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RATIONALE: This is the first multicenter randomized controlled trial to evaluate the effectiveness and safety of Zephyr Endobronchial Valve (EBV) in patients with little to no collateral ventilation out to 12 months. OBJECTIVES: To evaluate the effectiveness and safety of Zephyr EBV in heterogeneous emphysema with little to no collateral ventilation in the treated lobe. METHODS: Subjects were enrolled with a 2:1 randomization (EBV/standard of care [SoC]) at 24 sites. Primary outcome at 12 months was the ΔEBV-SoC of subjects with a post-bronchodilator FEV1 improvement from baseline of greater than or equal to 15%. Secondary endpoints included absolute changes in post-bronchodilator FEV1, 6-minute-walk distance, and St. George's Respiratory Questionnaire scores. MEASUREMENTS AND MAIN RESULTS: A total of 190 subjects (128 EBV and 62 SoC) were randomized. At 12 months, 47.7% EBV and 16.8% SoC subjects had a ΔFEV1 greater than or equal to 15% (P < 0.001). ΔEBV-SoC at 12 months was statistically and clinically significant: for FEV1, 0.106 L (P < 0.001); 6-minute-walk distance, +39.31 m (P = 0.002); and St. George's Respiratory Questionnaire, -7.05 points (P = 0.004). Significant ΔEBV-SoC were also observed in hyperinflation (residual volume, -522 ml; P < 0.001), modified Medical Research Council Dyspnea Scale (-0.8 points; P < 0.001), and the BODE (body mass index, airflow obstruction, dyspnea, and exercise capacity) index (-1.2 points). Pneumothorax was the most common serious adverse event in the treatment period (procedure to 45 d), in 34/128 (26.6%) of EBV subjects. Four deaths occurred in the EBV group during this phase, and one each in the EBV and SoC groups between 46 days and 12 months. CONCLUSIONS: Zephyr EBV provides clinically meaningful benefits in lung function, exercise tolerance, dyspnea, and quality of life out to at least 12 months, with an acceptable safety profile in patients with little or no collateral ventilation in the target lobe. Clinical trial registered with www.clinicaltrials.gov (NCT 01796392).
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Bronquios/cirugía , Prótesis e Implantes , Enfisema Pulmonar/cirugía , Broncoscopía , Diseño de Equipo , Tolerancia al Ejercicio , Femenino , Volumen Espiratorio Forzado , Humanos , Masculino , Persona de Mediana Edad , Encuestas y Cuestionarios , Resultado del TratamientoRESUMEN
An untargeted LC-MS/MS platform was implemented for monitoring variations in CHO cell culture media upon exposure to high temperature short time (HTST) treatment, a commonly used viral clearance upstream strategy. Chemically defined (CD) and hydrolysate-supplemented media formulations were not visibly altered by the treatment. The absence of solute precipitation effects during media treatment and very modest shifts in pH values observed indicated sufficient compatibility of the formulations evaluated with the HTST-processing conditions. Unsupervised chemometric analysis of LC-MS/MS data, however, revealed clear separation of HTST-treated samples from untreated counterparts as observed from analysis of principal components and hierarchical clustering sample grouping. An increased presence of Maillard products in HTST-treated formulations contributed to the observed differences which included organic acids, observed particularly in chemically defined formulations, and furans, pyridines, pyrazines, and pyrrolidines which were determined in hydrolysate-supplemented formulations. The presence of Maillard products in media did not affect cell culture performance with similar growth and viability profiles observed for CHO-K1 and CHO-DP12 cells when cultured using both HTST-treated and untreated media formulations.
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Medios de Cultivo/análisis , Calor , Animales , Células CHO , Células Cultivadas , Cromatografía Liquida , Cricetulus , Espectrometría de Masas en Tándem , Factores de TiempoRESUMEN
When compared with hormonal therapy alone, treatment with combined hormone and radiation therapy (CHRT) gives improved disease-specific survival outcomes for patients with prostate cancer; however, a significant number of CHRT patients still succumb to recurrent disease. The purpose of this study was to use longitudinal patient samples obtained as part of an ongoing noninterventional clinical trial (ICORG06-15) to identify and evaluate a potential serum protein signature of disease recurrence. Label-free LC-MS/MS based protein discovery was undertaken on depleted serum samples from CHRT patients who showed evidence of disease recurrence (n = 3) and time-matched patient controls (n = 3). A total of 104 proteins showed a significant change between these two groups. Multiple reaction monitoring (MRM) assays were designed for a subset of these proteins as part of a panel of putative prostate cancer biomarkers (41 proteins) for evaluation in longitudinal serum samples. These data revealed significant interpatient variability in individual protein expression between time of diagnosis, disease recurrence, and beyond and serve to highlight the importance of longitudinal patient samples for evaluating the use of candidate protein biomarkers in disease monitoring.
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Biomarcadores de Tumor/metabolismo , Proteínas de Neoplasias/metabolismo , Neoplasias de la Próstata/metabolismo , Cromatografía Liquida , Humanos , Estudios Longitudinales , Masculino , Recurrencia Local de Neoplasia , Espectrometría de Masas en TándemRESUMEN
Host cell proteins (HCPs) are bioprocess-related impurities arising from cell-death or secretion from nonhuman cells used for recombinant protein production. Clearance of HCPs through downstream purification (DSP) is required to produce safe and efficacious therapeutic proteins. While traditionally measured using anti-HCP ELISA, more in-depth approaches for HCP characterization may ensure that risks to patients from HCPs are adequately assessed. Mass spectrometry methods provide rationale for targeted removal strategies through the provision of both qualitative and quantitative HCP information. A high pH, low pH, reversed-phase data independent 2D-LC-MS(E) proteomic platform was applied to determine HCP repertoires in the Protein A purified monoclonal antibody (mAb) samples as a function of culture harvest time, elution buffer used for DSP and also following inclusion of additional DSP steps. Critical quality attributes (CQAs) were examined for mAbs purified with different Protein A elution buffers to ensure that the selected buffers not only minimized the HCP profile but also exhibited no adverse effect on product quality. Results indicated that an arginine based Protein A elution buffer minimized the levels of HCPs identified and quantified in a purified mAb sample and also demonstrated no impact on product CQAs. It was also observed that mAbs harvested at later stages of cell culture contained higher concentrations of HCPs but that these were successfully removed by the addition of DSP steps complementary to Protein A purification. Taken together, our results showed how mass spectrometry based methods for HCP determination in conjunction with careful consideration of processing parameters such as harvest time, Protein A elution buffers, and subsequent DSP steps can reduce the HCP repertoire of therapeutic mAbs.
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Cromatografía Liquida/métodos , Espectrometría de Masas/métodos , Proteómica/métodos , Animales , Anticuerpos Monoclonales/inmunología , Tampones (Química) , Células CHO , Bovinos , Cricetulus , Humanos , Concentración de Iones de Hidrógeno , Factores de TiempoRESUMEN
The Perceptual Crossing Device (PCD) introduced in this report is an updated tool designed to facilitate the exploration of brain activity during human interaction with seamless real time integration with EEG equipment. It incorporates haptic and auditory feedback mechanisms, enabling interactions between two users within a virtual environment. Through a unique circular motion interface that enables intuitive virtual interactions, users can experience the presence of their counterpart via tactile or auditory cues. This paper highlights the key characteristics of the PCD, aiming to validate its efficacy in augmenting the understanding of human interactions. Furthermore, by offering an accessible and intuitive interface, the PCD stands to foster greater community engagement in the realm of embodied cognitive science and human interaction studies. Through this device, we anticipate a deeper comprehension of the complex neural dynamics underlying human interaction, thereby contributing a valuable resource to both the scientific community and the broader public.
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Encéfalo , Electroencefalografía , Humanos , Encéfalo/fisiología , Interfaz Usuario-Computador , Masculino , Femenino , Adulto , Realidad VirtualAsunto(s)
Progresión de la Enfermedad , Enfermedades Pulmonares Intersticiales/mortalidad , Enfermedades Pulmonares Intersticiales/fisiopatología , Pérdida de Peso , Anciano , Índice de Masa Corporal , California/epidemiología , Femenino , Humanos , Masculino , Pronóstico , Análisis de Regresión , Pruebas de Función Respiratoria , Estudios RetrospectivosRESUMEN
Various guidelines for the antibiotic treatment of community-acquired pneumonia (CAP) are presented that include fluoroquinolone antibiotics. The efficacy of current fluoroquinolone antibiotics in the treatment of CAP is summarized. Healthcare resource utilization and shortened duration of clinical symptoms have been shown in some, but not all of CAP trials utilizing fluoroquinolone antibiotics. Although evidence for both the clinical and microbiological efficacy of fluoroquinolone antibiotics is abundant, no convincing data demonstrates that they are superior to other standard antibiotics included in CAP guidelines.
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INTRODUCTION: Septic and vasoplegic shock are common types of vasodilatory shock (VS) with high mortality. After fluid resuscitation and the use of catecholamine-mediated vasopressors (CMV), vasopressin, angiotensin II, methylene blue (MB), and hydroxocobalamin can be added to maintain blood pressure. AREAS COVERED: VS treatment utilizes a phased approach with secondary vasopressors added to vasopressor agents to maintain an acceptable mean arterial pressure (MAP). This review covers additional vasopressors and adjunctive therapies used when fluid and catecholamine-mediated vasopressors fail to maintain target MAP. EXPERT OPINION: Evidence supporting additional vasopressor agents in catecholamine-resistant VS is limited to case reports, series, and a few randomized control trials (RCTs) to guide recommendations. Vasopressin is the most common agent added next when MAPs are not adequately supported with CMV. VS patients failing fluids and vasopressors with cardiomyopathy may have cardiotonic agents such as dobutamine or milrinone added before or after vasopressin. Angiotensin II, another class of vasopressor, is used in VS to maintain adequate MAP. MB and/or hydroxocobalamin, vitamin C, thiamine, and corticosteroids are adjunctive therapies used in refractory VS. More RCTs are needed to confirm the utility of these drugs, at what doses, which combinations and in what order they should be given.
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Infecciones por Citomegalovirus , Choque Séptico , Choque , Angiotensina II/uso terapéutico , Ácido Ascórbico/farmacología , Ácido Ascórbico/uso terapéutico , Cardiotónicos/farmacología , Cardiotónicos/uso terapéutico , Catecolaminas/uso terapéutico , Dobutamina/uso terapéutico , Humanos , Hidroxocobalamina/uso terapéutico , Azul de Metileno/uso terapéutico , Milrinona/uso terapéutico , Choque/tratamiento farmacológico , Choque Séptico/tratamiento farmacológico , Tiamina/uso terapéutico , Vasoconstrictores/farmacología , Vasoconstrictores/uso terapéutico , Vasopresinas/farmacología , Vasopresinas/uso terapéuticoRESUMEN
BACKGROUND: Numerous abnormalities in cystic fibrosis (CF) could influence tocopherol absorption, transportation, storage, metabolism and excretion. We hypothesized that the oxidative distress due to inflammation in CF increases vitamin E utilization, which could be positively influenced by supplemental vitamin C administration. METHODS: Immediately before and after receiving vitamin C (500 mg) twice daily for 3.5 weeks, adult CF patients (n = 6) with moderately advanced respiratory tract (RT) disease consumed a standardized breakfast with 30% fat and a capsule containing 50 mg each hexadeuterium (d6)-α- and dideuterium (d2)-γ-tocopheryl acetates. Blood samples were taken frequently up to 72 h; plasma tocopherol pharmacokinetics were determined. During both trials, d6-α- and d2-γ-tocopherols were similarly absorbed and reached similar maximal plasma concentrations ~18-20 h. As predicted, during vitamin C supplementation, the rates of plasma d6-α-tocopherol decline were significantly slower. CONCLUSIONS: The vitamin C-induced decrease in the plasma disappearance rate of α-tocopherol suggests that vitamin C recycled α-tocopherol, thereby augmenting its concentrations. We conclude that some attention should be paid to plasma ascorbic acid concentrations in CF patients, particularly to those individuals with more advanced RT inflammatory disease and including those with severe exacerbations.
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Fibrosis Quística , alfa-Tocoferol , Adulto , Ácido Ascórbico , Fibrosis Quística/tratamiento farmacológico , Humanos , Tocoferoles , Vitamina E , Vitaminas , gamma-TocoferolRESUMEN
AIMS: There is a critical need for better biomarkers so that heart failure can be diagnosed at an earlier stage and with greater accuracy. The purpose of this study was to design a robust mass spectrometry (MS)-based assay for the simultaneous measurement of a panel of 35 candidate protein biomarkers of heart failure, in blood. The overall aim was to evaluate the potential clinical utility of this biomarker panel for prediction of heart failure in a cohort of 500 patients. METHODS AND RESULTS: Multiple reaction monitoring (MRM) MS assays were designed with Skyline and Spectrum Mill PeptideSelector software and developed using nanoflow reverse phase C18 chromatographic Chip Cube-based separation, coupled to a 6460 triple quadrupole mass spectrometer. Optimized MRM assays were applied, in a sample-blinded manner, to serum samples from a cohort of 500 patients with heart failure and non-heart failure (non-HF) controls who had cardiovascular risk factors. Both heart failure with reduced ejection fraction (HFrEF) patients and heart failure with preserved ejection fraction (HFpEF) patients were included in the study. Peptides for the Apolipoprotein AI (APOA1) protein were the most significantly differentially expressed between non-HF and heart failure patients (P = 0.013 and P = 0.046). Four proteins were significantly differentially expressed between non-HF and the specific subtypes of HF (HFrEF and HFpEF); Leucine-rich-alpha-2-glycoprotein (LRG1, P < 0.001), zinc-alpha-2-glycoprotein (P = 0.005), serum paraoxanse/arylesterase (P = 0.013), and APOA1 (P = 0.038). A statistical model found that combined measurements of the candidate biomarkers in addition to BNP were capable of correctly predicting heart failure with 83.17% accuracy and an area under the curve (AUC) of 0.90. This was a notable improvement on predictive capacity of BNP measurements alone, which achieved 77.1% accuracy and an AUC of 0.86 (P = 0.005). The protein peptides for LRG1, which contributed most significantly to model performance, were significantly associated with future new onset HF in the non-HF cohort [Peptide 1: odds ratio (OR) 2.345 95% confidence interval (CI) (1.456-3.775) P = 0.000; peptide 2: OR 2.264 95% CI (1.422-3.605), P = 0.001]. CONCLUSIONS: This study has highlighted a number of promising candidate biomarkers for (i) diagnosis of heart failure and subtypes of heart failure and (ii) prediction of future new onset heart failure in patients with cardiovascular risk factors. Furthermore, this study demonstrates that multiplexed measurement of a combined biomarker signature that includes BNP is a more accurate predictor of heart failure than BNP alone.
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Insuficiencia Cardíaca , Biomarcadores , Proteínas Sanguíneas , Insuficiencia Cardíaca/diagnóstico , Humanos , Péptido Natriurético Encefálico , Volumen SistólicoRESUMEN
OBJECTIVE: The SARS-CoV2 infection is associated with high mortality for individuals who undergo emergency surgery. The United Kingdom surgical associations and Colleges of Surgeons collectively recommended the addition of CT Thorax to all emergency CT abdomen/pelvis imaging in order to help identify possible COVID-19 patients. Early identification of these patients would lead to optimal treatment strategies for the patient and protection for staff members. However, an extension of CT would be associated with increased irradiation doses for the patient, and its diagnostic relevance was unclear. METHODS: This was a retrospective observational review looking at all surgical admissions that required a CT Thorax/Abdomen/Pelvis across 7 weeks during the COVID-19 pandemic, across four Scottish Hospitals. CT thorax investigations (of non-surgical patients) were also re-assessed by a single radiologist to assess the extent of pathology identified at the lung bases (and therefore would be included in a standard CT abdomen and pelvis). RESULTS: Of 216 patients identified who had a CT thorax/Abdomen/Pelvis during the timeframe, 5 were diagnosed with COVID-19. During this timeframe, 77 patients underwent solely CT thorax. Across the entire cohort, 98% of COVID pathology was identified at the lung bases. The estimated sensitivity and specificity of CT thorax was 60 and 86.4% respectively. CONCLUSIONS: In a region with relatively low prevalence of SARS-COV2 infection, inclusion of CT Thorax in surgical admission imaging does not significantly contribute to identification and management of SARS-COV2 patients. We therefore suggest that imaging the lung bases can be sufficient to raise clinical suspicion of COVID-19. ADVANCES IN KNOWLEDGE: This paper adds further evidence to that from other single UK centres that the addition of CT chest for all patients does not yield any further diagnostic information regarding coronavirus. Additionally, rapid SARS-CoV-2 testing in the UK (which is currently widely available) further demonstrates that inclusion of the entire chest during CT examination of the acute abdomen is not required.
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RATIONALE: Cystic fibrosis (CF) patients are known to produce cyanide (CN-) although challenges exist in determinations of total levels, the precise bioactive levels, and specificity of its production by CF microflora, especially P. aeruginosa. Our objective was to measure total CN- levels in CF sputa by a simple and novel technique in P. aeruginosa positive and negative adult patients, to review respiratory tract (RT) mechanisms for the production and degradation of CN-, and to interrogate sputa for post-translational protein modification by CN- metabolites. METHODS: Sputa CN- concentrations were determined by using a commercially available CN- electrode, measuring levels before and after addition of cobinamide, a compound with extremely high affinity for CN-. Detection of protein carbamoylation was measured by Western blot. MEASUREMENTS AND MAIN RESULTS: The commercial CN- electrode was found to overestimate CN- levels in CF sputum in a highly variable manner; cobinamide addition rectified this analytical issue. Although P. aeruginosa positive patients tended to have higher total CN- values, no significant differences in CN- levels were found between positive and negative sputa. The inflammatory oxidant hypochlorous acid (HOCl) was shown to rapidly decompose CN-, forming cyanogen chloride (CNCl) and the carbamoylating species cyanate (NCO-). Carbamoylated proteins were found in CF sputa, analogous to reported findings in asthma. CONCLUSIONS: Our studies indicate that CN- is a transient species in the inflamed CF airway due to multiple biosynthetic and metabolic processes. Stable metabolites of CN-, such as cyanate, or carbamoylated proteins, may be suitable biomarkers of overall CN- production in CF airways.
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Cianuros/análisis , Fibrosis Quística/metabolismo , Técnicas Electroquímicas , Ácido Hipocloroso/química , Procesamiento Proteico-Postraduccional , Esputo/química , Adulto , Cobamidas/química , Cianuros/metabolismo , Fibrosis Quística/diagnóstico , Fibrosis Quística/microbiología , Electrodos , Femenino , Humanos , Ácido Hipocloroso/metabolismo , Cinética , Masculino , Persona de Mediana Edad , Oxidación-Reducción , Carbamilación de Proteína , Pseudomonas aeruginosa/metabolismo , Esputo/microbiologíaRESUMEN
Cystic fibrosis (CF) typically follows a more severe clinical course than non-CF bronchiectasis. Despite this recognized difference, the underpinnings of respiratory biology support a common pathogeneses of the anatomic deformations of bronchiectasis. This article reviews the observed manifestations among the related diseases of bronchiectasis and CF and discusses some of their similarities and differences. As more details of the mechanisms of bronchiectasis are unveiled, more parallels among the seemingly disparate causes of CF and non-CF bronchiectasis are recognized. With these insights, more opportunities to halt the vicious circle have become apparent.
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Bronquiectasia/fisiopatología , Fibrosis Quística/fisiopatología , Bronquiectasia/diagnóstico , Humanos , Inflamación/fisiopatología , Pruebas de Función Respiratoria , Infecciones del Sistema Respiratorio/fisiopatología , Factores de RiesgoRESUMEN
RATIONALE: Pseudomonas aeruginosa lung infection in patients with bronchiectasis, a chronic airway disease that is characterized by episodes of exacerbation, is associated with more severe disease and a higher utilization of health-care resources. Inhaled tobramycin solution reduces the number of acute exacerbations in patients with cystic fibrosis (CF)-related bronchiectasis with P aeruginosa infection but remains untested in the treatment of exacerbations in patients with non-CF bronchiectasis. OBJECTIVES: This study tested the effect of adding inhaled tobramycin solution to oral ciprofloxacin (Cip) for the treatment of acute exacerbations of non-CF bronchiectasis in patients with P aeruginosa infection. METHODS: A double-blind, randomized, active comparator, parallel-design study conducted at 17 study centers (5 in the United Kingdom, and 12 in the United States) compared 2 weeks of therapy with Cip with either an inhaled tobramycin solution or placebo in 53 adults with known P aeruginosa infection who were having acute exacerbations of bronchiectasis. MEASUREMENTS: Clinical symptoms, pulmonary function, clinical efficacy, and sputum microbiology were investigated prospectively. MAIN RESULTS: An inhaled solution of Cip with tobramycin, compared to placebo, achieved greater microbiological response but no statistically significant difference in clinical efficacy at days 14 or 21. Clinical and microbiological outcomes at the test of cure (ie, the clinical outcome assessment at day 21) were concordant when an inhaled tobramycin solution was added to therapy with Cip and compared to placebo (p = 0.01). Both subject groups had similar overall adverse event rates, but subjects receiving therapy with an inhaled tobramycin solution reported an increased frequency of wheeze (50%; placebo group, 15%). CONCLUSIONS: The addition of an inhaled tobramycin solution to therapy with oral Cip for the treatment of acute exacerbations of bronchiectasis due to P aeruginosa improved microbiological outcome and was concordant with clinical outcome; the inability to demonstrate an additional clinical benefit may have been due to emergent wheeze resulting from treatment.
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Antibacterianos/uso terapéutico , Bronquiectasia/complicaciones , Bronquiectasia/tratamiento farmacológico , Bronquiectasia/microbiología , Ciprofloxacina/uso terapéutico , Infecciones por Pseudomonas/tratamiento farmacológico , Tobramicina/uso terapéutico , Administración por Inhalación , Administración Oral , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/administración & dosificación , Antibacterianos/efectos adversos , Ciprofloxacina/administración & dosificación , Ciprofloxacina/efectos adversos , Método Doble Ciego , Esquema de Medicación , Quimioterapia Combinada , Femenino , Humanos , Pulmón/microbiología , Pulmón/patología , Pulmón/fisiopatología , Masculino , Persona de Mediana Edad , Infecciones por Pseudomonas/etiología , Pseudomonas aeruginosa/patogenicidad , Tobramicina/administración & dosificación , Tobramicina/efectos adversos , Resultado del Tratamiento , Reino Unido , Estados UnidosAsunto(s)
Inteligencia Artificial , Neoplasias de la Mama , Actitud , Mama , Neoplasias de la Mama/diagnóstico , Femenino , Humanos , Tamizaje MasivoRESUMEN
We examined the effect of dietary supplementation with L-arginine on breath condensate VEGF, exhaled nitric oxide (NO), plasma erythropoietin, symptoms of acute mountain sickness, and respiratory related sensations at 4,342 m through the course of 24 h in seven healthy male subjects. Serum L-arginine levels increased in treated subjects at time 0, 8, and 24 h compared with placebo, indicating the effectiveness of our treatment. L-arginine had no significant effect on overall Lake Louise scores compared with placebo. However, there was a significant increase in headache within the L-arginine treatment group at 12 h compared with time 0, a change not seen in the placebo condition between these two time points. There was a trend (p = 0.087) toward greater exhaled NO and significant increases in breath condensate VEGF with L-arginine treatment, but no L-arginine effect on serum EPO. These results suggest that L-arginine supplementation increases HIF-1 stabilization in the lung, possibly through a NO-dependent pathway. In total, our observations indicate that L-arginine supplementation is not beneficial in the prophylactic treatment of AMS.
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Mal de Altura/tratamiento farmacológico , Arginina/administración & dosificación , Cefalea/tratamiento farmacológico , Óxido Nítrico/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Adulto , Mal de Altura/metabolismo , Mal de Altura/prevención & control , Análisis de Varianza , Pruebas Respiratorias/métodos , Estudios Cruzados , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Cefalea/etiología , Cefalea/metabolismo , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Trauma is an important matter of public health and a major cause of mortality. Since the late 1980s trauma care provision in the United Kingdom is lacking when compared to the USA. This has been attributed to a lack of organisation of trauma care leading to the formation of trauma networks and Major Trauma Centres in England and Wales. The need for similar centres in Scotland is argued currently. We assessed the activity of two quite different trauma systems by obtaining access to comparative data from two hospitals, one in the USA and the other in Scotland. Aggregate data on 5604 patients at Aberdeen Royal Infirmary (ARI) from 1993 to 2002 was obtained from the Scottish Trauma Audit Group. A comparable data set of 16,178 patients from Massachusetts General Hospital (MGH). Direct comparison of patient demographics; injury type, mechanism and Injury Severity Score (ISS); mode of arrival; length of stay and mortality were made. Statistical analysis was carried out using Chi-squared and Cochran-Mantel-Haenszel. There were significant differences in the data sets. There was a higher proportion of penetrating injuries at MGH, (8.6% vs 2.6%) and more severely injured patients at MGH, patients with an ISS>16 accounted for nearly 22.1% of MGH patients compared to 14.0% at ARI. ISS 8-15 made up 54.6% of ARI trauma with 29.6% at MGH. Falls accounted for 50.1% at ARI and 37.9% at MGH. Despite the higher proportion of severe injuries at MGH and crude mortality rates showing no difference (4.9% ARI vs 5.2% MGH), pooled odds ratio of mortality was 1.4 (95% confidence interval 1.2-1.6) showing worse mortality outcomes at ARI compared to MGH. In conclusion, there were some differences in case mix between both data sets making direct comparison of the outcomes difficult, but the effect of consolidating major trauma on the proportion and number of severely injured patients treated in the American Level 1 centre was clear with a significant improvement in mortality in all injury severity groups.
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Auditoría Clínica , Hospitalización/estadística & datos numéricos , Hospitales Generales/estadística & datos numéricos , Tiempo de Internación/estadística & datos numéricos , Heridas y Lesiones/terapia , Benchmarking , Mortalidad Hospitalaria , Humanos , Puntaje de Gravedad del Traumatismo , Massachusetts/epidemiología , Oportunidad Relativa , Escocia/epidemiología , Tasa de Supervivencia , Resultado del Tratamiento , Heridas y Lesiones/mortalidadRESUMEN
Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive form of lung disease of unknown etiology for which a paucity of therapies suggest benefit, and for which none have demonstrated improved survival. Acute exacerbation of IPF (AE-IPF) is defined as a sudden acceleration of the disease or an idiopathic acute injury superimposed on diseased lung that leads to a significant decline in lung function. An AE-IPF is associated with a mortality rate as high as 85% with mean survival periods of between 3 to 13 days. Under these circumstances, mechanical ventilation (MV) is controversial, unless used a as a bridge to lung transplantation. Judicious fluid management may be helpful. Pharmaceutical treatment regimens for AE-IPF include the use of high dose corticosteroids with or without immunosuppressive agents such as cyclosporine A (CsA), and broad spectrum antibiotics, despite the lack of convincing evidence demonstrating benefit. Newer research focuses on abnormal wound healing as a cause of fibrosis and preventing fibrosis itself through blocking growth factors and their downstream intra-cellular signaling pathways. Several novel pharmaceutical approaches are discussed.
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BACKGROUND: Airway obstruction from blood clots, airway secretions, and foreign bodies is a potentially life-threatening condition. Optimal management of this problem, whether by rigid or flexible bronchoscopy, has not been well studied. We report our single-center experience on the safety and clinical utility of cryoprobe extraction for this indication. METHODS: We performed a retrospective chart review from January 2006 to November 2014 of all subjects aged 18 and older who underwent flexible bronchoscopic cryoprobe extraction. Subjects with obstruction due to benign or malignant neoplasm or airway stenosis were excluded. RESULTS: A total of 38 cryotherapy sessions performed on 30 subjects were identified for inclusion. Cryoprobe extraction was successful in reestablishing airway patency in 32/38 (84%) sessions overall and in 24/26 (92%) for blood clots, 4/6 (67%) for mucous plugging, 2/4 (50%) for foreign bodies, and 2/2 (100%) for plastic bronchitis. Twenty-one of 31 (68%) sessions resulted in improvement in oxygenation or ventilation. There was 1 complication related to sedation. CONCLUSIONS: We conclude that flexible bronchoscopic cryoprobe extraction of blood clots, mucous secretions, plastic bronchitis, and foreign bodies is a safe and effective option. It can be safely performed at the bedside and in many cases eliminates the need for rigid bronchoscopy.
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Obstrucción de las Vías Aéreas/cirugía , Broncoscopía/métodos , Criocirugía/métodos , Broncoscopios , Broncoscopía/instrumentación , Criocirugía/instrumentación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Pancreatic insufficiency in cystic fibrosis (CF), even with replacement pancreatic enzyme therapy, is often associated with decreased carotenoid absorption. Because the macular pigment of the retina is largely derived from 2 carotenoids, lutein and zeaxanthin, the decreased serum concentrations seen in CF may have consequences for ocular and retinal health OBJECTIVES: Our aims were to determine plasma carotenoid concentrations, determine absorption and distribution of macular pigment, and assess retinal health and visual function in CF patients. DESIGN: In 10 adult CF patients (ages 21-47 y) and 10 age- and sex-matched healthy control subjects, we measured macular pigment density in vivo, measured serum lutein and zeaxanthin concentrations, and comprehensively assessed visual performance (including contrast sensitivity, color discrimination, and retinal function) under conditions of daylight illumination. RESULTS: Serum lutein and zeaxanthin were significantly reduced (P < 0.005) in CF patients ( +/- SD: 87 +/- 36.1 and 27 +/- 15.8 nmol/L, respectively) compared with control subjects (190 +/- 72.1 and 75 +/- 23.6 nmol/L, respectively). Although macular pigment optical density was significantly lower (P < 0.0001) in the CF group (0.24 +/- 0.11) than in the control group (0.53 +/- 0.12), no significant differences in visual function were observed. CONCLUSIONS: Adults with CF have dramatically low serum and macular concentrations of carotenoids (lutein and zeaxanthin), but their ocular status and visual function are surprisingly good. The clinical implications of low plasma concentrations of carotenoids in CF are yet to be clarified.