Search

Objectives: This study aims to identify infection etiology in febrile neutropenia (FN) is vital. This study explores different microbiological approaches and their impact on diagnosing infections in patients with hematologic malignancies and FN., Methods: This is a retrospective analysis conducted at the Hospital Clinic of Barcelona details microbiological testing strategies used to diagnose infections at FN onset between January 2020 and July 2022., Results: A total of 4520 microbiological tests were ordered in 462 FN episodes, achieving a 10% test positivity rate, with 200 (43.3%) episodes showing microbiological documentation of infection. Blood cultures (40.4%), non-culture blood tests (21.2%), and respiratory tract samples (16.2%) were the most requested. Blood cultures exhibited the highest (16.9%) test positivity rates, whereas non-culture blood tests showed the lowest (3.3%). Bacterial infections were present in 149 of 462 (32.3%) FN episodes. Viral infections (66 of 462, 14.3%)-notably, respiratory viruses-were also frequent. Mortality rate at 60 days was 9.1%; documented infections were associated with a higher risk (15%)., Conclusions: In the current landscape of antimicrobial diagnostics, our findings revealed the highest reported rate of microbiologically documented infections at FN onset. Bacterial infections are common; however, our data reiterate the significance of viral infections in causing fever. Optimizing FN management during respiratory viral infections remains a challenge for antimicrobial de-escalation. The low positivity rates observed in certain diagnostic tests emphasize the need for cost-effective diagnostic stewardship., Competing Interests: Declarations of competing interest CG-V has received honoraria for talks on behalf of Gilead Science, MSD, Pfizer, Jannsen, Novartis, Basilea, GSK, Shionogi, AbbVie, and Advanz Pharma and grant support from Gilead Science, Pfizer, GSK, MSD, and PharmaMar. PP-A has received honoraria for talks on behalf of Merck Sharp and Dohme, Lilly, ViiV Healthcare, and Gilead Science., (Copyright © 2024. Published by Elsevier Ltd.)

Objectives: Knowledge of frailty prevalence and incidence trends over time is essential for planning the necessary health and social resources. The objective of this study was to assess frailty prevalence, incidence, reversibility and mortality rates, and trends for the population aged ≥65 years in Catalonia over the period 2017-2021., Study Design: Longitudinal epidemiological study., Methods: An observational longitudinal 5-year study (1 January 2017 to 31 December 2021) of the population aged ≥65 years in Catalonia (approximately 1.5 million individuals) was performed using retrospectively collected data from different health databases. Frailty status was evaluated using the electronic Screening Index of Frailty (e-SIF) and categorised as robust, pre-frail, moderately frail or severely frail., Results: Standardised frailty prevalence rates were 10.5 % (2017), 11.8 % (2018), 13.1 % (2019), 12.9 % (2020) and 14.3 % (2021) [p-value for trend = 0.010]. Standardised frailty incidence rates per 1000 non-frail persons/year were 35 (2018), 36 (2019), 28 (2020) and 33 (2021) [p-value for trend = 0.492]. Both prevalence and incidence were higher in women and increased with age. Standardised frailty reversibility rates per 1000 frail persons/year were 123 (2018), 108 (2019) and 121 (2020) [p-value for trend = 0.406], and decreased with age. Standardised mortality rates for frail individuals per 1000 frail persons/year were 93 (2018), 84 (2019) and 110 (2020) [p-value for trend = 0.555], and increased with frailty severity., Conclusions: Frailty prevalence in Catalonia increased by 36 % between 2017 and 2021; however, no clear trend was evident for frailty incidence and reversibility, while results for mortality were likely to have been influenced by the COVID-19 pandemic., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: In reversed-phase liquid chromatography, solute retention is primarily influenced by interactions between a nonpolar stationary phase and a moderately polar hydro-organic mobile phase, based on the solute lipophilicity. However, challenges regarding retention and peak tailing can arise due to ionic interactions between positively charged analytes and free silanols present on silica-based stationary phases. To address these challenges, incorporating surfactants and ionic liquids (ILs) into the mobile phase offers an effective solution. These additives synergistically enhance chromatographic performance through electrostatic and lipophilic interactions, which enable fine-tuning of selectivity and improved separation efficiency., Results: This study explores the chromatographic behaviour of several basic compounds in aqueous mixtures containing the anionic surfactant sodium dodecyl sulphate (SDS), above its critical micellar concentration, combined with various 1-alkyl-3-methylimidazolium-based ionic liquids (ILs) featuring chloride, tetrafluoroborate, and hexafluorophosphate anions, all without the addition of organic solvents. Specifically, this research investigates the influence of different anion types within the ILs and considers the impact of the IL cations. Analysis of solute peak profiles reveals narrow and symmetrical peaks. By introducing tetrafluoroborate and hexafluorophosphate IL anions into a mobile phase that contains an anionic surfactant, the study sheds light on the interactions occurring within the chromatographic column. This enhanced understanding of the combined effects of surfactants and ILs contributes to refining chromatographic methodologies., Significance: This research highlights the importance of carefully selecting the appropriate IL when incorporating it into a micellar mobile phase alongside SDS. This combination results in practical retention times that surpass the performance achieved with either the surfactant or IL alone in the mobile phase. The study particularly emphasises the impact of the IL anion, especially in the absence of SDS and organic solvents. This unveils interactions that are otherwise obscured in micellar and hydro-organic media, providing new insights into chromatographic dynamics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Research Question: Is there a difference between the proportion of patients with serum progesterone <8.8 ng/ml on the day of embryo transfer when micronized vaginal progesterone (MVP) for luteal phase support (LPS) is given as pessaries versus capsules?, Design: This retrospective, matched-cohort, single-centre study compared pessaries (Cyclogest) versus capsules (Utrogestan, Progeffik) for LPS in hormone replacement treatment-embryo transfer (HRT-ET) cycles. Patients under 50 years old with a triple-layer endometrial thickness of ≥6.5 mm underwent transfer of one or two blastocysts. Serum progesterone concentrations were measured on the day of transfer; patients with concentrations <8.8 ng/ml received a single 'rescue' dose of additional progesterone by subcutaneous injection., Results: In total 2665 HRT-ET cycles were analysed; 663 (24.9%) used pessaries for LPS and 2002 (75.1%) used capsules. Mean serum progesterone concentrations with standard deviations on the day of embryo transfer were significantly higher in the group using MVP pessaries compared with those using capsules (14.5 ± 5.1 versus 13.0 ± 4.8 ng/ml; P = 0.000). The percentage of participants with suboptimal serum progesterone concentrations on the day of embryo transfer (<8.8 ng/ml) was significantly lower in the pessary group than the capsule group (10.3%, 95% confidence interval [CI] 7.9-12.6% versus 17.9%, 95% CI 16.2-19.6%; adjusted odds ratio 0.426, 95% CI 0.290-0.625; P = 0.000). No differences in pregnancy outcome were observed between the groups., Conclusions: Using MVP pessaries rather than capsules for LPS resulted in significantly fewer patients having suboptimal serum progesterone concentrations on the day of embryo transfer. Consequently, almost 50% fewer patients in the pessary group needed rescue treatment., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Pandemic preparedness is critical to respond effectively to existing and emerging/new viral pathogens. Important lessons have been learned during the last pandemic at various levels. This revision discusses some of the major challenges and potential ways to address them in the likely event of future pandemics., Objectives: To identify critical points of readiness that may help us accelerate the response to future pandemics from a clinical microbiology laboratory perspective with a focus on viral diagnostics and genomic sequencing. The potential areas of improvement identified are discussed from the sample collection to information reporting., Sources: Microbiologists and researchers from five countries reflect on challenges encountered during the COVID-19 pandemic, review published literature on prior and current pandemics, and suggest potential solutions in preparation for future outbreaks., Content: Major challenges identified in the pre-analytic and post-analytic phases from sample collection to result reporting are discussed. From the perspective of clinical microbiology laboratories, the preparedness for a new pandemic should focus on zoonotic viruses. Laboratory readiness for scalability is critical and should include elements related to material procurement, training personnel, specific funding programmes, and regulatory issues to rapidly implement "in-house" tests. Laboratories across various countries should establish (or re-use) operational networks to communicate to respond effectively, ensuring the presence of agile circuits with full traceability of samples., Implications: Laboratory preparedness is paramount to respond effectively to emerging and re-emerging viral infections and to limit the clinical and societal impact of new potential pandemics. Agile and fully traceable methods for sample collection to report are the cornerstone of a successful response. Expert group communication and early involvement of information technology personnel are critical for preparedness. A specific budget for pandemic preparedness should be ring-fenced and added to the national health budgets., Competing Interests: Transparency declaration The authors declare that they have no conflicts of interest., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: New evidence has emerged on the impact of frailty on prognosis in colon cancer, but the findings are not always consistent and conclusive. The aim of this systematic review was to assess the effect of frailty on postoperative complications and mortality in patients with non-metastatic colon cancer (CC) aged 65 years and older., Materials and Methods: We systematically searched for original studies published in the PubMed and Web of Science databases up to June 2021. Two independent reviewers selected the studies and extracted predefined data. A meta-analysis was performed using the random effects model to assess the effect of frailty on 30-day, 3- to 6-month and 1-year mortality, survival, and postoperative complications., Results: The search yielded 313 articles, of which 14 were included in this systematic review. The meta-analysis showed an effect for frailty on 30-day, 3- to 6-month, and 1-year mortality with respective pooled odds ratios (ORs) of 3.67 (95% confidence interval [CI] 1.53-8.79, p = 0.004), 8.73 (95% CI 4.03-18.94, p < 0.0001), and 3.99 (95% CI 2.12-7.52, p < 0.0001). Frailty also had an effect on survival, with a pooled hazard ratio of 2.99 (95% CI 1.70-5.25. p < 0.0001), and on overall and severe postoperative complications with pooled ORs of 2.34 (95% CI 1.75-3.15; p < 0.0001) and 2.43 (95% CI 1.72-3.43; p < 0.0001), respectively., Discussion: Frailty in older patients with CC is a risk factor for postoperative complications and mortality in the short term (30 days), medium term (3-6 months), and long term (1 year)., Competing Interests: Declaration of Competing Interest All authors declare that they have no conflicts of interest in relation to this study., (Copyright © 2023. Published by Elsevier Ltd.)

Objective: The aim of this work was 2-fold: (1) to evaluate current knowledge and identify key directions in the study of sluggish cognitive tempo (SCT); and (2) to arrive at a consensus change in terminology for the construct that reflects the current science and may be more acceptable to researchers, clinicians, caregivers, and patients., Method: An international Work Group was convened that, in early 2021, compiled an online archive of all research studies on SCT and summarized the current state of knowledge, noted methodological issues, and highlighted future directions, and met virtually on 10 occasions in 2021 to discuss these topics and terminology., Results: Major progress has been made over the last decade in advancing our understanding of SCT across the following domains of inquiry: construct measurement and stability; genetic, environmental, pathophysiologic, and neuropsychological correlates; comorbid conditions; functional impairments; and psychosocial and medication interventions. Findings across these domains are summarized, and potential avenues to pursue in the next generation of SCT-related research are proposed. Following repeated discussions on terminology, the Work Group selected "cognitive disengagement syndrome" (CDS) to replace "SCT" as the name for this construct. This term was deemed to best satisfy considerations that should apply when selecting terms for a condition or syndrome, as it does not overlap with established terms for other constructs, is not offensive, and reflects the current state of the science., Conclusion: It is evident that CDS (SCT) has reached the threshold of recognition as a distinct syndrome. Much work remains to further clarify its nature (eg, transdiagnostic factor, separate disorder, diagnostic specifier), etiologies, demographic factors, relations to other psychopathologies, and linkages to specific domains of functional impairment. Investigators are needed with interests and expertise spanning basic, clinical, and translational research to advance our understanding and to improve the lives of individuals with this unique syndrome., (Copyright © 2022 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Soil microbial communities (both Bacteria and Archaea) were studied after 16S rRNA genes massive sequencing in two hypersaline and gypsum-rich contrasted sites located in NE Spain. Soil microbial communities were also locally analysed according to environmental variables, including geological, physico-chemical, biogeochemically, and climatic data. Typical soil characteristics, climate data, and plant composition clearly split the two sites and major differences among the microbial communities for the areas were initially expected. Overall, high values of microbial species richness (up to 2300 taxa) and ecological diversity was detected in both sites. High genetic novelty levels were found mostly to environmental sequences, highlighting the high potential for microbiological studies. In contrast to the initial expectations, a substantial overlapping between Monegros and Gallocanta microbes was observed, indicating a high similarity despite of the geographical, botanical and environmental distances between sites, in agreement with both high dispersal and local selection inherent to the microbial world. The potential biogeochemical cycling showed small differences between sites, with presence of photosynthetic green and purple sulfur bacteria, cyanobacteria and aerobic and anaerobic chemolitotrophs. Potential for aerobic methane oxidation and anaerobic methanogenesis was observed in both sites, with predominance of potential nitrification mostly by ammonia-oxidizing archaea, nitrite oxidation and denitrification, and minor contribution for nitrate reduction and nitrate ammonification. The predicted functions based on the taxonomic composition showed high overlapping between the two studied regions, despite their difference in gypsum richness., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Oropharyngeal dysphagia (OD) is a prevalent risk factor for malnutrition (MN) in older patients and both conditions are related to poor outcome., Objective: To explore the nutritional status in older patients with OD in a chronic and an acute clinical situation., Design: We examined 95 older (≥70 years) patients with OD associated to chronic neurological diseases or aging, and 23 older patients with OD and acute community-acquired pneumonia (CAP) with videofluoroscopy; and 15 older people without OD. We collected nutritional status, measured with the Mini Nutritional Assessment (MNA ® ), anthropometric measurements, and biochemistry and bioimpedance for body composition. Functional status was assessed with the Barthel index., Results: 1) Taking into consideration patients with OD with chronic conditions, 51.1% presented a MNA ® ≤23.5; 16.7%, sarcopenia and a) reduced visceral and muscular protein compartments and fat compartment; b) muscular weakness c) intracellular water depletion, and d) reduced body weight. Patients with OD and MNA ® ≤23 needed higher levels of nectar viscosity for a safe swallow and had increased oropharyngeal residue at spoon-thick viscosity. 2) Patients with OD and CAP, 69.5%, presented an MNA ® ≤23.5 and 29.4% sarcopenia, the inflammatory response of the pneumonia adding to the more severe depletion in visceral protein and muscular mass., Conclusions: Prevalence of impaired nutritional status (malnutrition risk, and sarcopenia) among older patients with OD associated with either chronic or acute conditions is very high. In patients with OD and chronic diseases, poor nutritional status further impairs OD with an increase in oropharyngeal residue at spoon-thick viscosity. In the acute setting there is inflammation and an additional protein deficiency. These findings will help develop specific products both for OD and nutritional status in each specific clinical situation., (Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

A simple method for constructing versatile ordered biotin/avidin arrays on UV-curable perfluoropolyethers (PFPEs) is presented. The goal is the realization of a versatile platform where any biotinylated biological ligands can be further linked to the underlying biotin/avidin array. To this end, microcontact arrayer and microcontact printing technologies were developed for photobiotin direct printing on PFPEs. As attested by fluorescence images, we demonstrate that this photoactive form of biotin is capable of grafting onto PFPEs surfaces during irradiation. Bioaffinity conjugation of the biotin/avidin system was subsequently exploited for further self-assembly avidin family proteins onto photobiotin arrays. The excellent fouling release PFPEs surface properties enable performing avidin assembly step simply by arrays incubation without PFPEs surface passivation or chemical modification to avoid unspecific biomolecule adsorption. Finally, as a proof of principle biotinylated heparin was successfully grafted onto photobiotin/avidin arrays., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: The relation between hunger, satiation, and integrated gastrointestinal motility and hormonal responses in morbidly obese patients after sleeve gastrectomy has not been determined., Objective: The objective was to assess the effects of sleeve gastrectomy on hunger, satiation, gastric and gallbladder motility, and gastrointestinal hormone response after a liquid meal test., Design: Three groups were studied: morbidly obese patients (n = 16), morbidly obese patients who had had sleeve gastrectomy (n = 8), and nonobese patients (n = 16). The participants fasted for 10 h and then consumed a 200-mL liquid meal (400 kcal + 1.5 g paracetamol). Fasting and postprandial hunger, satiation, hormone concentrations, and gastric and gallbladder emptying were measured several times over 4 h., Results: No differences were observed in hunger and satiation curves between morbidly obese and nonobese groups; however, sleeve gastrectomy patients were less hungry and more satiated than the other groups. Antrum area during fasting in morbidly obese patients was statistically significant larger than in the nonobese and sleeve gastrectomy groups. Gastric emptying was accelerated in the sleeve gastrectomy group compared with the other 2 groups (which had very similar results). Gallbladder emptying was similar in the 3 groups. Sleeve gastrectomy patients showed the lowest ghrelin concentrations and higher early postprandial cholecystokinin and glucagon-like peptide 1 peaks than did the other participants. This group also showed an improved insulin resistance pattern compared with morbidly obese patients., Conclusions: Sleeve gastrectomy seems to be associated with profound changes in gastrointestinal physiology that contribute to reducing hunger and increasing sensations of satiation. These changes include accelerated gastric emptying, enhanced postprandial cholecystokinin and glucagon-like peptide 1 concentrations, and reduced ghrelin release, which together may help patients lose weight and improve their glucose metabolism after surgery. This trial was registered at clinicaltrials.gov as NCT02414893., (© 2015 American Society for Nutrition.)

Background & Aims: Oropharyngeal dysphagia and malnutrition are prevalent conditions in the older. The aim of this study was to explore the relationship between oropharyngeal dysphagia, nutritional status and clinical outcome in older patients admitted to an acute geriatric unit., Methods: We studied 1662 patients ≥70 years consecutively hospitalized with acute diseases, in whom dysphagia could be clinically assessed by the volume-viscosity swallow test and nutritional status with the Mini Nutritional Assessment(®). Anthropometric and laboratory measurements were taken and mortality recorded during hospital stay, at 6 months and one year after discharge was recorded., Results: 47.4% (95% CI 45-49.8%) patients presented oropharyngeal dysphagia and 30.6% (95% CI 27.9%-33.3%), malnutrition. Both conditions were associated with multimorbidity, multiple geriatric syndromes and poor functional capacity (p < 0.001). However, patients with dysphagia presented increased prevalence of malnutrition (MNA(®) < 17 45.3% vs 18%, p < 0.001) regardless of their functional status and comorbidities (OR 2.31 (1.70-3.14)) and lower albumin and cholesterol levels. Patients with malnutrition presented an increased prevalence of dysphagia (68.4% (95% CI 63.3-73.4)). Patients with dysphagia and patients with malnutrition presented increased intrahospital, 6-month and 1-year mortality rates (p < 0.05). The poorest outcome was for patients with both conditions (1-year mortality was 65.8%)., Conclusions: Prevalence of dysphagia was higher than malnutrition in our older patients. Dysphagia was an independent risk factor for malnutrition, and both conditions were related to poor outcome., (Copyright © 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: There are strong theoretical arguments that those high on Neuroticism (N) should normally exhibit higher prevailing levels of the stress-linked hormone cortisol (C), but findings are inconsistent, probably reflecting methodological weaknesses especially in taking account of C's diurnal cycle., Methods: High and low N students [Total N=118; mean age=20.99years] were recruited and their salivary cortisol measured, ensuring that saliva samples were numerically adequate to assess C's diurnal cycle over two days with objective verification of sample timing., Results: Cortisol secretion was approximately 20% higher in High N than low N participants in the period of 12h after awakening (p<.008), but no differences in secretion were evident during the first 0.75 of this period, when typically the Cortisol Awakening Response (CAR) rapidly takes cortisol to its daily peak. N effects were thus confined to the 0.75h-12h period (p<.007). Males had approximately 25% higher cortisol secretion levels than females, also confined to the 0.75h-12h period (p<.003). No significant differences between N groups were evident for dynamic measures of cortisol change, viz. the magnitude of CAR rise and subsequent diurnal fall. All effects were controlled for cohort date of study entry, age, smoking status, study day and time of awakening., Discussion: With careful control, it appears that an important theoretically predicted effect exists, and is replicated in different student intake cohorts recruited in different years. Most importantly, findings support several lines of evidence that the period of massive rise in the brief 0-0.75h CAR period should be seen as quite separate from the rest of the diurnal cycle, underpinned by different control mechanisms, and with potentially different correlates., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background: A population-based case-control study was designed to assess changes of serum levels of immunoglobulins and IgG subclasses between infected and convalescent phase in community-acquired pneumonia (CAP)., Methods: Over a 2-year period, all subjects who were >14 years of age living in the Maresme region (Barcelona, Spain) diagnosed of CAP were registered. Controls were healthy subjects selected from the municipal census. Prognostic factors were assessed and serum levels of total IgG, IgA, IgM, and IgG subclasses were measured at diagnosis and 1 month later (cases)., Results: We studied 171 patients with CAP and 90 controls. All immunoglobulins were significantly lower in cases than in controls. At diagnosis, 42.7% of cases showed low levels of some immunologic parameter, mainly total IgG and IgG2. Low immunoglobulin levels at diagnosis were more frequent in patients requiring in-patient care and in those with pneumonia of other etiology than Streptococcus pneumoniae. In the convalescent phase, 26 (23.6%) patients normalized immunological levels. In 27 (24.5%) cases, some parameter with low levels persisted especially in patients with etiology of CAP other than S. pneumoniae., Conclusions: Low serum levels of immunoglobulins particularly total IgG and IgG2 were a common finding in patients with CAP compared to healthy controls. Low immunoglobulin levels may be related to CAP prognosis and persisted in the convalescent phase in one-fourth of cases., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

There is great concern about the exposure to PCDD/Fs in areas near solid waste incineration (SWI) plants as, in the past, thermal waste treatment was a major source of PCDD/Fs, affecting negatively the environment and the population living nearby the area of influence. The aim of the present study was to monitor PCDD/Fs and PCBs levels in blood samples in general population living nearby a modern SWI. Up to 7 different campaigns were performed between 1995 and 2012. Overall, 104 exposed subjects (living <1000 m from the incinerator plant) and 97 non-exposed subjects (living >3000 m from the incinerator plant) were randomly selected from the municipal census of the City of Mataró in 1995. In addition, workers of the SWI plant were included in the study. Moreover, in 1999, 100 non-exposed subjects living in the nearby City of Arenys de Mar were added to the project. Overall, this study represents the longest consecutive human biomonitoring study of dioxins, furans and PCBs ever conducted in Spain. Concentrations of PCDD/Fs and PCBs were determined according to age, sex and distance to the SWI exposure in whole blood sample pools. No relevant differences in PCDD/Fs and PCBs levels were observed between SWI exposure groups. It could be noted that since 1999 all groups experienced a slight decrease in the levels of PCDD/Fs and marker PCBs. Moreover, concentrations of PCDD/Fs and marker PCBs were higher in women than in men, and in older age group in comparison to the younger ones., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background: Comatose patients present a high risk of early-onset ventilator-associated pneumonia (EO-VAP) for which antibiotic prophylaxis has been proposed. Comatose patients were studied to evaluate the efficacy of a single-dose of antibiotic prophylaxis at intubation against EO-VAP., Methods: A prospective cohort of comatose patients (Glasgow Coma Score ≤ 8) who were admitted in 2009-2010 and administered a single-dose of antibiotic within 4 h of intubation was compared with comatose patients (admitted ≥ 4 h after intubation in 2009-2010 or admitted in 2007-2008) who did not receive antibiotic prophylaxis. We analyzed the incidence of EO-VAP, late-onset VAP, and ventilator-associated tracheobronchitis in both groups. Propensity scores for receiving antibiotic prophylaxis were derived on the basis of patients' characteristics (eg, age and severity) to assess its impact on EO-VAP development., Results: We included 129 patients (71 in the prophylaxis group and 58 in the control group). The global incidence of VAP and incidence of EO-VAP were lower in the prophylaxis group: 10.8 vs 28.4 episodes/1,000 days on mechanical ventilation (P = .015) and 4.4 vs 23.1 episodes/1,000 days on mechanical ventilation (P = .02), respectively. The incidence of late-onset VAP did not differ. The prophylaxis group tended toward lower incidence of ventilator-associated tracheobronchitis (15.5% vs 25.9%, P = .14). No differences in mortality were found between groups. The propensity-score regression analysis confirmed that a single dose of antibiotic prophylaxis was independently associated with lower incidence of EO-VAP (OR, 0.11; 95% CI, 0.02-0.58; P = .009)., Conclusions: A single dose of antibiotic prophylaxis at intubation might lower the incidence of EO-VAP. However, a randomized clinical trial should be conducted to confirm our findings.

Objectives: Genetic variations in the Insulin/IGF-I genes pathway have been related to longevity, dementia, metabolic diseases and cancer. The purpose of the present study was to investigate the 192 bp allele of IGF-I gene promoter and its relationship with metabolic syndrome (MS) components, mental and nutritional state, muscle strength and functional capacity in an aged Spanish population., Design: Population-based study (Mataró Ageing Study), including 292 subjects (144 men and 148 women, mean age 77.0±5.4). Anthropometric variables, lipid profile, glucose and blood pressure (BP) were measured; mental state (MMSE), nutritional state (MNA) and Barthel scale were performed, and were correlated to the presence of the 192 bp allele of IGF-1 gene promoter polymorphisms., Results: MS (ATP-III criteria) was found in 49.5% (41.4% in men and 57.6% in women). The 192 bp allele of IGF-I gene promoter was distributed as: 41.9% homozygous, 44.3% heterozygous and 13.9% were non-carriers of this allele. A lower prevalence of metabolic syndrome was observed in homozygous (41.9% vs 54.9% in heterozygous+non-carriers, p=0.031). Mental state (MMSE), nutritional state (MNA) and Barthel scale were better in homozygous individuals compared to heterozygous and non-carriers (p=0.015, p=0.026 and 0.047, respectively). In men, MNA was better in homozygous with no differences in MMSE and Barthel scales. In homozygous women, BP was lower (p=0.009) and Barthel scale was better (p=0.05) with no differences in MMSE and MNA., Conclusion: Homozygosity for the 192 bp allele of the IGF-I gene polymorphism suggests a healthier aging condition, with less prevalence of cardiometabolic disturbances, and better mental, nutritional and functional state., (Copyright © 2011. Published by Elsevier Ltd.)

Rationale: A subgroup of patients with chronic obstructive pulmonary disease require frequent hospitalization because of exacerbations of the disease. We hypothesized that airway infection by non-usual pathogens is a major factor driving hospitalization needs in these patients., Objectives: 1) To describe the clinical and functional characteristics of a cohort of COPD patients requiring > or =2 hospitalizations per year; 2) to determine prospectively their microbiological pattern during exacerbations; and, 3) to analyze the prognostic value of several clinical, functional and microbiological variables with respect to hospitalizations and mortality., Methods: Open cohort study of 116 COPD patients who had been hospitalized at least twice during the last 12 months. Patients were followed for an average of 21 months., Measurements and Main Results: Clinical data, forced spirometry and 6min walking distance were determined, and the BODE index was calculated, at the time of inclusion in the study. During follow-up, sputum culture was obtained during exacerbations, and hospitalization and mortality were collected every two months. Mean age was 71 yrs, and 94% of patients were male. Main findings show that: 1) not all patients had severe disease according to either the degree of airflow limitation or the BODE index; 2) non-usual pathogens, mainly Pseudomonas aeruginosa, other gram-negative non-fermentative rods and Enterobacteriaceae, were isolated among 71.1% of the sputum obtained during exacerbations; and, 3) these pathogens were associated with poor prognosis and frequent hospitalization., Conclusions: Airway infection by non-usual pathogens appears to be a key driver of frequent hospitalizations and mortality in COPD., (Copyright 2009 Elsevier Ltd. All rights reserved.)

Background: Ghrelin and cholecystokinin (CCK) are among the peripheral signals that regulate hunger and satiety., Objective: The objective was to assess whether ghrelin and CCK responses to a standard nutritional load are related to age and frailty., Design: Ghrelin, CCK, insulin, glucose, and 4-h visual analog hunger scale curves after a standard nutritional load test (380 kcal) were described and compared between 3 groups: old (>75 y) and frail persons (group A), old (>75 y) but nonfrail persons (group B), and young (25-65 y) adults (group C)., Results: Frail persons showed no postprandial ghrelin suppression, and old subjects, frail and nonfrail, showed no significant postprandial ghrelin recovery compared with young adults. Frailty was also associated with lower fasting ghrelin concentrations. No differences in fasting CCK were observed between young and old persons; however, postprandial CCK concentrations were enhanced in young persons, whereas no frailty effect on the CCK curve was observed in the old subjects. No correlations between mean ghrelin and hunger values over time were found, but strong negative correlations were shown between CCK and hunger (group A: r(s) = -0.88, P = 0.009; group B: r(s) = -0.86, P = 0.014; group C: r(s) = -0.71, P = 0.071) and insulin and hunger (group A: r(s) = -0.901, P = 0.006; group B: r(s) = -0.964, P < 0.001; group C: r(s) = -0.929, P = 0.003)., Conclusions: Advanced age determines a poorer ghrelin postprandial recuperation phase, a reduced CCK postprandial response, and an exaggerated postprandial insulin release. A loss of ghrelin prandial rhythm is present in old frail persons. The impaired response of these hunger regulatory hormones with age might contribute to the mechanisms of anorexia associated with aging.

Aims: To determine the accuracy of the bedside volume-viscosity swallow test (V-VST) for clinical screening of impaired safety and efficacy of deglutition., Methods: We studied 85 patients with dysphagia and 12 healthy subjects. Series of 5-20 mL nectar (295.02 mPa.s), liquid (21.61 mPa.s) and pudding (3682.21 mPa.s) bolus were administered during the V-VST and videofluoroscopy. Cough, fall in oxygen saturation > or =3%, and voice changes were considered signs of impaired safety, and piecemeal deglutition and oropharyngeal residue, signs of impaired efficacy., Results: Videofluoroscopy showed patients had prolonged swallow response (> or =1064 ms); 52.1% had safe swallow at nectar, 32.9%, at liquid (p<0.05), and 80.6% at pudding viscosity (p<0.05); 29.4% had aspirations, and 45.8% oropharyngeal residue. The V-VST showed 83.7% sensitivity and 64.7% specificity for bolus penetration into the larynx and 100% sensitivity and 28.8% specificity for aspiration. Sensitivity of V-VST was 69.2% for residue, 88.4% for piecemeal deglutition, and 84.6% for identifying patients whose deglutition improved by enhancing bolus viscosity. Specificity was 80.6%, 87.5%, and 73.7%, respectively., Conclusions: The V-VST is a sensitive clinical method to identify patients with dysphagia at risk for respiratory and nutritional complications, and patients whose deglutition could be improved by enhancing bolus viscosity. Patients with a positive test should undergo videofluoroscopy.

Background: A few population-based studies assessing the etiology of community-acquired pneumonia in both hospitalized and ambulatory patients, with special emphasis on the etiologic role of viral infections, have been reported. The purpose of this study was to assess microbiological differences according to initial site of care in patients with community-acquired pneumonia., Methods: We studied 496 patients > 14 years of age collected from the study samples of three population-based studies carried out in the same geographical area ("Maresme" region in the Mediterranean coast in Barcelona, Spain) with the same methodology over an 8-year period (1987-1995)., Results: Fifty-six percent of patients were hospitalized and 44% were treated at home. Of the 474 patients with etiological evaluation, 195 patients had an identifiable etiology (overall diagnostic yield 41%). Streptococcus pneumoniae was the most common causative organism. Viral infection was diagnosed in 26.5% of hospitalized patients vs. 13.2% of ambulatory patients (P=0.03). Twenty-five percent of the 68 patients with documented etiology treated at home had Chlamydia pneumoniae infection compared with 14.3% of those treated in the hospital. Ten percent of hospitalized patients had pneumonia caused by two pathogens compared with 9.7% of ambulatory patients. The association of viruses and bacteria was the most frequent cause of dual infection (79% inpatients, 67% outpatients)., Conclusions: This study has provided information on etiology of community-acquired pneumonia in hospitalized patients and in patients treated at home. A considerable proportion of patients had viral pneumonia, frequently requiring hospital admission for inpatient care.

Background: RTS,S/AS02A is a pre-erythrocytic stage malaria vaccine that provides partial protection against infection in malaria-naive adult volunteers and hyperimmune adults. A previous report showed that this vaccine reduced risk of clinical malaria, delayed time to new infection, and reduced episodes of severe malaria over 6 months in African children. An important remaining issue is the durability of protection against clinical disease in these children., Methods: We did a randomised, controlled, phase IIb trial of RTS,S/AS02A given at 0, 1, and 2 months in 2022 Mozambican children aged 1-4 years. We previously determined vaccine efficacy (VE) against clinical malaria in a double-blind phase that included study months 2.5-8.5 (VE(2.5-8.5)). We now report VE in a single-blind phase up to month 21 (VE(8.5-21)). The primary endpoint was time to first or only clinical episode of Plasmodium falciparum malaria (axillary temperature 37.5 degrees C and P falciparum asexual parasitaemia >2500 per microL) detected through a passive case detection system. We also determined VE for other case definitions and for episodes of severe malaria. This study is registered with the ClinicalTrials.gov identifier NCT00197041., Findings: During the single-blind phase, VE(8.5-21) was 28.9% (95% CI 8.4-44.8; p=0.008). At month 21, prevalence of P falciparum infection was 29% lower in the RTS,S/AS02A group than in the control (p=0.017). Considering the entire study period, VE(2.5-21) was 35.3% (95% CI 21.6-46.6; p<0.0001) and VE(2.5-21) for severe malaria was 48.6% (95% CI 12.3-71.0; p=0.02)., Interpretation: These results show that RTS,S/AS02A confers partial protection in African children aged 1-4 years living in rural endemic areas against a range of clinical disease caused by P falciparum for at least 18 months, and confirm the potential of malaria vaccines to become credible control tools for public-health use.

Background: Development of an effective malaria vaccine could greatly contribute to disease control. RTS,S/AS02A is a pre-erythrocytic vaccine candidate based on Plasmodium falciparum circumsporozoite surface antigen. We aimed to assess vaccine efficacy, immunogenicity, and safety in young African children., Methods: We did a double-blind, phase IIb, randomised controlled trial in Mozambique in 2022 children aged 1-4 years. The study included two cohorts of children living in two separate areas which underwent different follow-up schemes. Participants were randomly allocated three doses of either RTS,S/AS02A candidate malaria vaccine or control vaccines. The primary endpoint, determined in cohort 1 (n=1605), was time to first clinical episode of P falciparum malaria (axillary temperature > or =37.5 degrees C and P falciparum asexual parasitaemia >2500 per microL) over a 6-month surveillance period. Efficacy for prevention of new infections was determined in cohort 2 (n=417). Analysis was per protocol., Findings: 115 children in cohort 1 and 50 in cohort 2 did not receive all three doses and were excluded from the per-protocol analysis. Vaccine efficacy for the first clinical episodes was 29.9% (95% CI 11.0-44.8; p=0.004). At the end of the 6-month observation period, prevalence of P falciparum infection was 37% lower in the RTS,S/AS02A group compared with the control group (11.9% vs 18.9%; p=0.0003). Vaccine efficacy for severe malaria was 57.7% (95% CI 16.2-80.6; p=0.019). In cohort 2, vaccine efficacy for extending time to first infection was 45.0% (31.4-55.9; p<0.0001)., Interpretation: The RTS,S/AS02A vaccine was safe, well tolerated, and immunogenic. Our results show development of an effective vaccine against malaria is feasible.

A cyclic disulfide peptide corresponding to the G-H loop sequence 134-155 [replacement Tyr136 and Arg153 with Cys] of the capsid protein VP1 of foot-and-mouth disease virus (FMDV) isolate C-S8c1 was examined by proton 2D-NMR spectroscopy in water and in 25% HFIP/water. In water, NMR data supported the presence of a non-canonical turn in the central, conserved cell adhesion RGD motif and suggested the presence of a nascent helix in the C-terminal part, stabilized and slightly extended upon addition of 25% HFIP, a secondary structure stabilizing cosolvent. The formation of the C-terminal helix was evidenced by combined analysis of NOE connectivities, H alpha chemical shifts, 3JNH-H alpha coupling constants and amide temperature coefficients. Surprisingly, these global structural features of the cyclic peptide in solution show similarities to previous X-ray structure analysis of (a) a shortened linear peptide complexed with a antivirus antibody and (b) the G-H loop represented on the chemical reduced viral surface of a different serotype. Thus, even in entirely different biological environments the cyclic peptide reflect similar structural features, reinforcing the concept that this viral loop behaves as an independent structural and functional unit.

The three-dimensional structure of the Fab fragment of a neutralizing monoclonal antibody (SD6) elicited against foot-and-mouth disease virus (FMDV) has been determined at 2.5 A resolution and refined to a crystallography agreement R-factor of 0.186. The structure has been compared with that of the same Fab molecule complexes with a 15 amino acid peptide (A15) representing a major antigenic site of FMDV, and determined at 2.8 A resolution. The Fab quaternary structure, defined both by the elbow angle between modules and by the relative disposition of the light and heavy domains inside the modules, remains essentially unchanged. However, the comparison shows important conformational variations in the paratope, especially in the hypervariable loops of the heavy chain. The CDR-H3 loop has a peculiar amino acid sequence (RREDGGDEGF) with a high content of charged residues. Some of these Fab residues were fully reoriented upon complex formation. The reorientation resulted not only in an alteration of shape but also in an important redistribution of charges, providing multiple points of interaction with the A15 antigen and in particular with the cell attachment Arg-Gly-Asp motif in the peptide. Thus the recognition of A15 by SD6 represents an extreme example of the induced fit mechanism in antibody interactions. The electron density maps provide evidence that in the uncomplexed Fab structure some CDR residues show, with lower occupancy, the conformations found in the complex, suggesting that the rearrangements observed can have only minor energetic requirements.

Skeletal muscle biopsy specimens were taken from 10 male horses naturally infected with Trypanosoma evansi and from 10 uninfected males. An indirect fluorescent antibody test was used to provide a rapid and reliable indication of infection. Histological, histochemical and transmission electron microscopical techniques were used to examine skeletal muscle. The ultrastructural features in muscle fibres were those usually seen in autoimmune disease, namely fibre and capillary necrosis and mononuclear cell infiltration, consisting of macrophages. Changes in fibre-type percentages did not occur in response to the parasite, but alterations in fibre size and capillary supply were found in the parasitized horses.

Between 1970 and 1985, seven patients were referred to us for surgical treatment of simultaneous hydatid cysts in the liver and the chest. Their mean age was 45.4 years (age range, 23-73 years), and they represented 46% of patients with hydatid cysts in the liver and thorax. Three patients had hepaticopleural involvement, and 3 patients had symptoms of pulmonary origin. In a single patient, only the diaphragm was involved along with the liver. Liver scintigraphy and ultrasonography were equally helpful in delineating the extent of the disease, but computed tomographic scanning is now the method of choice. The operations were through a thoracolaparotomy in 3 patients and a thoracotomy alone in 3 patients. A single patient had a thoracotomy with a transdiaphragmatic laparotomy. Complete drainage or excision of hydatid cavities was accomplished in all patients. Hydrogen peroxide instilled into the cysts was satisfactory for control of spread potentially secondary to possible intraoperative spillage. There have been no postoperative deaths. Follow-up has ranged from 6 months to 8 years, and 2 patients had relapsing hydatid disease 3 years postoperatively. These results suggest that, when hydatid disease of the liver is complicated by transdiaphragmatic extension and simultaneous pleural or pulmonary cysts, early surgical repair is indicated. Complete drainage and cyst excision are recommended.