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BACKGROUND: A pre-emptive transjugular intrahepatic portosystemic shunt (pTIPS) reduces mortality in high-risk patients with cirrhosis (Child-Pugh C/B+active bleeding) with acute variceal bleeding (AVB). Real-life studies point out that <15% of patients eligible for pTIPS ultimately undergo transjugular intrahepatic portosystemic shunt (TIPS) due to concerns about hepatic encephalopathy (HE). The outcome of patients undergoing pTIPS with HE is unknown. We aimed to (1) assess the prevalence of HE in patients with AVB; (2) evaluate the outcome of patients presenting HE at admission after pTIPS; and (3) determine if HE at admission is a risk factor for death and post-TIPS HE. PATIENTS AND METHODS: This is an observational study including 2138 patients from 34 centres between October 2011 and May 2015. Placement of pTIPS was based on individual centre policy. Patients were followed up to 1 year, death or liver transplantation. RESULTS: 671 of 2138 patients were considered at high risk, 66 received pTIPS and 605 endoscopic+drug treatment. At admission, HE was significantly more frequent in high-risk than in low-risk patients (39.2% vs 10.6%, p<0.001). In high-risk patients with HE at admission, pTIPS was associated with a lower 1-year mortality than endoscopic+drug (HR 0.374, 95% CI 0.166 to 0.845, p=0.0181). The incidence of HE was not different between patients treated with pTIPS and endoscopic+drug (38.2% vs 38.7%, p=0.9721), even in patients with HE at admission (56.4% vs 58.7%, p=0.4594). Age >56, shock, Model for End-Stage Liver Disease score >15, endoscopic+drug treatment and HE at admission were independent factors of death in high-risk patients. CONCLUSION: pTIPS is associated with better survival than endoscopic treatment in high-risk patients with cirrhosis with variceal bleeding displaying HE at admission.
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Doença Hepática Terminal , Varizes Esofágicas e Gástricas , Encefalopatia Hepática , Humanos , Encefalopatia Hepática/etiologia , Varizes Esofágicas e Gástricas/complicações , Varizes Esofágicas e Gástricas/cirurgia , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/cirurgia , Índice de Gravidade de Doença , Cirrose Hepática/complicações , ContraindicaçõesRESUMO
Many RNA-binding proteins undergo liquid-liquid phase separation, which underlies the formation of membraneless organelles, such as stress granules and P-bodies. Studies of the molecular mechanism of phase separation in vitro are hampered by the coalescence and sedimentation of organelle-sized droplets interacting with glass surfaces. Here, we demonstrate that liquid droplets of fused in sarcoma (FUS)-a protein found in cytoplasmic aggregates of amyotrophic lateral sclerosis and frontotemporal dementia patients-can be stabilized in vitro using an agarose hydrogel that acts as a cytoskeleton mimic. This allows their spectroscopic characterization by liquid-phase NMR and electron paramagnetic resonance spectroscopy. Protein signals from both dispersed and condensed phases can be observed simultaneously, and their respective proportions can be quantified precisely. Furthermore, the agarose hydrogel acts as a cryoprotectant during shock-freezing, which facilitates pulsed electron paramagnetic resonance measurements at cryogenic temperatures. Surprisingly, double electron-electron resonance measurements revealed a compaction of FUS in the condensed phase.
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Crioprotetores/química , Hidrogéis/química , Proteína FUS de Ligação a RNA/química , Sefarose/química , Materiais Biomiméticos/química , Clonagem Molecular , Citoesqueleto/química , Espectroscopia de Ressonância de Spin Eletrônica , Escherichia coli/genética , Escherichia coli/metabolismo , Células Eucarióticas/química , Expressão Gênica , Vetores Genéticos/química , Vetores Genéticos/metabolismo , Humanos , Ressonância Magnética Nuclear Biomolecular , Conformação Proteica , Proteínas Recombinantes/químicaRESUMO
The low-temperature Hahn echo decay signal of the pyrroline-based nitroxide H-mNOHex in ortho-terphenyl (OTP) shows two contributions on distinct time scales. Tunneling of the nitroxide's methyl groups cause electron spin echo envelope modulation (ESEEM) on a faster time scale compared to the slower matrix-induced decoherence contribution arising from nuclear pair ESEEM. Here we introduce the methyl quantum rotor (MQR) model that describes tunneling ESEEM originating from multiple methyl rotors coupled to the same electron spin. By formulating the MQR model based on a rotation barrier distribution P(V3), we account for the different local environments in a glassy matrix. Using this framework, we determine the methyl groups' rotation barrier distribution from experimental Hahn echo decay/two-pulse ESEEM data by a non-linear fitting approach. The inferred distributions are in good agreement with density functional theory (DFT) calculations of the methyl groups' rotation barriers in the low-temperature regime where tunneling constitutes the dominant methyl proton exchange process. In addition to comparing our results with previous decoherence studies performed on the same spin system, we experimentally confirm the characteristic properties of methyl tunneling by demonstrating that P(V3) is magnetic field independent and predominantly temperature independent between 10 and 50 K. This confirms the assignment of the fast Hahn echo decay contribution to methyl tunneling, showcasing how pulsed EPR sequences can coherently probe this quantum phenomenon for commonly employed nitroxide spin-labels.
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BACKGROUND & AIMS: Portal hypertension is the strongest predictor of hepatic decompensation and death in patients with cirrhosis. However, its discriminatory accuracy in patients with nonalcoholic fatty liver disease (NAFLD) has been challenged because hepatic vein catheterization may not reflect the real portal vein pressure as accurately as in patients with other etiologies. We aimed to evaluate the relationship between hepatic venous pressure gradient (HVPG) and presence of portal hypertension-related decompensation in patients with advanced NAFLD (aNAFLD). METHODS: Multicenter cross-sectional study included 548 patients with aNAFLD and 444 with advanced RNA-positive hepatitis C (aHCV) who had detailed portal hypertension evaluation (HVPG measurement, gastroscopy, and abdominal imaging). We examined the relationship between etiology, HVPG, and decompensation by logistic regression models. We also compared the proportions of compensated/decompensated patients at different HVPG levels. RESULTS: Both cohorts, aNAFLD and aHVC, had similar baseline age, gender, Child-Pugh score, and Model for End-Stage Liver Disease score. Median HVPG was lower in the aNAFLD cohort (13 vs 15 mmHg) despite similar liver function and higher rates of decompensation in aNAFLD group (32% vs 25%; P = .019) than in the aHCV group. For any of the HVPG cutoff analyzed (<10, 10-12, or 12 mmHg) the prevalence of decompensation was higher in the aNAFLD group than in the aHCV group. CONCLUSIONS: Patients with aNAFLD have higher prevalence of portal hypertension-related decompensation at any value of HVPG as compared with aHCV patients. Longitudinal studies aiming to identify HVPG thresholds able to predict decompensation and long-term outcomes in aNAFLD population are strongly needed.
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Doença Hepática Terminal , Hepatite C , Hipertensão Portal , Hepatopatia Gordurosa não Alcoólica , Estudos Transversais , Doença Hepática Terminal/complicações , Hepatite C/complicações , Humanos , Hipertensão Portal/etiologia , Cirrose Hepática/complicações , Hepatopatia Gordurosa não Alcoólica/complicações , Pressão na Veia Porta , RNA , Índice de Gravidade de DoençaRESUMO
Dipolar electron paramagnetic resonance (EPR) experiments such as double electron-electron resonance (DEER) measure distributions of nanometer-scale distances between unpaired electrons, which provide valuable information for structural characterization of proteins and other macromolecular systems. To determine these distributions from the experimental signal, it is critical to employ an accurate model of the signal. For dilute samples of doubly spin-labeled molecules, the signal is a product of an intramolecular and an intermolecular contribution. We present a general model based on dipolar pathways valid for dipolar EPR experiments with spin-1/2 labels. Our results show that the intramolecular contribution consists of a sum and the intermolecular contribution consists of a product over individual dipolar pathway contributions. We examine several commonly used dipolar EPR experiments in terms of dipolar pathways and show experimental results confirming the theoretical predictions. This multi-pathway model makes it possible to analyze a wide range of dipolar EPR experiments within a single theoretical framework.
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Dipolar electron paramagnetic resonance (EPR) experiments, such as double electron-electron resonance (DEER), measure distributions of nanometer-scale distances between unpaired electrons, which provide valuable information for structural characterization of proteins and other macromolecular systems. We present an extension to our previously published general model based on dipolar pathways valid for multi-dimensional dipolar EPR experiments with more than two spin-1/2 labels. We examine the 4-pulse DEER and TRIER experiments in terms of dipolar pathways and show experimental results confirming the theoretical predictions. This extension to the dipolar pathways model allows the analysis of previously challenging datasets and the extraction of multivariate distance distributions.
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Proteínas , Espectroscopia de Ressonância de Spin Eletrônica/métodos , Substâncias Macromoleculares , Proteínas/química , Marcadores de SpinRESUMO
AIM: To synthesize and describe the emotional and psychological implications for healthcare professionals who provided care in a mass casualty incident or disaster. BACKGROUND: The experience of healthcare providers immersed in the actual uncertainty of an ongoing disaster is real, challenging, complex and strongly connected with emotions. Identifying these implications for healthcare professionals is essential for developing strategies to help these professionals deliver high-quality care. EVALUATION: A systematic review was conducted in PubMed, CINAHL, Scopus, Nursing & Allied Health Database and PsycINFO using published data until February 2021 and following the PRISMA guidelines. KEY ISSUES: Nineteen articles were included. Factors associated with negative psychological implications were identified and different strategies have been synthesized to prevent or reduce them when caring for the victims of a disaster. CONCLUSIONS: Feelings of sadness, helplessness, fear and blockage, among others, were identified as common reactions among nurses and other healthcare professionals dealing in mass casualties or disasters. These reactions may lead to post-traumatic disorder, turning professionals into hidden victims. IMPLICATIONS FOR NURSING MANAGEMENT: Organizations, senior charge nurses and other health service managers need to foster resilience and flexibility among their workforce to improve self-care during a disaster, as well as ensure policies to address a lack of emotional preparedness among their personnel. Some strategies to consider include cognitive behavioural therapy, psychoeducation or meditation.
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Incidentes com Feridos em Massa , Atenção à Saúde , Emoções , Pessoal de Saúde , Humanos , Sistemas de Apoio PsicossocialRESUMO
Distance distribution information obtained by pulsed dipolar EPR spectroscopy provides an important contribution to many studies in structural biology. Increasingly, such information is used in integrative structural modeling, where it delivers unique restraints on the width of conformational ensembles. In order to ensure reliability of the structural models and of biological conclusions, we herein define quality standards for sample preparation and characterization, for measurements of distributed dipole-dipole couplings between paramagnetic labels, for conversion of the primary time-domain data into distance distributions, for interpreting these distributions, and for reporting results. These guidelines are substantiated by a multi-laboratory benchmark study and by analysis of data sets with known distance distribution ground truth. The study and the guidelines focus on proteins labeled with nitroxides and on double electron-electron resonance (DEER aka PELDOR) measurements and provide suggestions on how to proceed analogously in other cases.
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Óxidos N-Cíclicos/química , Espectroscopia de Ressonância de Spin Eletrônica/normas , Proteínas/química , Marcadores de Spin , Benchmarking , Espectroscopia de Ressonância de Spin Eletrônica/métodos , Reprodutibilidade dos TestesRESUMO
BACKGROUND AND AIM: Histological score systems may not fully capture the essential nonalcoholic steatohepatitis (NASH) features, which is one of the leading causes of screening failure in clinical trials. We assessed the NASH distribution and its components across the fibrosis stages and their impact on the prognosis and their relationship with the concept of metabolic-associated fatty liver disease (MAFLD). METHODS: Spanish multicenter study including 1893 biopsy-proven nonalcoholic fatty liver disease (NAFLD) patients from HEPAmet registry. NASH was diagnosed by NAS score ≥4 (including steatosis, ballooning and lobular inflammation) and fibrosis by Kleiner score. The presence of MAFLD was determined. Progression to cirrhosis, first episode of decompensated cirrhosis and death were collected during the follow-up (4.7 ± 3.8 years). RESULTS: Fibrosis was F0 34.3% (649/1893), F1 27% (511/1893), F2 16.5% (312/1893), F3 15% (284/1893) and F4 7.2% (137/1893). NASH diagnosis 51.9% (982/1893), and its individual components (severe steatosis, ballooning and lobular inflammation), increased from F0 (33.6%) to F2 (68.6%), and decreased significantly in F4 patients (51.8%) (P = .0001). More than 70% of non-NASH patients showed some inflammatory activity (ballooning or lobular inflammation), showing a similar MAFLD rate than NASH (96.2% [945/982] vs. 95.2% [535/562]) and significantly higher than nonalcoholic fatty liver (NAFL) subjects (89.1% [311/349]) (P < .0001). Progression to cirrhosis was similar between NASH (9.5% [51/539]) and indeterminate NASH (7.9% [25/316]), and higher than steatosis (5% [14/263]) (logRank 8.417; P = .015). Death and decompensated cirrhosis were similar between these. CONCLUSIONS: The prevalence of steatohepatitis decreased in advanced liver disease. However, most of these patients showed some inflammatory activity histologically and had metabolic disturbances. These findings should be considered in clinical trials whose main aim is to prevent cirrhosis progression and complications, liver transplant and death.
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Hepatopatia Gordurosa não Alcoólica , Biópsia , Humanos , Fígado/patologia , Cirrose Hepática/patologia , Estudos Longitudinais , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/patologiaRESUMO
Decoherence arises from a fluctuating spin environment, captured by its noise spectrum S(ω). Dynamical decoupling (DD) with n π pulses extends the dephasing time if the associated filter function attenuates S(ω). Inversely, DD noise spectroscopy (DDNS) reconstructs S(ω) from DD data by approximating the filters pass band by a δ-function. This restricts application to qubit-like spin systems with inherently long dephasing times and/or many applicable pulses. We introduce regularized DDNS to lift this limitation and thereby infer S(ω) from DD traces of paramagnetic centers in glassy o-terphenyl and water-glycerol matrices recorded with n ≤ 5. For nitroxide radicals at low temperatures, we utilize deuteration to identify distinct matrix- and spin center-induced spectral features. The former extends up to a matrix-specific cut-off frequency and characterizes nuclear spin diffusion. We demonstrate that rotational tunneling of intramolecular methyl groups drives the latter process, whereas at elevated temperatures S(ω) reflects the classical methyl group reorientation. Ultimately, S(ω) visualizes and quantifies variations in the electron spins couplings and thus reports on the underlying spin dynamics as a powerful decoherence descriptor.
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AIMS AND OBJECTIVES: The aim of review was to describe and synthesise the evidence on the use of tourniquets to control haemorrhages, summarising both civilian and military use. BACKGROUND: Trauma-related haemorrhage constitutes one of the most preventable deaths among injured patients, particularly in multi-casualty incidents and disasters. In this context, safe instruments such as tourniquets are essential to help healthcare professionals to minimise loss of life and maximise patient recovery. DESIGN AND METHODS: An integrative review was conducted in Medline, Nursing & Allied Health Premium, and Health & Medical Collection, using published data until March 2021 and following the PRISMA guidelines. RESULTS: A total of 25 articles were included. Evidence has been synthesised to understand the use of different types of tourniquets, environment of application, indication for their placement and potential complications associated with tourniquet placement. CONCLUSIONS: Commercial tourniquets such as Combat Application Tourniquet or Emergency Tourniquet models are a valuable and safe instrument for haemorrhage control in both military and civilian out-of-hospital care settings. Nurses, as part of emergency teams, and other professionals should be aware that there is a possibility of adverse complications, but they are directly proportional to the time of tourniquet placement and generally temporary. In addition, national and international guidelines ensure the need for all civilian emergency services to be equipped with these devices, as well as for the training of healthcare professionals and first responders in their use. RELEVANCE TO CLINICAL PRACTICE: Despite the lack of complications in the use of tourniquets in these cases, their use has been a matter of debate for decades. In this sense, this review yields up-to-date guidelines in the use of tourniquets, their recommendations and their significance among professionals to manage complicated situations.
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INTRODUCTION: liver enzyme elevation has been reported in SARS-CoV-2 disease (COVID-19) in heterogeneous cohorts, mainly from China. Comprehensive reports from other countries are needed. In this study, we dissect the pattern, evolution, and predictive value of such abnormalities in a cohort from Madrid, Spain. METHODS: a retrospective study with a prospective 14-day follow-up of 373 patients with confirmed COVID-19 in five Madrid hospitals, including 50 outpatients. A COVID-19 severe course was defined as the need for mechanical ventilation. RESULTS: a total of 33.1 % of hospitalized patients showed baseline AST elevation and 28.5 % showed ALT elevation, compared with 12 % and 8 % of outpatients (p ≤ 0.001). Baseline AST, ALT and GGT levels correlated with LDH and C-reactive protein (CRP) levels (r ≤ 0.598, p < 0.005). AST elevation was associated with other severity markers such as male sex, lymphopenia, and pneumonia on X-Ray (p < 0.05 for all). ALP and bilirubin levels were rarely increased. Patients with elevated baseline AST showed a progressive normalization of this enzyme and an increase in ALT and GGT levels. Patients with normal baseline AST showed a flattened evolution pattern with levels within the range. Patients with a severe course of COVID-19 more frequently showed elevated baseline AST than those with a milder evolution (54.2 % vs. 25.4 %, p < 0.001). Age, AST and CRP were independent risk factors for a severe course of COVID-19. CONCLUSION: mild liver enzyme elevation is associated with COVID-19 severity. Baseline AST is an independent predictor of severe COVID-19 course, and tends to normalize over time. ALT and GGT show a late elevation.
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COVID-19 , Hepatopatias , Humanos , Masculino , Estudos Prospectivos , Estudos Retrospectivos , SARS-CoV-2RESUMO
Symptomatic uncomplicated diverticular colon disease (SUDCD) is a highly prevalent disease in our setting, which significantly affects the quality of life of patients. Recent changes in understanding the natural history of this disease and technological and pharmacological advances have increased the available options for both diagnosis and treatment. However, consensus regarding the use of these options is scarce and sometimes lacks scientific evidence. The objective of this systematic review is to clarify the existing scientific evidence and analyse the use of the different diagnostic and therapeutic options for SUDCD, comparing their advantages and disadvantages, to finally suggest a diagnostic-therapeutic algorithm for this pathology and, at the same time, propose new research questions.
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Diverticulose Cólica/diagnóstico , Diverticulose Cólica/terapia , Árvores de Decisões , HumanosRESUMO
BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) could play a catalytic role in the development of metabolic comorbidities, although the magnitude of this effect in metabolically healthy patients with NAFLD remains unclear. We assessed the role of biopsy-proven NAFLD on the risk of developing type 2 diabetes mellitus (T2DM) and other metabolic comorbidities (arterial hypertension [AHT], and dyslipidemia) in metabolically healthy patients. METHODS: We included 178 metabolically healthy-defined by the absence of baseline T2DM, AHT, dyslipidemia-patients with biopsy-proven NAFLD from the HEPAmet Registry (N = 1,030). Hepamet fibrosis score (HFS), NAFLD fibrosis score, and Fibrosis-4 were calculated. Follow-up was computed from biopsy to the diagnosis of T2DM, AHT, or dyslipidemia. RESULTS: During a follow-up of 5.6 ± 4.4 years, T2DM occurred in 9% (16/178), AHT in 8.4% (15/178), low HDL in 9.6% (17/178), and hypertriglyceridemia in 23.6% (42/178) of patients. In multivariate analysis, significant fibrosis predicted T2DM and AHT. Independent variables related to T2DM appearance were significant fibrosis (HR 2.95; 95% CI 1.19-7.31; p = 0.019), glucose levels (p = 0.008), age (p = 0.007) and BMI (p = 0.039). AHT was independently linked to significant fibrosis (HR 2.39; 95% CI 1.14-5.10; p = 0.028), age (p = 0.0001), BMI (p = 0.006), glucose (p = 0.021) and platelets (p = 0.050). The annual incidence rate of T2DM was higher in patients with significant fibrosis (4.4 vs. 1.2 cases per 100 person-years), and increased in the presence of obesity, similar to AHT (4.6 vs. 1.1 cases per 100 person-years). HFS >0.12 predicted the risk of T2DM (25% [4/16] vs. HFS <0.12 4.5% [4/88]; logRank 6.658, p = 0.010). CONCLUSION: Metabolically healthy patients with NAFLD-related significant fibrosis were at greater risk of developing T2DM and AHT. HFS >0.12, but not NAFLD fibrosis score or Fibrosis-4, predicted the occurrence of T2DM. LAY SUMMARY: Patients with biopsy-proven non-alcoholic fatty liver disease and significant fibrosis were at risk of developing type 2 diabetes mellitus and arterial hypertension. The risk of metabolic outcomes in patients with significant fibrosis was increased in the presence of obesity. In addition to liver biopsy, patients at intermediate-to-high risk of significant fibrosis by Hepamet fibrosis score were at risk of type 2 diabetes mellitus.
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Diabetes Mellitus Tipo 2 , Hipertensão , Cirrose Hepática , Fígado/patologia , Hepatopatia Gordurosa não Alcoólica , Adulto , Biópsia/métodos , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Progressão da Doença , Dislipidemias/sangue , Dislipidemias/diagnóstico , Dislipidemias/epidemiologia , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Incidência , Cirrose Hepática/diagnóstico , Cirrose Hepática/etiologia , Cirrose Hepática/metabolismo , Cirrose Hepática/fisiopatologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Prognóstico , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Espanha/epidemiologiaRESUMO
Treatment of the background in dipolar EPR spectroscopy signals is a critical processing step for the recovery of the underlying distance distributions. Here we present new mathematical considerations that show pitfalls of background subtraction and division. In order to overcome these problems we propose an improved background treatment approach. We show, empirically, that this new method outperforms the established ones and analyze the established practice of post-correction signal truncation, as well as the influence of moderate background-fit errors, on accuracy of distance distributions.
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Along the medical practice of an Otologist he/she will face middle cranial fossa (MCF) bone defects. The purpose of this study is to contribute to the understanding of this possible life threatening condition, and to share and discuss our management approach. A literature review is also presented. STUDY DESIGN: Retrospective case series at García-Ibáñez Otology and Skull base private center referral. METHODS: This study is based on the analysis of data collected from 19 cases of temporal bone meningoencephalic herniations surgically treated from 2006 to 2018. The follow-up ranged from 18 to 162 months with a mean average of 44.5 months. MAIN FINDINGS: Meningoencephalic herniations were divided into four etiologic groups: spontaneous (24.8%), secondary to chronic otitis media (21.8%), iatrogenic (45.9%), and posttraumatic (7.5%). Different surgical techniques were used as treatment: transmastoid (TM) approach (27.8%), MCF approach (27.8%), combined technique (transmastoid plus minicraniotomy, 3%), and middle ear obliteration with blind sac closure of the external auditory canal (41.4%). CONCLUSIONS: Variables like bilateral hearing level, size and location of the bone defect and existence of CSF leak should be analyzed to select the safest and most effective closing surgical approach.
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Vazamento de Líquido Cefalorraquidiano , Fossa Craniana Média/cirurgia , Encefalocele/cirurgia , Meningocele/cirurgia , Procedimentos Neurocirúrgicos/métodos , Osso Temporal/cirurgia , Adulto , Idoso , Encefalocele/etiologia , Feminino , Seguimentos , Humanos , Masculino , Meningocele/etiologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Adulto JovemRESUMO
BACKGROUND & AIMS: Patients with hepatitis C virus-associated cirrhosis and clinical significant portal hypertension (CSPH, hepatic venous pressure gradient [HVPG] 10 mmHg or greater), despite achieving sustained virological response (SVR) to therapy, remain at risk of liver decompensation. We investigated hemodynamic changes following SVR in patients with CSPH and whether liver stiffness measurements (LSMs) can rule out the presence of CSPH. METHODS: We performed a multicenter prospective study of 226 patients with hepatitis C virus-associated cirrhosis and CSPH who had SVR to interferon-free therapy at 6 Liver Units in Spain. The portal pressure gradient was determined based on HVPG at baseline and 24 weeks after therapy; patients also underwent right-heart catheterization and LSM at these time points. Primary outcomes were effects of SVR on the hepatic, pulmonary, and systemic hemodynamics; factors related to HVPG ≥10% reduction and to CSPH persistence; and whether LSMs can rule out the presence of CSPH after SVR. RESULTS: Most patients (75%) had esophageal varices, 21% were Child-B, and 29% had at least 1 previous episode of liver decompensation. Overall, HVPG decreased from 15 (IQR: 12-18) before treatment to 13 (10-16) mmHg after SVR (reduction of 2.1 ± 3.2 mmHg; P < .01). However, CSPH persisted in 78% of patients. HVPG decreased by 10% or more from baseline in 140 patients (62%). Baseline level of albumin below 3.5 g/dL was the only negative factor associated with an HVPG reduction of 10% or more. LSM decreased from 27 (20-37) kPa before treatment to 18 (14-28) kPa after SVR (P < .05). One third of patients with a reduction in LSM to below 13.6 kPa after SVR still had CSPH. A higher baseline HVPG and a lower decrease in LSM after treatment were associated with persistence of CSPH after SVR. Systemic hemodynamics improved after SVR. Interestingly, pulmonary hypertension was present in 13 patients at baseline and 25 after SVR, although only 3 patients had increased pulmonary resistance. CONCLUSIONS: In a multicenter prospective study of patients with hepatitis C virus-associated cirrhosis, an SVR to all-oral therapy significantly reduced HVPG, compared with before treatment. Nevertheless, CSPH persists in most patients despite SVR, indicating persistent risk of decompensation. In this population, changes in LSM do not correlate with HVPG and cut-off values are not reliable in ruling out CSPH after SVR.
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Antivirais/administração & dosagem , Hepatite C/tratamento farmacológico , Hipertensão Portal/fisiopatologia , Cirrose Hepática/fisiopatologia , Pressão na Veia Porta , Circulação Pulmonar , Administração Oral , Idoso , Cateterismo Cardíaco , Quimioterapia Combinada , Feminino , Hepatite C/diagnóstico , Humanos , Hipertensão Portal/diagnóstico , Hipertensão Portal/virologia , Fígado/patologia , Cirrose Hepática/patologia , Cirrose Hepática/virologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Espanha , Resposta Viral Sustentada , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVE: To show that patients with unilateral hearing loss (UHL), with one ear fulfilling cochlear implant (CI) indication criteria, and an additional severe tinnitus handicap can be treated effectively with a CI. METHOD: A prospective multi-centre study was conducted in five Spanish centres. Sixteen adult patients with UHL and a mean Tinnitus Handicap Inventory (THI) score of at least 58 were implanted. The study design included repeated within-subject measures of quality of life (Health Utility Index Mark 3 [HUI3]), tinnitus (THI, Visual Analogue Scale [VAS] on tinnitus loudness), hearing (Speech, Spatial, and Qualities of Hearing Scale- [SSQ]), and hyperacusis (Test de Hipersensibilidad al Sonido [THS]) up to 12 months after the initial CI fitting. RESULTS: Group data showed significant subjective benefit from CI treatment: the preoperative HUI3 total utility score of 0.45 went up to 0.57 at 6 months and 0.63 at 12 months; the preoperative THI total score of 75 decreased to 40 at 6 months and 35 at 12 months. The preoperative tinnitus loudness VAS score of 8.2 decreased to 2.4 at 6 months and 2.2 at 12 months with the implant "On" and to 6.7 at 6 months and 6.5 at 12 months with the implant "Off." The preoperative THS total score of 26 decreased to 17 at 12 months. The preoperative SSQ total score of 4.2 increased to 5.1 at 6 months and 6.3 at 12 months. No unanticipated adverse events were reported during the study period. At 12 months after CI activation all subjects (except 1 subject who used the device 6 days a week) wore their devices all day and every day. The primary reason for CI use was split evenly between tinnitus suppression (n = 6) and both hearing and tinnitus (n = 6). CONCLUSION: A CI should be considered as a treatment option in patients with UHL and a concomitant severe tinnitus handicap. However, appropriate counselling of candidates on the anticipated risks, benefits, and limitations that are inherent to cochlear implantation is imperative.
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Implantes Cocleares , Perda Auditiva Unilateral/reabilitação , Qualidade de Vida , Zumbido/reabilitação , Adulto , Idoso , Implante Coclear/métodos , Feminino , Perda Auditiva Unilateral/complicações , Testes Auditivos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Zumbido/etiologia , Resultado do TratamentoRESUMO
Few technologies are more widespread in modern biological laboratories than imaging. Recent advances in optical technologies and instrumentation are providing hitherto unimagined capabilities. Almost all these advances have required the development of software to enable the acquisition, management, analysis and visualization of the imaging data. We review each computational step that biologists encounter when dealing with digital images, the inherent challenges and the overall status of available software for bioimage informatics, focusing on open-source options.