La violencia como problema de salud / Violence as a health problem

La violencia es un problema de salud pública. Esta, cuando afecta a la infancia, puede generar enfermedad a lo largo de toda la vida del individuo. Aparte de poder producir daños en la esfera física, psíquica y social, supone una vulneración de los derechos de los niños afectados y un elevado consumo de recursos tanto económicos como sociales.Multitud de investigaciones han mejorado la atención a esta violencia. Sin embargo, estos avances no son parejos con el manejo práctico que se realiza a las víctimas tanto en la atención primaria como en la hospitalaria. Existe una significativa área de mejora para la atención pediátrica.A través de este artículo, distintos profesionales de todas las áreas sanitarias pediátricas establecidas desarrollan líneas generales de conocimiento y actuación con respecto a la violencia contra la infancia. Se hace un recorrido a través de la legislación relacionada con la infancia, las distintas tipologías de maltrato que existen, sus efectos, manejo y prevención. Concluye con un epílogo, a través del cual pretendemos mover sensibilidades.En resumen, este es un trabajo que pretende fomentar la formación y sensibilización de todos los profesionales especializados en la salud infantil, para que persigan como objetivo el que sus pacientes alcancen su mayor potencial en la vida y, de esa manera, ayudar a crear una sociedad más sana, con menos enfermedad y más justa.(AU)

Violence is a public health problem, and when it affects childhood, it can cause illness throughout the individual's life. Apart from being able to cause damage in the physical, mental and social spheres, it represents a violation of the rights of the affected children, and a high consumption of resources, both economic and social.A multitude of investigations have improved attention to this violence. However, these advances are not consistent with the practical management of victims, both in Primary and Hospital Care. There is a significant area of improvement for paediatric care.Through this article, different professionals from all established paediatric health care facilities develop general lines of knowledge and action regarding violence against children. An overview is taken of the legislation related to childhood, the different types of abuse that exist, their effects, management and prevention. It concludes with an epilogue, through which we aim to move sensibilities.In summary, this work aims to promote the training and awareness of all professionals specialized in children's health, so that they pursue the goal of achieving their patients’ greatest potential in life, and in this way, to help create a healthier society, with less disease, and more justice.(AU)

Violence as a Health Problem.

Violence is a public health problem, and when it affects childhood, it can cause illness throughout the individual's life. Apart from being able to cause damage in the physical, mental and social spheres, it represents a violation of the rights of the affected children, and a high consumption of resources, both economic and social. A multitude of investigations have improved attention to this violence. However, these advances are not consistent with the practical management of victims, both in Primary and Hospital Care. There is a significant area of improvement for paediatric care. Through this article, different professionals from all established paediatric health care facilities develop general lines of knowledge and action regarding violence against children. An overview is taken of the legislation related to childhood, the different types of abuse that exist, their effects, management and prevention. It concludes with an epilogue, through which we aim to move sensibilities. In summary, this work aims to promote the training and awareness of all professionals specialized in children's health, so that they pursue the goal of achieving their patients' greatest potential in life, and in this way, to help create a healthier society, with less disease, and more justice.

Clinical Profile and Prognosis of Patients with Left-Sided Infective Endocarditis with Surgical Indication Who Are Not Operated.

Approximately a quarter of patients with infective endocarditis (IE) who have surgical indication only receive antibiotic treatment. Their short-term prognosis is dismal. We aimed to describe the characteristics of this group of patients to evaluate the mortality according to the cause of rejection and type of surgical indication and to analyze their prognostic factors of mortality. From 2005 to 2022, 1105 patients with definite left-sided IE were consecutively attended in three tertiary hospitals. Of them, 912 (82.5%) had formal surgical indication according to the most recent European Guidelines available in each period of the study and 303 (33%) only received medical treatment. These were older, had more comorbidities and higher in-hospital (46% vs. 24%; p < 0.001) and one year mortality (57.1% vs. 27.6%; p < 0.001) than operated patients. The main reason for surgical rejection was high surgical risk (57.1%) and the highest mortality when the cause were severe neurological conditions (76%). When the endocarditis team took the decision not to operate (25.5% of the patients), in-hospital (7%) and one-year mortality (17%) were low. In-hospital mortality associated with each surgical indication was 67% in heart failure, 53% in uncontrolled infection and 45% in prevention of embolisms (p < 0.001). Heart failure (OR: 2.26 CI95%: 1.29-3.96; p = 0.005), Staphylococcus aureus (OR: 3.17; CI95%: 1.72-5.86; p < 0.001) and persistent infection (OR: 5.07 CI95%: 2.85-9.03) are the independent risk factors of in-hospital mortality. One third of the patients with left-sided IE and formal surgical indication are rejected for surgery. In-hospital mortality is very high, especially when heart failure is the indication for surgery and when severe neurological conditions the reason for rejection. Short term prognosis of patients rejected by a specialized endocarditis team is favorable.

Decrease in Mortality after the Implementation of a Hospital Model to Improve Performance in Sepsis Care: Princess Sepsis Code.

Sepsis is a time-dependent disease whose prognosis is influenced by early diagnosis and therapeutic measures. Mortality from sepsis remains high, and for this reason, the guidelines of the Surviving Sepsis Campaign recommend establishing specific care programs aimed at patients with sepsis. We present the results of the application of a hospital model to improve performance in sepsis care, called Princess Sepsis Code, with the aim of reducing mortality. A retrospective study was conducted using clinical, epidemiological, and outcome variables in patients diagnosed with sepsis from 2015 to 2022. A total of 2676 patients were included, 32% of whom required admission to the intensive care unit, with the most frequent focus of the sepsis being abdominal. Mortality in 2015, at the beginning of the sepsis code program, was 24%, with a declining rate noted over the study period, with mortality reaching 17% in 2022. In the multivariate analysis, age > 70 years, respiratory rate > 22 rpm, deterioration in the level of consciousness, serum lactate > 2 mmol/L, creatinine > 1.6 mg/dL, and the focus of the sepsis were identified as variables independently related to mortality. The implementation of the Princess Sepsis Code care model reduces the mortality of patients exhibiting sepsis and septic shock.

Occurrence of SARS-CoV-2 viremia is associated with genetic variants of genes related to COVID-19 pathogenesis.

Introduction: SARS-CoV-2 viral load has been related to COVID-19 severity. The main aim of this study was to evaluate the relationship between SARS-CoV-2 viremia and SNPs in genes previously studied by our group as predictors of COVID-19 severity. Materials and methods: Retrospective observational study including 340 patients hospitalized for COVID-19 in the University Hospital La Princesa between March 2020 and December 2021, with at least one viremia determination. Positive viremia was considered when viral load was above the quantifiable threshold (20 copies/ml). A total of 38 SNPs were genotyped. To study their association with viremia a multivariate logistic regression was performed. Results: The mean age of the studied population was 64.5 years (SD 16.6), 60.9% patients were male and 79.4% white non-Hispanic. Only 126 patients (37.1%) had at least one positive viremia. After adjustment by confounders, the presence of the minor alleles of rs2071746 (HMOX1; T/T genotype OR 9.9 p < 0.0001), rs78958998 (probably associated with SERPING1 expression; A/T genotype OR 2.3, p = 0.04 and T/T genotype OR 12.9, p < 0.0001), and rs713400 (eQTL for TMPRSS2; C/T + T/T genotype OR 1.86, p = 0.10) were associated with higher risk of viremia, whereas the minor alleles of rs11052877 (CD69; A/G genotype OR 0.5, p = 0.04 and G/G genotype OR 0.3, p = 0.01), rs2660 (OAS1; A/G genotype OR 0.6, p = 0.08), rs896 (VIPR1; T/T genotype OR 0.4, p = 0.02) and rs33980500 (TRAF3IP2; C/T + T/T genotype OR 0.3, p = 0.01) were associated with lower risk of viremia. Conclusion: Genetic variants in HMOX1 (rs2071746), SERPING1 (rs78958998), TMPRSS2 (rs713400), CD69 (rs11052877), TRAF3IP2 (rs33980500), OAS1 (rs2660) and VIPR1 (rs896) could explain heterogeneity in SARS-CoV-2 viremia in our population.

Contaminants of emerging concern in the urban aquifers of Barcelona: Do they hamper the use of groundwater?

Urban aquifers are an alternative to obtain freshwater, but they are frequently polluted by contaminants of emerging concern (CECs). Therefore, there is a need to ascertain whether CECs are a water management challenge as they might limit the use of groundwater as safe drinking water even at ng L-1 concentration levels. To answer this question, it is required to evaluate human health-risk effects of measured CECs in the groundwater and to understand their behaviour at a field-scale. This study compiles data about the presence of CECs in the aquifers of Barcelona and its metropolitan area, evaluates health risk effects of measured CECs in the groundwater and presents approaches implemented to identify and quantify the coupled hydro-thermo-chemical processes that govern their fate in the subsurface. Some CECs might be harmful to humans, such as 5-methyl-1H-benzotriazole and the pharmaceuticals azithromycin valsartan, valsartan acid, lamotrigine, gabapentin, venlafaxine and lidocaine, which show very high to intermediate health risk effects. The number of harmful CECs and the level of their hazard increase from the groups of adults and 14-18 years old teens to the groups of 4-8 years old and 1-2 years old children. Thus, some CECs can limit the use of groundwater in Barcelona as potential drinking water source. Finally, knowledge gaps in understanding the integration of these processes into urban water resources management plans are identified, which will help to define groundwater potential uses and to assure the adequate protection of the human health and the environment.

Parp Inhibitors and Radiotherapy: A New Combination for Prostate Cancer (Systematic Review).

PARPi, in combination with ionizing radiation, has demonstrated the ability to enhance cellular radiosensitivity in different tumors. The rationale is that the exposure to radiation leads to both physical and biochemical damage to DNA, prompting cells to initiate three primary mechanisms for DNA repair. Two double-stranded DNA breaks (DSB) repair pathways: (1) non-homologous end-joining (NHEJ) and (2) homologous recombination (HR); and (3) a single-stranded DNA break (SSB) repair pathway (base excision repair, BER). In this scenario, PARPi can serve as radiosensitizers by leveraging the BER pathway. This mechanism heightens the likelihood of replication forks collapsing, consequently leading to the formation of persistent DSBs. Together, the combination of PARPi and radiotherapy is a potent oncological strategy. This combination has proven its efficacy in different tumors. However, in prostate cancer, there are only preclinical studies to support it and, recently, an ongoing clinical trial. The objective of this paper is to perform a review of the current evidence regarding the use of PARPi and radiotherapy (RT) in PCa and to give future insight on this topic.

Nanoemulsion Increases the Antifungal Activity of Amphotericin B against Four Candida auris Clades: In Vitro and In Vivo Assays.

Candida auris is an emerging yeast of worldwide interest due to its antifungal resistance and mortality rates. The aim of this study was to analyse the in vitro and in vivo antifungal activity of a nanoemulsion loaded with amphotericin B (NEA) against planktonic cells and biofilm of C. auris clinical isolates belonging to four different clades. In vivo assays were performed using the Galleria mellonella model to analyse antifungal activity and histopathological changes. The in vitro results showed that NEA exhibited better antifungal activity than free amphotericin B (AmB) in both planktonic and sessile cells, with >31% inhibition of mature biofilm. In the in vivo assays, NEA demonstrated superior antifungal activity in both haemolymph and tissue. NEA reduced the fungal load in the haemolymph more rapidly and with more activity in the first 24 h after infection. The histological analysis of infected larvae revealed clusters of yeast, immune cells, melanisation, and granulomas. In conclusion, NEA significantly improved the in vitro and in vivo antifungal activity of AmB and could be considered a promising therapy for C. auris infections.

The three-noes right-sided infective endocarditis: An unrecognized type of right-sided endocarditis.

The "3 noes right-sided infective endocarditis" (3no-RSIE: no left-sided, no drug users, no cardiac devices) was first described more than a decade ago. We describe the largest series to date to characterize its clinical, microbiological, echocardiographic and prognostic profile. Eight tertiary centers with surgical facilities participated in the study. Patients with right-sided endocarditis without left sided involvement, absence of drug use history and no intracardiac electronic devices were retrospectively included in a multipurpose database. A total of 53 variables were analyzed in every patient. We performed a univariate analysis of in-hospital mortality to determine variables associated with worse prognosis. the study was comprised of 100 patients (mean age 54.1 ± 20 years, 65% male) with definite 3no-RSIE were included (selected from a total of 598 patients with RSIE of all the series, which entails a 16.7% of 3no-RSIE). Most of the episodes were community-acquired (72%), congenital cardiopathies were frequent (32% of the group of patients with previous known predisposing heart disease) and fever was the main manifestation at admission (85%). The microbiological profile was led by Staphylococci spp (52%). Vegetations were detected in 94% of the patients. Global in-hospital mortality was 19% (5.7% in patients operated and 26% in patients who received only medical treatment, P < .001). Non-community acquired infection, diabetes mellitus, right heart failure, septic shock and acute renal failure were more common in patients who died. the clinical profile of 3no-RSIE is closer to other types of RSIE than to LSIE, but mortality is higher than that reported on for other types of RSIE. Surgery may play an important role in improving outcome.

Impact of transfer to reference centres and surgical timing on the prognosis of surgically treated patients with infective endocarditis: a prospective multi-centre cohort study.

OBJECTIVES: To compare outcomes in patients with infective endocarditis (IE) first treated in secondary hospitals and then transferred to reference centres for surgery with those in patients diagnosed in reference centres, and to evaluate the impact of surgery timing on prognosis. METHODS: Analysis of a prospective cohort of patients with active IE admitted to three reference centres between 1996 and 2022 who underwent cardiac surgery in the first month after diagnosis. Multi-variable analysis was performed to evaluate the impact of transfer to reference centres and time to surgery on 30-day mortality. Adjusted ORs with 95% CIs were calculated. RESULTS: Amongst 703 patients operated on for IE, 385 (54.8%) were referred cases. All-cause 30-day mortality did not differ significantly between referred patients and those diagnosed at reference centres (102/385 [26.5%] vs. 78/385 [24.5%], respectively; p 0.552). Variables independently associated with 30-day mortality in the whole cohort were diabetes (OR, 1.76 [95% CI, 1.15-2.69]), chronic kidney disease (OR, 1.83 [95% CI, 1.08-3.10]), Staphylococcus aureus (OR, 1.88 [95% CI, 1.18-2.98]), septic shock (OR, 2.76 [95% CI, 1.67-4.57]), heart failure (OR, 1.41 [95% CI, 0.85-2.11]), acute renal failure before surgery (OR, 1.76 [95% CI, 1.15-2.69]), and the interaction between transfer to reference centres and surgery timing (OR, 1.18 [95% CI, 1.03-1.35]). Amidst referred patients, time from diagnosis to surgery longer than a week was independently associated with 30-day mortality (OR, 2.19 [95% CI, 1.30-3.69]; p 0.003). CONCLUSION: Among referred patients, surgery performed >7 days after diagnosis was associated with two-fold higher 30-day mortality.

Cisplatin-induced cell death increases the degradation of the MRE11-RAD50-NBS1 complex through the autophagy/lysosomal pathway.

Cisplatin and other platinum-based anticancer agents are among the most widely used chemotherapy drugs in the treatment of different types of cancer. However, it is common to find patients who respond well to treatment at first but later relapse due to the appearance of resistance to cisplatin. Among the mechanisms responsible for this phenomenon is the increase in DNA damage repair. Here, we elucidate the effect of cisplatin on the MRN (MRE11-RAD50-NBS1) DNA damage sensor complex. We found that the tumor suppressor FBXW7 is a key factor in controlling the turnover of the MRN complex by inducing its degradation through lysosomes. Inhibition of lysosomal enzymes allowed the detection of the association of FBXW7-dependent ubiquitylated MRN with LC3 and the autophagy adaptor p62/SQSTM1 and the localization of MRN in lysosomes. Furthermore, cisplatin-induced cell death increased MRN degradation, suggesting that this complex is one of the targets that favor cell death. These findings open the possibility of using the induction of the degradation of the MRN complex after genotoxic damage as a potential therapeutic strategy to eliminate tumor cells.

PARP Inhibitors: A New Horizon for Patients with Prostate Cancer.

The introduction of PARP inhibitors (PARPi) in prostate cancer is a milestone and provides a pathway to hope in fighting this disease. It is the first time that drugs, based on the concept of synthetic lethality, have been approved for prostate cancer. In addition, it is also the first time that genetic mutation tests have been included in the therapeutic algorithm of this disease, representing a significant step forward for precision and personalized treatment of prostate cancer. The objectives of this review are: (1) understanding the mechanism of action of PARPi in monotherapy and combinations; (2) gaining insights on patient selection for PARPi; (3) exposing the pivotal studies that have allowed its approval, and; (4) offering an overview of the ongoing trials. Nevertheless, many unsolved questions remain, such as the number of patients who could potentially benefit from PARPi, whether to use PARPi in monotherapy or in combination, and when is the best time to use them in advanced or localized disease. To answer these and other questions, many clinical trials are underway. Some of them have recently demonstrated promising results that may favor the introduction of new combinations in metastatic castration-resistant prostate cancer.

Contemporary comparison of infective endocarditis caused by Candida albicans and Candida parapsilosis: a cohort study.

Among 1655 consecutive patients with infective endocarditis treated from 1998 to 2020 in three tertiary care centres, 16 were caused by Candida albicans (CAIE, n = 8) and Candida parapsilosis (CPIE, n = 8). Compared to CAIE, CPIE were more frequently community-acquired. Prosthetic valve involvement was remarkably more common among patients with CPIE. CPIE cases presented a higher rate of positive blood cultures at admission, persistently positive blood cultures after antifungals initiation and positive valve cultures. All patients but four underwent cardiac surgery. Urgent surgery was more frequently performed in CPIE. No differences regarding in-hospital mortality were documented, even after adjusting for therapeutic management.

Accuracy, feasibility and predictive ability of different frailty instruments in an acute geriatric setting.

PURPOSE: To analyze the feasibility, accuracy and the ability of different frailty instruments to predict adverse outcomes. METHODS: A prospective cohort study was conducted in patients ≥ 70 years admitted to the acute care setting (ACS). Feasibility and prevalence of frailty were assessed by FRAIL, Clinical Frailty Scale (CFS), hand grip strength (HGS) and the Spanish Frailty-VIG. Receiver operator characteristic (ROC) curves and area under the curve (AUC) were performed to identify frailty according to each instrument, setting VIG as the reference. For each instrument, multiple logistic regressions were used to examine the effect of frailty on primary outcome (i.e., three-month mortality) and secondary outcomes (i.e., in-hospital mortality, length of stay, institutionalization, functional decline and 30-day readmission). RESULTS: A total of 185 patients were included, with a median age of 89 years. The feasibility of the instruments was 100%, except for HGS (67%). The prevalence of frailty varied from 65.2% (FRAIL) to 86.7% (VIG). AUCs against VIG ranged from 0.69 (95% confidence interval [CI] 0.57-0.81: FRAIL) to 0.77 (95% CI 63.5-90.2: CFS). Frail patients defined by FRAIL were 2.7times more likely to have a prolonged length of stay than non-frail patients (95% CI 1.385-5.416). Three-month mortality occurred more among frail patients, either defined by FRAIL (OR 2.5; 95% CI 1.072-5.881) or CFS (OR 3.7; 95% CI 1.255-10.812), than in non-frail patients. CONCLUSION: The four instruments had high feasibility providing variable prevalence of frailty. FRAIL and CFS predicted well for three-month mortality, and FRAIL also for length of stay. However, none of the instruments predicted for the other secondary outcomes of the study.

Reassessment of Vegetation Size as a Sole Indication for Surgery in Left-Sided Infective Endocarditis.

BACKGROUND: Guidelines recommend surgery for left-sided infective endocarditis (LSIE) that is associated with large vegetations. Given that most patients who undergo surgery also have other indications (heart failure and/or uncontrolled infection), it is not settled whether surgery should be routinely recommended in patients with large vegetations but no other predictors of poor outcome. METHODS: A total of 726 patients with definitive LSIE were included in our analysis. The mean age was 64.9 years, and 61% were male. Multivariate analysis of all patients was performed to determine whether vegetation size is related to death in LSIE. Then patients were divided into two groups according to vegetation size: group A (>10 mm, n = 420) and group B (≤10 mm, n = 306). Univariate and multivariate analyses of group A patients were carried out to identify the variables related to death in this group. The impact of surgery on mortality in group A patients without heart failure or uncontrolled local infection (n = 139) was assessed. RESULTS: Age, Staphylococcus aureus, perivalvular complications, heart failure, kidney failure, and septic shock, but not vegetation size, were associated with death. Patients with large vegetations showed increased mortality (31.7% in group A vs 24.8% in group B; P = .045). Group A had more valve rupture and valve regurgitation than group B, but heart failure (55% vs 53%; P = .678), stroke (22% vs 17.0%, P = .091), systemic embolism (39% vs 32%; P = .074), perivalvular complication (28% vs 28%; P = .865), and septic shock (15% vs 13%; P = .288) were similar in both groups. In patients from group A without heart failure or uncontrolled infection, mortality was similar with and without surgery (n = 139; n = 70 with surgery and n = 69 without surgery; mortality, 18.6% vs 11.6%, respectively; P = .251). CONCLUSIONS: Large vegetations identify patients with poor outcomes in the context of LSIE. However, surgery is not associated with a better prognosis in patients with large vegetations if they do not present with another predictor of poor outcome such as heart failure or uncontrolled infection. These findings challenge whether vegetation size alone should be an indication for surgery in LSIE.

Health Risk Assessment of Exposure to 15 Essential and Toxic Elements in Spanish Women of Reproductive Age: A Case Study.

This case study investigates the exposure of 119 Spanish women of reproductive age to 5 essential (Co, Cu, Mn, V, Zn) and 10 toxic (Ba, Be, Cs, Ni, Pb, Pt, Sb, Th, Al, U) elements and assesses their risk. The essential elements (Co, Cu, Mn, V, and Zn) showed average concentrations (GM: geometric mean) of 0.8, 35, 0.5, 0.2, and 347 µg/L, respectively. Five of the toxic elements (Ba, Cs, Ni, Al, U) exhibited detection frequencies of 100%. The GM concentrations of the novel toxic elements were 12 µg/L (Al), 0.01 µg/L (Pt), 0.02 µg/L (U), 0.12 µg/L (Th), 0.009 µg/L (Be) and 4 µg/L (Cs). The urine analysis was combined with a survey to assess any variations between subgroups and potential predictors of exposure to elements in the female population. Significant differences were obtained between the rural and urban areas studied for the toxic element Cs, with higher levels found in mothers living in urban areas. In relation to diet, statistically significantly higher levels of essential (Cu) and toxic (Ba) elements were detected in women with a high consumption of fish, while mothers who consumed a large quantity of legumes presented higher levels of the toxic element Ni (p = 0.0134). In a risk-assessment context, hazard quotients (HQs) greater than 1 were only observed for the essential elements Zn and Cu in P95. No deficiency was found regarding the only essential element for which a biomonitoring equivalent for nutritional deficit is available (Zn). For the less-studied toxic elements (Al, Pt, U, Th, Be, and Cs), HQs were lower than 1, and thus, the health risk due to exposure to these elements is expected to be low for the female population under study.

Prognostic impact of cardiac surgery in left-sided infective endocarditis according to risk profile.

OBJECTIVE: To evaluate the prognostic impact of urgent cardiac surgery on the prognosis of left-sided infective endocarditis (LSIE) and its relationship to the basal risk of the patient and to the surgical indication. METHODS: 605 patients with LSIE and formal surgical indication were consecutively recruited between 2000 and 2020 among three tertiary centres: 405 underwent surgery during the active phase of the disease and 200 did not despite having indication. The prognostic impact of urgent surgery was evaluated by multivariable analysis and propensity score analysis. We studied the benefit of surgery according to baseline mortality risk defined by the ENDOVAL score and according to surgical indication. RESULTS: Surgery is an independent predictor of survival in LSIE with surgical indication both by multivariable analysis (OR 0.260, 95% CI 0.162 to 0.416) and propensity score (mortality 40% vs 66%, p<0.001). Its greatest prognostic benefit is seen in patients at highest risk (predicted mortality 80%-100%: OR 0.08, 95% CI 0.021 to 0.299). The benefit of surgery is especially remarkable for uncontrolled infection indication (OR 0.385, 95% CI 0.194 to 0.765), even in combination with heart failure (OR 0.220, 95% CI 0.077 to 0.632). CONCLUSIONS: Surgery during active LSIE seems to significantly reduce in-hospital mortality. The higher the risk, the higher the improvement in outcome.

Infective endocarditis in patients with aortic grafts.

BACKGROUND: Infective endocarditis (IE) in patients with a valve-tube ascending aortic graft (AAG) is a rare entity with a challenging diagnosis and treatment. This study describes the clinical features, diagnosis and outcome of these patients. METHODS: Between 1996 and 2019, 1654 episodes of IE were recruited in 3 centres, of which 37 patients (2.2%) had prosthetic aortic valve and AAG-IE (21 composite valve graft, 16 supracoronary graft) and conformed our study group. RESULTS: Patients with aortic grafts were predominantly male (91.9%) and the mean age was 67.7 years. Staphylococci were the most frequently isolated microorganisms (32%). Viridans group streptococci were only isolated in patients with composite valve graft. TEE was positive in 89.2%. PET/CT was positive in all 15 patients in whom it was performed. Surgical treatment was performed in 62.2% of patients. In-hospital mortality was 16.2%. Heart failure and the type of infected graft (supracoronary aortic graft) were associated with mortality. Mortality among operated patients was 21.7%. Interestingly, 14 patients received antibiotic therapy alone, and only one died. Mortality was lower among patients with a composite valve graft compared to those with a supracoronary graft (4.8% vs 31.3%; p = 0.03). CONCLUSIONS: In patients with AAG and prosthetic aortic valve IE, mortality is not higher than in other patients with prosthetic IE. Multimodality imaging plays an important role in the diagnosis and management of these patients. Heart failure and the type of surgery were risk factors associated with in-hospital mortality. Although surgical treatment is usually recommended, a conservative management might be a valid alternative treatment in selected patients.

Wnt/ß-Catenin Signaling Contributes to Paclitaxel Resistance in Bladder Cancer Cells with Cancer Stem Cell-Like Properties.

The Wnt/ß-catenin pathway plays an important role in tumor progression and chemotherapy resistance and seems to be essential for the maintenance of cancer stem cells (CSC) in several tumor types. However, the interplay of these factors has not been fully addressed in bladder cancer. Here, our goal was to analyze the role of the Wnt/ß-catenin pathway in paclitaxel resistance and to study the therapeutic efficacy of its inhibition in bladder cancer cells, as well as to determine its influence in the maintenance of the CSC-like phenotype in bladder cancer. Our results show that paclitaxel-resistant HT1197 cells have hyperactivation of the Wnt/ß-catenin pathway and increased CSC-like properties compared with paclitaxel-sensitive 5637 cells. Paclitaxel sensitivity diminishes in 5637 cells after ß-catenin overexpression or when they are grown as tumorspheres, enriched for the CSC-like phenotype. Additionally, downregulation of ß-catenin or inhibition with XAV939 sensitizes HT1197 cells to paclitaxel. Moreover, a subset of muscle-invasive bladder carcinomas shows aberrant expression of ß-catenin that associates with positive expression of the CSC marker ALDH1A1. In conclusion, we demonstrate that Wnt/ß-catenin signaling contributes to paclitaxel resistance in bladder cancer cells with CSC-like properties.