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1.
EClinicalMedicine ; 69: 102461, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38374968

RESUMEN

Background: The Paediatric Difficult Intubation Collaborative identified multiple attempts and persistence with direct laryngoscopy as risk factors for complications in children with difficult tracheal intubations and subsequently engaged in initiatives to reduce repeated attempts and persistence with direct laryngoscopy in children. We hypothesised these efforts would lead to fewer attempts, fewer direct laryngoscopy attempts and decrease complications. Methods: Paediatric patients less than 18 years of age with difficult direct laryngoscopy were enrolled in the Paediatric Difficult Intubation Registry. We define patients with difficult direct laryngoscopy as those in whom (1) an attending or consultant obtained a Cormack Lehane Grade 3 or 4 view on direct laryngoscopy, (2) limited mouth opening makes direct laryngoscopy impossible, (3) direct laryngoscopy failed in the preceding 6 months, and (4) direct laryngoscopy was deferred due to perceived risk of harm or poor chance of success. We used a 5:1 propensity score match to compare an early cohort from the initial Paediatric Difficult Intubation Registry analysis (August 6, 2012-January 31, 2015, 785 patients, 13 centres) and a current cohort from the Registry (March 4, 2017-March 31, 2023, 3925 patients, 43 centres). The primary outcome was first attempt success rate between cohorts. Success was defined as confirmed endotracheal intubation and assessed by the treating clinician. Secondary outcomes were eventual success rate, number of attempts at intubation, number of attempts with direct laryngoscopy, the incidence of persistence with direct laryngoscopy, use of supplemental oxygen, all complications, and severe complications. Findings: First-attempt success rate was higher in the current cohort (42% vs 32%, OR 1.5 95% CI 1.3-1.8, p < 0.001). In the current cohort, there were fewer attempts (2.2 current vs 2.7 early, regression coefficient -0.5 95% CI -0.6 to -0.4, p < 0.001), fewer attempts with direct laryngoscopy (0.6 current vs 1.0 early, regression coefficient -0.4 95% CI -0.4 to 0.3, p < 0.001), and reduced persistence with direct laryngoscopy beyond two attempts (7.3% current vs 14.1% early, OR 0.5 95% CI 0.4-0.6, p < 0.001). Overall complication rates were similar between cohorts (19% current vs 20% early). Severe complications decreased to 1.8% in the current cohort from 3.2% in the early cohort (OR 0.55 95% CI 0.35-0.87, p = 0.011). Cardiac arrests decreased to 0.8% in the current cohort from 1.8% in the early cohort. We identified persistence with direct laryngoscopy as a potentially modifiable factor associated with severe complications. Interpretation: In the current cohort, children with difficult tracheal intubations underwent fewer intubation attempts, fewer attempts with direct laryngoscopy, and had a nearly 50% reduction in severe complications. As persistence with direct laryngoscopy continues to be associated with severe complications, efforts to limit direct laryngoscopy and promote rapid transition to advanced techniques may enhance patient safety. Funding: None.

2.
Anaesthesia ; 78(9): 1093-1101, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37322572

RESUMEN

Children with difficult tracheal intubation are at increased risk of severe complications, including hypoxaemia and cardiac arrest. Increasing experience with the simultaneous use of videolaryngoscopy and flexible bronchoscopy (hybrid) in adults led us to hypothesise that this hybrid technique could be used safely and effectively in children under general anaesthesia. We reviewed observational data from the international Pediatric Difficult Intubation Registry from 2017 to 2021 to assess the safety and efficacy of hybrid tracheal intubation approaches in paediatric patients. In total, 140 patients who underwent 180 attempts at tracheal intubation with the hybrid technique were propensity score-matched 4:1 with 560 patients who underwent 800 attempts with a flexible bronchoscope. In the hybrid group, first attempt success was 70% (98/140) compared with 63% (352/560) in the flexible bronchoscope group (odds ratio (95%CI) 1.4 (0.9-2.1), p = 0.1). Eventual success rates in the matched groups were 90% (126/140) for hybrid vs. 89% (499/560) for flexible bronchoscope (1.1 (0.6-2.1), p = 0.8). Complication rates were similar in both groups (15% (28 complications in 182 attempts) hybrid; 13% (102 complications in 800 attempts) flexible bronchoscope, p = 0.3). The hybrid technique was more likely than flexible bronchoscopy to be used as a rescue technique following the failure of another technique (39% (55/140) vs. 25% (138/560), 2.1 (1.4-3.2) p < 0.001). While technically challenging, the hybrid technique has success rates similar to other advanced airway techniques, few complications and may be considered an alternative technique when developing an airway plan for paediatric patients whose tracheas are difficult to intubate under general anaesthesia.


Asunto(s)
Laringoscopios , Laringoscopía , Adulto , Niño , Humanos , Laringoscopía/métodos , Broncoscopía/métodos , Intubación Intratraqueal/métodos , Sistema de Registros
3.
Eur J Nucl Med Mol Imaging ; 50(7): 1929-1939, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36826476

RESUMEN

INTRODUCTION: Immune-mediated interstitial pneumonitis may be treated with anti-CD20 therapy after failure of conventional therapies. However, clinical response is variable. It was hypothesized that autoreactive CD20-positive cells may play an important role in this variability. This prospective study aims to elucidate if imaging of CD20-positive cells in the lungs allows prediction of the response to anti-CD20 treatment. METHODS: Twenty-one patients with immune-mediated interstitial lung disease (ILD) with deteriorated pulmonary function received a dose of 1000 mg rituximab on day 1 and day 14 spiked with a tracer dose of radiolabeled [89Zr]-rituximab. PET/CT was performed on days 3 and 6. Standardized uptake values (SUV) were calculated as a measure for pulmonary CD20 expression. Based on pulmonary function tests (PFT), forced vital capacity (FVC), and diffusing capacity for carbon monoxide (DLCO), prior to and 6 months after treatment, patients were classified as responder (stable disease or improvement) or non-responder. RESULTS: Fifteen patients (71%) were classified as responder. Pulmonary [89Zr]-rituximab PET SUVmean was significantly correlated with the change in FVC and DLCO (K = 0.49 and 0.56, respectively) when using target-to-background ratios, but not when using SUVmean alone. [89Zr]-rituximab SUVmean was significantly higher in responders than in non-responders (0.35 SD 0.09 vs. 0.23 SD 0.06; P = 0.02). CONCLUSION: Rituximab treatment was effective in the majority of patients. As a higher pulmonary uptake of [89Zr]-rituximab correlated with improvement of PFT and treatment outcome, [89Zr]-rituximab PET imaging may serve as a potential predictive biomarker for anti-CD20 therapy. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT02251964.


Asunto(s)
Enfermedades Pulmonares Intersticiales , Radioisótopos , Humanos , Rituximab/efectos adversos , Radioisótopos/uso terapéutico , Circonio , Tomografía Computarizada por Tomografía de Emisión de Positrones , Estudios Prospectivos , Enfermedades Pulmonares Intersticiales/diagnóstico por imagen , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Pulmón , Tomografía de Emisión de Positrones
4.
Artículo en Inglés | MEDLINE | ID: mdl-38883231

RESUMEN

Tics and tic disorders can significantly impact children, but limited screening tools and diagnostic challenges may delay access to care. The current study attempted to address these gaps by evaluating sensitivity and specificity of the Motor or Vocal Inventory of Tics (MOVeIT), a tic symptom screener, and the Description of Tic Symptoms (DoTS), a brief diagnostic assessment for tic disorders. Children (n=100, age 6-17 years old) with tic disorders attending a Tourette specialty clinic and a community-recruited sample without tics completed a gold-standard assessment by a tic expert; these evaluations were compared to child self-report and parent and teacher report versions of the MOVeIT, and child and parent versions of the DoTS. The parent and child MOVeIT met or exceeded pre-specified 85% sensitivity and specificity criteria for detecting the presence of tics when compared to a gold-standard tic expert diagnosis. The Teacher MOVeIT had lower sensitivity (71.4%) but good specificity (95.7%) for identifying any tic symptoms compared to gold standard. For determination of the presence or absence of any tic disorder, sensitivity of both parent and child DoTS was 100%; specificity of the parent DoTS was 92.7% and child DoTS specificity was 75.9%. More work may be needed to refine the teacher MOVeIT, but it is also recognized that tic expression may vary by setting. While the MOVeIT and DoTS parent and child questionnaires demonstrated adequate sensitivity and specificity for determining the presence of tics and tic disorders in this well-defined sample, additional testing in a general population is warranted.

5.
Mol Genet Metab ; 137(1-2): 201-209, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36115283

RESUMEN

Due to the surge in new brain-directed treatments, metrics to detect the alteration in developmental trajectories in cognition and adaptive behavior have become increasingly important. We propose Growth Scale Values (GSVs) as a solution to monitoring children with severe neurologic/neurodegenerative conditions. This report stems from a panel of experts presenting at the Gorlin symposium (WORLD Symposium) and a subsequent open Webinar sponsored by the National MPS Society. Because norm-referenced scores (Standard Scores or Intelligence Quotient, i.e., IQ) do not yield information about gain, stability, or loss of skills, they are not suitable for natural history studies or clinical trials. Age-equivalent (AE) scores have been the standard metric used in natural history studies. While AEs are familiar and interpretable to clinicians and parents, they are imprecise due to lack of standard deviations, standard errors of measurement, and equal intervals between scores. Raw scores also have unequal intervals and are not comparable between ages or ability levels. The GSV, a nonlinear transformation of raw scores using item calibration to make an interval scale score, can be used for accurate measures of within-person change. GSVs have been identified as a useful metric for longitudinal measurement of other conditions involving neurodiversity. These growth scores circumvent inaccurate AEs in infants, are not limited by age and can be used for impaired patients who are chronologically above the normative age range. GSVs have interval properties (a given difference between GSV values represents the same difference in ability at all score levels) and each GSV value has a known standard error of measurement (SEM). GSVs are recommended to measure change in cognitive and adaptive behavior in natural history studies and in clinical trials for children with neurologic disease.


Asunto(s)
Enfermedades Neurodegenerativas , Niño , Lactante , Humanos , Enfermedades Neurodegenerativas/diagnóstico , Pruebas de Inteligencia , Cognición
6.
Pancreatology ; 22(7): 925-936, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35927150

RESUMEN

Pancreatic ductal adenocarcinoma (PDAC) is predicted to become the second leading cause of cancer-related mortality within the next decade, with limited effective treatment options and a dismal long-term prognosis for patients. Surgical resection of early, localised disease provides the only chance for potentially curative treatment; however, most patients with PDAC present with advanced disease and are not suitable for surgery. Genomic analyses of PDAC tumour lesions have identified a small number of recurrent alterations that are detected across most tumours, and beyond that a large number that either occur at a low (<5%) prevalence or are patient-specific in nature. This molecular heterogeneity has presented a significant challenge for the characterisation of tumour subtypes and effective molecular biomarkers, which have not yet manifested clinical benefits for diagnosis, treatment or prognosis in PDAC. These challenges are compounded by the overall lack of tumour biopsies for sequencing, the invasive nature of tissue sampling and the confounding effects of low tumour cellularity in many PDAC biopsy specimens, which have limited the applications of molecular profiling in unresectable patients and for longitudinal tumour monitoring. Further investigation into alternative sources of tumour analytes that can be sampled using minimally invasive methods and used to complement molecular analyses from tissue sequencing are required.


Asunto(s)
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patología , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patología , Pronóstico , Genómica , Biomarcadores de Tumor/genética , Neoplasias Pancreáticas
7.
Fungal Genet Biol ; 150: 103541, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33639303

RESUMEN

In this study, we investigated to possible role of Ras2 in Fusarium circinatum- a fungus that causes pine pitch canker disease on many different pine species and has a wide geographic distribution. This protein is encoded by the RAS2 gene and has been shown to control growth and pathogenicity in a number of fungi in a mitogen-activated protein kinase- and/or cyclic adenosyl monophosphate pathway-dependent manner. The aim was therefore to characterize the phenotypes of RAS2 gene knockout and complementation mutants of F. circinatum. These mutants were generated by transforming protoplasts of the fungus with suitable split-marker constructs. The mutant strains, together with the wild type strain, were used in growth studies as well as pathogenicity assays on Pinus patula seedlings. Results showed that the knockout mutant strain produced significantly smaller lesions compared to the complementation mutant and wild type strains. Growth studies also showed significantly smaller colonies and delayed conidial germination in the knockout mutant strain compared to the complement mutant and wild type strains. Interestingly, the knockout mutant strain produced more macroconidia than the wild type strain. Collectively, these results showed that Ras2 plays an important role in both growth and pathogenicity of F. circinatum. Future studies will seek to determine the pathway(s) through which Ras2 controls these traits in F. circinatum.


Asunto(s)
Fusarium/genética , Fusarium/patogenicidad , Esporas Fúngicas/crecimiento & desarrollo , Esporas Fúngicas/genética , Proteínas ras/genética , Fusarium/crecimiento & desarrollo , Técnicas de Inactivación de Genes , Genoma Fúngico , Mutación , Pinus/microbiología , Enfermedades de las Plantas/microbiología , Virulencia , Factores de Virulencia/genética , Proteínas ras/clasificación
8.
Pancreatology ; 21(2): 363-378, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33451936

RESUMEN

Pancreatic ductal adenocarcinoma (PDAC) is predicted to become the second leading cause of cancer-related mortality within the next decade, with limited effective treatment options and a dismal long-term prognosis for patients. Genomic profiling has not yet manifested clinical benefits for diagnosis, treatment or prognosis in PDAC, due to the lack of available tissues for sequencing and the confounding effects of low tumour cellularity in many biopsy specimens. Increasing focus is now turning to the use of minimally invasive liquid biopsies to enhance the characterisation of actionable PDAC tumour genomes. Circulating tumour DNA (ctDNA) is the most comprehensively studied liquid biopsy analyte in blood and can provide insight into the molecular profile and biological characteristics of individual PDAC tumours, in real-time and in advance of traditional imaging modalities. This can pave the way for identification of new therapeutic targets, novel risk variants and markers of tumour response, to supplement diagnostic screening and provide enhanced scrutiny in treatment stratification. In the roadmap towards the application of precision medicine for clinical management in PDAC, ctDNA analyses may serve a leading role in streamlining candidate biomarkers for clinical integration. In this review, we highlight recent developments in the use of ctDNA-based liquid biopsies for PDAC and provide new insights into the technical, analytical and biological challenges that must be overcome for this potential to be realised.


Asunto(s)
Biomarcadores de Tumor/sangre , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/metabolismo , ADN Tumoral Circulante/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Humanos , Transcriptoma
9.
Environ Res Lett ; 16(2)2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36034333

RESUMEN

To date, projections of human migration induced by sea-level change (SLC) largely suggest large-scale displacement away from vulnerable coastlines. However, results from our model of Bangladesh suggest counterintuitively that people will continue to migrate toward the vulnerable coastline irrespective of the flooding amplified by future SLC under all emissions scenarios until the end of this century. We developed an empirically calibrated agent-based model of household migration decision-making that captures the multi-faceted push, pull and mooring influences on migration at a household scale. We then exposed ~4800 000 simulated migrants to 871 scenarios of projected 21st-century coastal flooding under future emissions pathways. Our model does not predict flooding impacts great enough to drive populations away from coastlines in any of the scenarios. One reason is that while flooding does accelerate a transition from agricultural to non-agricultural income opportunities, livelihood alternatives are most abundant in coastal cities. At the same time, some coastal populations are unable to migrate, as flood losses accumulate and reduce the set of livelihood alternatives (so-called 'trapped' populations). However, even when we increased access to credit, a commonly-proposed policy lever for incentivizing migration in the face of climate risk, we found that the number of immobile agents actually rose. These findings imply that instead of a straightforward relationship between displacement and migration, projections need to consider the multiple constraints on, and preferences for, mobility. Our model demonstrates that decision-makers seeking to affect migration outcomes around SLC would do well to consider individual-level adaptive behaviors and motivations that evolve through time, as well as the potential for unintended behavioral responses.

10.
Anesth Analg ; 131(2): 469-479, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-31567318

RESUMEN

BACKGROUND: Ventilation is critical in airway management, and failure can be fatal. The optimal ventilation approach for endotracheal intubation in children with difficult airways remains controversial. The Pediatric Difficult Intubation (PeDI) Registry is an international multicenter registry that collects intubation data in difficult to intubate children. The registry captures the initial (at induction) and final ventilation technique (at intubation), the use of neuromuscular blocking drugs (NMBDs), airway reactivity during intubation, and complications. We analyzed data in the PeDI Registry to determine the frequency of use of various ventilation techniques and associated complications. Because spontaneously breathing patients ventilate throughout intubation, we hypothesized that spontaneous ventilation would be associated with fewer complications than other approaches. METHODS: We queried the PeDI Registry for cases entered between September 2012 and February 2016, from 16 children's hospitals. We categorized the attending anesthesiologist's ventilation plan into 3 groups: spontaneous ventilation, controlled ventilation after administering an NMBD, and controlled ventilation without administering an NMBD. Generalized Estimating Equation (GEE) model, with a binomial family distribution and logit link, was used to determine the association between ventilation technique and the risk of complications, as well as to account for within-site clustering. Propensity score matching was further applied to balance pretreatment characteristics of ventilation groups. RESULTS: Of 1289 anticipated difficult intubations, 507 (39%) were managed with spontaneous ventilation, 453 (35%) controlled ventilation with an NMBD, and 329 (26%) controlled ventilation without an NMBD. Complications occurred in 242 (18.8%; 95% confidence interval [CI], 16.6%-20.9%) patients. Of these, 218 (16.9%) were nonsevere, and 24 (1.9%) were severe. The spontaneous ventilation group had 114 (22.5%, standardized residual [Std.Res] = 4.29) nonsevere complications, which was higher than the controlled ventilation with an NMBD 60 (13.3%, Std.Res = -2.58), and controlled ventilation without an NMBD 44 (13.4%, Std.Res = -1.98), P < .001. Nearest neighbor matching with caliper width equal to 0.2 of the standard deviation (SD) of the logit of the propensity score also demonstrated that patients with spontaneous ventilation had greater odds of complications compared to controlled ventilation techniques: odds ratio (OR) = 2.07 (95% CI, 1.36-3.15; P = .001). CONCLUSIONS: Spontaneous ventilation is associated with more nonsevere complications, such as hypoxemia and laryngospasm, than controlled ventilation techniques during intubation of children with difficult airways. Inadequate anesthetic depth may contribute to increased complications.


Asunto(s)
Manejo de la Vía Aérea/métodos , Intubación Intratraqueal/métodos , Bloqueo Neuromuscular/métodos , Puntaje de Propensión , Sistema de Registros , Respiración Artificial/métodos , Adolescente , Niño , Preescolar , Estudios de Cohortes , Femenino , Humanos , Lactante , Intubación Intratraqueal/efectos adversos , Masculino , Bloqueo Neuromuscular/efectos adversos , Respiración Artificial/efectos adversos , Estudios Retrospectivos
11.
Sci Rep ; 8(1): 8474, 2018 05 31.
Artículo en Inglés | MEDLINE | ID: mdl-29855530

RESUMEN

Due to the different craniocervical structures in humans and cetaceans, a standardised method assessing the normal craniocervical relationship in cetaceans is lacking, causing difficulties in defining the presence of atlanto-occipital dissociation (AOD) in cetaceans. The present study aimed to 1) describe a novel standardised method of determining the normal craniocervical relationships, and 2) define the 95% accuracy range of the normal craniocervical relationship in finless porpoises (genus Neophocaena), that allowed AOD diagnosis. Fifty-five out 83 stranded or by-caught finless porpoise carcasses were analyzed in term of their craniocervical relationship in dorsal-ventral and medial-lateral dimension, using postmortem computed tomography measurements. The normal craniocervical relationship in both dorsal-ventral (mean BD/OV: 0.87 ± 0.24 [2 SD]) and medial-lateral dimension (mean VR/VL: 0.98 ± 0.17 [2 SD]) was first defined. The 95% accuracy ranges of the normal craniocervical relationship in dorsal-ventral (0.63-1.11) and medial-lateral dimension (0.82-1.15) were proposed. The baseline ranges could facilitate AOD assessment, and provide an objective means of record for AOD related injury and death of cetaceans caused by anthropogenic trauma. The technique developed may be applied to live cetaceans with abnormal craniocervical relationship to aid diagnosis and guide corrective therapy.


Asunto(s)
Articulación Atlantooccipital/fisiología , Luxaciones Articulares/diagnóstico , Tomografía Computarizada por Rayos X , Animales , Articulación Atlantooccipital/diagnóstico por imagen , Articulación Atlantooccipital/lesiones , Femenino , Masculino , Marsopas
12.
Methods Mol Biol ; 1792: 47-54, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29797251

RESUMEN

Mass cytometry has emerged as a new state-of-the-art technology that enables in-depth characterization of cellular populations and functions at a single cell resolution. We describe the application of this technology to deeply phenotype the blood and bone marrow components of multiple myeloma patients in a clinical setting. This technology allows for simultaneous quantification of more than 40 markers, overcoming the challenges of traditional fluorescence-based flow cytometry.


Asunto(s)
Biomarcadores , Citometría de Flujo , Sistema Inmunológico/inmunología , Sistema Inmunológico/metabolismo , Mieloma Múltiple/inmunología , Mieloma Múltiple/metabolismo , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Células Sanguíneas , Células de la Médula Ósea/inmunología , Células de la Médula Ósea/metabolismo , Citometría de Flujo/métodos , Humanos , Inmunofenotipificación , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos
13.
Circulation ; 138(8): 793-805, 2018 08 21.
Artículo en Inglés | MEDLINE | ID: mdl-29700121

RESUMEN

BACKGROUND: Whether the adult mammalian heart harbors cardiac stem cells for regeneration of cardiomyocytes is an important yet contentious topic in the field of cardiovascular regeneration. The putative myocyte stem cell populations recognized without specific cell markers, such as the cardiosphere-derived cells, or with markers such as Sca1+, Bmi1+, Isl1+, or Abcg2+ cardiac stem cells have been reported. Moreover, it remains unclear whether putative cardiac stem cells with unknown or unidentified markers exist and give rise to de novo cardiomyocytes in the adult heart. METHODS: To address this question without relying on a particular stem cell marker, we developed a new genetic lineage tracing system to label all nonmyocyte populations that contain putative cardiac stem cells. Using dual lineage tracing system, we assessed whether nonmyocytes generated any new myocytes during embryonic development, during adult homeostasis, and after myocardial infarction. Skeletal muscle was also examined after injury for internal control of new myocyte generation from nonmyocytes. RESULTS: By this stem cell marker-free and dual recombinases-mediated cell tracking approach, our fate mapping data show that new myocytes arise from nonmyocytes in the embryonic heart, but not in the adult heart during homeostasis or after myocardial infarction. As positive control, our lineage tracing system detected new myocytes derived from nonmyocytes in the skeletal muscle after injury. CONCLUSIONS: This study provides in vivo genetic evidence for nonmyocyte to myocyte conversion in embryonic but not adult heart, arguing again the myogenic potential of putative stem cell populations for cardiac regeneration in the adult stage. This study also provides a new genetic strategy to identify endogenous stem cells, if any, in other organ systems for tissue repair and regeneration.


Asunto(s)
Células Madre Adultas/fisiología , Diferenciación Celular , Linaje de la Célula , Rastreo Celular/métodos , Corazón/embriología , Integrasas/genética , Células Madre Embrionarias de Ratones/fisiología , Miocitos Cardíacos/fisiología , Células Madre Adultas/metabolismo , Animales , Proliferación Celular , Modelos Animales de Enfermedad , Proteínas de Escherichia coli/genética , Femenino , Regulación del Desarrollo de la Expresión Génica , Masculino , Ratones , Ratones de la Cepa 129 , Ratones Endogámicos C57BL , Ratones Transgénicos , Células Madre Embrionarias de Ratones/metabolismo , Músculo Esquelético/metabolismo , Músculo Esquelético/patología , Músculo Esquelético/fisiopatología , Infarto del Miocardio/genética , Infarto del Miocardio/metabolismo , Infarto del Miocardio/patología , Infarto del Miocardio/fisiopatología , Miocitos Cardíacos/metabolismo , Fenotipo , Recombinasas/genética , Regeneración , Transducción de Señal
15.
Acta Neurochir Suppl ; 126: 209-212, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29492563

RESUMEN

OBJECTIVES: Retrospective data from patients with severe traumatic brain injury (TBI) indicate that deviation from the continuously calculated pressure reactivity-based "optimal" cerebral perfusion pressure (CPPopt) is associated with worse patient outcome. The objective of this study was to assess the relationship between prospectively collected CPPopt data and patient outcome after TBI. METHODS: We prospectively collected intracranial pressure (ICP) monitoring data from 231 patients with severe TBI at Addenbrooke's Hospital, UK. Uncleaned arterial blood pressure and ICP signals were recording using ICM+® software on dedicated bedside computers. CPPopt was determined using an automatic curve fitting procedure of the relationship between pressure reactivity index (PRx) and CPP using a 4-h window, as previously described. The difference between an instantaneous CPP value and its corresponding CPPopt value was denoted every minute as ΔCPPopt. A negative ΔCPPopt that was associated with impaired PRx (>+0.15) was denoted as being below the lower limit of reactivity (LLR). Glasgow Outcome Scale (GOS) score was assessed at 6 months post-ictus. RESULTS: When ΔCPPopt was plotted against PRx and stratified by GOS groupings, data belonging to patients with a more unfavourable outcome had a U-shaped curve that shifted upwards. More time spent with a ΔCPPopt value below the LLR was positively associated with mortality (area under the receiver operating characteristic curve = 0.76 [0.68-0.84]). CONCLUSIONS: In a recent cohort of patients with severe TBI, the time spent with a CPP below the CPPopt-derived LLR is related to mortality. Despite aggressive CPP- and ICP-oriented therapies, TBI patients with a fatal outcome spend a significant amount of time with a CPP below their individualised CPPopt, indicating a possible therapeutic target.


Asunto(s)
Presión Arterial , Lesiones Traumáticas del Encéfalo/terapia , Circulación Cerebrovascular , Presión Intracraneal , Adulto , Estudios de Cohortes , Manejo de la Enfermedad , Femenino , Escala de Consecuencias de Glasgow , Humanos , Masculino , Monitoreo Fisiológico , Estudios Retrospectivos , Índices de Gravedad del Trauma
17.
Anesthesiology ; 127(3): 432-440, 2017 09.
Artículo en Inglés | MEDLINE | ID: mdl-28650415

RESUMEN

BACKGROUND: The success rates and related complications of various techniques for intubation in children with difficult airways remain unknown. The primary aim of this study is to compare the success rates of fiber-optic intubation via supraglottic airway to videolaryngoscopy in children with difficult airways. Our secondary aim is to compare the complication rates of these techniques. METHODS: Observational data were collected from 14 sites after management of difficult pediatric airways. Patient age, intubation technique, success per attempt, use of continuous ventilation, and complications were recorded for each case. First-attempt success and complications were compared in subjects managed with fiber-optic intubation via supraglottic airway and videolaryngoscopy. RESULTS: Fiber-optic intubation via supraglottic airway and videolaryngoscopy had similar first-attempt success rates (67 of 114, 59% vs. 404 of 786, 51%; odds ratio 1.35; 95% CI, 0.91 to 2.00; P = 0.16). In subjects less than 1 yr old, fiber-optic intubation via supraglottic airway was more successful on the first attempt than videolaryngoscopy (19 of 35, 54% vs. 79 of 220, 36%; odds ratio, 2.12; 95% CI, 1.04 to 4.31; P = 0.042). Complication rates were similar in the two groups (20 vs. 13%; P = 0.096). The incidence of hypoxemia was lower when continuous ventilation through the supraglottic airway was used throughout the fiber-optic intubation attempt. CONCLUSIONS: In this nonrandomized study, first-attempt success rates were similar for fiber-optic intubation via supraglottic airway and videolaryngoscopy. Fiber-optic intubation via supraglottic airway is associated with higher first-attempt success than videolaryngoscopy in infants with difficult airways. Continuous ventilation through the supraglottic airway during fiber-optic intubation attempts may lower the incidence of hypoxemia.


Asunto(s)
Tecnología de Fibra Óptica , Intubación Intratraqueal/instrumentación , Intubación Intratraqueal/métodos , Laringoscopía/instrumentación , Laringoscopía/métodos , Grabación de Cinta de Video , Niño , Preescolar , Diseño de Equipo , Femenino , Humanos , Lactante , Laringoscopios , Masculino , Sistema de Registros/estadística & datos numéricos
18.
Eur J Pain ; 21(7): 1234-1242, 2017 08.
Artículo en Inglés | MEDLINE | ID: mdl-28493479

RESUMEN

BACKGROUND: Emerging evidence suggests that perceived injustice is a risk factor for work disability in individuals with whiplash injury. At present, however, little is known about the processes by which perceived injustice impacts on return to work. The purpose of this study was to examine whether expectancies mediated the relationship between perceived injustice and return to work in patients with whiplash injury. METHOD: One hundred and fifty-two individuals (81 men, 71 women) with a primary diagnosis of whiplash injury completed self-report measures of pain intensity, perceived injustice and return-to-work expectancies following admission to a rehabilitation programme. Work status was assessed 1 year after discharge. RESULTS: Consistent with previous research, high scores on a measure of perceived injustice were associated with prolonged work disability. Results indicated that high perceptions of injustice were associated with low return-to-work expectancies. Causal mediation analyses revealed that expectancies fully mediated the relationship between perceived injustice and return to work. CONCLUSION: The findings suggest that intervention techniques designed to target expectancies could improve return-to-work outcomes in patients with whiplash injury. Discussion addresses the processes by which expectancies might impact on return-to-work outcomes and the manner in which negative return-to-work expectancies might be modified through intervention. SIGNIFICANCE: The study confirms that expectancies are the mechanism through which perceived injustice impacts return to work following whiplash injury. The findings suggest that interventions designed to specifically target return-to-work expectancies might improve rehabilitation outcomes in patients with whiplash injury.


Asunto(s)
Reinserción al Trabajo/psicología , Lesiones por Latigazo Cervical/complicaciones , Adulto , Femenino , Humanos , Masculino , Percepción , Estudios Prospectivos , Factores de Riesgo , Autoinforme , Resultado del Tratamiento
19.
J Anim Breed Genet ; 134(3): 275-285, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28508489

RESUMEN

Hyperketonemia (HYK), a common early postpartum health disorder characterized by elevated blood concentrations of ß-hydroxybutyrate (BHB), affects millions of dairy cows worldwide and leads to significant economic losses and animal welfare concerns. In this study, blood concentrations of BHB were assessed for 1,453 Holstein cows using electronic handheld meters at four time points between 5 and 18 days postpartum. Incidence rates of subclinical (1.2 ≤ maximum BHB ≤ 2.9 mmol/L) and clinical ketosis (maximum BHB ≥ 3.0 mmol/L) were 24.0 and 2.4%, respectively. Variance components, estimated breeding values, and predicted HYK phenotypes were computed on the original, square-root, and binary scales. Heritability estimates for HYK ranged from 0.058 to 0.072 in pedigree-based analyses, as compared to estimates that ranged from 0.071 to 0.093 when pedigrees were augmented with 60,671 single nucleotide polymorphism genotypes of 959 cows and 801 male ancestors. On average, predicted HYK phenotypes from the genome-enhanced analysis ranged from 0.55 mmol/L for first-parity cows in the best contemporary group to 1.40 mmol/L for fourth-parity cows in the worst contemporary group. Genome-enhanced predictions of HYK phenotypes were more closely associated with actual phenotypes than pedigree-based predictions in five-fold cross-validation, and transforming phenotypes to reduce skewness and kurtosis also improved predictive ability. This study demonstrates the feasibility of using repeated cowside measurement of blood BHB concentration in early lactation to construct a reference population that can be used to estimate HYK breeding values for genomic selection programmes and predict HYK phenotypes for genome-guided management decisions.


Asunto(s)
Enfermedades de los Bovinos/diagnóstico , Bovinos/genética , Genoma , Cetosis/veterinaria , Modelos Genéticos , Selección Genética , Ácido 3-Hidroxibutírico/sangre , Animales , Cruzamiento , Enfermedades de los Bovinos/genética , Enfermedades de los Bovinos/terapia , Manejo de la Enfermedad , Femenino , Variación Genética , Cetosis/genética , Masculino , Linaje , Carácter Cuantitativo Heredable , Factores de Riesgo
20.
Ann Afr Med ; 16(2): 59-64, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28469118

RESUMEN

BACKGROUND: Hepatitis B virus (HBV) Infection is endemic in Nigeria. Healthcare students are more vulnerable because of direct contact with patients' body fluids and blood. Risk perception of HBV and HB vaccine uptake are also poor. The aim of this study was to assess the level of risk perception of hepatitis B infection, and uptake of the HBV vaccine, between medical and other students of the University of Jos. METHODS: A comparative cross sectional study was conducted among 1,200 students of the departments of Medicine, Nursing sciences and Public Administration, University of Jos (400 from each arm) using a pretested self-administered questionnaire. A five point Likert scoring system was used to assess risk perception. Data was analyzed using SPSS version 20. A P -value of <0.05 was considered significant. RESULTS: Awareness on HB vaccine prevention was high (88.4%) among University of Jos students. Awareness was similar among medical and nursing students (36.2% and 36.0% respectively) but lower among public administration student (27.8%), P< 0.001. The overall risk perception was 76.8%. This was also similar for medical and nursing students (40.7% and 40.1% respectively), but lower for public administration students (9.1%), P< 0.001. Risk perception is 5x higher among medical students compared to public administration students (OR = 5.22, 95% CI = 2.19 - 12.93; P < 0.001). The uptake of full dose HB vaccine was 60.2%, 20.6% and 15.1% for medical, nursing and public administration students respectively. Medical students are 4x more likely to go for HB vaccination compared with public administration students (OR=3.62; 95% CI=2.39 - 5.48; P< 0.001). CONCLUSIONS: Awareness and risk perception on HBV infection are high among University of Jos students, but uptake of HB vaccine is low. Findings are worst for non-health students.


Asunto(s)
Conocimientos, Actitudes y Práctica en Salud , Vacunas contra Hepatitis B , Virus de la Hepatitis B/inmunología , Hepatitis B/prevención & control , Estudiantes/estadística & datos numéricos , Adolescente , Adulto , Femenino , Hepatitis B/epidemiología , Humanos , Masculino , Nigeria/epidemiología , Percepción , Estudiantes/psicología , Encuestas y Cuestionarios , Universidades , Vacunación , Adulto Joven
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