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PURPOSE: Split abdominal wall muscle flap (SAWMF) is a technique to repair large defects in congenital diaphragmatic hernia (CDH). A possible objection to this intervention could be any associated abdominal muscle weakness. Our aim is to analyze the evolution of this abdominal muscle wall weakness. METHODS: Retrospective review of CDH repair by SAWMF (internal oblique muscle and transverse) from 2004 to 2023 focusing on the evolution of muscle wall weakness. RESULTS: Eighteen neonates of 148 CDH patients (12,1%) were repaired using SAWMF. Mean gestational age and birth weight were 35.7 ± 3.5 weeks and 2587 ± 816 g. Mean lung-to-head ratio was 1.49 ± 0.28 and 78% liver-up. Seven patients (38%) were prenatally treated by tracheal occlusion. Ninety-four percent of the flaps were used for primary repair and one to repair a recurrence. One patient (5.6%) experienced recurrence. Abdominal muscle wall weakness was present in the form of a bulge. Resolution of weakness at 1, 2 and 3 years was 67%, 89% and 94%, respectively. No patient required treatment for weakness or died. CONCLUSIONS: Abdominal muscular weakness after a split abdominal wall muscle flap repair is not a limitation for its realization since it is asymptomatic and presents a prompt spontaneous resolution. LEVEL OF EVIDENCE: IV.
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Músculos Abdominales , Pared Abdominal , Hernias Diafragmáticas Congénitas , Debilidad Muscular , Colgajos Quirúrgicos , Humanos , Hernias Diafragmáticas Congénitas/cirugía , Hernias Diafragmáticas Congénitas/complicaciones , Recién Nacido , Estudios Retrospectivos , Masculino , Femenino , Pared Abdominal/cirugía , Debilidad Muscular/etiología , Debilidad Muscular/cirugía , Músculos Abdominales/cirugía , Herniorrafia/métodos , Complicaciones Posoperatorias/cirugía , Resultado del TratamientoRESUMEN
BACKGROUND: The long-term survival of patients hospitalized with COVID-19 and the factors associated with poorer survival months after infection are not well understood. The aims of the present study were to analyze the overall mortality 10 months after admission. METHODS: 762 patients with COVID-19 disease were included. Patients underwent a complete clinical evaluation, routine laboratory analysis and chest X-ray. Data collected included demographic and clinical data, such as vascular risk factors, tobacco or alcohol use, comorbidity, and institutionalization. RESULTS: Ten-month mortality was 25.6%: 108 deaths occurred in-hospital, while 87 patients died after discharge. In-hospital mortality was independently related to NT-proBNP values > 503.5 pg/mL [OR = 4.67 (2.38-9.20)], urea > 37 mg/dL [3.21 (1.86-7.31)] and age older than 71 years [OR = 1.93 (1.05-3.54)]. NT-proBNP values > 503.5 pg/mL [OR = 5.00 (3.06-8.19)], urea > 37 mg/dL [3.51 (1.97-6.27)], cognitive impairment [OR = 1.96 (1.30-2.95), cancer [OR = 2.23 (1.36-3.68), and leukocytes > 6330/mm3 [OR = 1.64 (1.08-2.50)], were independently associated with long-term mortality. CONCLUSIONS: the risk of death remains high even months after COVID-19 infection. Overall mortality of COVID-19 patients during 10 months after hospital discharge is nearly as high as that observed during hospital admission. Comorbidities such as cancer or cognitive impairment, organ dysfunction and inflammatory reaction are independent prognostic markers of long-term mortality.
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Transition metal catalysis has contributed to the discovery of novel methodologies and the preparation of natural products, as well as new chances to increase the chemical space in drug discovery programs. In the case of marine drugs, this strategy has been used to achieve selective, sustainable and efficient transformations, which cannot be obtained otherwise. In this perspective, we aim to showcase how a variety of transition metals have provided fruitful couplings in a wide variety of marine drug-like scaffolds over the past few years, by accelerating the production of these valuable molecules.
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Organismos Acuáticos , Productos Biológicos , Elementos de Transición , Catálisis , Productos Biológicos/síntesis química , Productos Biológicos/química , Elementos de Transición/química , Descubrimiento de Drogas/métodos , AnimalesRESUMEN
Dichloromethane, as a readily available and inexpensive C1 synthon is proposed as a powerful building block for cyclopropanation of alkenes under mild conditions. Herein, we report a highly efficient and versatile dual photoredox system, involving a nickel aminopyridine coordination complex and a photocatalyst, for the cyclopropanation of aromatic olefins using dichloromethane, under visible-light irradiation. The cyclopropanation protocol has been successfully applied at gram scale. Mechanistic studies suggest a Ni(II) pyridyl radical complex as the key intermediate for the homolytic cleavage of the Csp3-Cl bond, generating a chloromethyl radical that is captured by the olefin coupling partner. Our findings also highlight the versatility of this methodology. By directing the radical/polar crossover process, we were able to selectively drive the reaction towards either the formation of cyclopropyl derivatives or the corresponding non-cyclic alkyl chloride products. The methodology also successfully apply to geminal dichloroalkanes, including the formation of spiro[2,2] compounds. Moreover, our methodology extends to the synthesis of deuterium-labelled cyclopropanes, demonstrating its utility in isotopic labelling and broadening its applicability in chemical synthesis and drug development.
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OBJECTIVES: To describe the in vivo emergence of ceftazidime-avibactam resistance in GES-type carbapenemases and to characterize an unusual outbreak of GES-6-producing Serratia marcescens during the COVID-19 pandemic in Spain. METHODS: Retrospective study to describe a GES-CPSM outbreak based on whole genome sequencing and antimicrobial susceptibility testing (AST). Transferability of blaGES-carrying plasmid was assessed by conjugation experiments. RESULTS: In December 2020, we identified a cluster of S. marcescens harbouring blaGES-6 involving 9 patients. Whole-genome sequence analysis revealed a clonal relationship (≤3 SNPs) between the first isolates identified in each of the evolved patients and environmental samples with GES-CPSM detection. Plasmid analysis showed that the blaGES-6 gene was located in an IncQ3-type plasmid. Triparental mating experiments using a helper plasmid demonstrated mobilization of the blaGES-6-carrying plasmid. Our results also demonstrate within-host evolution in S. marcescens isolates, leading to a transition from blaGES-6 to the new blaGES-55, caused by the P162S mutation, in a subsequent infection in one of the affected patients. In blaGES-55 we identified emergence of ceftazidime-avibactam resistance along with an increase of carbapenems susceptibility. This patient had been treated with a 14-day course of ceftazidime-avibactam. AST of the transformants bearing blaGES-6 and blaGES-55 plasmids, confirmed susceptibility variation affecting ceftazidime-avibactam and carbapenems. CONCLUSIONS: We report an unusual outbreak of GES-6 whose incidence is becoming increasing. Transition from GES-6 to GES-55 may readily occur in vivo leading to ceftazidime-avibactam resistance, which brings to the fore the critical need for developing more accurate diagnosis tools for detection of GES ß-lactamases and optimise the use of antimicrobials.
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Antibacterianos , Compuestos de Azabiciclo , Carbapenémicos , Ceftazidima , Brotes de Enfermedades , Combinación de Medicamentos , Pruebas de Sensibilidad Microbiana , Infecciones por Serratia , Serratia marcescens , beta-Lactamasas , Humanos , Ceftazidima/farmacología , Serratia marcescens/genética , Serratia marcescens/efectos de los fármacos , Serratia marcescens/aislamiento & purificación , Compuestos de Azabiciclo/farmacología , Infecciones por Serratia/microbiología , Infecciones por Serratia/epidemiología , beta-Lactamasas/genética , beta-Lactamasas/metabolismo , Estudios Retrospectivos , Carbapenémicos/farmacología , Masculino , Antibacterianos/farmacología , Femenino , Persona de Mediana Edad , Plásmidos/genética , España/epidemiología , COVID-19/epidemiología , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Secuenciación Completa del Genoma , Anciano , Farmacorresistencia Bacteriana Múltiple/genéticaRESUMEN
Objectives: To analyse the susceptibility profile to cefepime, carbapenems and new ß-lactam/ß-lactamase inhibitor combinations in Enterobacter cloacae complex and Klebsiella aerogenes isolated from intra-abdominal, urinary, respiratory and bloodstream infections in the SMART (Study for Monitoring Antimicrobial Resistance Trends) surveillance study in Spain. Methods: The susceptibilities of 759 isolates (473 E. cloacae complex and 286 K. aerogenes) collected in 11 Spanish hospitals from 2016 to 2022 were analysed following the EUCAST 2023 criteria. Molecular characterization looking for ß-lactamase genes was performed through PCR and DNA sequencing analysis. Results: E. cloacae complex showed resistance to third-generation cephalosporins in 25% of the cases, whereas K. aerogenes was resistant in 35%. Regarding cefepime, resistance in E. cloacae was higher (10%) than in K. aerogenes (2%). Carbapenems showed >85% activity in both microorganisms. Ceftazidime/avibactam, imipenem/relebactam and meropenem/vaborbactam had good activity against these microorganisms (>95%). In contrast, the activity of ceftolozane/tazobactam was lower (80%). A high proportion of the isolates resistant to new ß-lactam/ß-lactamase inhibitor combinations carried a carbapenemase, mainly OXA-48-like and VIM-1. Conclusions: Ceftazidime/avibactam, imipenem/relebactam and meropenem/vaborbactam show high activity against both E. cloacae complex and K. aerogenes isolates recovered in the SMART-Spain study. In contrast, differences have been found in the case of cefepime, showing more activity against K. aerogenes than E. cloacae complex. These results are useful for antimicrobial stewardship programmes and for the implementation of local and national guidelines.
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INTRODUCTION AND OBJECTIVES: Cardiac resynchronization therapy (CRT) is an effective treatment for patients with nonischemic dilated cardiomyopathy associated with left bundle branch block (LBBB). In these patients, the device can normalize left ventricular ejection fraction (LVEF). Nevertheless, it remains unclear whether CRT responders still require neurohormonal blockers. The aim of this study is to determine the long-term safety of withdrawing drug therapy in these patients. METHODS: The REMOVE trial is a prospective, multicenter, open-label and randomized 1:1 study designed to assess the effect of withdrawing neurohormonal blockers in patients with nonischemic dilated cardiomyopathy associated with left bundle branch block who recovered LVEF after CRT. The study will include a 12-month follow-up with the option to continue into the follow-up extension phase for up to 24 months. The primary endpoint is the recurrence of cardiomyopathy defined as any of the following criteria: a) a reduction in LVEF >10% (provided the LVEF is <50%); b) a reduction in LVEF >10% accompanied by an increase >15% in the indexed end-systolic volume relative to the previous value and in a range higher than the normal values, or c) decompensated heart failure requiring intravenous diuretic administration. In patients meeting the primary endpoint, drug therapy will be restarted. CONCLUSIONS: The results of this study will help to enhance our understanding of CRT superresponders, a specific group of patients. Registred at ClinicalTrials.gov (Identifier: NCT05151861).
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The construction of carbonyl compounds via carbonylation reactions using safe CO sources remains a long-standing challenge to synthetic chemists. Herein, we propose a catalyst cascade Scheme in which CO2 is used as a CO surrogate in the carbonylation of benzyl chlorides. Our approach is based on the cooperation between two coexisting catalytic cycles: the CO2-to-CO electroreduction cycle promoted by [Fe(TPP)Cl] (TPP=meso-tetraphenylporphyrin) and an electrochemical carbonylation cycle catalyzed by [Ni(bpy)Br2] (2,2'-bipyridine). As a proof of concept, this protocol allows for the synthesis of symmetric ketones from good to excellent yields in an undivided cell with non-sacrificial electrodes. The reaction can be directly scaled up to gram-scale and operates effectively at a CO2 concentration of 10 %, demonstrating its robustness. Our mechanistic studies based on cyclic voltammetry, IR spectroelectrochemistry and Density Functional Theory calculations suggest a synergistic effect between the two catalysts. The CO produced from CO2 reduction is key in the formation of the [Ni(bpy)(CO)2], which is proposed as the catalytic intermediate responsible for the C-C bond formation in the carbonylation steps.
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Indole is a versatile pharmacophore widely distributed in bioactive natural products. This privileged scaffold has been found in a variety of molecules isolated from marine organisms such as algae and sponges. Among these, indole alkaloids represent one of the biggest, most promising family of compounds, having shown a wide range of pharmacological properties including anti-inflammatory, antiviral, and anticancer activities. The aim of this review is to show the current scenario of marine indole alkaloid derivatives, covering not only the most common chemical structures but also their promising therapeutic applications as well as the new general synthetic routes developed during the last years.
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Productos Biológicos , IndolesRESUMEN
Despite the wealth of publicly available single-cell datasets, our understanding of distinct resident immune cells and their unique features in diverse human organs remains limited. To address this, we compiled a meta-analysis dataset of 114,275 CD45+ immune cells sourced from 14 organs in healthy donors. While the transcriptome of immune cells remains relatively consistent across organs, our analysis has unveiled organ-specific gene expression differences (GTPX3 in kidney, DNTT and ACVR2B in thymus). These alterations are linked to different transcriptional factor activities and pathways including metabolism. TNF-α signaling through the NFkB pathway was found in several organs and immune compartments. The presence of distinct expression profiles for NFkB family genes and their target genes, including cytokines, underscores their pivotal role in cell positioning. Taken together, immune cells serve a dual role: safeguarding the organs and dynamically adjusting to the intricacies of the host organ environment, thereby actively contributing to its functionality and overall homeostasis.
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Perfilación de la Expresión Génica , Sistema Inmunológico , Transcriptoma , Humanos , Citocinas , Regulación de la Expresión Génica , Timo , Riñón , Sistema Inmunológico/citología , Factores de TranscripciónRESUMEN
BACKGROUND: Milk and egg allergies significantly impact the quality of life, particularly in children. In this regard, food oral immunotherapy (OIT) has emerged as an effective treatment option; however, the occurrence of frequent adverse reactions poses a challenge, necessitating close monitoring during treatment. OBJECTIVE: This study aims to evaluate the ability of a new mobile/web app called OITcontrol to monitor milk and egg OIT. METHODS: Patients undergoing milk or egg OIT were recruited and divided into 2 groups: the active group used the OITcontrol app in conjunction with standard written monitoring methods, whereas the control group relied solely on written diaries. Investigators documented hospital doses, hospital reactions, and administered treatments on the website. Patients recorded their daily allergen home-dose intake, home reactions, and administered treatments using the app. The following variables were compared between both groups: number and severity of hospital and reported home reactions, patient's adhesion to the OITcontrol app or written diary or both in terms of daily home-dose intake and home reactions recording, and treatment and dose adjustment compliance at home in case of reaction. RESULTS: Sixteen patients were assigned to be monitored using the OITcontrol app along with additional written methods (active group), while 14 patients relied solely on a written paper diary (control group). A similar distribution was observed in terms of sex, age, basal characteristics, allergen treated in OIT, premedication, and sensitization profile. Active patients reported a comparable number of hospital and home reactions compared with the control group. In terms of recording system usage, 13/16 (81%) active patients used the OITcontrol app, while 10/14 (71%) control patients relied on the written diary. Among active patients, 6/16 (38%) used both methods, and 1 active patient used only written methods. However, control patients recorded home reactions more frequently than active patients (P=.009). Among active patients, the app was the preferred method for recording reactions (59/86, 69%), compared with the written diary (15/86, 17%) or both methods (12/86, 14%; P<.001). Treatment compliance in home-recorded reactions was similar between both groups (P=.15). However, treatment indications after an adverse reaction were more frequently followed (P=.04) in reactions recorded solely in the app (36/59, 61%) than in the written diary (29/71, 41%) or both systems (4/12, 33%). Moreover, compliance with dose adjustments after a moderate-severe reaction in home-recorded reactions was higher in the active group than in the control group (P<.001). Home reactions recorded only in the app (16/19, 84%) were more likely to follow dose adjustments (P<.001) than those recorded in the written diary (3/20, 15%) or using both methods (2/3, 67%). CONCLUSIONS: The OITcontrol app appears to be a valuable tool for monitoring OIT treatment in children with food allergies. It proves to be a suitable method for recording daily home dose intakes and reactions, and it seems to enhance adherence to treatment indications following an adverse reaction as well as compliance with dose adjustments in home reactions. However, additional studies are necessary to comprehensively grasp the benefits and limitations of using the OITcontrol app in the management of OIT.
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ABSTRACT: The process of reproductive decision making among women living with HIV is intricate and multifaceted, influenced by health considerations, societal factors, and personal values. In this study, we employed Charmaz's Constructivist Grounded Theory to understand how Spanish women living with HIV make decisions regarding reproduction. We conducted 26 face-to-face interviews until data saturation was achieved. Findings suggested that social constructs such as femininity and motherhood play a significant role in the reproductive decision-making process for women living with HIV. The women's beliefs about HIV, doubts, marginalizing situations, and health barriers create challenges to making reproductive decisions. These findings provide valuable implications for designing care plans that meet the unique sexual and reproductive health needs of women with HIV. An integrated and comprehensive multidisciplinary counseling approach is necessary to improve the quality of care.
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Toma de Decisiones , Teoría Fundamentada , Infecciones por VIH , Entrevistas como Asunto , Investigación Cualitativa , Humanos , Femenino , Infecciones por VIH/psicología , Adulto , España , Conocimientos, Actitudes y Práctica en Salud , Persona de Mediana Edad , Conducta Reproductiva/psicología , Salud Reproductiva , ReproducciónRESUMEN
Palatine tonsils are secondary lymphoid organs (SLOs) representing the first line of immunological defense against inhaled or ingested pathogens. We generated an atlas of the human tonsil composed of >556,000 cells profiled across five different data modalities, including single-cell transcriptome, epigenome, proteome, and immune repertoire sequencing, as well as spatial transcriptomics. This census identified 121 cell types and states, defined developmental trajectories, and enabled an understanding of the functional units of the tonsil. Exemplarily, we stratified myeloid slan-like subtypes, established a BCL6 enhancer as locally active in follicle-associated T and B cells, and identified SIX5 as putative transcriptional regulator of plasma cell maturation. Analyses of a validation cohort confirmed the presence, annotation, and markers of tonsillar cell types and provided evidence of age-related compositional shifts. We demonstrate the value of this resource by annotating cells from B cell-derived mantle cell lymphomas, linking transcriptional heterogeneity to normal B cell differentiation states of the human tonsil.
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Linfocitos B , Tonsila Palatina , Humanos , Adulto , Linfocitos B/metabolismoRESUMEN
The study of specific T-cell responses against SARS-CoV-2 is important for understanding long-term immunity and infection management. The aim of this study was to assess the dual IFN-γ and IL-2 detection, using a SARS-CoV-2 specific fluorescence ELISPOT, in patients undergoing acute disease, during convalescence, and after vaccination. We also evaluated humoral response and compared with T-cells with the aim of correlating both types of responses, and increase the number of specific response detection. Blood samples were drawn from acute COVID-19 patients and convalescent individuals classified according to disease severity; and from unvaccinated and vaccinated uninfected individuals. IgGs against Spike and nucleocapsid, IgMs against nucleocapsid, and neutralizing antibodies were also analyzed. Our results show that IFN-γ in combination with IL-2 increases response detection in acute and convalescent individuals (p = 0.023). In addition, IFN-γ detection can be a useful biomarker for monitoring severe acute patients, as our results indicate that those individuals with a poor outcome have lower levels of this cytokine. In some cases, the lack of cellular immunity is compensated by antibodies, confirming the role of both types of immune responses in infection, and confirming that their dual detection can increase the number of specific response detections. In summary, IFN-γ/IL-2 dual detection is promising for characterizing and assessing the immunization status, and helping in the patient management.
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COVID-19 , SARS-CoV-2 , Humanos , Interleucina-2 , Inmunidad Celular , Anticuerpos Neutralizantes , Anticuerpos Antivirales , Inmunidad HumoralRESUMEN
Los PEComas pancreáticos son neoplasias con potencial maligno extremadamente raras, que afectan mayoritariamente a mujeres de mediana edad y que se caracterizan por presentar marcadores melanocíticos y miogénicos en el análisis inmunohistoquímico. No existen síntomas ni pruebas de imagen patognomónicas. El diagnóstico se establece con el análisis de la pieza quirúrgica o de la PAAF obtenida con ecoendoscopia preoperatoria. El tratamiento más habitual consiste en la exéresis radical, adecuando la intervención a la localización del tumor. Hasta la fecha se han descrito 34 casos, no obstante, más del 80% de los mismos han sido reportados en la última década, lo que sugiere que es una patología más frecuente de lo esperado. Se reporta un nuevo caso de PEComa pancreático y se realiza una revisión sistemática de la literatura de acuerdo con las guías PRISMA con el objetivo de difundir su existencia, profundizar en su conocimiento y actualizar su manejo (AU)
Pancreatic PEComas are extremely rare neoplasms with malignant potential, which mostly affect middle-aged women and are characterized by presenting melanocytic and myogenic markers in immunohistochemical analysis. There are no symptoms or pathognomonic imaging tests, so the diagnosis is established with the analysis of the surgical specimen or the FNA obtained with preoperative endoscopic ultrasound. The mean treatment consists on radical excision, adapting the intervention to the location of the tumor. To date, 34 cases have been described; however, more than 80% of them have been reported in the last decade, which suggests that it is a more frequent pathology than expected. A new case of pancreatic PEComa is reported and a systematic review of the literature is carried out according to the PRISMA guidelines with the aim of divulge this pathology, deepening its knowledge and updating its management (AU)
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Humanos , Neoplasias de Células Epitelioides Perivasculares/diagnóstico , Neoplasias de Células Epitelioides Perivasculares/terapia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/terapiaRESUMEN
PURPOSE: To evaluate the outcomes of adding arthroscopy to osteosynthesis of distal radius fractures (DRF) with volar locking plate (VLP), by Patient-Rated Wrist Evaluation (PRWE) 1 year after surgery. METHODS: In total, 186 functionally independent adult patients who met the inclusion criteria (DRF and a clinical decision for surgery with a VLP) were randomized to arthroscopic assistance or not. Primary outcome was PRWE questionnaire results 1 year after surgery. For the main variable, PRWE, we obtained the minimal clinically important difference based on a distribution-based method. Secondary outcomes included Disabilities of the Arm, Shoulder and Hand and 12-Item Short Form Health Survey questionnaires, range of motion, strength, radiographic measures, and presence of joint step-offs by computed tomography. Data were collected preoperatively and at +1 and +4 weeks, +3 and +6 months, and +1 year after surgery. Complications were recorded throughout the study. RESULTS: In total, 180 patients (mean age: 59.0 ± 14.9 years; 76% women) were analyzed by modified intention to treat. A total of 82% of the fractures were intra-articular (AO type C). No significant difference between arthroscopic (AG) and control (CG) groups in median PRWE was found at +1 year (median AG: 5.0, median CG: 7.5, difference in medians 2.5; 95% confidence interval [CI] -2.0, 7.0, P = .328). The proportion of patients who exceeded the minimal clinically important difference of 12.81 points in the AG and CG was 86.4% vs 85.1%, P = .819, respectively. Percentage of associated injuries and step-offs reduction maneuvers was greater with arthroscopy (mean differences: 17.1 95% CI -0.1, 26.1, P < .001) and 17.4 (95% CI 5.0, 29.7, P = .007). The difference in percentage of residual joint step-offs at the postsurgical computed tomography in radioulnar, radioscaphoid, and radiolunate joints was not significant (P = .990, P = .538, and P = .063). Complications were similar between groups (16.9% vs 20.9%, P = .842). CONCLUSIONS: Adjuvant arthroscopy did not significantly improve PRWE score +1 year after surgery for DRF with VLP, although the statistical power of the study is below the initially estimated to detect the expected difference. LEVEL OF EVIDENCE: Level I, randomized controlled trial.
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Fracturas del Radio , Fracturas de la Muñeca , Adulto , Humanos , Femenino , Persona de Mediana Edad , Anciano , Masculino , Resultado del Tratamiento , Artroscopía , Fracturas del Radio/cirugía , Fracturas del Radio/diagnóstico , Fijación Interna de Fracturas/métodos , Placas Óseas , Rango del Movimiento ArticularRESUMEN
Pancreatic PEComas are extremely rare neoplasms with malignant potential, which mostly affect middle-aged women and are characterized by presenting melanocytic and myogenic markers in immunohistochemical analysis. There are no symptoms or pathognomonic imaging tests, so the diagnosis is established with the analysis of the surgical specimen or the FNA obtained with preoperative endoscopic ultrasound. The mean treatment consists on radical excision, adapting the intervention to the location of the tumor. To date, 34 cases have been described; however, more than 80% of them have been reported in the last decade, which suggests that it is a more frequent pathology than expected. A new case of pancreatic PEComa is reported and a systematic review of the literature is carried out according to the PRISMA guidelines with the aim of divulge this pathology, deepening its knowledge and updating its management.
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Neoplasias de Células Epitelioides Perivasculares , Femenino , Humanos , Persona de Mediana Edad , Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico , Neoplasias de Células Epitelioides Perivasculares/diagnóstico , Neoplasias de Células Epitelioides Perivasculares/cirugíaRESUMEN
The exploration for noble metals substitutes in catalysis has become a highly active area of research, driven by the pursuit of sustainable chemical processes. Although the utilization of base metals holds great potential as an alternative, their successful implementation in predictable catalytic processes necessitates the development of appropriate ligands. Such ligands must be capable of controlling their intricate redox chemistry and promote two-electron events, thus mimicking well-established organometallic processes in noble metal catalysis. While numerous approaches for infusing nobility to base metals have been explored, metal-ligand cooperation has garnered significant attention in recent years. Within this context, aluminium-based ligands offer interesting features to fine-tune the activity of metal centres, but their application in base metal catalysis remains largely unexplored. This perspective seeks to highlight the most recent breakthroughs in the reactivity of heterobimetallic aluminium-base-metal complexes, while also showcasing their potential to develop novel and predictable catalytic transformations. By turning the spotlight on such heterobimetallic species, we aim to inspire chemists to explore aluminium-base-metal species and expand the range of their applications as catalysts.
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Carbapenem-resistant pathogens have been recognized as a health concern as they are both difficult to treat and detect in clinical microbiology laboratories. Researchers are making great efforts to develop highly specific, sensitive, accurate, and rapid diagnostic techniques, required to prevent the spread of these microorganisms and improve the prognosis of patients. In this context, CRISPR-Cas systems are proposed as promising tools for the development of diagnostic methods due to their high specificity; the Cas13a endonuclease can discriminate single nucleotide changes and displays collateral cleavage activity against single-stranded RNA molecules when activated. This technology is usually combined with isothermal pre-amplification reactions in order to increase its sensitivity. We have developed a new LAMP-CRISPR-Cas13a-based assay for the detection of OXA-48 and GES carbapenemases in clinical samples without the need for nucleic acid purification and concentration. To evaluate the assay, we used 68 OXA-48-like-producing Klebsiella pneumoniae clinical isolates as well as 64 Enterobacter cloacae complex GES-6, 14 Pseudomonas aeruginosa GES-5, 9 Serratia marcescens GES-6, 5 P. aeruginosa GES-6, and 3 P. aeruginosa (GES-15, GES-27, and GES-40) and 1 K. pneumoniae GES-2 isolates. The assay, which takes less than 2 h and costs approximately 10 per reaction, exhibited 100% specificity and sensitivity (99% confidence interval [CI]) for both OXA-48 and all GES carbapenemases. IMPORTANCE Carbapenems are one of the last-resort antibiotics for defense against multidrug-resistant pathogens. Multiple nucleic acid amplification methods, including multiplex PCR, multiplex loop-mediated isothermal amplification (LAMP) and multiplex RPAs, can achieve rapid, accurate, and simultaneous detection of several resistance genes to carbapenems in a single reaction. However, these assays need thermal cycling steps and specialized instruments, giving them limited application in the field. In this work, we adapted with high specificity and sensitivity values, a new LAMP CRISPR-Cas13a-based assay for the detection of OXA-48 and GES carbapenemases in clinical samples without the need for RNA extraction.