Oral quinolones versus intravenous ß-lactam for the treatment of acute focal bacterial nephritis: a retrospective cohort study.

BACKGROUND: Evidence regarding the best antibiotic regimen and the route of administration to treat acute focal bacterial nephritis (AFBN) is scarce. The aim of the present study was to compare the effectiveness of intravenous (IV) ß-lactam antibiotics versus oral quinolones. METHODS: This is a retrospective single centre study of patients diagnosed with AFBN between January 2017 and December 2018 in Hospital Universitari Vall d'Hebron, Barcelona (Spain). Patients were identified from the diagnostic codifications database. Patients treated with oral quinolones were compared with those treated with IV ß-lactam antibiotics. Therapeutic failure was defined as death, relapse, or evolution to abscess within the first 30 days. RESULTS: A total of 264 patients fulfilled the inclusion criteria. Of those, 103 patients (39%) received oral ciprofloxacin, and 70 (26.5%) IV ß-lactam. The most common isolated microorganism was Escherichia coli (149, 73.8%) followed by Klebsiella pneumoniae (26, 12.9%). Mean duration of treatment was 21.3 days (SD 7.9). There were no statistical differences regarding therapeutic failure between oral quinolones and IV ß-lactam treatment (6.6% vs. 8.7%, p = 0.6). Out of the 66 patients treated with intravenous antibiotics, 4 (6.1%) experienced an episode of phlebitis and 1 patient (1.5%) an episode of catheter-related bacteraemia. CONCLUSIONS: When susceptible, treatment of AFBN with oral quinolones is as effective as IV ß-lactam treatment with fewer adverse events.

Glacier retreat reorganizes river habitats leaving refugia for Alpine invertebrate biodiversity poorly protected.

Alpine river biodiversity around the world is under threat from glacier retreat driven by rapid warming, yet our ability to predict the future distributions of specialist cold-water species is currently limited. Here we link future glacier projections, hydrological routing methods and species distribution models to quantify the changing influence of glaciers on population distributions of 15 alpine river invertebrate species across the entire European Alps, from 2020 to 2100. Glacial influence on rivers is projected to decrease steadily, with river networks expanding into higher elevations at a rate of 1% per decade. Species are projected to undergo upstream distribution shifts where glaciers persist but become functionally extinct where glaciers disappear completely. Several alpine catchments are predicted to offer climate refugia for cold-water specialists. However, present-day protected area networks provide relatively poor coverage of these future refugia, suggesting that alpine conservation strategies must change to accommodate the future effects of global warming.

Molecular analysis in cytological samples obtained by endobronchial or oesophageal ultrasound guided needle aspiration in non-small cell lung cancer.

INTRODUCTION: Cytological samples obtained by endobronchial ultrasound (EBUS) are capital for diagnosis, staging and molecular profile in non-small cell lung carcinoma (NSCLC). OBJECTIVE: To assess the success rate of complete, partial and individual of molecular analysis in samples obtained by EBUS-guided transbronchial needle aspiration (TBNA) and/or by oesophageal ultrasound-guided fine needle aspiration with an echobronchoscope (EUS-B-FNA) in patients with NSCLC. METHODS: Prospective study including 90 patients with non-squamous NSCLC, or non-smoking squamous. Cytological samples were classified into two groups. Group 1: PEN membrane slide and/or cell blocks for the determination of mutations of EGFR, KRAS, ERBB2 and BRAF. Group 2: silane coated slides or cell blocks for rearrangements of ALK, ROS1 and MET amplification. RESULTS: The success rate was 78.6% for 4 molecular alterations (EGFR, KRAS, ALK and ROS1), and 44% for 7 determinations. The individual success rate for EGFR was 97%, KRAS 96.3%, ALK 85%, ROS1 82.3%, ERBB2 71.4%, BRAF 67.7% and MET 81.1%. There were no significant differences (p=0.489) in the number of molecular analyses (1-3 vs. 4) in group 1, depending on the types of samples (cell block vs. PEN membrane slide vs. cell block and PEN membrane slide). CONCLUSIONS: In patients with NSCLC, the cytological material obtained by ultrasound-guided needle aspiration is sufficient for individual and partial molecular analysis in the vast majority of cases. Membrane slides such as cell blocks are valid samples for molecular analysis.

Identification of oestrogen, progesterone receptor and human epidermal growth factor receptor 2 expression in mediastinal metastases of breast cancer obtained by endobronchial ultrasound-guided transbronchial needle aspiration.

BACKGROUND: In breast cancer patients, the expression statuses of oestrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) are crucial in the choice of treatment. Receptor expression in metastatic lesions can differ from the primary tumour. The aim of our study was to analyse the utility of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) to obtain samples allowing the identification of ER, PR and HER2 expression in patients with mediastinal metastases of breast cancer. PATIENTS AND METHODS: The clinical files of all patients with a final diagnosis of breast cancer mediastinal metastases diagnosed by EBUS-TBNA in our institution were retrospectively analysed. The ability of EBUS-TBNA to obtain samples that allowed hormone receptor and HER2 expression analysis was calculated. RESULTS: Twenty-four patients were included. ER, PR and HER2 assessments could be performed in 22, 20 and 22 patients, respectively. In 20 of the 24 patients it was possible to investigate all three types of receptor expression. In the remaining four cases, where ER, PR or HER2 expression tests could not be performed, it was due to a lack of tissue. In cases with adequate results for EBUS-TBNA and the primary tumour agreement was greater for ER (16/19) and HER2 (12/14) than PR (8/17). Based on receptor status, there was a change in the choice of treatment for five patients. CONCLUSION: In patients with breast cancer mediastinal metastases, ER, PR and HER2 expression can be assessed in samples obtained by EBUS-TBNA whenever a sufficient tissue sample is collected.

Stem cell-like transcriptional reprogramming mediates metastatic resistance to mTOR inhibition.

Inhibitors of the mechanistic target of rapamycin (mTOR) are currently used to treat advanced metastatic breast cancer. However, whether an aggressive phenotype is sustained through adaptation or resistance to mTOR inhibition remains unknown. Here, complementary studies in human tumors, cancer models and cell lines reveal transcriptional reprogramming that supports metastasis in response to mTOR inhibition. This cancer feature is driven by EVI1 and SOX9. EVI1 functionally cooperates with and positively regulates SOX9, and promotes the transcriptional upregulation of key mTOR pathway components (REHB and RAPTOR) and of lung metastasis mediators (FSCN1 and SPARC). The expression of EVI1 and SOX9 is associated with stem cell-like and metastasis signatures, and their depletion impairs the metastatic potential of breast cancer cells. These results establish the mechanistic link between resistance to mTOR inhibition and cancer metastatic potential, thus enhancing our understanding of mTOR targeting failure.

Representativeness of nodal sampling with endobronchial ultrasonography in non-small-cell lung cancer staging.

The objective of our study was to determine the procedure-related requirements of mediastinal node sampling with endobronchial ultrasonography with real-time transbronchial needle aspiration (EBUS-TBNA) that would provide negative predictive value (NPV) for the identification of stage III disease in non-small-cell lung cancer (NSCLC) high enough to consider the technique equivalent to cervical mediastinoscopy. Representative EBUS-TBNA was defined as a sampling procedure obtaining satisfactory samples from normal nodes in regions 4R, 4L and 7 or diagnosing malignancy in mediastinal nodes. NPV was estimated using the results of postsurgical staging in patients who underwent surgery as a reference. Two-hundred ninety-six patients staged with EBUS-TBNA were included. Representative samples from regions 4R, 4L and 7 showing nonmalignant cytology were obtained from 98 patients (33.1%) and EBUS-TBNA detected N2/N3 disease in 150 (50.7%). Accordingly, an EBUS-TBNA procedure accomplishing the representativeness criteria required for sampling was attained in 248 of the participating patients (83.8%). The NPV of the procedure in this setting was 93.6%, with false-negative results only found in 5 patients, four of them with nodal metastasis out of the reach of EBUS-TBNA (regions 5, 8 and 9). In conclusion, representative sampling of regions 4R, 4L and 7 is achieved in more than 80% of patients staged using EBUS-TBNA, and in the procedures that attain this requirement a NPV >90% for mediastinal malignancy is reached, a figure equivalent to cervical mediastinoscopy.

Endobronchial ultrasound-guided transbronchial needle aspiration for identifying EGFR mutations.

The presence of somatic mutations of the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene in patients with advanced nonsmall cell lung cancer (NSCLC) correlates with a good response to tyrosine kinase inhibitors. The usefulness of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for the detection of EGFR mutations in cells recovered from malignant mediastinal nodes in patients with NSCLC was assessed. All patients with lung adenocarcinoma or unspecified NSCLC referred for staging with EBUS-TBNA were included. Nodes with a short-axis diameter of >5 mm were sampled, and genomic DNA from metastatic tumour cells was obtained for analysis of exons 19 and 21. The impact of sampling on management was assessed. EGFR gene analysis of the EBUS-TBNA sample was feasible in 26 (72.2%) out of the 36 patients with lymph node metastasis. Somatic mutations of the EGFR gene were detected in tissue obtained through EBUS-TBNA in two (10%) out of 20 patients with metastasic lung adenocarcinoma. Malignant tissue samples obtained by EBUS-TBNA from patients with nodal metastasis of NSCLC are suitable for the detection of EGFR mutations in most cases, and this technique demonstrates mutated neoplastic cells in a tenth of patients with adenocarcinoma.

Doxorubicin and cyclophosphamide followed by weekly docetaxel as neoadjuvant treatment of early breast cancer: analysis of biological markers in a GEICAM phase II study.

INTRODUCTION: To evaluate the sequential administration of doxorubicin (A) and cyclophosphamide (C) followed by weekly docetaxel in women with stage II to IIIA breast cancer. PATIENTS AND METHODS: Patients received 60 mg/m(2) of A and 600 mg/m(2) of C every three weeks for four cycles followed by 12 infusions of weekly docetaxel at a dose of 36 mg/m(2) and with a 2-week resting period. RESULTS: Sixty-three women were included. On an intention-to- treat basis, clinical response rate was 90% (95% CI: 83-98), with 46% complete responses. Breast-conserving surgery could be performed in 43 patients (68%). Complete pathological responses in the breast were confirmed in 17% of patients. No correlations between levels of expression of topoisomerase II alpha, survivin or p27 and the pathological response were detected. The study treatment was generally well tolerated. CONCLUSION: Neoadjuvant AC followed by weekly docetaxel is a feasible regimen for patients with early-stage breast cancer.

Evolutionary aspects of population structure for molecular and quantitative traits in the freshwater snail Radix balthica.

Detecting the action of selection in natural populations can be achieved using the QST-FST comparison that relies on the estimation of FST with neutral markers, and QST using quantitative traits potentially under selection. QST higher than FST suggests the action of directional selection and thus potential local adaptation. In this article, we apply the QST-FST comparison to four populations of the hermaphroditic freshwater snail Radix balthica located in a floodplain habitat. In contrast to most studies published so far, we did not detect evidence of directional selection for local optima for any of the traits we measured: QST calculated using three different methods was never higher than FST. A strong inbreeding depression was also detected, indicating that outcrossing is probably predominant over selfing in the studied populations. Our results suggest that in this floodplain habitat, local adaptation of R. balthica populations may be hindered by genetic drift, and possibly altered by uneven gene flow linked to flood frequency.

[Having diabetes without knowing it]. / Tener diabetes y no saberlo. Cribaje de diabetes desconocida en una muestra oportunista de población residente en Cataluña.

As part of the activities on the World Day for Diabetes in 2002, nine professors, one nurse who teaches about diabetes and 126 nursing students at University Schools of Nursing in Barcelona, Lleida, Tarragona, Tortosa and Girona, in collaboration with the Association of Diabetics in Catalonia and with the help of the Advisory Council for Diabetes in Catalonia participated in a diabetes screening campaign on the population residing in Catalonia. This campaign studied the prevalence of type two diabetes in a random sample of the Catalan population. This campaign also proposed to raise the awareness among the general population and among nursing students about the important health consequences diabetes has and to increase investigation and social support measures by nurses related to diabetes. This study checked 4083 persons and discovered 77 cases of altered blood-sugar levels among people who did not know they had diabetes. This finding means that there is a 2.2% prevalence of altered blood-sugar levels in the population who are not diagnosed diabetics. Professors and student participants all gave this experience positive marks and the students' degree of satisfaction was very high.

Breast hemangioma mimicking carcinoma.

Breast hemangiomas are rare, and usually appear as well-delimited round or oval nodules at mammography. We report a case of a woman with a breast hemangioma, which mammographic features simulated malignancy, and present its pathologic correlation. Hemangiomas are benign vascular tumors that are rarely present in the breast, usually found incidentally on microscopy of biopsy material for other. They are occasionally detected by mammography, presenting as well-delimited round, lobulated nodules, sometimes with calcifications. We present the mammographic findings and pathologic correlation in a case of breast hemangioma with an atypical radiological manifestation, simulating a carcinoma. To our knowledge, this is the first reported case with these radiologic characteristics.

Effect of L-arginine on the course of experimental colitis.

BACKGROUND AND AIMS: L-Arg is the substrate for nitric oxide, and also for L-ornithine which, in turn, is the precursor for the synthesis of collagen and polyamines. By these different metabolic pathways, L-Arg is involved in the mechanisms of inflammation, tissue repair and fibrosis. Thus, the aim of this study was to assess the effect of both different amounts of L-Arg supplementation and L-Arg-free diets upon colonic inflammatory damage and fibrosis in experimental colitis. METHODS: Sprague-Dawley rats with trinitrobenzene sulphonic acid (TNBS)-induced colitis received increasing doses of L-Arg (30, 100, 500 mg/day), or D-Arg (500 mg/day). In a second experiment, two L-Arg-free diets (one supplemented with L-Gly) were compared to a L-Arg diet. Nitrite/nitrate release in the lumen of the colon and colonic damage were evaluated. In the first experiment, tissue collagen levels and colonic mucosal proliferation were also assessed. RESULTS: In the acute phase of colitis, intracolonic nitrite/nitrate levels were significantly higher in the 100 and 500 mg supplemented L-Arg groups than in D-Arg group. However, only rats treated with 500 mg of L-Arg showed moderately higher inflammatory and fibrosis colonic scores than the D-Arg treated rats. There was no significant influence of L-Arg-free diets on the course of TNBS-induced colitis. However, L-Arg diet accelerated weight gain both pre- and post-TNBS. CONCLUSIONS: These results suggest that normal amounts of L-Arg in the diet are not harmful, whereas both absence of L-Arg or supplementation with high doses of this amino acid may be deleterious. In the former this might be due to a decrease of nitrogen retention in injured rats, whereas in the latter it may result from both nitric oxide-mediated tissue damage and collagen deposition.

Improved diagnosis of hepatic perfusion disorders: value of hepatic arterial phase imaging during helical CT.

The liver has a unique dual blood supply, which makes helical computed tomography (CT) a highly suitable technique for hepatic imaging. Helical CT allows single breath-hold scanning without motion artifacts. Because of rapid image acquisition, two-phase (hepatic arterial phase and portal venous phase) evaluation of the hepatic parenchyma is possible, improving tumor detection and tumor characterization in a single CT study. The arterial and portal venous supplies to the liver are not independent systems. There are several communications between the vessels, including transsinusoidal, transvasal, and transplexal routes. When vascular compromise occurs, there are often changes in the volume of blood flow in individual vessels and even in the direction of blood flow. These perfusion disorders can be detected with helical CT and are generally seen as an area of high attenuation on hepatic arterial phase images that returns to normal on portal venous phase images; this finding reflects increased arterial blood flow and arterioportal shunting in most cases. Familiarity with the helical CT appearances of these perfusion disorders will result in more accurate diagnosis. By recognizing these perfusion disorders, false-positive diagnosis (hypervascular tumors) or overestimation of the size of liver tumors (eg, hepatocellular carcinoma) can be avoided.

Sentinel node biopsy as a practical alternative to axillary lymph node dissection in breast cancer patients: an approach to its validity.

BACKGROUND: Sentinel node biopsy (SNB) has been proposed as an alternative to axillary lymph-node dissection (ALND) in breast cancer. Before implementing SNB in our practice, we wished to test its validity by comparing it to the standard ALND, both in our hands and with other reported series. PATIENTS AND METHODS: One hundred thirty-two patients were included prospectively. SNB and immediate ALND were performed. For SNB, a technetium-colloid was used to produce preoperative lymphoscintigraphy and intraoperative gamma-probe search for the SN. Serial sectioning and immunostains were used on the SN. A comprehensive review of the literature was done in order to run a meta-analysis of diagnostic tests using a summary receiver operating characteristic curve (SROC) to calculate the pooled parameters of sensitivity and associated 95% confidence interval (95% CI), including our own data. RESULTS: Our technical success rate was 96%. Local sensitivity was 96%, with a 95% CI from 85%-99%. Seven patients were upstaged by the SNB. A literature search identified 18 studies published from 1996-1999. Estimates of sensitivity ranged from 83%-100%. The pooled data meta-analysis gave a global sensitivity of 91%, with a 95% CI from 89%-93%. The area under the global SROC curve was 0.9967. CONCLUSIONS: The minimally invasive SNB was shown to be a practical alternative to ALND. We propose to use local as well as global sensitivity and associated 95% CI to test the validity of SNB in the clinical setting. Due to limitations of ALND as the golden standard, SNB can in fact be considered a more accurate method for nodal staging.

Therapeutic drug monitoring of tacrine: simple and fast high-performance liquid chromatography assay method for its determination in human plasma.

A new high-performance liquid chromatography (HPLC) assay method was developed for the therapeutic monitoring of tacrine. The method involved a simple protein precipitation by means of either acetonitrile or cold methanol followed by a fast isocratic separation on a CN column eluted in reversed-phase mode. The entire sample preparation took place in an HPLC vial and no further liquid transfer was required. The validation data showed that the assay method was precise, accurate, and robust. Analysis of more than 1,000 plasma samples collected from patients with Alzheimer disease demonstrates the suitability of the assay.

Effect of olive oil on early and late events of colon carcinogenesis in rats: modulation of arachidonic acid metabolism and local prostaglandin E(2) synthesis.

BACKGROUND: Animal model studies have shown that the colon tumour promoting effect of dietary fat depends not only on the amount but on its fatty acid composition. With respect to this, the effect of n9 fatty acids, present in olive oil, on colon carcinogenesis has been scarcely investigated. AIMS: To assess the effect of an n9 fat diet on precancer events, carcinoma development, and changes in mucosal fatty acid composition and prostaglandin (PG)E(2) formation in male Sprague-Dawley rats with azoxymethane induced colon cancer. METHODS: Rats were divided into three groups to receive isocaloric diets (5% of the energy as fat) rich in n9, n3, or n6 fat, and were administered azoxymethane subcutaneously once a week for 11 weeks at a dose rate of 7.4 mg/kg body weight. Vehicle treated groups received an equal volume of normal saline. Groups of animals were colectomised at weeks 12 and 19 after the first dose of azoxymethane or saline. Mucosal fatty acids were assessed at 12 and 19 weeks. Aberrant crypt foci and the in vivo intracolonic release of PGE(2) were assessed at week 12, and tumour formation at week 19. RESULTS: Rats on the n6 diet were found to have colonic aberrant crypt foci and adenocarcinomas more often than those consuming either the n9 or n3 diet. There were no differences between the rats on the n9 and n3 diets. On the other hand, administration of both n9 and n3 diets was associated with a decrease in mucosal arachidonate concentrations as compared with the n6 diet. Carcinogen treatment induced an appreciable increase in PGE(2) formation in rats fed the n6 diet, but not in those fed the n3 and n9 diets. CONCLUSIONS: Dietary olive oil prevented the development of aberrant crypt foci and colon carcinomas in rats, suggesting that olive oil may have chemopreventive activity against colon carcinogenesis. These effects may be partly due to modulation of arachidonic acid metabolism and local PGE(2) synthesis.