Effects of Albumin Treatment on Systemic and Portal Hemodynamics and Systemic Inflammation in Patients With Decompensated Cirrhosis.

BACKGROUND & AIMS: We investigated the effect of albumin treatment (20% solution) on hypoalbuminemia, cardiocirculatory dysfunction, portal hypertension, and systemic inflammation in patients with decompensated cirrhosis with and without bacterial infections. METHODS: We performed a prospective study to assess the effects of long-term (12 weeks) treatment with low doses (1 g/kg body weight every 2 weeks) and high doses (1.5 g/kg every week) of albumin on serum albumin, plasma renin, cardiocirculatory function, portal pressure, and plasma levels of cytokines, collecting data from 18 patients without bacterial infections (the Pilot-PRECIOSA study). We also assessed the effect of short-term (1 week) treatment with antibiotics alone vs the combination of albumin plus antibiotics (1.5 g/kg on day 1 and 1 g/kg on day 3) on plasma levels of cytokines in biobanked samples from 78 patients with bacterial infections included in a randomized controlled trial (INFECIR-2 study). RESULTS: Circulatory dysfunction and systemic inflammation were extremely unstable in many patients included in the Pilot-PRECIOSA study; these patients had intense and reversible peaks in plasma levels of renin and interleukin 6. Long-term high-dose albumin, but not low-dose albumin, was associated with normalization of serum level of albumin, improved stability of the circulation and left ventricular function, and reduced plasma levels of cytokines (interleukin 6, granulocyte colony-stimulating factor, interleukin 1 receptor antagonist, and vascular endothelial growth factor) without significant changes in portal pressure. The immune-modulatory effects of albumin observed in the Pilot-PRECIOSA study were confirmed in the INFECIR-2 study. In this study, patients given albumin had significant reductions in plasma levels of cytokines. CONCLUSIONS: In an analysis of data from 2 trials (Pilot-PRECIOSA study and INFECIR-2 study), we found that albumin treatment reduced systemic inflammation and cardiocirculatory dysfunction in patients with decompensated cirrhosis. These effects might be responsible for the beneficial effects of albumin therapy on outcomes of patients with decompensated cirrhosis. ClinicalTrials.gov, Numbers: NCT00968695 and NCT03451292.

Relative adrenal insufficiency in decompensated cirrhosis: Relationship to short-term risk of severe sepsis, hepatorenal syndrome, and death.

UNLABELLED: The prevalence of relative adrenal insufficiency (RAI) in critically ill cirrhosis patients with severe sepsis is over 60% and associated features include poor liver function, renal failure, refractory shock, and high mortality. RAI may also develop in noncritically ill cirrhosis patients but its relationship to the clinical course has not yet been assessed. The current study was performed in 143 noncritically ill cirrhosis patients admitted for acute decompensation. Within 24 hours after hospitalization adrenal function, plasma renin activity, plasma noradrenaline and vasopressin concentration, and serum levels of nitric oxide, interleukin-6 and tumor necrosis factor alpha were determined. RAI was defined as a serum total cortisol increase <9 µg/dL after 250 µg of intravenous corticotropin from basal values <35 µg/dL. Patients were followed for 3 months. RAI was detected in 26% of patients (n = 37). At baseline, patients with RAI presented with lower mean arterial pressure (76 ± 12 versus 83 ± 14 mmHg, P = 0.009) and serum sodium (131 ± 7 versus 135 ± 5 mEq/L, P = 0.007) and higher blood urea nitrogen (32 ± 24 versus 24 ± 15 mg/dl, P = 0.06), plasma renin activity (7.1 ± 9.9 versus 3.4 ± 5.6 ng/mL*h, P = 0.03), and noradrenaline concentration (544 ± 334 versus 402 ± 316 pg/mL, P = 0.02). During follow-up, patients with RAI exhibited a higher probability of infection (41% versus 21%, P = 0.008), severe sepsis (27% versus 9%, P = 0.003), type-1 hepatorenal syndrome (HRS) (16% versus 3%, P = 0.002), and death (22% versus 7%, P = 0.01). CONCLUSION: RAI is frequent in noncritically ill patients with acute decompensation of cirrhosis. As compared with those with normal adrenal function, patients with RAI have greater impairment of circulatory and renal function, higher probability of severe sepsis and type-1 HRS, and higher short-term mortality.

Effects of the dietary incorporation of olive leaves on growth performance, digestibility, blood parameters and meat quality of growing pigs.

BACKGROUND: In a preliminary study the oxidative stability and tocopherol content of pork meat were shown to be improved by olive leaf (OL) feed supplementation at 50 and 100 g kg(-1) . However, growth performance was affected negatively. Therefore the objective of the present study was to assess the influence of OL supplementation at a lower level on feed digestibility, growth performance and meat quality. RESULTS: Pigs were fed a basal diet (control), a basal diet with 25 g OL kg(-1) (OL2.5) or a basal diet with 50 g OL kg(-1) (OL5). The incorporation of OL significantly decreased growth rates (P = 0.010) and backfat thickness (P = 0.035) and increased feed/gain ratio (P = 0.032) in the OL5 group. Feed/gain ratio increased more for females (P = 0.001). The incorporation of OL decreased the crude fat (P = 0.006) and protein (P = 0.037) digestibility of both OL diets. Nevertheless, OL was effective in increasing the tocopherol content of meat (P = 0.009). However, meat from pigs fed the OL diets showed similar conjugated diene content, pH and colour parameters to that from pigs fed the control diet, even after 6 days of storage at 4 °C. CONCLUSION: The data indicate that olive leaves may be included in pig diets at 25 g kg(-1) in order to improve the tocopherol content of meat without excessively compromising growth performance.

Prevalence and risk factors of infections by multiresistant bacteria in cirrhosis: a prospective study.

UNLABELLED: Epidemiology, risk factors, and clinical effect of infections by multiresistant bacteria in cirrhosis are poorly known. This work was a prospective evaluation in two series of cirrhotic patients admitted with infection or developing infection during hospitalization. The first series was studied between 2005 and 2007 (507 bacterial infections in 223 patients) and the second between 2010 and 2011 (162 bacterial infections in 110 patients). In the first series, 32% of infections were community acquired (CA), 32% healthcare associated (HCA), and 36% nosocomial. Multiresistant bacteria (92 infections; 18%) were isolated in 4%, 14%, and 35% of these infections, respectively (P < 0.001). Extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-E; n = 43) was the main multiresistant organism identified, followed by Pseudomonas aeruginosa (n = 17), methicillin-resistant Staphylococcus aureus (n = 14), and Enterococcus faecium (n = 14). The efficacy of currently recommended empirical antibiotic therapy was very low in nosocomial infections (40%), compared to HCA and CA episodes (73% and 83%, respectively; P < 0.0001), particularly in spontaneous bacterial peritonitis, urinary tract infection, and pneumonia (26%, 29%, and 44%, respectively). Septic shock (26% versus 10%; P < 0.0001) and mortality rate (25% versus 12%; P = 0.001) were significantly higher in infections caused by multiresistant strains. Nosocomial origin of infection (hazard ratio [HR], 4.43), long-term norfloxacin prophylaxis (HR, 2.69), recent infection by multiresistant bacteria (HR, 2.45), and recent use of ß-lactams (HR, 2.39) were independently associated with the development of multiresistant infections. Results in the second series were similar to those observed in the first series. CONCLUSIONS: Multiresistant bacteria, especially ESBL-producing Enterobacteriaceae, are frequently isolated in nosocomial and, to a lesser extent, HCA infections in cirrhosis, rendering third-generation cephalosporins clinically ineffective. New antibiotic strategies tailored according to the local epidemiological patterns are needed for the empirical treatment of nosocomial infections in cirrhosis.

On the Impact of Synchronous Electrocardiogram Signals for Heart Sounds Segmentation.

In this paper we study the heart sound segmentation problem using Deep Neural Networks. The impact of available electrocardiogram (ECG) signals in addition to phonocardiogram (PCG) signals is evaluated. To incorporate ECG, two different models considered, which are built upon a 1D U-net - an early fusion one that fuses ECG in an early processing stage, and a late fusion one that averages the probabilities obtained by two networks applied independently on PCG and ECG data. Results show that, in contrast with traditional uses of ECG for PCG gating, early fusion of PCG and ECG information can provide more robust heart sound segmentation. As a proof of concept, we use the publicly available PhysioNet dataset. Validation results provide, on average, a sensitivity of 97.2%, 94.5%, and 95.6% and a Positive Predictive Value of 97.5%, 96.2%, and 96.1% for Early-fusion, Late-fusion, and unimodal (PCG only) models, respectively, showing the advantages of combining both signals at early stages to segment heart sounds.Clinical relevance- Cardiac auscultation is the first line of screening for cardiovascular diseases. Its low cost and simplicity are especially suitable for screening large populations in underprivileged countries. The proposed analysis and algorithm show the potential of effectively including electrocardiogram information to improve heart sound segmentation performance, thus enhancing the capacity of extracting useful information from heart sound recordings.

PERCUTANEOUS ENDOSCOPIC LUMBAR INTERBODY FUSION: RESULTS OVER 47 MONTHS OF FOLLOW-UP.

Introduction: This study aims to investigate the clinical-functional results of a new surgical technique, Percutaneous Endoscopic Lumbar Interbody Fusion (PELIF), in patients with a clinical diagnosis of low back or sciatic pain and segmental instability who were submitted to surgery using this technique assisted by the attending physician. Materials and methods: Patients completed a consent form and were clinically and radiographically re-assessed by independent evaluators using the visual analog scale (VAS) for pain, the Oswestry Disability Index (ODI), and the SF-36 Quality of Life Score in the pre- and postoperative periods. Their medical records were also reviewed for surgical time, length of hospital stay, need for blood transfusion, return to work, and radiographic fusion evaluation. Results: In the group of 19 patients with 33 levels operated, VAS and ODI decreased from 10.0 and 64% to 2.0 and 28%, respectively. The SF-36 showed significantly higher scores in 5 of its 7 domains at the end of the follow-up as compared to the preoperative period scores. Only 1 case of pseudoarthrosis was diagnosed radiographically. Conclusions: Percutaneous Endoscopic Lumbar Interbody Fusion (PELIF) has been shown to be a safe and efficient technique for the treatment of patients with segmental instability associated with low back or sciatic pain. Level of Evidence VI; Therapeutic Study; Case Series.

Introdução: Este estudo tem como objetivo investigar os resultados clínico-funcionais de uma nova técnica cirúrgica, artrodese lombar endoscópica percutânea (PELIF) em pacientes com diagnóstico clínico de dor lombar ou ciática e instabilidade segmentar, submetidos à referida técnica pelo médico responsável. Materiais e métodos: Os pacientes preencheram um termo de consentimento livre e esclarecido e foram reavaliados clínica e radiograficamente por avaliadores independentes que usaram a Escala Visual Analógica (EVA) para dor, Índice de Incapacidade de Oswestry (ODI) e o Short Form Health Questionnaire SF-36 nos períodos pré e pós-operatório. Foram também pesquisados nos prontuários médicos tempo de cirurgia, tempo de internação hospitalar, necessidade de transfusão de sangue, retorno ao trabalho e avaliação radiográfica da fusão. Resultados: Na amostra final de 19 pacientes com 33 níveis operados, EVA e ODI diminuíram de 10,0% e 64% para 2,0% e 28%, respectivamente. O SF-36 mostrou escores significativamente maiores em 5 de seus 7 domínios no final do acompanhamento, em comparação com o período pré-operatório. Somente 1 caso de pseudoartrose foi diagnosticado por radiografia. Conclusões: A artrodese lombar endoscópica percutânea (PELIF) tem se mostrado uma técnica segura e eficiente para o tratamento dos pacientes com instabilidade segmentar associada a lombalgia ou ciatalgia. Nível de Evidência IV; Estudos Terapêuticos; Série de Casos.

Antimicrobial Activity of Myrtus communis L. and Rosmarinus officinalis L. Essential Oils against Listeria monocytogenes in Cheese.

Listeria monocytogenes has been referred to as a concern microorganism in cheese making due to its ability to survive and grow in a wide range of environmental conditions, such as refrigeration temperatures, low pH and high salt concentration at the end of the production process. Since cheese may be a potential hazard for consumers, especially high-risk consumers (e.g., pregnant, young children, the elderly, people with medical conditions), efforts of the dairy industry have been aimed at investigating new conservation techniques based on natural additives to meet consumers' demands on less processed foods without compromising the food safety. Thus, the aim of this study was to evaluate the efficacy of Myrtus communis L. (myrtle) and Rosmarinus officinalis L. (rosemary) essential oils (EO) against Listeria monocytogenes ATCC 679 spiked in sheep cheese before ripening. After the cheesemaking process, the samples were stored at 8 °C for 2 h, 1 d, 3 d, 14 d and 28 d. The composition of EO was identified by gas chromatography-mass spectrometry (GC-MS) analysis. Constituents such as 1,8-cineole, limonene, methyl-eugenol, α-pinene, α-terpineol, α-terpinolene and ß-pinene were present in both EO, accounting for 44.61% and 39.76% from the total of chemical compounds identified for myrtle and rosemary EO, respectively. According to the chemical classification, both EO were mainly composed of monoterpenes. Minimum inhibitory concentration (MIC) against L. monocytogenes was obtained at 31.25 µL/mL to myrtle EO and at 0.40 µL/mL to rosemary EO. Then, cheeses were inoculated with L. monocytogenes (Ca. 6 log CFU/mL) and EO was added at MIC value. The addition of rosemary and myrtle EO displayed lower counts of L. monocytogenes (p < 0.01) (about 1-2 log CFU/g) during the ripening period compared to control samples. Ripening only influences (p < 0.001) the growth of L. monocytogenes in control samples. Since rosemary and myrtle EO do not exert any negative impact on the growth of native microflora (p > 0.05), their use as natural antimicrobial additives in cheese demonstrated a potential for dairy processors to assure safety against L. monocytogenes.

Minimally invasive spine surgery: evaluation of clinical and functional outcomes and their correlation with the return to work.

BACKGROUND: Intervertebral disc changes are a multi-factorial problem whose main clinical feature is pain. Studies show that when clinical treatments fail, the proposed surgical treatments frequently present unsatisfactory results. Traditional lumbar arthrodesis causes important clinical and functional changes that can result in complications and jeopardize the patients' quality of life. OBJECTIVES: This study aims to investigate the clinical and functional results of minimally invasive spine surgery in patients with a clinical diagnosis of low-back or sciatic pain and segmental instability, finally correlating these results with the patients' return to work. METHODS: Patients signed an informed consent form and were clinical and radiographically re-evaluated by independent professionals in the pre- and postoperative periods. Evaluation methods used the Oswestry disability index, as well as visual analog scale and Medical Outcomes Short Form Health Survey (SF-36) scores. We also retrieved epidemiological data, information on work resumption, and bone consolidation evaluations from the medical records. RESULTS: We evaluated 19 patients who had been operated on 33 levels; visual analog scale and Oswestry disability index scores were initially reduced from 10% to 2% and from 64% to 28%, respectively. SF-36 scores were significantly higher in 5 of the 7 questionnaire scales at the end of the follow-up period. Most patients (68.4%) did not return to work after surgery; the others returned 2 to 67 months after the procedure. All patients received social security benefits after the surgery. CONCLUSION: Although the procedure presented positive results, it did not result in a satisfactory return-to-work rate. Our results should be analyzed in view of the low educational level and income of the patients, the manual nature of their labor, and the validity of social security benefits.

Percutaneous endoscopic lumbar interbody fusion: results over 47 months of follow-up / Artrodese lombar intersomática endoscópica percutânea: resultados depois de 47 meses de acompanhamento

ABSTRACT Introduction This study aims to investigate the clinical-functional results of a new surgical technique, Percutaneous Endoscopic Lumbar Interbody Fusion (PELIF), in patients with a clinical diagnosis of low back or sciatic pain and segmental instability who were submitted to surgery using this technique assisted by the attending physician. Materials and methods Patients completed a consent form and were clinically and radiographically re-assessed by independent evaluators using the visual analog scale (VAS) for pain, the Oswestry Disability Index (ODI), and the SF-36 Quality of Life Score in the pre- and postoperative periods. Their medical records were also reviewed for surgical time, length of hospital stay, need for blood transfusion, return to work, and radiographic fusion evaluation. Results In the group of 19 patients with 33 levels operated, VAS and ODI decreased from 10.0 and 64% to 2.0 and 28%, respectively. The SF-36 showed significantly higher scores in 5 of its 7 domains at the end of the follow-up as compared to the preoperative period scores. Only 1 case of pseudoarthrosis was diagnosed radiographically. Conclusions Percutaneous Endoscopic Lumbar Interbody Fusion (PELIF) has been shown to be a safe and efficient technique for the treatment of patients with segmental instability associated with low back or sciatic pain. Level of Evidence VI; Therapeutic Study; Case Series.

RESUMO Introdução Este estudo tem como objetivo investigar os resultados clínico-funcionais de uma nova técnica cirúrgica, artrodese lombar endoscópica percutânea (PELIF) em pacientes com diagnóstico clínico de dor lombar ou ciática e instabilidade segmentar, submetidos à referida técnica pelo médico responsável. Materiais e métodos Os pacientes preencheram um termo de consentimento livre e esclarecido e foram reavaliados clínica e radiograficamente por avaliadores independentes que usaram a Escala Visual Analógica (EVA) para dor, Índice de Incapacidade de Oswestry (ODI) e o Short Form Health Questionnaire SF-36 nos períodos pré e pós-operatório. Foram também pesquisados nos prontuários médicos tempo de cirurgia, tempo de internação hospitalar, necessidade de transfusão de sangue, retorno ao trabalho e avaliação radiográfica da fusão. Resultados Na amostra final de 19 pacientes com 33 níveis operados, EVA e ODI diminuíram de 10,0% e 64% para 2,0% e 28%, respectivamente. O SF-36 mostrou escores significativamente maiores em 5 de seus 7 domínios no final do acompanhamento, em comparação com o período pré-operatório. Somente 1 caso de pseudoartrose foi diagnosticado por radiografia. Conclusões A artrodese lombar endoscópica percutânea (PELIF) tem se mostrado uma técnica segura e eficiente para o tratamento dos pacientes com instabilidade segmentar associada a lombalgia ou ciatalgia. Nível de Evidência IV; Estudos Terapêuticos; Série de Casos.

The new epidemiology of nosocomial bacterial infections in cirrhosis: therapeutical implications.

Cirrhotic patients are at increased risk of developing infection, sepsis and death. Enterobacteriaceae and nonenterococcal streptococci are the main bacteria responsible for spontaneous and urinary infections in this population. Prompt and appropriate treatment is basic in the management of cirrhotic patients with infection. Third-generation cephalosporins continue to be the gold-standard antibiotic treatment of the majority of infections acquired in the community because responsible strains are usually susceptible to ß-lactams. By contrary, nosocomial infections are nowadays frequently caused by multiresistant bacteria (extended-spectrum ß-lactamase-producing Enterobacteriaceae, Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus, and vancomycin-resistant enterococci among others) that are nonsusceptible to the main antibiotics. Treatment of these infections requires the use of broader spectrum antibiotics (carbapenems) or of antibiotics that are active against specific resistant bacteria (glycopeptides, linezolid, daptomycin, amikacin and colistin). Empirical antibiotic schedules must be adapted to the local epidemiological pattern of antibiotic resistance. Careful restriction of antibiotic prophylaxis to the high-risk population is also mandatory to reduce the spread of multiresistant bacteria in cirrhosis.

Protective activity of hydroxytyrosol metabolites on erythrocyte oxidative-induced hemolysis.

The capacity of important hydroxytyrosol metabolites (homovanillyl alcohol, hydroxytyrosol acetate, homovanillyl alcohol acetate, hydroxytyrosol 3' and 4'-O-glucuronides, and homovanillyl alcohol 4'-O-glucuronide) to protect red blood cells (RBCs) from oxidative injury induced by the radical initiator 2,2'-azo-bis(2-amidinopropane) dihydrochloride (AAPH) or by the natural radical initiator H2O2 was evaluated. In the presence of AAPH, all compounds showed to protect RBCs from hemolysis in a dose-dependent manner, exccept for the homovanillyl alcohol glucuronide, with the order of activity being at 20 µM hydroxytyrosol > hydroxytyrosol glucuronides = hydroxytyrosol acetate = homovanillyl alcohol = homovanillyl acetate > homovanillyl alcohol glucuronide. At 10 µM, hydroxytyrosol, hydroxytyrosol acetate, and hydroxytyrosol glucuronides still protected hemoglobine from oxidation and from morphological RBC changes. In the presence of H2O2, hydroxytyrosol showed to significantly protect RBCs from oxidative hemolysis in a dose-dependent manner, but the hydroxytyrosol glucuronides showed only a limited protection that was independent of the concentration used.

Effects of pentoxifylline on intestinal bacterial overgrowth, bacterial translocation and spontaneous bacterial peritonitis in cirrhotic rats with ascites.

BACKGROUND: Prophylaxis of spontaneous bacterial peritonitis with norfloxacin has been associated to development of antibiotic resistance. We investigated whether pentoxifylline compared to norfloxacin reduces bacterial translocation and spontaneous bacterial peritonitis in rats with CCl(4)-induced cirrhosis and ascites. METHOD: After development of cirrhosis and ascites, animals were randomly allocated to receive pentoxifylline (16 mg/kg/d every 8h, oral route, n=13) or placebo (n=12) for 15 days. An additional group of 8 cirrhotic rats was given norfloxacin (5mg/kg/d for 15 days). Six healthy rats served as controls. Cecal flora and the prevalence of bacterial translocation and spontaneous bacterial peritonitis were analysed. Serum and ascitic fluid levels of TNF-alpha and cecal levels of malondialdehyde were also measured. RESULTS: Pentoxifylline in comparison to placebo reduced intestinal bacterial overgrowth (21% vs. 67%, p=0.04), bacterial translocation to cecal lymph nodes (23% vs. 75%, p=0.03) and prevented spontaneous bacterial peritonitis (0% vs. 33%, p=0.04) by Enterobacteriaceae. Norfloxacin administration induced similar results. Pentoxifylline (0.18 ± 0.10 nmol/mg), but not norfloxacin (0.25 ± 0.13; p=0.02), significantly reduced cecal mucosal levels of malondialdehyde compared to placebo (0.33 ± 0.16; p=0.03). CONCLUSION: In cirrhotic rats with ascites: (a) pentoxifylline as well as norfloxacin reduced intestinal bacterial overgrowth and bacterial translocation and prevented spontaneous bacterial peritonitis; (b) pentoxifylline, but not norfloxacin, reduced oxidative stress in cecal mucosal.

Osteoblastoma na coluna vertebral: 27 anos de experiência / Spinal osteoblastoma: 27 years of experience

O osteoblastoma é tumor benigno primário do osso e corresponde a 1 por cento destes tumores. Acomete indivíduos jovens, principalmente na coluna vertebral, onde produz sintomatologia variada, desde dor até deformidades estruturadas. O tratamento é eminentemente cirúrgico. Os autores mostram a experiência do Grupo de Afecções da Coluna Vertebral do Pavilhão "Fernandinho Simonsen" da Santa Casa de Misericórdia de São Paulo (SCMSP) com o tratamento do osteoblastoma da coluna vertebral. Foram avaliados os prontuários de 16 pacientes, tratados no período de 1975 a 2002, sendo oito homens e oito mulheres, com média de idade de 23,9 anos. O quadro clínico principal foi dor, presente em todos os pacientes, e a região mais acometida foi a coluna cervical (oito pacientes). O tempo médio de seguimento foi de 51 meses. Discutem-se, comparando com a literatura, o diagnóstico, a evolução e os resultados do tratamento desses pacientes.