Value of PHI and PHID in the detection of intermediate- and high-risk prostate cancer.

BACKGROUND AND AIMS: PSA testing practice results in a large number of unnecessary prostate biopsies and the overdiagnosis of clinically insignificant prostate cancer (PCa). The aim of our study was to evaluate the value of PHI and PHID for the detection of PCa. MATERIALS AND METHODS: We measured tPSA, fPSA and p2PSA in 455 patients scheduled for biopsy, including 243 patients with PCa. D'Amico criteria were used to classify these patients in three groups related to risk of progression. Intermediate- and high-risk PCa were considered as aggressive PCa. RESULTS: The best area under the curve (AUC) value obtained in the detection of aggressive PCa was achieved for PHI and PHID (0.766 and 0.760, respectively). We found a relationship of the performance of by these tests with the calculated prostate volume or the estimated prostate size by digital rectal exam, obtaining the higher AUC in patients with a small prostate. Thus, the AUC for PHI was 0,843 for patients with small calculated prostate volume and 0,817 for patients with small estimated prostate size. CONCLUSIONS: Our results underline that PHI and PHID outperforms the efficacy obtained with tPSA and %fPSA. Substantial differences in their value in relation to prostate volume were found.

Development of a nomogram predicting the probability of stone free rate in patients with ureteral stones eligible for semi-rigid primary laser uretero-litothripsy.

PURPOSE: Few tools are available to predict uretero-lithotripsy outcomes in patients with ureteral stones. Aim of our study was to develop a nomogram predicting the probability of stone free rate in patients undergoing semi-rigid uretero-lithotripsy (ULT) for ureteral stones. METHODS: From January 2014 onwards, patients undergoing semi-rigid Ho: YAG laser uretero-lithotripsy for ureteral stones were prospectively enrolled in two centers. Patients were preoperatively evaluated with accurate clinical history, urinalysis and renal function. Non-contrast CT was used to define number, location and length of the stones and eventually the presence of hydronephrosis. A nomogram was generated based on the logistic regression model used to predict ULT success. RESULTS: Overall, 356 patients with mean age of 54 years (IQR 44/65) were enrolled. 285/356 (80%) patients were stone free at 1 month. On multivariate analysis single stone (OR 1.93, 95% CI 1.05-3.53, p = 0.034), stone size (OR 0.92, 95% CI 0.87-0.97, p = 0.005), distal position (OR 2.12, 95% CI 1.29-3.48, p = 0.003) and the absence of hydronephrosis (OR 2.02, 95% CI 1.08-3.78, p = 0.029) were predictors of success and these were used to develop a nomogram. The nomogram based on the model presented good discrimination (area under the curve [AUC]: 0.75), good calibration (Hosmer-Lemeshow test, p > 0.5) and a net benefit in the range of probabilities between 15 and 65%. Internal validation resulted in an AUC of 0.74. CONCLUSIONS: The implementation of our nomogram could better council patients before treatment and could be used to identify patients at risk of failure. External validation is warranted before its clinical implementation.

Granzyme A inhibition reduces inflammation and increases survival during abdominal sepsis.

Aims: Peritonitis is one of the most common causes of sepsis, a serious syndrome characterized by a dysregulated systemic inflammatory response. Recent evidence suggests that Granzyme A (GzmA), a serine protease mainly expressed by NK and T cells, could act as a proinflammatory mediator and could play an important role in the pathogenesis of sepsis. This work aims to analyze the role and the therapeutic potential of GzmA in the pathogenesis of peritoneal sepsis. Methods: The level of extracellular GzmA as well as GzmA activity were analyzed in serum from healthy volunteers and patients with confirmed peritonitis and were correlated with the Sequential Organ Failure Assessment (SOFA) score. Peritonitis was induced in C57Bl/6 (WT) and GzmA-/- mice by cecal ligation and puncture (CLP). Mice were treated intraperitoneally with antibiotics alone or in combination serpinb6b, a specific GzmA inhibitor, for 5 days. Mouse survival was monitored during 14 days, levels of some proinflammatory cytokines were measured in serum and bacterial load and diversity was analyzed in blood and spleen at different times. Results: Clinically, elevated GzmA was observed in serum from patients with abdominal sepsis suggesting that GzmA plays an important role in this pathology. In the CLP model GzmA deficient mice, or WT mice treated with an extracellular GzmA inhibitor, showed increased survival, which correlated with a reduction in proinflammatory markers in both serum and peritoneal lavage fluid. GzmA deficiency did not influence bacterial load in blood and spleen and GzmA did not affect bacterial replication in macrophages in vitro, indicating that GzmA has no role in bacterial control. Analysis of GzmA in lymphoid cells following CLP showed that it was mainly expressed by NK cells. Mechanistically, we found that extracellular active GzmA acts as a proinflammatory mediator in macrophages by inducing the TLR4-dependent expression of IL-6 and TNFα. Conclusions: Our findings implicate GzmA as a key regulator of the inflammatory response during abdominal sepsis and provide solid evidences about its therapeutic potential for the treatment of this severe pathology.

Takotsubo cardiomyopathy after cesarean section: A case report and literature review.

Takotsubo cardiomyopathy (TCM) is clinically identical to acute myocardial infarction. We report an unusual case of TCM and review similar cases in pregnant women. A young woman with no pre-existing cardiovascular risk factors suffered sudden dyspnea during a cesarean section. Electrocardiography (ECG) showed T-wave inversion. We observed acute lung edema and left ventricular systolic dysfunction on echocardiography. A cardiac catheterization diagnosed TCM. We reviewed 20 cases of TCM; 17 cases occurred during the post-partum period and three during pregnancy. Five of these cases had vaginal deliveries and the remaining cases had cesarean sections. Within the latter group, five cases appeared intraoperatively. With the exception of one patient with normal ECG results, all other patients progressed, with changes in ECG readings and elevation of cardiac enzyme serum levels. However, cardiac catheterization revealed that coronary arterial damage did not occur in any of the cases. After three months, each patient fully recovered.

Marked testosterone deficiency-related symptoms may be associated to higher metabolic risk in men with low testosterone levels.

INTRODUCTION: Testosterone deficiency syndrome (TDS) is usually suspected on the basis of signs/symptoms. However, some men with low testosterone levels (low T) are asymptomatic or present mild, unnoticed symptoms. Would they have the same cardiovascular risk as symptomatic men? AIMS: This study aims to assess the relationship between presence/severity of low T-related symptoms and the likelihood of metabolic syndrome (MetS). METHODS: Data were taken from a multicenter, cross-sectional study conducted in Spain among men visiting men's healthcare offices aged ≥45 with low T (total T <8 nmol/L or <12 nmol/L and calculated free T <250 nmol/L). Only subjects whose MetS components and symptoms had been assessed were selected. Data available included anthropometrics, toxic habits, comorbidities, and total testosterone (TT) levels. MAIN OUTCOME MEASURES: MetS was defined using the harmonized definition. Erectile dysfunction was classified using the International Index of Erectile Function questionnaire. The Ageing Male Symptoms (AMS) scale assessed symptoms. Symptom severity was classified as "none/mild" and "moderate/severe." Bivariate and multivariate logistic regression analyses were performed to calculate the effect of moderate/severe symptoms on the odds ratio (OR) for MetS. RESULTS: Mean age (SD) was 61.2 (8.1) years. Erectile dysfunction (ED), AMS, and MetS prevalence were 97.4%, 94.9%, and 69.6%. Prevalence of MetS was higher in men with moderate/severe symptoms vs. men with no/mild ones (75.3% vs. 57.9%, P < 0.001). Age and prevalence of TT <8 nmol/L, moderate/severe ED, and obesity were significantly higher in men with moderate/severe symptoms. Multivariate analysis showed that besides obesity and moderate/severe ED, moderate/severe symptoms increased the likelihood of MetS. This effect disappeared in men with severe ED and in the nonobese. Three symptoms showed relationship with MetS after adjusting for all confounding factors. CONCLUSION: Severity of TDS symptoms may indicate higher cardiovascular risk in men with low T.

Real-time PCR PCA3 assay is a useful test measured in urine to improve prostate cancer detection.

BACKGROUND: The usefulness of PCA3 in the management of early prostate cancer (PCa) is on debate. The aim of this study was to evaluate PCA3 in the detection of PCa and its relationship with tumor aggressiveness. METHODS AND PATIENTS: PCA3 score was measured by real time PCR in urinary sediments of 122 patients who underwent prostate biopsy for PSA >4µg/L. RESULTS: Analysis of ROC curves showed an area under the curve (AUC) of 0.804 for PCA3 score, while the AUCs were 0.587 and 0.697 for PSA and % free PSA, respectively. The probability of positive biopsy increased in relation to PCA3 score, with variations from 37% to 96% for patients with PCA3 score lower than 0.90 or higher than 1.04, respectively. We chose the cut-off value of 0.90, corresponding to a sensitivity of 92.5%, for which we obtained a specificity of 41.5%. No significant differences in PCA3 score were found in relation to Gleason score or clinical stage. CONCLUSIONS: The results show a high probability of PCa in patients with an elevated PCA3 score, although we did not find any relationship with aggressiveness of the tumor. PCA3 score can help to select more precisely which patients will need to perform a biopsy of the prostate.

Metabolic syndrome in men with low testosterone levels: relationship with cardiovascular risk factors and comorbidities and with erectile dysfunction.

INTRODUCTION: Testosterone deficiency and metabolic syndrome (MetS) are strongly associated. Patients consulting for sexual dysfunction may have testosterone deficiency, providing a valuable opportunity to assess MetS. The identification of variables predicting MetS is of great importance. AIMS: To identify cardiovascular comorbidities and risk factors, including erectile dysfunction (ED), associated with MetS in men aged≥45 with total testosterone (TT)<8 nmol/L (or <12 nmol/L when calculated free testosterone was <50 pmol/L) and to gain further insight into the relationship between both conditions. METHODS: Data were collected from a multicenter, cross-sectional, observational study conducted in Spain among men visiting men's health-care offices with a confirmed diagnosis of testosterone deficiency. Subjects with data for MetS assessment were included in this analysis. Other data available were anthropometrics, toxic habits, cardiovascular comorbidities, ED diagnosis, and TT values. MAIN OUTCOME MEASURES: The MetS harmonized definition was used. Waist circumference threshold was 94 cm. ED was diagnosed and classified using the International Index of Erectile Function-5 (IIEF-5) questionnaire. Bivariate and multivariate logistic regression analyses were performed to calculate odds ratios (ORs) for MetS. RESULTS: Mean age was 61.2±8.1 years. Prevalences of ED and MetS were 97.6% and 69%, respectively, both increasing with age. Bivariate analysis showed that moderate or severe ED, obesity, and peripheral vascular disease (PVD) were the variables associated with the greatest odds of MetS (OR=2.672 and 2.514, respectively), followed by alcohol intake (OR=1.911). Tobacco use, ag,e and testosterone deficiency severity had a minimal effect that disappeared on multivariate analysis. Elevated triglycerides and HDL-cholesterol were MetS risk factors associated with a lower TT level. CONCLUSION: The high prevalence of MetS among men with testosterone deficiency highlights the opportunity to assess cardiovascular health in patients consulting for sexual dysfunction. Moderate to severe ED, obesity, PVD, and alcohol intake significantly increase the likelihood of MetS.

Prevalence and risk factors of erectile dysfunction and testosterone deficiency symptoms in a rural population in Uganda.

OBJECTIVES: To determine the prevalence and risk factors of erectile dysfunction (ED) and the prevalence of hypogonadism symptoms in Buluba, a rural population in Uganda. METHODS: Prospective, consecutive, cross-sectional study was conducted between September and December 2010. 902 men attending the outpatient clinic of Saint Francis Hospital in Buluba were enrolled. From these 902 men, 204 had been previously diagnosed as HIV+ followed in a specific HIV outpatient clinic in the same centre. Variables age, weight, height, tobacco use and drinking habits, Erection Hardness Score and Aging Male Symptoms Scale (AMSS), as well as Hypertension, Diabetes, Dyslipidemia, lung diseases, peptic ulcer, urinary symptoms and HIV were prospectively recorded. A multivariate analysis was used to analyze the variables related to erectile function and AMSS. RESULTS: Mean age was 39±11,8 years. ED rate was 47,8% (Mild ED 28,8%; Moderate 14%; Severe 5%). In the multivariate analysis, variables age (Odds ratio (OR) 1,032), HIV+ (OR 11,280), AMSS (OR 1,138) and AMSS≥50 (OR 1,164) were related to ED. When excluding HIV+ population, 36,8% of men suffered ED (Mild ED 23%; Moderate 10,2%; Severe 3,6%). 5,7% of men had severe symptoms(≥50) of hypogonadism according to AMSS. No clinical variable was related to the presence of AMSS≥50 in the multivariate analysis. CONCLUSIONS: The rate of ED in a rural milieu in Uganda is high. Variables age, AMSS and AMSS≥50 and HIV+ were related to ED. The rate of AMSS≥50 was 5,7%. No variable was found to be related to AMSS≥50.

Update on invasive mycoses by filamentous fungi in critically ill patients.

The present article is an update of the literature on invasive fungal infections caused by filamentous fungi in critically ill patients. A multidisciplinary group of Spanish physicians with an interest in these infections organized a joint session and selected the most important papers produced lately in the field. Each article was analyzed and discussed by one of the members of the panel. Studies from the fields of causative microorganisms, epidemiology, and diagnosis are discussed; including the assessment of different strategies for the early identification and treatment of patients at risk of fungal infections by filamentous fungi in the intensive care unit setting.

Acute kidney injury in critical ill patients affected by influenza A (H1N1) virus infection.

INTRODUCTION: Little information exists about the impact of acute kidney injury (AKI) in critically ill patients with the pandemic 2009 influenza A (H1N1) virus infection. METHODS: We conducted a prospective, observational, multicenter study in 148 Spanish intensive care units (ICUs). Patients with chronic renal failure were excluded. AKI was defined according to Acute Kidney Injury Network (AKIN) criteria. RESULTS: A total of 661 patients were analyzed. One hundred eighteen (17.7%) patients developed AKI; of these, 37 (31.4%) of the patients with AKI were classified as AKI I, 15 (12.7%) were classified as AKI II and 66 (55.9%) were classified as AKI III, among the latter of whom 50 (75.7%) required continuous renal replacement therapy. Patients with AKI had a higher Acute Physiology and Chronic Health Evaluation II score (19.2 ± 8.3 versus 12.6 ± 5.9; P < 0.001), a higher Sequential Organ Failure Assessment score (8.7 ± 4.2 versus 4.8 ± 2.9; P < 0.001), more need for mechanical ventilation (MV) (87.3% versus 56.2%; P < 0.01, odds ratio (OR) 5.3, 95% confidence interval (CI) 3.0 to 9.4), a greater incidence of shock (75.4% versus 38.3%; P < 0.01, OR 4.9, 95% CI, 3.1 to 7.7), a greater incidence of multiorgan dysfunction syndrome (92.4% versus 54.7%; P < 0.01, OR 10.0, 95% CI, 4.9 to 20.21) and a greater incidence of coinfection (23.7% versus 14.4%; P < 0.01, OR 1.8, 95% CI, 1.1 to 3.0). In survivors, patients with AKI remained on MV longer and ICU and hospital length of stay were longer than in patients without AKI. The overall mortality was 18.8% and was significantly higher for AKI patients (44.1% versus 13.3%; P < 0.01, OR 5.1, 95% CI, 3.3 to 7.9). Logistic regression analysis was performed with AKIN criteria, and it demonstrated that among patients with AKI, only AKI III was independently associated with higher ICU mortality (P < 0.001, OR 4.81, 95% CI 2.17 to 10.62). CONCLUSIONS: In our cohort of patients with H1N1 virus infection, only those cases in the AKI III category were independently associated with mortality.

Nosocomial outbreak of methicillin- and linezolid-resistant Staphylococcus epidermidis associated with catheter-related infections in intensive care unit patients.

A total of 128 isolates associated with catheter-related infections was recovered from 101 intensive care unit patients in a Spanish hospital during March 2008 to August 2009, and 27 of these isolates (from 21 patients) were typed as methicillin- and linezolid-resistant Staphylococcus epidermidis. Thirteen of these 21 patients (62%) had received linezolid during the 3 months preceding S. epidermidis recovery. Two closely related pulsotypes (P1a and P1b) were identified among the 27 studied isolates that belonged to the sequence type ST2 and harboured the mecA gene and the SCCmecIII type. The strains recovered from patients 1-4 (pulsotype P1a) showed the nucleotide mutation G2474T inside the amplified fragment of the 23S rRNA region and carried the aac(6')-Ie-aph(2″)-Ia, ant(4'), and catA genes, whereas the strains from patients 5-21 (pulsotype P1b) showed the mutation G2603T and carried the aac(6')-Ie-aph(2″)-Ia gene. None of the strains amplified the cfr gene. The ica gene and the IS256 element were detected in all strains. The emergence of 2 closely related methicillin- and linezolid-resistant S. epidermidis strains with 2 different mutations in the 23S rRNA region (G2474T and G2603T) is reported in this study as a cause of a nosocomial outbreak. The presence of G2474T or G2603T point mutations suggests that there are multiple potential sites within domain V of the 23S rRNA region at which mutations could confer resistance to linezolid in the clinical isolates. To our knowledge, this is the first report in which the G2474T mutation has been detected in domain V of the 23S rRNA gene of clinical S. epidermidis.

Community-acquired respiratory coinfection in critically ill patients with pandemic 2009 influenza A(H1N1) virus.

BACKGROUND: Little is known about the impact of community-acquired respiratory coinfection in patients with pandemic 2009 influenza A(H1N1) virus infection. METHODS: This was a prospective, observational, multicenter study conducted in 148 Spanish ICUs. RESULTS: Severe respiratory syndrome was present in 645 ICU patients. Coinfection occurred in 113 (17.5%) of patients. Streptococcus pneumoniae (in 62 patients [54.8%]) was identified as the most prevalent bacteria. Patients with coinfection at ICU admission were older (47.5±15.7 vs 43.8±14.2 years, P<.05) and presented a higher APACHE (Acute Physiology and Chronic Health Evaluation) II score (16.1±7.3 vs 13.3±7.1, P<.05) and Sequential Organ Failure Assessment (SOFA) score (7.0±3.8 vs 5.2±3.5, P<.05). No differences in comorbidities were observed. Patients who had coinfection required vasopressors (63.7% vs 39.3%, P<.05) and invasive mechanical ventilation (69% vs 58.5%, P<.05) more frequently. ICU length of stay was 3 days longer in patients who had coinfection than in patients who did not (11 [interquartile range, 5-23] vs 8 [interquartile range 4-17], P=.01). Coinfection was associated with increased ICU mortality (26.2% vs 15.5%; OR, 1.94; 95% CI, 1.21-3.09), but Cox regression analysis adjusted by potential confounders did not confirm a significant association between coinfection and ICU mortality. CONCLUSIONS: During the 2009 pandemics, the role played by bacterial coinfection in bringing patients to the ICU was not clear, S pneumoniae being the most common pathogen. This work provides clear evidence that bacterial coinfection is a contributor to increased consumption of health resources by critical patients infected with the virus and is the virus that causes critical illness in the vast majority of cases.

Prognostic value of IL-6 in localized prostatic cancer.

AIM: The usefulness of interleukin 6 (IL-6) and its soluble receptor IL-6sR in the prediction of the biochemical recurrence was evaluated in patients with prostate cancer treated with radical prostatectomy. PATIENTS AND METHODS: IL-6 and sIL-6R serum levels were measured in 96 patients with prostate cancer. RESULTS: Using the log-rank test, it was evident that patients with preoperative serum levels of IL-6 higher than 1.2 pg/ml had a significantly increased probability of biochemical recurrence (p=0.031). We also observed that the Gleason score was associated with the risk of progression (p=0.033), but no relation was observed with TNM classification, PSA, % free PSA or sIL-6R. In a multivariate analysis, only IL-6 serum levels remained as a predictor of biochemical recurrence (p=0.040). CONCLUSION: The results presented here demonstrated the usefulness of IL-6 in predicting the biochemical progression of prostate cancer, pointing towards an association between inflammation and the aggressiveness of the tumor.

[Sexuality during menopause. Educational guide]. / Sexualidad en la menopausia.

Sexuality constitutes a vital, powerful energy which pushes us to search for contact and companionship, which leads us to communicate and relate in a forum of pleasure and affectivity. This is all considered to be a natural process, deemed necessary for adequate personal development, besides being very healthy.

[Cardiovascular diseases]. / Enfermedad cardiovascular (ECV).

The authors of this article analyze the relationship between menopause and cardiovascular diseases, specifying the healthiest recommendations in terms of living habits and specifically recommendations with regards to diet.

Thrombospondin-1 mRNA expression in experimental kidney transplantation with heart-beating and non-heart-beating donors.

BACKGROUND: Ischemia-reperfusion (IR) is a risk factor for delayed graft function, a clinical syndrome more frequently observed in non-heart-beating donors (NHBDs). Previous studies have reported that transforming growth factor-beta1 (TGF-beta1) and hypoxia-inducible factor-1alpha (HIF-1alpha) gene expression increase in the first few days after kidney transplant and that this increase in TGF-beta1 expression is lower in NHBD animals. The purpose of this study was to extend the gene profile analysis by characterizing TGF-beta1 activator thrombospondin-1 (TSP-1) and genes related to HIF-1alpha such as heme oxygenase-1 (HO-1), nitric oxide synthase-2 (NOS-2) and NOS-3. METHODS: The experimental pig model of kidney transplantation comprised heart-beating donors (HBDs, n=9) and NHBDs (n=22). Cortical biopsies were collected after anesthetic induction (baseline), after warm ischemia (WI), after cold ischemia (CI), after 1 hour of reperfusion (1R) and 5 days (5D) after transplant. TSP-1, HO-1, NOS-2 and NOS-3 mRNA expression was determined by real-time PCR. RESULTS: No change in expression of any of the genes analyzed was found during the transplant procedure (WI, CI, 1R) in HBD and NHBD cortical samples. TSP-1 mRNA was significantly increased at 5D in NHBD animals but unchanged in the HBD group. HO-1 was up-regulated in HBD (p<0.05) and NOS-2 mRNA was significantly increased in both groups (p<0.05). No difference in NOS-3 expression was observed at 5D. CONCLUSIONS: The increased TSP-1 expression in NHBDs may indicate a compensatory response to the reported diminished TGF-beta1 expression. The augmented NOS-2 and HO-1 expression in HBDs could have a positive effect on the recovery of kidney function.

[Menopause and physical activity]. / Menopausia y actividad física.

Menopause is another stage in a woman's life. For this reason, none of us should live it as a disease, since it is not. This stage brings with it a series of physical and emotional changes which, if one does not bear these in mind, can lead to alterations in one's daily lifestyle. Among these possible alterations is the loss of bone mass and, in order to prevent this, it is essential to perform physical exercise. This article deals with the importance of physical exercise and correct posture as factors to maintain bone structure in its best possible condition in women undergoing menopause.

Usefulness of proprostate-specific antigen in the diagnosis of prostate cancer.

BACKGROUND: Free prostate-specific antigen (fPSA), the minor form of total PSA, contains different molecular subforms, including BPSA and proPSA. Whereas BPSA is associated with benign prostate hyperplasia, proPSA is associated with prostate tumor. PATIENTS AND METHODS: The serum levels of PSA, fPSA and proPSA were measured using automated electrochemiluminescent immunoassays (Elecsys 2010, Roche Diagnostics) in 87 patients with prostate cancer and 138 patients with benign prostate hyperplasia. Also, we calculated the derived tests of these assays through the subtraction or the ratio between the measured tests. RESULTS: Receiver operating characteristics curves were used for comparison of the diagnostic utility of tests assessed. The biggest areas were obtained for the free/total PSA ratio (0.705), the calculated Bfree PSA/total PSA ratio (0.719) and the calculated Bfree PSA/bound PSA ratio (0. 726). CONCLUSION: Applying a multivariate logistic regression analysis, it was determined that the combination of the proPSA concentration, the proPSA/total PSA ratio and the calculated Bfreeltotal PSA ratio improves the area under the curve obtained for individual tests (0.753). ProPSA may be useful in the diagnosis of prostate cancer.

[Specific self-care treatments for menopause symptoms]. / Autocuidados específicos en los síntomas de la menopausia.

In order to have good health, education is the key factor. To instill in the general population the importance of adopting healthy habits in each of the different stages of life constitutes educators' key to success.

Empiric broad-spectrum antibiotic therapy of nosocomial pneumonia in the intensive care unit: a prospective observational study.

INTRODUCTION: Antibiotic de-escalation, which consists of the initial institution of empiric broad-spectrum antibiotics followed by antibiotic streamlining driven by microbiological documentation, is thought to provide maximum benefit for the individual patient, while reducing the selection pressure for resistance. METHODS: To assess a carbapenem-based de-escalating strategy in nosocomial pneumonia (NP), a prospective observational study was conducted in critically ill patients with NP treated empirically with imipenem +/- aminoglycoside/glycopeptide in 24 intensive care units of Spanish general hospitals. Overall, 244 patients were assessable (91% with late-onset NP). The primary outcome was therapeutic success 7-9 days post therapy. RESULTS: Microbial identification--based on cultures of tracheal aspirates in 82% of patients, cultures of protected specimen brush in 33%, and cultures of bronchoalveolar lavage in 4%--was only available for 131 (54%) patients. Initial antibiotics were inadequate for 23 (9%) patients. Of the remaining patients, antibiotics were streamlined in 56 (23%) patients and remained unchanged in 14 (6%) patients based on microbiology data, in 38 (16%) patients despite microbiology data favouring de-escalation, and in 113 (46%) patients due to unknown aetiology. Overall, de-escalation was implemented in only 23% of patients with potentially multiresistant pathogens, compared with 68% of patients with the remaining pathogens (P < 0.001). Response rates were 53% for patients continuously treated with imipenem-based regimens and 50% for the de-escalated patients. Higher Acute Physiology, Age, and Chronic Health Evaluation II scores were associated with greater mortality, whereas adequate empiric antibiotic therapy protected against fatal outcomes. No increase of superinfection rates caused by emerging pathogens was observed. The costs associated with de-escalation were mainly dependent on the duration of hospitalization. CONCLUSION: This study mainly highlights the current practice of a specific algorithm of de-escalation solely based on the available microbiological data, and highlights the barriers to using it more widely. In this setting, de-escalation was less likely to occur in the presence of potentially multiresistant pathogens. Prior antibiotic administration and the low use of bronchoscopic techniques may have influenced negatively the implementation of de-escalation. Optimization of de-escalation strategies for NP should rely on a correct choice of empiric antibiotics, on appropriate microbiological investigations, and on a balanced interpretation of microbiological and clinical data.