Hiccups in Parkinson's disease: an analysis of cases reported in the European pharmacovigilance database and a review of the literature.

BACKGROUND: Some reports have suggested an association between dopamine agonists and hiccups, involuntary contractions that merit full clinical attention because they can be very debilitating. Many drugs frequently used to treat hiccups are formally contraindicated in Parkinson's disease due to their liability to worsen motor symptoms, making the treatment of hiccups problematic in this disease. The objective of the present study was to analyze all spontaneous reports of hiccups from the European Pharmacovigilance Database in patients with Parkinson's disease and/or on dopaminergic drugs. Finally, we sought to identify evidence-based recommendations on the management of hiccups in Parkinson's disease. METHODS: We searched for all reports of hiccups in the European Pharmacovigilance Database (EudraVigilance) and calculated proportional reporting ratios for dopamine agonists and hiccups. We reviewed the literature on Parkinson's disease, dopamine agonists, and hiccups, searching for specific treatment recommendations for hiccups in this disease. RESULTS: Both rotigotine and pramipexole fulfilled the criteria to generate a safety signal. We found 32 and 13 cases of hiccups associated with dopamine agonists in EudraVigilance and the literature, respectively. There were no specific recommendations for the management of hiccups in Parkinson's disease in the clinical guidelines consulted. CONCLUSIONS: We have found evidence that rotigotine and pramipexole are associated with the appearance of hiccups and that this adverse reaction occurs predominantly in males. Given the scarce information available, specific recommendations are needed in clinical guidelines for the adequate management of hiccups in Parkinson's disease.

Search and analysis of genes involved in antibiotic resistance in Chilean strains of Piscirickettsia salmonis.

Piscirickettsia salmonis is the pathogen causing Piscirickettsiosis. For treatment, the industry mainly uses oxytetracycline and florfenicol, so it is essential to understand the degree of susceptibility of this pathogen to these drugs. But this is still unknown for a large number of P. salmonis strains, as are the molecular mechanisms responsible for greater or lesser susceptibility. However, genes that confer resistance to these antimicrobials have been reported and characterized for this and other bacterial species, among which are membrane proteins that take out the drug. Our results identified differences in the degree of susceptibility to both antibiotics among different Chilean isolated of these bacteria. We analysed 10 available genomes in our laboratory and identified ~140 genes likely to be involved in antibiotic resistance. We analysed six specific genes, which suggests that some of them would eventually be relevant in conferring resistance to both antibiotics, as they encode for specific transporter proteins, which increase the number of transcripts when grown in media with these antibiotics. Our results were corroborated with EtBr permeability analysis, which revealed that the LF-89 strain accumulates this compound and has a reduced capacity to expulse it compared with the field strains.

Meropenem dosing requirements against Enterobacteriaceae in critically ill patients: influence of renal function, geographical area and presence of extended-spectrum ß-lactamases.

The aim of this study was the evaluation of the influence of the susceptibility patterns of Escherichia coli and Klebsiella pneumoniae isolates, specifically the presence of extended-spectrum ß-lactamases and the geographical area (Europe and USA), on the meropenem dosing requirements in critically ill patients with different degrees of renal function by estimation of the probability of pharmacokinetic/pharmacodynamic (PK/PD) target attainment. Additionally, estimation of the PK/PD breakpoints according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) approach was also an objective. Six dosing regimens were evaluated: 0.5 g, 1 g and 2 g every 8 h given as 0.5-h or 3-h infusions. Pharmacokinetic data were obtained from the literature, and susceptibility data to meropenem for E. coli and K. pneumoniae were collected from the Tigecycline Evaluation and Surveillance Trial (T.E.S.T.) surveillance study. For the same dose level, the 3-h infusion provided a probability of target attainment (PTA) ≥90 % for minimum inhibitory concentration (MIC) values up to two-fold dilution higher than those obtained with the 0.5-h infusion. For E. coli, the cumulative fraction of response (CFR) was 100 % in most cases, and neither the dose nor the infusion length nor the geographical area significantly affected the probability to reach the target. With regards to K. pneumoniae, the CFR increased when increasing the dose and decreasing the creatinine clearance (CLCR). The CFR for Spanish and USA strains was higher than that calculated for European strains. Meropenem PK/PD breakpoints are dependent on the dose, infusion length and CLCR, ranging from 2 to 32 mg/L. Based on our results, meropenem administered as a extended infusion is the best option to treat infections due to E. coli and K. pneumoniae.

Immunostimulatory effects of prolactin on TLR1 and TLR5M in SHK-1 cells infected with Piscirickettsia salmonis.

The innate immune system is the first line of defense against infection by pathogens. It consists of various elements, including Toll-like receptors (TLRs), which recognize molecular patterns associated with pathogens and trigger the immune response, through activation of important transcription factors such as NF-κB, which are usually found sequestered in the cytoplasm by IκBα until it receives the release signal. Piscirickettsia salmonis causes piscirickettsiosis or salmonid rickettsial septicemia, a disease of great importance in Chile, representing 79.4% of the secondary mortality in important species such as Salmo salar, which is reflected in the Chilean economy. Prolactin (PRL) is a peptide hormone which has immunomodulating functions in mammals and some fish. Olavarría et al. (2010, J Immunol 185:3873-3883) determined its ability to increase the respiratory burst, its relationship with the JAK/STAT pathway, and the expression of interleukin IL-1ß in Sparus aurata. Therefore, the present study was intended to establish a possible correlation and modulation between the signal transduction pathway of PRL (JAK/STAT), the pathways of NF-κB, and TLRs, in an infection caused by P. salmonis in salmon head kidney (SHK­1) cells of S. salar. Stimulus with native PRL from S. salar was performed, and gene expression was analyzed for IL-1ß, IκBα, TLR1, and TLR5M (membrane-bound form). In addition, the effect of PRL in the nuclear translocation of the transcription factor NF-κB and the possible involvement of JAK2 were analyzed by using a pharmacological inhibitor of this kinase. The results show a positive modulation of PRL in all analyzed genes and a significant increase in the translocation of NF-κB, recording a maximum at 2 h post-treatment, supporting the stimulatory hypothesis of PRL.

Immunostimulatory effect of salmon prolactin on expression of Toll-like receptors in Oncorhynchus mykiss infected with Piscirickettsia salmonis.

In aquaculture, antibiotics are the traditional treatment used against bacterial infections. However, their use has increasingly come into question given their effects on fish and, possibly, on human health. Consequently, there is interest in developing alternative treatments aimed at stimulating the innate immune response of fish, which is the first line of defense against pathogens. In relation to this, the Toll-like receptors (TLR) aid in the selective identification of pathogens. The present study evaluated immunostimulatory activity of prolactin (PRL) hormone on expression levels of TLR1, 9, and 22, MyD88, and IL-1ß during in vitro infection with the fish pathogen Piscirickettsia salmonis, in primary cultures of Oncorhynchus mykiss head kidney cells. Results indicated that PRL increased expression of TLRs and MyD88 during the first hours of bacterial infection, while a constant increase in expression was found for IL-1ß. These findings suggest that PRL indirectly modulates expression of TLRs by activating expression of suppressors of cytokine signaling, thereby regulating immune response over long periods of time during bacterial infection.

Use of Nursing Concepts in Program and Course Descriptions: An Analysis of Prelicensure Baccalaureate Nursing Programs in the United States.

BACKGROUND: Ongoing discussions address how and when to introduce nursing concepts in nursing education. PURPOSE: To examine whether baccalaureate nursing programs use 4 nursing concepts in their program and course descriptions. METHODS: Researchers explored websites of 300 US bachelor of science in nursing (BSN) programs and assigned scores based on how many of 4 nursing concepts (context, holism, health, and caring) were represented in program and 3 course descriptions. RESULTS: Mean program and course scores were 2.51, 0.96, 1.17, and 1.18, respectively. Programs and courses included between 0 and 4 concepts in their descriptions. There was a significant difference in program scores between BSN programs in 4 US regions. The most frequently identified concept was "context" in program descriptions and "holism" in course descriptions. CONCLUSIONS: Discipline-specific concepts are missing in many baccalaureate programs and course descriptions, which raises questions about how and when nursing students are learning what nursing is.

Pharmacokinetic-pharmacodynamic evaluation of daptomycin, tigecycline, and linezolid versus vancomycin for the treatment of MRSA infections in four western European countries.

PURPOSE: To evaluate the usefulness of daptomycin, tigecycline, and linezolid for the treatment of MRSA infection compared with vancomycin in Belgium, the United Kingdom/Ireland, and Spain. METHODS: The methodology included the following steps: acquisition of microbiological and pharmacokinetic data, Monte Carlo simulation, estimation of the probability of target attainment (PTA), and calculation of the cumulative fraction of response (CFR). RESULTS: We showed that differences in the susceptibility of MRSA strains among countries may justify differences in the antibiotic dose selection. Two, 3, and 4 g daily of vancomycin seem be adequate in Belgium, Spain, and United Kingdom/Ireland respectively. The CFR obtained with 50 mg tigecycline every 12 h was higher in Spain than in Belgium and the United Kingdom/Ireland, but with the highest dose (100 mg q12h) the CFR was always 100%. At least 8 mg/kg daptomycin is necessary in United Kingdom/Ireland, but 4 mg/kg may be sufficient in Spain, and probably in Belgium. Six hundred mg q12h linezolid may be adequate in the four countries. CONCLUSION: Our study reinforces the idea that the local MIC distribution must be considered in order to increase the probability of success of empirical treatment and must be periodically updated.

Traction-induced aneurysm of an accessory left hepatic artery: a potentially fatal but synchronously treatable complication of a large hiatus hernia.

A 59-year-old man presented to our surgical clinic with a long-standing history of heart burn, and upper abdominal pain. Gastroscopy showed a large sliding hiatus hernia associated with severe reflux oesophagitis. Oesophageal pH manometry revealed a high DeMeester score of 36.03. A computed tomography (CT) scan was performed for preoperative hiatal hernia repair planning. This showed the incidental finding of an accessory left hepatic artery (ALHA) and an aneurysm of this accessory artery. The aneurysm occurred at the point where the ALHA traversed the diaphragmatic crus and was only present in association with the hiatus hernia. These observations suggest that the aetiology of the aneurysm was due to traction during development of the hiatus hernia. The patient went onto have a laparoscopic hiatus hernia repair and Toupet fundoplication with ligation of the accessory left hepatic artery and made an excellent recovery. ALHAs are not uncommon, occurring in around 15% of the general population, with aneurysms of the hepatic arteries accounting for about 20% of cases of visceral artery aneurysms. The case presented herein highlights the importance of performing an arterial phase CT when planning surgery for large hiatus hernias to detect more cases like this one. This would allow early detection and concurrent treatment of an associated aneurysm with repair of the hiatus hernia, to prevent aneurysmal complications later on.

[Non-functioning pituitary adenomas: epidemiology, clinical and postoperative outcome]. / Adenomas hipofisarios no funcionantes: epidemiología, clínica y evolución posquirúrgica.

INTRODUCTION: Non-functioning pituitary adenomas are the most frequent tumor group in the sellar region. They are usually benign neoplasms diagnosed after visual or hormonal symptoms, although it is not uncommon to detect them as a casual finding. AIM: To analyze the clinical aspects found in this disease and its response after surgical treatment. PATIENTS AND METHODS: In a series of 100 cases, epidemiological, clinical, endocrinological, visual and radiological data were analyzed before and after surgical treatment, as well as the complications related to surgery and long-term follow-up. RESULTS: The most frequent symptom at the time of diagnosis was visual field involvement (62%), and only the 7% of adenomas were a casual finding. The most common hormonal deficit was hypogonadotropic hypogonadism (48%). After surgery, complete recovery of the visual field defect was observed in 54.8% of the patients, only 1% worsening after surgery, and the incidence of diabetes insipidus was 4%. The resection was superior to 95% in 63% of cases, although the percentage of adenomas with invasion of the cavernous sinus in Knosp grades 3 and 4 it was high (45%). CONCLUSIONS: Although the most frequent symptom of non-functioning pituitary adenomas is campimetric involvement, it has an excellent response to surgery if it is performed within the appropriate time. The grade of invasion of the cavernous sinus is the most limiting factor for a complete surgical resection.

TITLE: Adenomas hipofisarios no funcionantes: epidemiología, clínica y evolución posquirúrgica.Introducción. Los adenomas hipofisarios no funcionantes son el grupo tumoral más frecuente en la región selar. Suelen ser neoplasias benignas diagnosticadas por síntomas visuales u hormonales, aunque no es infrecuente detectarlos como un hallazgo casual. Objetivo. Analizar los aspectos clínicos hallados en esta enfermedad y su respuesta tras el tratamiento quirúrgico. Pacientes y métodos. En una serie de 100 casos, se analizaron datos epidemiológicos, clínicos, endocrinológicos, visuales y radiológicos antes y después del tratamiento quirúrgico, y se recogen las complicaciones relacionadas con la cirugía y el seguimiento a largo plazo. Resultados. El síntoma más frecuente en el momento del diagnóstico fue la afectación del campo visual (62%), y sólo el 7% de los adenomas se trataba de un hallazgo casual. El déficit hormonal más frecuente era el hipogonadismo hipogonadótropo (48%). Tras la cirugía se observó recuperación completa del defecto campimétrico en el 54,8% de los pacientes, con sólo un 1% de empeoramiento tras la cirugía, y la incidencia de diabetes insípida fue del 4%. La resección fue superior al 95% en el 63% de los casos, a pesar de que el porcentaje de adenomas con invasión del seno cavernoso en grados altos fue elevado (45%). Conclusiones. Aunque el síntoma más frecuente de los adenomas hipofisarios no funcionantes es la afectación campimétrica, ésta tiene una excelente respuesta a la cirugía si se realiza dentro del tiempo adecuado. El grado de invasión del seno cavernoso parece el factor más limitante para una resección quirúrgica completa.

Laparoscopic management of insulinomas.

BACKGROUND: Conventional surgical management of insulinomas involves an open technique. The laparoscopic approach has advantages in terms of improved postoperative pain and recovery time. This retrospective study evaluated the laparoscopic management of pancreatic insulinomas. METHODS: Between December 2000 and March 2007, 23 patients were referred for consideration of laparoscopic insulinoma resection. Two patients were not deemed appropriate for the laparoscopic approach and were managed with open surgery. All surgery was performed by one experienced pancreatic surgeon. Laparoscopic intraoperative ultrasonography was not available for the first six procedures, but was used thereafter. RESULTS: Twenty-one patients (five men and 16 women, median age 46 (range 22-70) years) had a successful resection. All had single tumours, five in the head, nine in the body and seven in the tail of the pancreas. One conversion to open operation was performed in a patient with an insulinoma in the head of the pancreas who had dense adhesions resulting from pancreatitis. Three patients developed a postoperative pancreatic fistula. There has been no recurrence of symptoms in any patient. CONCLUSION: Laparoscopic management of insulinomas is feasible and safe. Laparoscopic intraoperative ultrasonography is a promising adjunct to the procedure, even after accurate preoperative localization.

The role of arterial stimulation and simultaneous venous sampling in addition to cross-sectional imaging for localisation of biochemically proven insulinoma.

Insulinomas, although rare, cause considerable morbidity but are frequently amenable to surgical cure. Laparoscopic surgery can now be considered if the tumour is localised pre-operatively, but the optimal imaging approach has not been determined. The objective of this study was to evaluate the ability of different imaging investigations, including CT, MRI, endoscopic ultrasound, octreotide scintigraphy and arterial stimulation with simultaneous venous sampling (ASVS), to localise insulinomas. All patients with biochemically proven insulinoma at our institution underwent ASVS along with other imaging investigations as part of their routine investigation. The results of these investigations were compared with histological findings. Twenty-eight patients with biochemically proven insulinoma confirmed by histology were identified. Ultimately ASVS localised a lesion in all patients. Seventeen patients (61%) had laparoscopic surgery. Tumor-detection rates for other imaging investigations included 43.5% of cases using CT, 71% using MRI, 86% using endoscopic ultrasound and 33% using octreotide scintigraphy. In four patients, the ASVS was the only test to correctly localise the lesion. ASVS should be considered routinely before surgery to ensure accurate localisation of insulinomas.

Bioassay for diagnosis of plant viruses.

Bioassay provides a useful means of detecting and identifying plant viruses. The choice of procedure and environmental conditions for the test depends on the virus under investigation.

[Identification of genetic alterations by multiple ligation-dependent probe amplification (MLPA) analysis in oligodendrogliomas]. / Identificación de alteraciones genéticas en oligodendrogliomas mediante amplificación dependiente de ligasa de múltiples sondas (MLPA) (multiple ligation-dependent probe amplification).

Concurrent deletion at 1p/19q is a common signature of oligodendrogliomas, and it may be identified in low-grade tumours (grade II) suggesting it represents an early event in the development of these brain neoplasms. Additional non-random changes primarily involve CDKN2A, PTEN and EGFR. Identification of all of these genetic changes has become an additional parameter in the evaluation of the clinical patients' prognosis, including good response to conventional chemotherapy. Multiple ligation-dependent probe amplification (MLPA) analysis is a new methodology that allows an easy identification of the oligodendrogliomas' abnormalities in a single step. No need of the respective constitutional DNA from each patient is another advantage of this method. We used MLPA kits P088 and P105 to determine the molecular characteristics of a series of 40 oligodendrogliomas. Deletions at l p and 19q were identified in 45% and 65% of cases, respectively. Alterations of EGFR, CDKN2A, ERBB2, PTEN and TP53 were also identified in variable frequencies among 7% to 35% of tumours. These findings demonstrate that MLPA is a reliable technique to the detection of molecular genetic changes in oligodendrogliomas.

Application of pharmacokinetic/pharmacodynamic analysis to evaluate the adequacy of antimicrobial therapy for pediatric acute otitis media in Spain before and after the introduction of the PCV7 vaccine.

OBJECTIVE: To evaluate, by applying pharmacokinetic/pharmacodynamic (PK/PD) analysis, if the change in antibiotic susceptibility after the introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) in Spain had any influence on the usefulness of the antimicrobials more frequently used as empirical treatment of pediatric acute otitis media (AOM). METHODS: PK parameters and susceptibility of Streptococcus pneumoniae and Haemophilus influenzae were obtained from bibliography. Monte Carlo simulation was used to estimate the cumulative fraction of response (CFR), understood as the expected probability of therapy success. For amoxicillin and amoxicillin/clavulanate, the target was free antibiotic concentration remaining above the minimum inhibitory concentration (MIC) for ≥50% of the dosing interval (fT>MIC≥50%), whereas for cefuroxime axetil and cefotaxime, the target was fT>MIC≥60%. CFR values ≥90% were considered successful. RESULTS: When all serotypes of S. pneumoniae are considered, amoxicillin and cefotaxime turned out to reach a high probability of success, and difference before and after vaccination was scarce. For H. influenzae, CFR values were higher with amoxicillin/clavulanate than with amoxicillin. For both microorganisms, cefuroxime axetil resulted in low probability of success in the two periods of study. CONCLUSIONS: We have shown that the introduction of the PCV7 vaccination did not lead to changes in the probability of success of the current empiric treatments of the AOM. Integrated PK/PD analysis has demonstrated to be a useful tool to identify changes in antimicrobial activity after the implantation of a vaccination program, providing complementary information to the simple assessment of MIC values.

Update on the pathophysiology and management of syringomyelia unrelated to Chiari malformation. / Siringomielia no secundaria a Chiari. Actualización en fisiopatología y manejo.

INTRODUCTION: Much has been published on syringomyelia related to Chiari malformation. In contrast, little is known about the condition when it is not associated with this malformation, but this presentation of syringomyelia constitutes a different entity and therefore requires specific management. We conducted a literature review to summarise the most accepted and widespread ideas about the pathophysiology, management and other aspects of syringomyelia unrelated to Chiari malformation. DEVELOPMENT: We reviewed the most relevant literature on this condition, focusing on the pathophysiology, clinical presentation, diagnosis, and treatment. CONCLUSIONS: Syringomyelia unrelated to Chiari malformation is a distinct entity that must be well understood to guarantee correct diagnosis, monitoring, and management. When the disease is suspected, a thorough study should be conducted to identify its aetiology. Treatment must aim to eliminate the cause of the disease; symptomatic treatment should remain a second-line option.

Infections related to healthcare in patients hospitalized in a Urology service: resistance patterns and adequacy of empirical antibiotic treatment as a prognostic factor. / Infecciones relacionadas con la asistencia sanitaria en pacientes ingresados en un servicio de Urología: patrones de resistencia y adecuación del tratamiento antibiótico empírico como factor pronóstico.

OBJECTIVES: To evaluate the suitability of empirical antibiotic therapy in HAIs and the antibiotic resistance patterns of the responsible microorganisms, as well as the incidence of mortality and risk factors involved. METHOD: A prospective observational study was carried out on patients of both sexes older than 16years, admitted by any urological process during a period of 4years. The incidence and characteristics of HAIs, as well as the causative organism and its resistance, the initial empirical antibiotic therapy and its modification, if required, and mortality rates are analysed. RESULTS: Out of 6,546 patients, 6.3% suffered HAIs, 70.5% corresponding to urinary tract infection and 22.1% to infection of the surgical wound. E.coli, Enterococcus spp., Klebsiella spp. y P.aeruginosa were the most frequently implicated (25.1%, 17.5%, 13.5% and 12.3%, respectively). E.coli and Klebsiella spp. were producers of extended-spectrum beta-lactamases (ESBL) in 24.7% and 47.8%, respectively. 4.3% of Klebsiella and 33.3% of Pseudomonas were carbapenems-resistant. The overall resistance to quinolones was approximately 50%. The most commonly used antibiotics for empirical therapy were cephalosporins of 3rd and 4th generation (33.6%) and carbapenems (28.2%). An overall rate of adequacy of empirical antibiotic therapy of 82.9% was obtained. The mortality rate in patients with HAIs was 2.2%, compared with 0.3% in patients without infection. In a multivariate analysis, the variables associated with the highest mortality risk were the isolation of ESBL-producing enterobacteria and the inadequate empirical antibiotic treatment. CONCLUSIONS: The selection of empirical antibiotic therapy was quite accurate. An increase in HAIs by multiresistant microorganisms, such as ESBL Enterobacteria or multiresistant P.aeruginosa is being observed. The mortality risk increases with inadequate initial empirical antibiotic therapy or when the responsible microorganism is an ESBL enterobacteria.

Bronchoesophageal fistula in a patient with non-Hodgkin's lymphoma.

Bronchoesophageal fistula secondary to lymphoma is a very rare condition, usually associated with chemo-radiotherapy. We report a case of a patient with a non-Hodgkin's lymphoma (NHL) who, after chemotherapy, developed an oesophago-tracheal fistula. Initially it was treated conservatively but due to the lack of response, a stent was inserted. After nearly one year without success, surgery was considered. Right thoracotomy oesophagectomy and closure of the tracheal defect with an intercostal muscle flap and pericardial patch was performed. This was followed by laparoscopic creation of a gastric tube, which was successfully anastomosed to the cervical oesophagus through a cervicotomy. Unlike oesophageal cancer, NHL can have a good prognosis, so curative treatment of the fistula can be considered. Conservative treatment must always be the first option, leaving stenting or surgery for when the problem persists.

Population pharmacokinetics of daptomycin in critically ill patients.

Daptomycin has shown activity against a wide range of Gram-positive bacteria; however, the approved dosages usually seem insufficient for critically ill patients. The aim of this study was to develop a population pharmacokinetic model for daptomycin in critically ill patients and to estimate the success of the therapy by applying pharmacokinetic/pharmacodynamic (PK/PD) criteria. Sixteen intensive care unit patients were included, four of whom underwent continuous renal replacement therapies (CRRT). Blood and, when necessary, effluent samples were drawn after daptomycin administration at previously defined time points. A population approach using NONMEM 7.3 was performed to analyse data. Monte Carlo simulations were executed to evaluate the suitability of different dosage regimens. The probabilities of achieving the PK/PD target value associated with treatment success (ratio of the area under the plasma concentration-time curve over 24 h divided by the minimum inhibitory concentration (AUC24/MIC ≥ 666)) and to reach daptomycin concentrations linked to toxicity (minimum concentration at steady-state (Cminss) ≥ 24.3 mg/L) were calculated. The pharmacokinetics of daptomycin was best described by a one-compartment model. Elimination was conditioned by the creatinine clearance (Clcr) and also by the extra-corporeal clearance when patients were subjected to continuous renal replacement therapy (CRRT). The PK/PD analysis confirmed that 280- and 420-mg/d dosages would not be enough to achieve high probabilities of target attainment for MIC values ≥ 1 mg/L in patients with Clcr ≥ 60 mL/min or in subjects with lower Clcrs but receiving CRRT. In these patients, higher dosages (560-840 mg/d) should be needed. When treating infections due to MIC values ≥ 4 mg/L, even the highest dose would be insufficient.

Infections by carbapenemase-producing enterobacteriaceae in a department of urology. A new challenge. / Infecciones por enterobacterias productoras de carbapenemasas en un servicio de urología. Un nuevo desafío.

OBJECTIVES: To analyse infections by carbapenemase-producing enterobacteriaceae (CPE) and describe the characteristics and potential risk factors associated with patients of a department of urology. MATERIAL AND METHODS: Observational and retrospective study. The inclusion criterion was hospitalisation in our department of Urology between August 2013 and December 2016. We analysed those patients who were positive for CPE in at least 1 culture. We reviewed their baseline characteristics, risk factors and variables such as the presence of previous urinary tract infections, subsequent readmissions, the microorganism, type of CPE, treatment, origin (hospital or community) and mortality. RESULTS: Of the 5,657 patients who met the inclusion criterion, a CPE was isolated in 12 cases. CPE infections represented 3.6% of all healthcare-associated infections and 9.7% of those caused by enterobacteria. The analysed factors associated with CPE infection in our series were the presence of urinary catheters (100%), undergoing surgery (58.3%), previous ICU admission (8.3%) and immunosuppression (16.6%). In terms of mortality, 8.3% of the patients who presented CPE infection died during hospitalisation. CONCLUSIONS: Approximately 10% of enterobacteria present a carbapenemase-resistance pattern in urological patients in our setting. Carrying a urinary catheter and/or undergoing surgery are risk factors associated with the development of these infections in urological patients in our setting. CPE infections increase morbidity and mortality.

DAPK1 promoter hypermethylaiton in brain metastases and peripheral blood.

The DAPK1 gene works as a regulator of apoptosis and is frequently inactivated in cancer by aberrant promoter hypermethylation. Loss of DAPK1 expression is associated with a selective advantage for tumor cells to resist apoptotic stimuli, allowing them to separate from the original tumor; from this point of view, DAPK1 could be considered a tumor metastases inhibitor gene. To verify the participation of DAPK1 silencing in cerebral invasion, we analyzed its promoter methylation status in a series of 28 samples from cerebral metastases using MSP and sequencing of the MSP-product. We have found hypermethylation in 53.6% (15/28) metastatic tumor samples as well as in 27.8% (5/18) of its peripheral blood samples. Our data suggest an important role of DAPK1 for silencing through promoter CpG island hypermethylation in the development of brain metastases from solid tumors. The detection of aberrant hypermethylation on DAPK1 promoter from peripheral blood samples has potential clinical implications as a tumor prognosis marker.