Four-year overall survival update from the phase III HIMALAYA study of tremelimumab plus durvalumab in unresectable hepatocellular carcinoma.

BACKGROUND: In the phase III HIMALAYA study (NCT03298451) in unresectable hepatocellular carcinoma (uHCC), STRIDE (Single Tremelimumab Regular Interval Durvalumab) significantly improved overall survival (OS) versus sorafenib; durvalumab monotherapy was noninferior to sorafenib for OS. Results reported herein are from a 4-year updated OS analysis of HIMALAYA. PATIENTS AND METHODS: Participants with uHCC and no previous systemic treatment were randomized to STRIDE (n = 393), durvalumab (n = 389), or sorafenib (n = 389). The updated data cut-off was 23 January 2023. OS and serious adverse events (AEs) were assessed. Additionally, baseline characteristics and subsequent therapies were analyzed in long-term survivors (≥36 months beyond randomization). RESULTS: For STRIDE, durvalumab, and sorafenib, median [95% confidence interval (CI)] follow-up was 49.12 months (46.95-50.17 months), 48.46 months (46.82-49.81 months), and 47.31 months (45.08-49.15 months), respectively. OS hazard ratio (95% CI) for STRIDE versus sorafenib was 0.78 (0.67-0.92). The 36-month OS rate for STRIDE was 30.7% versus 19.8% for sorafenib. The 48-month OS rate remained higher for STRIDE at 25.2%, versus 15.1% for sorafenib. The long-term OS benefit of STRIDE was observed across clinically relevant subgroups and was further improved in participants who achieved disease control. Long-term survivors with STRIDE (n = 103) included participants across clinically relevant subgroups, and 57.3% (59/103) had no reported subsequent anticancer therapy. No new serious treatment-related AEs occurred with STRIDE from the primary analysis (17.5%; 68/388). Durvalumab maintained OS noninferiority to sorafenib and no late-onset safety signals were identified. CONCLUSIONS: These data represent the longest follow-up to date in phase III studies in uHCC. The unprecedented 3- and 4-year OS rates reinforce the sustained long-term OS benefit of STRIDE versus sorafenib. STRIDE maintained a tolerable yet differentiated safety profile from other current uHCC therapies. Results continue to support the long-term benefits of STRIDE in a diverse population, reflective of uHCC globally.

Integration of membrane processes for the recovery and separation of polyphenols from winery and olive mill wastes using green solvent-based processing.

Winery and olive mill industries generate large amounts of wastes causing important environmental problems. The main aim of this work is the evaluation of different membrane separation processes like microfiltration, ultrafiltration, nanofiltration, and reverse osmosis for the recovery of polyphenols from winery and olive mill wastes in aqueous solutions. Membrane processes were tested separately in a closed-loop system, and by an integration in a concentration mode sequential design (open-loop). Feed flow rate was varied from 1 to 10 mL min-1, and permeate samples were taken in order to measure the polyphenols concentration. The separation and concentration efficiency were evaluated in terms of total polyphenol content, and by polyphenols families (hydroxybenzoic acids (HB), hydroxycinnamic acids (HC), and flavonoids (F)), using high performance liquid chromatography. Results showed that MF and UF membranes removed suspended solids and colloids from the extracts. NF was useful for polyphenols separation (HB rejections were lower than for HC and F: HB rejections of 50 and 63% for lees filters and olive pomace extracts, respectively), and RO membranes were able to concentrate polyphenols streams (86 and 95% rejection from lees filters and olive pomace, respectively). Membranes sequential designs for lees filters and olive pomace extracts, using a selective membrane train composed by UF, NF and RO membranes, were able to obtain polyphenol rich streams and high-quality water streams for reuse purposes.

Valorisation options for Zn and Cu recovery from metal influenced acid mine waters through selective precipitation and ion-exchange processes: promotion of on-site/off-site management options.

Acid mine waters (AMWs), generated in the processing of polymetallic sulphides, contain copper and zinc as the main valuable transition metal ions, which are typically removed by liming, due to their great environmental impact. In this context, this work proposes the integration of selective precipitation (SP) and ion-exchange (IX) processes for the separation and recovery of both valuable metals to encourage on-site and off-site management options promoting valorisation routes. Thus, the main objectives of this work were (i) the selective removal of Fe(III) and Al(III), using NaOH under pH control (pH < 5) to avoid the precipitation of Cu(II) and Zn(II) and (ii) the evaluation of a solvent-impregnated resin (Lewatit VP OC 1026, named VP1026) and a cation IX resin (Lewatit TP 207, named TP207) for the sequential extraction of both metal ions from AMW (batch and column experiments). Results indicated that the metallic pollution load was mostly removed during the SP process of Fe(III) (>99%) and Al(III) (>90%) as hydroxylsulphates (e.g., schwertmannite and basaluminite). The metal extraction profiles were determined for both metals from pH 1 to pH 5 by batch experiments, and indicated that the best extraction of Zn(II) was obtained using VP1026, being higher than 96% (pH = 2.6-2.8), whereas TP207 extraction performance was optimal for Cu(II) extraction (>99%) at pH = 3-4. Moreover, in dynamic experiments using a fixed-bed configuration, it was possible to separate and concentrate Zn(II) (concentration factor = 10) and Cu(II) (concentration factor = 40) using VP1026 and TP207, respectively. Overall, the integration of SP and IX processes showed a great potential in the separation and recovery of valuable metals from mine waters to promote a circular economy, based on the management proposal for non-ferrous metallurgical industries. The recovered Zn-rich and Cu-rich sulphuric concentrated streams were theoretically evaluated for further on-site or off-site re-use treatments (e.g., electrowinning, precipitation, crystallization).

Arsenic impact on the valorisation schemes of acidic mine waters of the Iberian Pyrite Belt: Integration of selective precipitation and spiral-wound nanofiltration processes.

Arsenic and selenium presence in acid mine waters (AMWs) limits their disposal due to environmental regulations. The focus to solve the economic infeasibility is directed to sustainable solutions, promoting resource recovery. In fact, rare earth elements (REEs) recovery is proposed in most of the Iberian Pyrite Belt AMWs. However, the presence of arsenic and selenium may impact in the REEs recovery. Among different alternatives, nanofiltration (NF) provides a concentration stage on REEs recovery, reduces the nominal flow and removes hazardous species. In this work, Iberian Pyrite Belt AMWs with up to 10 mg/L REEs, containing arsenic (2 mg/L), were treated with a NF membrane. Firstly, AMWs were pre-treated with H2O2/NaOH, to oxidise Fe(II) to Fe(II) and As(III) to As(V), promoting their removal and avoiding their potential precipitation at the membrane. Subsequently, NF pressure effect (6-20 bar) was studied, removing metals (>95 %), whereas arsenic rejections ranged from 60 to 71 %. Then, water recovery potential was evaluated at 10, 15 and 22 bar by reproducing a 10-stages NF plant. Results showed that the proposed treatment could be an alternative for arsenic and selenium removal (70 µg/L and 0.5 µg/L permeate concentrations, respectively) to achieve mining discharge limits according to regulations.

From nanofiltration membrane permeances to design projections for the remediation and valorisation of acid mine waters.

Acidic Mine Waters (AMWs) are characterised by high acidity (pH < 3) as H2SO4 and elevated contents of metals (Al, Fe, Cu, Zn), including rare earth elements (REEs). Due to the exhaustion of minable REE containing-minerals, AMWs are increasingly regarded as an alternative source of REEs. Among the different alternatives for the pre-concentration of AMWs required to make the REE extraction possible, nanofiltration (NF) membranes emerge as a promising technology because they not only successfully reject multivalent ions (metals), allowing its concentration in the retentate stream, but also permit the transport of monovalent ones, such as H+ and HSO4-, allowing the recovery of sulphuric acid in the permeate. Despite this potential of NF, there is still a lack of modelling tools for predicting the performance of NF membranes because of its dependence on solution composition, membrane properties and interaction between both. In this study, a prediction tool based on the Solution-Electro-Diffusion model (including the effect of solution composition) was developed and experimentally validated for the application of two polyamide-based NF membranes (NF270 and Desal DL) for the recovery of REEs and H2SO4 from three different synthetic solutions mimicking AMWs (pH 1.0, 60 mg/L REEs and, 25-600 mg/L Al, Cu, Ca and Zn) differing in their Fe concentration (0-2125 mg/L). Metals were effectively rejected (>98%), whereas H2SO4 was transported across the membrane (H+ rejections <30%). The mathematical model was able to predict the performance of both membranes as well as the potential scaling events associated with Fe and Al hydroxides and hydroxy-sulphates.

Integration of liquid-liquid membrane contactors and electrodialysis for ammonium recovery and concentration as a liquid fertilizer.

The accumulation of ammonia in water bodies can cause eutrophication and reduce water quality. Furthermore, 80% of the ammonia in the world is consumed as fertilizer, which makes it a resource that can be recovered under the circular economy concept. Then, ammonia from wastewater can be valorised for agricultural applications. Liquid-liquid membrane contactors (LLMCs) have been postulated as a novel and eco-friendly technology for ammonia recovery, because they can convert dissolved ammonia into ammonium salts by an acid stripping solution. The concentration of the ammonium salt produced is limited by the co-transport of water in LLMC. Further concentration by electrodialysis (ED) is presented as a solution to overcome this problem. In this work, ammonia streams with different initial ammonia concentrations (1.7-4.0 g/L) were treated by LLMCs to produce liquid ammonium salt fertilizers (as NH4NO3 and NH4H2PO4). Then, these ammonium solutions were concentrated by ED in order to achieve the nitrogen content required for direct application in agriculture for fertigation. After the LLMC process, the fertilizer obtained was composed of approximately 5.1% or 10.1% (w/w) nitrogen, depending on the initial ammonia concentration. After that, it was possible to concentrate these ammonium salts by a factor of 1.6 ± 0.3 using ED with an optimal energy consumption of 0.21 ± 0.08 kWh/kg ammonium salt and 93.1 ± 4.2% of faradaic yield. This gave a liquid fertilizer composed of 15.6% (w/w) nitrogen as NH4NO3. Overall, it was possible to integrate two innovative membrane technologies for the valorisation and concentration of nutrients from ammonia wastewater streams.

Socioeconomic Position and Malnutrition among Older Adults: Results from the FRADEA Study.

OBJECTIVES: Low socioeconomic position (SEP) is related to many health-related conditions in older adults. However, there is a lack of knowledge on the association between SEP and malnutrition, a condition with serious consequences for older people in terms of quality of life and adverse health events. In the current study, we investigated socioeconomic inequalities in malnutrition and sub-domains of malnutrition in a sample of Spanish older adults. DESIGN: Cross-sectional population-based study. SETTING: Urban area of Albacete, Spain. PARTICIPANTS: 836 participants over age 70 from the first measurement wave (2007-2009) of the Frailty and Dependence in Albacete (FRADEA) study, a population-based cohort study. MEASUREMENTS: Educational level and occupational level were the indicators of SEP. Nutritional risk was measured with the Mini Nutrition Assessment® Short Form (MNA®-SF). Logistic regression analyses were performed. RESULTS: For both socioeconomic indicators there was a statistically significant association with nutritional risk (OR low education=1.99, 95% CI=1.18-3.35; OR low occupational level=1.71, 95% CI=1.08-2.72). However, these associations disappeared after adjusting for age and sex (OR low education=1.51, 95% CI=0.88-2.60 ; OR low occupational level=1.32, 95% CI=0.80-2.17). In adjusted models, statistically significant associations between SEP and sub-domains of the MNA®-SF were observed, but these associations were not consistent across socioeconomic indicators. CONCLUSIONS: This study found that malnutrition is a condition that can appear in any older adult, regardless of their socioeconomic group. These findings suggest that interventions to prevent malnutrition in older adults can be targeted at a general older population, and do not have to be SEP specific.

Evaluación postratamiento locorregional y sistémico del carcinoma hepatocelular / Evaluating the response to locoregional and systemic treatment for hepatocellular carcinoma

La evaluación de la respuesta a los diferentes tratamientos aplicados es un factor decisivo en el manejo clínico de los pacientes con carcinoma hepatocelular. Con ella se logra determinar la eficacia del tratamiento y detectar de forma precoz la recidiva del tumor tratado o la aparición de nuevas lesiones que puedan ser candidatas a nuevos tratamientos. Cuando se aplican tratamientos locorregionales, que inducen necrosis, o terapias moleculares, que tienen efectos antiangiogénicos, las lesiones tratadas suelen presentar un cambio en su comportamiento por imagen. Cabe resaltar que no suelen presentar una disminución de su tamaño, al menos inicialmente, e incluso algunas lesiones pueden aparentemente aumentar de tamaño. Por ello es imprescindible conocer el mecanismo de acción de cada tratamiento utilizado y el espectro de imagen que pueden producir esos tratamientos en las distintas técnicas que se emplean en su valoración

Evaluating the response to different treatments is a decisive factor in the clinical management of patients with hepatocellular carcinoma because it can determine the efficacy of the treatment and because it can detect the recurrence of treated tumors or the appearance of new lesions that can be candidates for new treatments. When locoregional treatments that induce necrosis or molecular therapies are applied, the treated lesions usually change their behavior on imaging studies. It is important to point out that the size of the lesions does not usually decrease, at least initially, and some lesions can even appear to increase in size. For this reason, it is essential to know the mechanisms of action for each treatment applied and the spectrum of findings that these treatments can cause in the different imaging techniques used to assess the response

Evaluating the response to locoregional and systemic treatment for hepatocellular carcinoma. / Evaluación postratamiento locorregional y sistémico del carcinoma hepatocelular.

Evaluating the response to different treatments is a decisive factor in the clinical management of patients with hepatocellular carcinoma because it can determine the efficacy of the treatment and because it can detect the recurrence of treated tumors or the appearance of new lesions that can be candidates for new treatments. When locoregional treatments that induce necrosis or molecular therapies are applied, the treated lesions usually change their behavior on imaging studies. It is important to point out that the size of the lesions does not usually decrease, at least initially, and some lesions can even appear to increase in size. For this reason, it is essential to know the mechanisms of action for each treatment applied and the spectrum of findings that these treatments can cause in the different imaging techniques used to assess the response.

Frailty and Fear of Falling: The FISTAC Study.

OBJECTIVE: To analyze the association between frailty and Fear of Falling (FoF) in a cohort of older adults with previous falls. DESIGN: Cross-sectional study (FISTAC). SETTING: Falls Unit, Complejo Hospitalario Universitario of Albacete (Spain). PARTICIPANTS: 183 adults older than 69 years, from the Falls Unit, with a history of a previous fall in the last year. MEASUREMENTS: FoF was assessed at baseline using the Falls Efficacy Scale International (FES-I) and three questions previously validated. Frailty was assessed with the frailty phenotype criteria. Age, gender, comorbidity, nutritional status, cognitive status and risk of depression were determined. RESULTS: Mean age 78.4, 80.3% women. FoF was present in 140 (76.5%) participants with the three questions and 102 (55.7%) presented high concern of falling with the FES-I. 88.8% of frail older adults presented FoF compared to 62.4% of those who were not frail, and only 37.8% of non frail had a high concern of falling, compared to 77.2% of those who were frail measured with the FES-I. Frail participants had an adjusted risk of FoF that was 3.18 (95% CI 1.32 to 7.65) higher compared to those who were not frail assessed with the three questions and 3.93 (95% CI 1.85 to 8.36) higher concern of falling when using the FES-I scale. Only female sex and depression risk were also associated to FoF in the final adjusted models. CONCLUSION: Frailty is independently associated with the FoF syndrome in older faller subjects.

Don Antonio Gimbernat and his involvement in Ophthalmology. A historical view of cataract surgery

The present article aims to bring together a modest homage to Don Antonio Gimbernat, who felt a great passion for ophthalmology and devoted part of his life to it. In the second half of the eighteenth century, in the surgical field of ophthalmology a race of technical changes and advances began, which have led to the present situation (AU)

No disponible

Diagnosis and treatment of hepatocellular carcinoma. Update consensus document from the AEEH, SEOM, SERAM, SERVEI and SETH / Diagnóstico y tratamiento del carcinoma hepatocelular. Actualización del documento de consenso de la AEEH, SEOM, SERAM, SERVEI y SETH

Hepatocellular carcinoma is the most common primary malignancy of the liver and one of the most frequent causes of death in patients with liver cirrhosis. Simultaneously with the recognition of the clinical relevance of this neoplasm, in recent years there have been important developments in the diagnosis, staging and treatment of HCC. Consequently, the Asociación Española para el Estudio del Hígado has driven the need to update clinical practice guidelines, continuing to invite all the societies involved in the diagnosis and treatment of this disease to participate in the drafting and approval of the document (Sociedad Española de Trasplante Hepático, Sociedad Española de Radiología Médica, Sociedad Española de Radiología Vascular e Intervencionista y Sociedad Española de Oncología Médica). The clinical practice guidelines published in 2009 accepted as Clinical Practice Guidelines of the National Health System has been taken as reference document, incorporating the most important advances that have been made in recent years. The scientific evidence for the treatment of HCC has been evaluated according to the recommendations of the National Cancer Institute (www.cancer.gov) and the strength of recommendation is based on the GRADE system.

El carcinoma hepatocelular es la neoplasia primaria de hígado más común y una de las causas de muerte más frecuentes en los pacientes afectos de cirrosis hepática. Simultáneamente al reconocimiento de la relevancia clínica de esta neoplasia, en los últimos años han aparecido novedades importantes en el diagnóstico, estadificación y tratamiento del carcinoma hepatocelular. Por tal motivo, desde la Asociación Española para el Estudio del Hígado se ha impulsado la necesidad de actualizar las guías de práctica clínica, invitando de nuevo a todas las sociedades involucradas en el diagnóstico y tratamiento de esta enfermedad a participar en la redacción y aprobación del documento (la Sociedad Española de Trasplante Hepático, la Sociedad Española de Radiología Médica, la Sociedad Española de Radiología Vascular e Intervencionista y la Sociedad Española de Oncología Médica). Se ha tomado como documento de referencia las guías de práctica clínica publicadas en 2009 aceptadas como Guía de Práctica Clínica del Sistema Nacional de Salud, incorporando los avances más importantes que se han obtenido en los últimos años. La evidencia científica en el tratamiento del carcinoma hepatocelular se ha evaluado de acuerdo con las recomendaciones del National Cancer Institute (www.cancer.gov) y la fuerza de la recomendación se basa en el sistema GRADE.

Age, frailty, disability, institutionalization, multimorbidity or comorbidity. Which are the main targets in older adults?

OBJECTIVES: Age, frailty, disability, institutionalization, multimorbidity or comorbidity are main risk factors for serious health adverse outcomes in older adults. However, the adjusted relevance of each of them in order to determine which characteristics must be of importance for health policies in this population group, has not been established. DESIGN: Concurrent population-based cohort study. SETTING: Albacete city, Spain. PARTICIPANTS: 842 participants over age 70 from the FRADEA Study. MEASUREMENTS: Age, gender, institutionalization, frailty (Fried's criteria), previous disability in basic activities of daily living (BADL) (Barthel index), comorbidity (Charlson index), and multimorbidity (≥ 2 from 14 selected diseases) were recorded in the basal visit. The combined event of mortality or incident disability in BADL was determined in the follow-up visit. The risk of presenting adverse events was determined by Kaplan-Meier analysis and logistic regression adjusted for age, sex, and institutionalization. RESULTS: Mean follow-up 520 days. 63 participants died (7.5%). Among the remaining 779, 191 lost at least one BADL (24.5%). The combined event of mortality or disability was present in 254 participants (30.2%). Age (OR 1.10, 95%CI 1.06-1.14), frailty (OR 3.07, 95%CI 1.63-5.77), disability (OR 2.19, 95%CI 1.43-3.36) and institutionalization (OR 2.73, 95%CI 1.68-4.44) were independently associated with the combined adverse event, but not comorbidity or multimorbidity. In subjects younger than 80, only frailty, disability and institutionalization were risk factors, and in those aged ≥ 80, only age, disability and institutionalization were. CONCLUSIONS: Health policies for older adults must take into account mainly frailty and disability in subjects younger than 80 and disability in those older than 80.

Nutritional risk, nutritional status and incident disability in older adults. The FRADEA study.

OBJECTIVES: To analyze if body mass index (BMI) and waist circumference (WC) as measures of nutritional status, and the Mini Nutritional Assessment Short Form (MNA-SF) as a nutritional risk measure are associated with increased risk of incident disability in basic activities of daily living (BADL) in a population based cohort of Spanish older adults. DESIGN: Concurrent cohort study. SETTING: Albacete City, Spain. PARTICIPANTS: 678 subjects over age 70 from the FRADEA Study (Frailty and Dependence in Albacete). MEASUREMENTS: BMI, WC and MNA-SF were recorded at the basal visit of the FRADEA Study. Incident disability in BADL was defined as loss of the ability to perform bathing, grooming, dressing, toilet use, or feeding from basal to follow-up visit, using the Barthel index. The association between nutritional status and nutritional risk with incident BADL disability was determined by Kaplan-Meier analysis and logistic regression adjusted for age, sex, basal function, comorbidity, cognitive decline, depression risk and frailty status. RESULTS: Each point less of MNA-SF (OR 1.17, 95%CI 1.04-1.31) and MNA-SF<14 (OR 2.33, 95%CI 1.39-3.89), but not MNA-SF<12 (OR 1.47, 95%CI 0.89-2.42) had a greater adjusted risk of incident disability in BADL. Neither BMI (OR 1.02, 95%CI 0.97-1.06) nor WC (OR 1.01, 95%CI 0.99-1.03) were associated. Weight loss (OR 1.75, 95%CI 1.08-2.83) and mobility impairment (OR 3.35, 95%CI 1.67-6.73) remained as adjusted predictors of incident BADL disability, while anorexia almost reached the significance (OR 1.65, 95%CI 0.94-2.87). CONCLUSION: Nutritional risk measured with the MNA-SF is associated with incident disability in BADL in older adults, while nutritional status measured with BMI or WC is not.

[Early diagnosis of primary liver cancer: imaging versus genetics]. / Diagnóstico precoz del cáncer primario de hígado: imagen versus genética.

Early diagnosis of hepatocellular carcinoma (HCC) in nodules smaller than 2 cm detected by screening ultrasounds becomes essential given that, at that stage, no vascular invasion is usually detected and treatment is associated with a high rate of long-term survival. Improvements in imaging techniques in the last few years have allowed a conclusive diagnosis of HCC in these small nodules without invasive procedures. However, a conclusive diagnosis of HCC by imaging is not always possible and, in more than half of cases, biopsy is needed. On the other hand, histological confirmation of HCC in such tiny nodules is very complex, and in most cases impossible because of the limited sample obtained. In addition, serum tumor markers currently available show low accuracy and are useless for early diagnosis. Progress in the knowledge of molecular mechanisms associated with malignant transformation will allow the use of new techniques that will facilitate diagnosis for HCC in very early stages.

Diagnóstico precoz del cáncer primario de hígado: imagen versus genética / No disponible

El diagnóstico precoz del carcinoma hepatocelular (CHC) es fundamental,especialmente si se consigue cuando los nódulos son menoresde 2 cm, dado que en esta fase la mayoría aún no han presentadoinvasión vascular y la aplicación de tratamientos radicales seacompaña de una alta tasa de supervivencia a largo plazo. Los avancesen las técnicas de imagen en los últimos años han permitido llegara un diagnóstico concluyente de CHC en algunos de estos nódulos depequeño tamaño sin necesidad de realizar procedimientos invasivos.Sin embargo, el número de CHC que pueden ser diagnosticados mediantepruebas de imagen es bajo y en más de la mitad de los casos siguesiendo necesaria la realización de una biopsia. Por otro lado, laconfirmación histológica de CHC en este tipo de nódulos es complejay en muchas ocasiones imposible, dado el posible error de muestreo yla dificultad para diferenciar CHC bien diferenciado de nódulos displásicosen una muestra habitualmente con escaso material. Además, losmarcadores tumorales séricos disponibles en la actualidad presentanun bajo rendimiento y carecen de utilidad en el diagnóstico precoz deCHC. Los progresos en el conocimiento de los mecanismos molecularesresponsables de la transformación maligna permitirán aplicaruna serie de técnicas de biología molecular para facilitar el diagnósticode CHC de forma precoz, con resultados iniciales prometedores

Early diagnosis of hepatocellular carcinoma (HCC) in nodulessmaller than 2 cm detected by screening ultrasounds becomes essentialgiven that, at that stage, no vascular invasion is usually detectedand treatment is associated with a high rate of long-termsurvival. Improvements in imaging techniques in the last few yearshave allowed a conclusive diagnosis of HCC in these small noduleswithout invasive procedures. However, a conclusive diagnosisof HCC by imaging is not always possible and, in more than halfof cases, biopsy is needed. On the other hand, histological confirmationof HCC in such tiny nodules is very complex, and in mostcases impossible because of the limited sample obtained. In addition,serum tumor markers currently available show low accuracyand are useless for early diagnosis. Progress in the knowledge ofmolecular mechanisms associated with malignant transformationwill allow the use of new techniques that will facilitate diagnosisfor HCC in very early stages

[Comparative in vitro activity of ertapenem against aerobic and anaerobic bacteria]. / Actividad comparativa in vitro de ertapenem frente a bacterias aerobias y anaerobias.

The in vitro activity of ertapenem (MK-0826), a new carbapenem, was studied against 389 aerobic microorganisms (187 Enterobacteriaceae, 15 Aeromonas spp., 42 Staphylococcus spp., 43 Streptococcus spp., 15 Enterococcus spp., 30 Haemophilus spp., 15 Moraxella catarrhalis, 12 Neisseria gonorrhoeae, 15 Pseudomonas aeruginosa and 15 Acinetobacter spp.) and 54 anaerobic isolates (15 Clostridium spp., 12 Peptostreptococcus spp. and 27 fragilis group Bacteroides recovered from four Spanish hospitals. Ertapenem activity was compared with that of imipenem, piperacillin-tazobactam, cefoxitin, ceftriaxone, ceftazidime, cefepime, and norfloxacin. Ertapenem was the most active antibiotic against Enterobacteriaceae (MIC(90) < or =0.5 mg/l) particularly in the case of broad-spectrum, extended-spectrum and chromosomally encoded AmpC betalactamase-producing strains. Ertapenem exhibited less activity, even lower than that of imipenem, against P. aeruginosa, Acinetobacter spp. and enterococci (MIC(90) > or =16 mg/l). Ertapenem was active against methicillin-susceptible S. aureus and coagulase-negative staphylococci, beta-haemolytic streptococci, and Streptococcus pneumoniae (MIC(90) < or =1 mg/l). In the case of Haemophilus spp., M. catarrhalis and N. gonorrhoeae, ertapenem, with a MIC(90) < or =0.06 mg/l resulted the most active antibiotic tested. When considering the anaerobes, ertapenem displayed a broad spectrum of activity, similar to that of imipenem, against Clostridium spp. (MIC(90) 2 mg/l) and was slightly less active against Bacteroides fragilis (MIC(90) 0.5 mg/l). Both carbapenems were the most active among the tested compounds. Due to its activity against almost all pathogens studied, ertapenem appears to be an option for the treatment of mixed bacterial infections.

Actividad comparativa in vitro de ertapenemfrente a bacterias aerobias y anaerobias / Comparative in vitro activity of ertapenem against aerobic and anaerobic bacteria

Se estudió la actividad in vitro de ertapenem (MK-0826), un nuevo carbapenémico, frente a 389 microorganismos aerobios (187 Enterobacteriaceae, 15 Aeromonas spp., 42 Staphylococcus spp., 43 Streptococcus spp., 15 Enterococcus spp., 30 Haemophilus spp., 15 Moraxella catarrhalis, 12 Neisseria gonorrhoeae, 15 Pseudomonas aeruginosa y 15 Acinetobacter spp.) y 54 anaerobios (15 Clostridium spp., 12 Peptostreptococcus spp. y 27 Bacteroides del grupo fragilis), procedentes de cuatro hospitales españoles, y se comparó con la de imipenem, piperacilina-tazobactam, cefoxitina, ceftriaxona, ceftazidima, cefepima y norfloxacino. El ertapenem fue el antibiótico más activo frente a enterobacterias (CMI90 0,5 mg/l), particularmente frente a cepas productores de betalactamasas de amplio espectro, de espectro extendido y cromosómicas de tipo AmpC. Frente a P. aeruginosa, Acinetobacter spp. y enterococos fue poco efectivo (CMI90 16 mg/l) e inferior a imipenem. Mostró actividad sobre S. aureus y estafilococos coagulasa negativos sensibles a la meticilina, estreptococos beta hemolíticos y Streptococcus pneumoniae (CMI90 1 mg/l). En Haemophilus spp., M. catarrhalis y N. gonorrhoeae el ertapenem fue el más activo (CMI90 0,06 mg/l) de los antibióticos estudiados. Mostró un amplio espectro de actividad frente a anaerobios; similar al del imipenem en Clostridium spp. (CMI90 2 mg/l) y ligeramente inferior en Bacteroides del grupo fragilis (CMI90 0,5 mg/l), siendo ambos carbapenémicos los antibióticos más activos frente a este grupo de microorganismos. La actividad del ertapenem frente a la mayoría de los patógenos bacterianos apoya su utilidad en el tratamiento de las infecciones bacterianas mixtas (AU)