Assessment of risk-adjusted mortality ratio (RAMR) in bloodstream infections using all-patient refined diagnosis-related groups (APR-DRGs).

OBJECTIVES: To calculate a risk-adjusted mortality ratio (RAMR) for bloodstream infections (BSIs) using all-patient refined diagnosis-related groups (APR-DRGs) and compare it with the crude mortality rate (CMR). METHODS: Retrospective observational study of prevalent BSI at our institution from January 2019 to December 2022. In-hospital mortality was adjusted with a binary logistic regression model adjusting for sex, age, admission type and mortality risk for the hospitalization episode according to the four severity levels of APR DRGs. The RAMR was calculated as the ratio of observed to expected in-hospital mortality, and the CMR was calculated as the proportion of deaths among all bacteraemia episodes. RESULTS: Of 2939 BSIs, 2541 were included: Escherichia coli (n = 1310), Klebsiella pneumoniae (n = 428), Pseudomonas aeruginosa (n = 209), Staphylococcus aureus (n = 498) and candidaemia (n = 96). A total of 436 (17.2%) patients died during hospitalization and 279 died within the first 14 days after the onset of BSI. Throughout the period, all BSI cases had a mortality rate above the expected adjusted mortality (RAMR value greater than 1), except for Escherichia coli (1.03; 95% CI 0.86-1.21). The highest overall RAMR values were observed for P. aeruginosa, Candida and S. aureus with 2.06 (95% CI 1.57-2.62), 1.99 (95% CI 1.3-2.81) and 1.8 (95% CI 1.47-2.16), respectively. The temporal evolution of CMR may differ from RAMR, especially in E. coli, where it was reversed. CONCLUSIONS: RAMR showed higher than expected mortality for all BSIs studied except E. coli and provides complementary to and more clinically comprehensive information than CMR, the currently recommended antibiotic stewardship programme mortality indicator.

Bacteremia due to Leuconostoc species: A 13-year single-center case series / Bacteriemia por Leuconostoc spp: serie de casos en un hospital de tercer nivel a lo largo de 13 años

Introduction: Leuconostoc spp. are facultatively anaerobic Gram-positive cocci involved in cases of hospital-acquired bacteremia, mainly in immunocompromised hosts. The available data is scarce due to its uncommon presentation. Methods: We describe all the episodes of Leuconostoc spp. bacteremia in a third level hospital in a 13-year period (2008–2021). Results: Four cases of clinically relevant bacteremia were detected. All cases were categorized as catheter-related. The following risk factors were found: previous glycopeptide therapy (75%), use of parenteral nutrition (100%) and cancer (75%). All isolates showed susceptibility to beta-lactams. Catheter removal was performed and wide spectrum antimicrobials were administered, with clinical response in all cases except one. Discussion: Apart from cancer and glycopeptide exposure, disruption of skin barrier and gastrointestinal conditions were identified as risk factors, as it was concordantly underlined in other case series. Susceptibility to beta-lactams is usually maintained. Catheter removal and administration of an active antibacterial therapy seem to be the best approach for Leuconostoc spp. catheter-related bacteremia.(AU)

Introducción: Los microorganismos del género Leuconostoc son cocos grampositivos anaerobios facultativos, involucrados en casos de bacteriemia en pacientes hospitalizados, especialmente con factores de inmunosupresión. La literatura disponible es escasa por su baja frecuencia. Métodos: Describimos todos los episodios de bacteriemia por Leuconostoc spp. en un hospital de tercer nivel en un periodo de 13 años (2008-2021). Resultados: Se detectaron 4 aislamientos clínicamente significativos. Todos ellos fueron categorizados como bacteriemia relacionada con catéter. Se identificaron como factores de riesgo: la exposición previa a glucopéptidos (75%), nutrición parenteral (100%) y cáncer (75%). Todos los aislamientos presentaron sensibilidad a betalactámicos. Se procedió a retirada del catéter y se administraron antimicrobianos de amplio espectro con buena respuesta clínica, salvo en un caso. Discusión: Además del cáncer y la exposición a glucopéptidos, la disrupción de la barrera cutánea y las enfermedades gastrointestinales se identificaron como factores de riesgo, al igual que en otras series. La sensibilidad a betalactámicos suele mantenerse. La retirada del catéter y el uso de terapia antibiótica activa parece ser la mejor alternativa terapéutica para la bacteriemia relacionada con catéter por Leuconostoc spp.(AU)

Bacteremia due to Leuconostoc species: A 13-year single-center case series.

INTRODUCTION: Leuconostoc spp. are facultatively anaerobic Gram-positive cocci involved in cases of hospital-acquired bacteremia, mainly in immunocompromised hosts. The available data is scarce due to its uncommon presentation. METHODS: We describe all the episodes of Leuconostoc spp. bacteremia in a third level hospital in a 13-year period (2008-2021). RESULTS: Four cases of clinically relevant bacteremia were detected. All cases were categorized as catheter-related. The following risk factors were found: previous glycopeptide therapy (75%), use of parenteral nutrition (100%) and cancer (75%). All isolates showed susceptibility to beta-lactams. Catheter removal was performed and wide spectrum antimicrobials were administered, with clinical response in all cases except one. DISCUSSION: Apart from cancer and glycopeptide exposure, disruption of skin barrier and gastrointestinal conditions were identified as risk factors, as it was concordantly underlined in other case series. Susceptibility to beta-lactams is usually maintained. Catheter removal and administration of an active antibacterial therapy seem to be the best approach for Leuconostoc spp. catheter-related bacteremia.

Predictive value of fecal calprotectin and lactoferrin levels for negative outcomes in Clostridioides difficile infection.

PURPOSE: We investigated the role of fecal calprotectin (FC) and lactoferrin (FL) as predictive biomarkers in Clostridioides difficile infection (CDI). METHODS: We assembled a prospective cohort including all patients with a laboratory-confirmed CDI diagnosis between January and December 2017. FL and FC levels were measured at diagnosis by commercial ELISA and EIA kits. We investigated the diagnostic accuracy of FC and FL to predict CDI recurrence and severity (study outcomes) and explored optimal cut-off values in addition to those proposed by the manufacturers (200 µg/g and 7.2 µg/mL, respectively). RESULTS: We included 170 CDI cases (152 first episodes and 18 recurrences). The rates of recurrence (first episodes only) and severity (entire cohort) were 9.2% (14/152) and 46.5% (79/170). Both FL and FC levels were significantly higher in patients who developed study outcomes. Optimal cut-off values for FC and FL to predict CDI recurrence were 1052 µg/g and 6.0 µg/mL. The optimal cut-off value for FC yielded higher specificity (60.9%) and positive predictive value (PPV) (16.9%) than that proposed by the manufacturer. Regarding CDI severity, the optimal cut-off value for FC (439 µg/g) also provided higher specificity (43.9%) and PPV (54.1%) than that of the manufacturer, whereas the optimal cut-off value for FL (4.6 µg/mL) resulted in an improvement of PPV (57.5%). CONCLUSION: By modifying the thresholds for assay positivity, the measurement of FC and FL at diagnosis is useful to predict recurrence and severity in CDI. Adding these biomarkers to current clinical scores may help to individualize CDI management.

Bacteremia in Patients with Solid Organ Cancer: Insights into Epidemiology and Antibiotic Consumption.

Epidemiology and risk factors associated to bacterial resistance in solid organ cancer (SOC) patients has been barely described. This retrospective monocentric study analyzed clinical variables in SOC patients who developed bacteremia between 1 January 2019 and 31 December 2022. We described rates of bacterial resistance in Gram negative bacteria (80.6%): E. coli-ESBL, K. pneumoniae-ESBL, Carbapenem-Resistant K. pneumoniae and Meropenem-Resistant P. aeruginosa, as well as antibiotic consumption, and compared these rates between the medical and oncology wards. In total, we included 314 bacteremias from 253 patients. SOC patients are frequently prescribed antibiotics (40.8%), mainly fluoroquinolones. Nosocomial bacteremia accounted for 18.2% of the cases and only 14.3% of patients were neutropenic. Hepatobiliary tract was the most frequent tumor (31.5%) and source of bacteremia (38.5%). Resistant bacteria showed a decreased rate of resistance during the years studied in the oncology ward. Both K-ESBL and K-CBP resistance rates decreased (from 45.8% to 20.0%, and from 29.2% to 20.0%, respectively), as well as MRPA, which varied from a resistance rate of 28% to 16.7%. The presence of a urinary catheter (p < 0.001) and previous antibiotic prescription (p = 0.002) were risk factors for bacterial resistance. Identifying either of these risk factors could help in guiding antibiotic prescription for SOC patients.

The Use and Efficacy of Oral Phenylephrine Versus Placebo Treating Nasal Congestion Over the Years on Adults: A Systematic Review.

Nasal congestion is a common issue stemming from various factors such as allergies and anatomical variations. Allergic rhinitis frequently leads to nasal congestion. The pathophysiology involves inflammation, swelling, and mucus production in the nasal mucosa. Multiple treatments are available, including oral phenylephrine, an over-the-counter or prescription option. However, the effectiveness and safety of phenylephrine have been subjects of debate. This systematic review aims to provide an updated perspective on the efficacy of oral phenylephrine versus placebo in addressing nasal congestion in adults. We conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, a systematic review involving searches on PubMed, Cochrane, and Scopus databases. Inclusion/exclusion criteria were defined to identify high-quality studies. The focus was on randomized controlled trials (RCTs) and case-control studies published in English between 1998 and 2023, involving adult populations. The interventions compared oral phenylephrine with placebo or standard care, with outcomes centering on changes in nasal congestion symptoms and nasal airway resistance. We identified four articles that met the criteria. These studies exhibited varied designs and populations. The findings consistently indicated that phenylephrine was not more effective than a placebo in relieving nasal congestion. This systematic review demonstrates that oral phenylephrine did not offer substantial relief from nasal congestion compared to a placebo in adults. The studies featured diverse designs, yet the prevailing conclusion was that phenylephrine's efficacy was limited. Safety assessments showed no life-threatening adverse events, with common side effects including headaches and mild discomfort. In summary, this systematic review indicates that oral phenylephrine is not significantly more effective than a placebo in alleviating nasal congestion in adults. Clinicians should explore alternative treatment options, considering the review's limitations. Additional research may be needed to clarify the role of oral phenylephrine in managing nasal congestion.

PACTA-Ped: programa de optimización de antimicrobianos en un hospital de tercer nivel en España / PACTA-Ped: Antimicrobial stewardship programme in a tertiary care hospital in Spain

Introducción: La lucha contra la resistencia a los antimicrobianos es actualmente prioritaria; son necesarios esfuerzos para mejorar la prescripción y reducir la propagación de infecciones en el entorno pediátrico. Métodos: Estudio longitudinal prospectivo sobre el uso de antimicrobianos realizado desde el inicio del programa de optimización del uso de antimicrobianos (PROA) en enero de 2016 hasta diciembre de 2017 (período 2; P2) en el hospital infantil. Los resultados obtenidos se han comparado retrospectivamente con el periodo anterior al inicio del PROA (2014-2015, periodo 1; P1). La población estudiada fueron niños ingresados que recibieron antimicrobianos de amplio espectro, antifúngicos o tratamiento antibiótico intravenoso durante más de 5 días.Resultados: Durante el P2 se incluyeron un total de 160 pacientes. Los antibióticos más comunes para los que se realizó una recomendación fueron: meropenem (41,6%) y cefotaxima (23,4%). En el 45% de los episodios se recomendó «no cambiar» el antimicrobiano prescrito. La tasa de aceptación de las recomendaciones por parte de los facultativos responsables fue del 89%. Se objetivó una disminución promedio del 27,8 y del 22,9% en los días de tratamiento (DOT)/1.000 días de ingreso y el número de tratamientos iniciados/1.000 ingresos, respectivamente. El uso de carbapenémicos, cefalosporinas y glucopéptidos disminuyó del P1 al P2. El coste medio anual del tratamiento antimicrobiano pasó de 150.356€/año durante en el P1 a 98.478€/año en el P2. Conclusiones: Nuestro PROA conllevó una disminución significativa en el uso de antibióticos y antifúngicos de amplio espectro. Los costes asociados con la prescripción de antimicrobianos disminuyeron desde el inicio del PROA y resultó una acción coste-efectiva durante el período de estudio.(AU)

Introduction: Fighting against antimicrobial resistance is a current priority, and further efforts need to be made to improve antimicrobial prescribing and reduce the spread of infections in paediatric care settings. Methods: We conducted a prospective longitudinal study on the use of antimicrobials from the time the antimicrobial stewardship programme (ASP) was introduced in January 2016 to December 2017 (period 2 [P2]) in our children's hospital. We compared the obtained results on antimicrobial prescribing with retrospective data from the period preceding the introduction of the ASP (2014–2015, period 1 [P1]). The sample consisted of paediatric in patients who received broad-spectrum antimicrobials, antifungals or intravenous antibiotherapy lasting more than 5 days. We compared the use of antimicrobials in P1 versus P2. Results: A total of 160 patients were included during P2. The antibiotics for which a recommendation was made most frequently were meropenem (41.6%) and cefotaxime (23.4%). In 45% of care episodes, the consultant recommended “no change” to the prescribed antimicrobial. The final rate of acceptance of received recommendations by the prescribing physicians was 89%. We found average decreases of 27.8% in the days of treatment per 1000 inpatient days and 22.9% in the number of antimicrobial starts per 1000 admissions in P2. The use of carbapenems, cephalosporins and glycopeptides decreased in P2 compared to P1. The average annual cost of antimicrobial treatment decreased from €150 356/year during P1 to €98 478/year in P2. Conclusion: Our ASP achieved a significant decrease in the use of broad-spectrum antibiotics and antifungals. The costs associated with antimicrobial prescribing decreased following the introduction of the ASP, which was a cost-effective action in this study period.(AU)

PACTA-Ped: Antimicrobial stewardship programme in a tertiary care hospital in Spain.

INTRODUCTION: Fighting against antimicrobial resistance is a current priority, and further efforts need to be made to improve antimicrobial prescribing and reduce the spread of infections in paediatric care settings. METHODS: We conducted a prospective longitudinal study on the use of antimicrobials from the time the antimicrobial stewardship programme (ASP) was introduced in January 2016 to December 2017 (period 2 [P2]) in our children's hospital. We compared the obtained results on antimicrobial prescribing with retrospective data from the period preceding the introduction of the ASP (2014-2015, period 1 [P1]). The sample consisted of paediatric inpatients who received broad-spectrum antimicrobials, antifungals or intravenous antibiotherapy lasting more than 5 days. We compared the use of antimicrobials in P1 versus P2. RESULTS: A total of 160 patients were included during P2. The antibiotics for which a recommendation was made most frequently were meropenem (41.6%) and cefotaxime (23.4%). In 45% of care episodes, the consultant recommended "no change" to the prescribed antimicrobial. The final rate of acceptance of received recommendations by the prescribing physicians was 89%. We found average decreases of 27.8% in the days of treatment per 1000 inpatient days and 22.9% in the number of antimicrobial starts per 1000 admissions in P2. The use of carbapenems, cephalosporins and glycopeptides decreased in P2 compared to P1. The average annual cost of antimicrobial treatment decreased from є150 356/year during P1 to є98 478/year in P2. CONCLUSION: Our ASP achieved a significant decrease in the use of broad-spectrum antibiotics and antifungals. The costs associated with antimicrobial prescribing decreased following the introduction of the ASP, which was a cost-effective action in this study period.

Evaluation of the effectiveness and safety of oral vancomycin versus placebo in the prevention of recurrence of Clostridioides difficile infection in patients under systemic antibiotic therapy: a phase III, randomised, double-blind clinical trial.

INTRODUCTION: Clostridioides difficile infection (CDI) is the most prevalent cause of nosocomial bacterial diarrhoea and it is strongly associated with antibiotic use. The recurrence of CDI is a growing medical problem. Data from real-life studies and one open label randomised clinical trial (RCT) suggest that secondary prophylaxis with oral vancomycin (SPV) during subsequent courses of systemic antibiotics is a promising approach for reducing the risk of CDI recurrence. Our aim is to confirm the role of SPV through a double-blind RCT. METHODS AND ANALYSIS: We will perform a phase III, multicentre, placebo-controlled RCT (PREVAN trial) in a 2:1 ratio in favour of SPV (experimental treatment), in four tertiary care hospitals in Spain. Adult patients (≥18 years) with a previous history of CDI in the previous 180 days and with requirement for hospitalisation and systemic antibiotic therapy will be randomly allocated to receive either 125 mg of oral vancomycin or placebo every 6 hours for 10 days. Patients will be followed for 60 days after the end of treatment to verify a reduction in the rate of CDI recurrence in the experimental group. We assume a recurrence rate of 5% in the experimental group versus 25% in the placebo group. Accepting an alpha risk of 0.05 and a beta risk of 0.2 in a two-sided test, 104 subjects will be required in total (68 assigned to the SPV group and 34 to the placebo group). ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Ethic Committee for Research with medicinal products of the University Hospital '12 de Octubre' (AC069/18) and from the Spanish Medicines and Healthcare Product Regulatory Agency (AEMPS, AC069/18), which is valid for all participating centres under existing Spanish legislation. The results will be presented at international meetings and will be made available to patients and funders. TRIAL REGISTRATION NUMBER: NCT05320068.

Gaps Between the Indication and the Home Execution of Massage Therapy in Children in the Postsurgical Stage of Primary Cheiloplasty or Rhinocheiloplasty.

PURPOSE: This study describes the compliance rate with home massage therapy in children in the postsurgical stage of primary cheiloplasty or rhinocheiloplasty and the factors that facilitate or hinder its execution. METHODS: The parents of 15 children treated at the Gantz Foundation - Children's hospital for cleft lip and palate in Santiago, Chile were recruited. Parents received instructions to perform massages at home 5 times daily and were followed up for 3 months by recording in a log. Qualitative information on facilitators and barriers was collected in a focus group session. RESULTS: Compliance rate was close to 75%, and the factors that facilitated the execution were performing the massage with some distracting activity and noticing the positive changes in the appearance of the scars. The most important factors that hindered the execution were the infant's crying and changes in the routine. CONCLUSION: The authors conclude that the compliance rate is high and suggest that parents and guardians identify and implement a routine with a distracting activity that allows the massage to be carried out effectively.

The impact of a two-year long COVID-19 public health restriction program on mechanical thrombectomy outcomes in a stroke network.

OBJECTIVE: The purpose of this study was to evaluate the impact of COVID-19 pandemic public health restrictions on our drip and ship mechanical thrombectomy program in Santiago Chile. MATERIALS AND METHODS: This was a retrospective analysis of a prospectively collected database comparing two cohorts, one during a two-year period before COVID-19 and the second during the two years of the pandemic at our metropolitan stroke program. RESULTS: A total of 100 patients were included in the pre COVID-19 cohort (cohort 1) and 121 in the COVID-19 cohort (cohort 2). There was a significant difference between cohorts, with older patients, different occlusion sites and higher door to arterial puncture time during the COVID-19 period. A non-significant trend for worse 90-day outcomes and higher mortality was present in cohort 2. There were no statistical differences in safety treatment parameters. CONCLUSIONS: COVID-19 pandemic has had a measurable impact on our mechanical thrombectomy program. Results showed similarities to other reported Latin American series, where less robust health systems could adapt less efficiently compared to developed countries. After two years of public health restrictions, there were changes in the treatment population characteristics, delay in some internal management metrics and a non-significant trend to worse 90-day outcomes and higher mortality.

Direct oral anticoagulants for the treatment of atrial fibrillation in patients with hematologic malignancies.

Atrial fibrillation (AF) is common in patients with cancer due to both the proinflammatory effect of neoplastic cells and to cardiotoxicity of anti-tumor therapies. Anticoagulation is still challenging in cancer patients due to increased bleeding risk related to specific neoplasms such us hematologic malignancies. The aim of this retrospective study was to evaluate the safety and the efficacy of direct oral anticoagulants (DOACs) in AF patients affected by hematologic neoplasms. We included 97 patients on active anticancer treatment. The median follow-up was 25 months (range 10-108). No thromboembolic complications occurred, while 14 bleeding events were recorded: 1 major, 12 clinical relevant non major bleeding and 1 minor bleeding. Although retrospective and with a small number of enrolled patients, our data support the efficacy and safety of DOACs in patients affected by hematologic malignancies suggesting caution to particular situations, such as thrombocytopenia.

Pharmacological Profile, Bioactivities, and Safety of Turmeric Oil.

The pharmacological attributes of turmeric have been extensively described and frequently related to the action of curcuminoids. However, there is also scientific evidence of the contribution of turmeric oil. Since the oil does not contain curcuminoids in its composition, it is crucial to better understand the therapeutic role of other constituents in turmeric. The present review discusses the pharmacokinetics of turmeric oil, pointing to the potential application of its active molecules as therapeutic compounds. In addition, the bioactivities of turmeric oil and its safety in preclinical and clinical studies were revised. This literature-based research intends to provide an updated overview to promote further research on turmeric oil and its constituents.

Clinical impact of time-to-positivity of blood cultures on mortality in patients with Pseudomonas aeruginosa bacteremia.

OBJECTIVES: To investigate the impact of the time-to-positivity of blood cultures (TTP) on 30-day mortality in patients with Pseudomonas aeruginosa bacteremia. METHODS: All nonduplicated episodes of P. aeruginosa monomicrobial bacteremia in adult patients from January 2013 to February 2020 were analysed. Epidemiological and clinical data were collected. TTP of blood cultures for P. aeruginosa isolates was automatically recorded. Multivariate analysis identified factors predicting 30-day overall mortality. RESULTS: A total of 328 patients were identified. The median TTP for P. aeruginosa isolates was 15 h (interquartile range [IQR] 12-18 h). All multidrug-resistant and extensively drug-resistant (MDR/XDR) episodes were positive within the first 36 h. The 30-day mortality rate was 32.3%. The best cut-off value of the TTP for predicting mortality was 16 h (area under the receiver operating characteristic curve 0.62, 95% confidence interval [CI] 0.56-0.67, P = 0.001). The 30-day mortality rate was significantly higher in the TTP ≤16 h group (41.0% vs. 19.5%, P < 0.001). In a multivariate analysis, severe neutropenia (adjusted odds ratio [aOR] 2.67, 95% CI 1.4-5.09, P = 0.002), septic shock (aOR 3.21, 95% CI 1.57-5.89, P < 0.001), respiratory source (aOR 4.37, 95% CI 2.24-8.52, P < 0.001), nosocomial acquisition (aOR 1.99, 95% CI 1.06-3.71, P = 0.030), TTP ≤16 h (aOR 2.27, 95% CI 2.12-4.25, P = 0.010), and MDR/XDR phenotype (aOR 2.54, 95% CI 1.38-4.67, P = 0.002) were independently associated with 30-day mortality. CONCLUSIONS: A short TTP (≤16 h) was independently associated with increased 30-day mortality. After local validation, this routinely available microbiological parameter might be useful for guiding empirical antipseudomonal therapies and supporting the close monitoring of patients with P. aeruginosa bacteremia.

The Role of Colchicine in Atherosclerosis: From Bench to Bedside.

Inflammation is a key feature of atherosclerosis. The inflammatory process is involved in all stages of disease progression, from the early formation of plaque to its instability and disruption, leading to clinical events. This strongly suggests that the use of anti-inflammatory agents might improve both atherosclerosis progression and cardiovascular outcomes. Colchicine, an alkaloid derived from the flower Colchicum autumnale, has been used for years in the treatment of inflammatory pathologies, including Gout, Mediterranean Fever, and Pericarditis. Colchicine is known to act over microtubules, inducing depolymerization, and over the NLRP3 inflammasome, which might explain its known anti-inflammatory properties. Recent evidence has shown the therapeutic potential of colchicine in the management of atherosclerosis and its complications, with limited adverse effects. In this review, we summarize the current knowledge regarding colchicine mechanisms of action and pharmacokinetics, as well as the available evidence on the use of colchicine for the treatment of coronary artery disease, covering basic, translational, and clinical studies.

Genomic Analysis of Ceftazidime/Avibactam-Resistant GES-Producing Sequence Type 235 Pseudomonas aeruginosa Isolates.

The emergence of ceftazidime/avibactam (CZA) resistance among Guiana extended-spectrum ß-lactamase (GES)-producing Pseudomonas aeruginosa isolates has rarely been described. Herein, we analyze the phenotypic and genomic characterization of CZA resistance in different GES-producing P. aeruginosa isolates that emerged in our institution. A subset of nine CZA-resistant P. aeruginosa isolates was analyzed and compared with thirteen CZA-susceptible isolates by whole-genome sequencing (WGS). All CZA-resistant isolates belonged to the ST235 clone and O11 serotype. A variety of GES enzymes were detected: GES-20 (55.6%, 5/9), GES-5 (22.2%, 2/9), GES-1 (11.1%, 1/9), and GES-7 (11.1%, 1/9). WGS revealed the presence of two mutations within the blaGES-20 gene comprising two single-nucleotide substitutions, which caused aspartic acid/serine and leucine/premature stop codon amino acid changes at positions 165 (D165S) and 237 (L237X), respectively. No major differences in the mutational resistome (AmpC, OprD porin, and MexAB-OprM efflux pump-encoding genes) were found among CZA-resistant and CZA-susceptible isolates. None of the mutations that have been previously demonstrated to cause CZA resistance were observed. Different mutations within the blaGES-20 gene were documented in CZA-resistant GES-producing P. aeruginosa isolates belonging to the ST235 clone in our institution. Although further analysis should be performed, according to our results, other resistance mechanisms might be involved in CZA resistance.

Oncological Benefit versus Cardiovascular Risk in Breast Cancer Patients Treated with Modern Radiotherapy.

Radiotherapy (RT) is an essential part of breast cancer (BC) treatments. Unfortunately, heart exposure to radiation can also impair the long-term survival of patients. Our study aimed to quantify the oncological benefit and the cardiovascular (CV) risk associated with modern RT in a real-world cohort of BC patients. Our descriptive study enrolled BC patients who received adjuvant RT. Ten-year overall survival (OS) was estimated using Predict® version 2.1 (National Health Service, London, UK). The basal risk of CV events was estimated using the American Heart Association (ACC/AHA) CV score. Treatment volumes and mean cardiac doses were obtained from RT treatment plan records. The increased risk of CV events due to RT was estimated using a model proposed by Darby. The risk of acute myocardial infarction or stroke mortality was estimated using HeartScore® (European Society of Cardiology, Brussels, Belgium). A total of 256 BC patients were included in the study. The average age of patients was 57 years old (range: 25-91); 49.6% had left BC. The mean cardiac dose was 166 cGy (interquartile range (IQR) 94-273); the estimated hazard ratio (HR) for CV disease was HR 1.12 (confidence interval (CI) 1.04-1.24). The estimated baseline 10-year CV risk was 5.6% (0.2 to 51.2); CV risk increased by 0.9% (range 0.02-35.47%) after RT. The absolute risk of 10-year mortality from CV disease was 2.5% (0.1-9); RT was associated with an estimated 4.9% survival benefit (3.73-6.07) against BC death and a 0.23% (0.17-0.29) estimated increase in CV mortality. Modern RT decreased 10-year BC mortality by 4% but increased CV mortality by 0.2% in this cohort. Our findings encourage the implementation of personalized adjuvant RT treatments that balance risks and benefits to improve long-term BC patient survival.

New Insights into the Determinants of Specificity in Human Type I Arginase: Generation of a Mutant That Is Only Active with Agmatine as Substrate.

Arginase catalyzes the hydrolysis of L-arginine into L-ornithine and urea. This enzyme has several analogies with agmatinase, which catalyzes the hydrolysis of agmatine into putrescine and urea. However, this contrasts with the highlighted specificity that each one presents for their respective substrate. A comparison of available crystal structures for arginases reveals an important difference in the extension of two loops located in the entrance of the active site. The first, denominated loop A (I129-L140) contains the residues that interact with the alpha carboxyl group or arginine of arginase, and the loop B (D181-P184) contains the residues that interact with the alpha amino group of arginine. In this work, to determine the importance of these loops in the specificity of arginase, single, double, and triple arginase mutants in these loops were constructed, as well as chimeras between type I human arginase and E. coli agmatinase. In previous studies, the substitution of N130D in arginase (in loop A) generated a species capable of hydrolyzing arginine and agmatine. Now, the specificity of arginase is completely altered, generating a chimeric species that is only active with agmatine as a substrate, by substituting I129T, N130Y, and T131A together with the elimination of residues P132, L133, and T134. In addition, Quantum Mechanic/Molecular Mechanic (QM/MM) calculations were carried out to study the accommodation of the substrates in in the active site of this chimera. With these results it is concluded that this loop is decisive to discriminate the type of substrate susceptible to be hydrolyzed by arginase. Evidence was also obtained to define the loop B as a structural determinant for substrate affinity. Concretely, the double mutation D181T and V182E generate an enzyme with an essentially unaltered kcat value, but with a significantly increased Km value for arginine and a significant decrease in affinity for its product ornithine.

Role of Self-Sampling for Cervical Cancer Screening: Diagnostic Test Properties of Three Tests for the Diagnosis of HPV in Rural Communities of Cuenca, Ecuador.

BACKGROUND: HPV primary screening has shown effectiveness for cancer prevention; however, gynaecological examination is considered uncomfortable. Self-sampling methods increase the acceptance of screening. The aim of this study is to compare the sensitivity and specificity of clinician sampling versus vaginal and urine self-sampling for HPV diagnosis. METHODS: A diagnostic test study was conducted in a rural parish of Cuenca, Ecuador. A total of 120 women participated. Each participant self-collected urine and vaginal samples and underwent clinician sampling for HPV testing. The latter was considered as the golden standard. All three samples were processed with the same amplification and hybridization protocol for HPV detection (Hybribio) following the manufacturer's instructions. RESULTS: Characteristics of the participants were: median age 35 years; 40.8% married; 46.7% had a primary level of education; and median age of sexual onset, 17.6 years. The prevalence of any type of HPV with clinician sampling was 15.0%, 17.5% with urine sampling and 18.3% with vaginal self-sampling. Self-sampling sensitivity reached 94.4% (IC 74.2-99.9), and specificity 92.1% (IC 85.2-95.9). Urine sampling had a sensitivity of 88.8% (IC 67.2, 96.9), and specificity 94.1% (IC 67.2-96.9). The negative predictive value was 98.9% (IC 94.2-99.8) for vaginal self-sampling and 97.6% (IC 92.6-99.4) for urine sampling. CONCLUSIONS: This study shows that vaginal and urine self-sampling methods have similar sensitivity and specificity compared with clinician sampling for the diagnosis of HPV. The correlation between HPV genotypes among the three tests is satisfactory.