
Climate change drives species distribution shifts, affecting the availability of resources people rely upon for food and livelihoods. These impacts are complex, manifest at local scales, and have diverse effects across multiple species. However, for wild capture fisheries, current understanding is dominated by predictions for individual species at coarse spatial scales. We show that species-specific responses to localized environmental changes will alter the collection of co-occurring species within established fishing footprints along the U.S. West Coast. We demonstrate that availability of the most economically valuable, primary target species is highly likely to decline coastwide in response to warming and reduced oxygen concentrations, while availability of the most abundant, secondary target species will potentially increase. A spatial reshuffling of primary and secondary target species suggests regionally heterogeneous opportunities for fishers to adapt by changing where or what they fish. Developing foresight into the collective responses of species at local scales will enable more effective and tangible adaptation pathways for fishing communities.