Helios-Negative Regulatory T Cells as a Key Factor of Immune Tolerance in Nonallergic Beekeepers.

BACKGROUND AND OBJECTIVES: Although exposure to stings has been identified as the leading risk factor for anaphylaxis due to Hymenoptera venom allergy, professional beekeepers receive hundreds of stings yearly without developing systemic reactions. This study aims to analyze the mechanisms underlying bee venom tolerance in beekeepers. METHODS: A cross-sectional study was conducted. Participants were recruited and classified into 3 groups: allergic patients (APs), who experienced systemic reactions after bee stings, with a positive intradermal test and specific IgE (sIgE) to Apis mellifera venom (AmV); tolerant beekeepers (TBKs), who received ≥50 stings/year; and healthy nonexposed controls (HCs). We measured serum levels of sIgE and specific IgG4 (sIgG4) to AmV, rApi m 1, rApi m 2, rApi m 3, Api m 4, rApi m 5, and rApi m10, as well as AmV-induced basophil degranulation, percentage of T-cell subsets, regulatory T cells (Treg), and IL-10 production. RESULTS: Compared with TBKs, APs had high levels of sIgE to AmV and all its allergic components (P<.001), together with a high basophil activation rate (P<.001). Conversely, compared with APs, TBKs had higher levels of sIgG4 (P<.001) and IL-10 (P<.0001), as well as an enhanced CTLA-4+ Treg population (P=.001), expanded Helios- Treg (P<.003), and reduced type 1 helper T cells (TH1) (P=.008), TH2 (P=.004), and TH17 (P=.007) subsets. CONCLUSIONS: The profile of TBKs, which was strongly marked by Treg activity, differed from that of TBKs. This natural tolerance would be led by the expansion of inducible Helios- Treg cells at the peripheral level. The Helios- Treg population could be a novel candidate biomarker for monitoring tolerance.

Psychological profile of teenagers toward organ donation: a multicentric study in Spain.

BACKGROUND: It is important for teenagers to have a favorable attitude toward organ donation and transplantation (ODT) in order to increase the number of future donors. To determine the attitude of teenagers in the South East of Spain toward ODT and to analyze the psychosocial variables related to this attitude. METHODS: The study population consisted of young teenagers in the South East of Spain. A stratified sample was selected by geographical location, sex and age (n = 4, 117). Attitude was assessed using a validated questionnaire about ODT (PCID-ODT Ríos). Statistical analysis: Student's t-test, Chi-squared test and a multivariate analysis. RESULTS: The questionnaire completion rate was 87% (n = 3572). Attitude toward ODT was favorable in 46% of cases (n = 1633) and undecided in 43% (n = 1543). Several psychosocial variables had a favorable effect on donation: believing that one has good information about ODT (Odds Ratio [OR] 1.706); discussing the subject with the family (OR 1.543) and friends (OR 1.818); carrying out pro-social activities (OR 1.642); having a favorable attitude toward cremation (OR 1.466) and autopsy (OR 1.470); and, finally, not being afraid of scars (OR 4.184). CONCLUSIONS: Teenagers in the South East of Spain are not currently inclined to support organ donation. This attitude is related to many psychosocial factors, mainly connected to not having good information about the subject, not discussing it in social circles and the fear of body mutilation. It would be appropriate to create educational interventional strategies in this group to prevent a negative impact on future donation rates.

A Multicentre and stratified study of the attitude of medical students towards organ donation in Spain.

INTRODUCTION: Medical students represent a new generation of medical thought, and if they have a favourable attitude towards organ donation this will greatly encourage its promotion. OBJECTIVE: To analyse the attitude of medical students in Spanish universities towards the donation of their own organs and to determine the factors affecting this attitude. MATERIAL AND METHODS: Type of study: A sociological, interdisciplinary, multicentre, and observational study in Spain. STUDY POPULATION: Students studying a degree in medicine enrolled in Spain (n = 34,000). SAMPLE SIZE: A sample of 9598 students (confidence of 99% and precision of ±1%), stratified by geographical area and academic year. Instrument of measurement: A validated questionnaire of attitude towards organ donation and transplantation (PCID-DTO RIOS) was self-administered and completed anonymously. RESULTS: The questionnaire completion rate was 95.7% (n = 9.275). 80% were in favour of donation, 2% against and 18% were undecided. The following main variables were related to a favourable attitude: being of the female sex (Odds Ratio = 1.739); being in the sixth year of the degree (OR = 2.506); knowing a donor (OR = 1.346); having spoken about the subject with one's family (OR = 2.132) and friends (OR = 1.333); having a family circle that is in favour, more specifically, having a father (OR = 1.841), mother (OR = 2.538) or partner in favour (OR = 2.192); being a blood donor (OR = 2.824); acceptance of the mutilation of the body if it were necessary (OR = 2.958); and being an atheist or an agnostic (OR = 1.766). CONCLUSIONS: Spanish medical students generally have a favourable attitude towards organ donation, although 20% are not in favour.

Functional insights into the infective larval stage of Anisakis simplex s.s., Anisakis pegreffii and their hybrids based on gene expression patterns.

BACKGROUND: Anisakis simplex sensu stricto and Anisakis pegreffii are sibling species of nematodes parasitic on marine mammals. Zoonotic human infection with third stage infective larvae causes anisakiasis, a debilitating and potentially fatal disease. These 2 species show evidence of hybridisation in geographical areas where they are sympatric. How the species and their hybrids differ is still poorly understood. RESULTS: Third stage larvae of Anisakis simplex s.s., Anisakis pegreffii and hybrids were sampled from Merluccius merluccius (Teleosti) hosts captured in waters of the FAO 27 geographical area. Specimens of each species and hybrids were distinguished with a diagnostic genetic marker (ITS). RNA was extracted from pools of 10 individuals of each taxon. Transcriptomes were generated using Illumina RNA-Seq, and assembled de novo. A joint assembly (here called merged transcriptome) of all 3 samples was also generated. The inferred transcript sets were functionally annotated and compared globally and also on subsets of secreted proteins and putative allergen families. While intermediary metabolism appeared to be typical for nematodes in the 3 evaluated taxa, their transcriptomes present strong levels of differential expression and enrichment, mainly of transcripts related to metabolic pathways and gene ontologies associated to energy metabolism and other pathways, with significant presence of excreted/secreted proteins, most of them allergens. The allergome of the 2 species and their hybrids has also been thoroughly studied; at least 74 different allergen families were identified in the transcriptomes. CONCLUSIONS: A. simplex s.s., A. pegreffi and their hybrids differ in gene expression patterns in the L3 stage. Strong parent-of-origin effects were observed: A. pegreffi alleles dominate in the expression patterns of hybrids albeit the latter, and A. pegreffii also display significant differences indicating that hybrids are intermediate biological entities among their parental species, and thus of outstanding interest in the study of speciation in nematodes. Analyses of differential expression based on genes coding for secreted proteins suggests that co-infections presents different repertoires of released protein to the host environment. Both species and their hybrids, share more allergen genes than previously thought and are likely to induce overlapping disease responses.

Do Spanish Medical Students Understand the Concept of Brain Death?

OBJECTIVE: To analyze the level of understanding of the brain death concept among medical students in universities in Spain. METHODS: This cross-sectional sociological, interdisciplinary, and multicenter study was performed on 9598 medical students in Spain. The sample was stratified by geographical area and academic year. A previously validated self-reported measure of brain death knowledge (questionnaire Proyecto Colaborativo Internacional Donante sobre la Donación y Transplante de Organos) was completed anonymously by students. RESULTS: Respondents completed 9275 surveys for a completion rate of 95.7%. Of those, 67% (n = 6190) of the respondents understood the brain death concept. Of the rest, 28% (n = 2652) did not know what it meant, and the remaining 5% (n = 433) believed that it did not mean that the patient was dead. The variables related to a correct understanding of the concept were: (1) being older ( P < .001), (2) studying at a public university ( P < .001), (3) year of medical school ( P < .001), (4) studying at one of the universities in the south of Spain ( P = .003), (5) having discussed donation and transplantation with the family ( P < .001), (6) having spoken to friends about the matter ( P < .001), (7) a partner's favorable attitude toward donation and transplantation ( P < .001), and (8) religious beliefs ( P < .001). CONCLUSIONS: Sixty-seven percent of medical students know the concept of brain death, and knowledge improved as they advanced in their degree.

Incidence and risk factors for post-traumatic stress disorder in a population affected by a severe flood.

OBJECTIVES: We aimed to study the risk of developing post-traumatic stress disorder (PTSD) symptoms in people who resided in an affected area by an extremely severe flood, and sociodemographic risk factors associated with this condition. STUDY DESIGN: A geographic information system (GIS) was used to distribute the rainfall data. A case-control study was developed to study the relationship between PTSD and sociodemographic risk factors. METHODS: To delineate the areas affected by the flood and the intensity of this rainfall in comparison with historical hydrological data, we employed geographical information systems (GIS). Then, we recruited a representative sample of the affected population and another population sample that lived at the time of this disaster in adjacent geographical areas that were not affected. Both groups were randomly selected in primary care practices, from December 1st 2012 to January 31st 2013. All participants, 70 from the affected areas and 91 from the non-affected, filled a sociodemographic questionnaire and the trauma questionnaire (TQ) to identify and rate PTSD symptoms. RESULTS: Our GIS analysis confirmed that the amount of precipitation in 2012 in the areas affected by the flood was exceptionally high compared with historical average rainfall data (461l per square metre vs 265). Individuals who resided in the affected areas at the time of the flood were at much higher risk of developing PTSD symptoms (OR: 8.18; 95% CI: 3.99-17.59) than those living in adjacent, non-affected localities. Among the sociodemographic variables included in this study, only material and financial losses were strongly associated with the onset of PTSD (P < 0.001). Physical risk during this life-threatening catastrophe also indicated a positive correlation with later development of PTSD symptoms; however, it did not reach statistical significance (P = 0.06). CONCLUSIONS: Populations affected by severe floods may suffer an increase of PTSD symptoms in the following months. This finding, along with the importance of material losses as a predictor for such disorder, may help develop effective plans to minimize the negative impact of these natural disasters on public health.

Variability in source sediment contributions by applying different statistic test for a Pyrenean catchment.

Information on sediment contribution and transport dynamics from the contributing catchments is needed to develop management plans to tackle environmental problems related with effects of fine sediment as reservoir siltation. In this respect, the fingerprinting technique is an indirect technique known to be valuable and effective for sediment source identification in river catchments. Large variability in sediment delivery was found in previous studies in the Barasona catchment (1509 km2, Central Spanish Pyrenees). Simulation results with SWAT and fingerprinting approaches identified badlands and agricultural uses as the main contributors to sediment supply in the reservoir. In this study the <63 µm sediment fraction from the surface reservoir sediments (2 cm) are investigated following the fingerprinting procedure to assess how the use of different statistical procedures affects the amounts of source contributions. Three optimum composite fingerprints were selected to discriminate between source contributions based in land uses/land covers from the same dataset by the application of (1) discriminant function analysis; and its combination (as second step) with (2) Kruskal-Wallis H-test and (3) principal components analysis. Source contribution results were different between assessed options with the greatest differences observed for option using #3, including the two step process: principal components analysis and discriminant function analysis. The characteristics of the solutions by the applied mixing model and the conceptual understanding of the catchment showed that the most reliable solution was achieved using #2, the two step process of Kruskal-Wallis H-test and discriminant function analysis. The assessment showed the importance of the statistical procedure used to define the optimum composite fingerprint for sediment fingerprinting applications.

Medical students faced with related and unrelated living kidney donation: a stratified and multicentre study in Spain.

INTRODUCTION: The attitude of medical students towards living kidney donation (LKD) is of great interest given that they will become promoters of this technique in the near future. OBJECTIVE: To analyse the attitude of Spanish medical students towards related and unrelated LKD and to determine the factors affecting this attitude. MATERIALS AND METHODS: Type of study: A sociological, interdisciplinary, multicentre, and observational study. STUDY POPULATION: Medical students enrolled in Spain (n = 34.000). SAMPLE SIZE: A sample of 9598 students (99 % confidence and precision of ±1 %), stratified by geographical area and academic year. Measurement instrument: A validated questionnaire (PCID-DVR RIOS) was administered and completed anonymously. RESULTS: There was a completion rate of 95.7 % (n = 9275); 93 % (n = 8630) were in favour of related LKD, and 30 % (n = 2784) were in favour of unrelated LKD. The following factors were associated with this attitude: (1) age (p = 0.008); (2) sex (p < 0.001); (3) year of university degree (p < 0.001); (4) a belief that a transplant might be necessary in the future (p < 0.001); (5) attitude towards deceased organ donation (p < 0.001); (6) a willingness to accept a kidney from a living donor (p < 0.001); (7) attitude towards living liver donation (p < 0.001); (8) a partner's attitude towards donation (p < 0.001); (9) having spoken about the subject with one's family (p < 0.001), or friends (p < 0.001); (10) pro-social behaviour (p < 0.001); (11) the respondent's religious attitude (p < 0.001); and (12) fear of possible mutilation of the body after donation (p < 0.001). CONCLUSIONS: The attitude of medical students towards LKD is very favourable when it is the related kind of donation, and it is associated with factors of general knowledge about organ donation and transplantation and social interaction and religion.

Latin Americans in Spain and their attitude toward living kidney donation.

INTRODUCTION: The Latin American (LA) population in Spain is ever increasing in size and is perfectly integrated into the social structure. The objectives were to analyze the attitude of citizens, born in Latin America and living in Spain, toward living kidney donation (LKD) and to determine the psychosocial variables affecting this attitude. MATERIAL AND METHODS: A sample of LA residents living in Spain was obtained randomly in 2010 and stratified according to the respondent's nationality (n = 1314). Attitude was evaluated using a validated questionnaire ("Proyecto Colaborativo Internacional Donante sobre Donación de Vivo Renal" Ríos). The survey was self-administered and completed anonymously. RESULTS: The questionnaire completion rate was 86% (n = 1.132). A total of 89% (n = 1003) were in favor of related living donation, and 30% if the donation were unrelated. The variables associated with attitude toward LKD were as follows: sex (p = 0.043); marital status (p = 0.013); previous experience of organ donation (p = 0.009); attitude toward deceased organ donation (p < 0.001); a respondent's belief that he or she could be a possible recipient of a future transplant (p < 0.001); knowledge of a partner's opinion (p = 0.021); family discussion about organ donation (p = 0.001); knowledge of the view of one's religion toward donation (p < 0.001); concern about "mutilation" after donation (p = 0.004); and evaluation of the risk from living donation (p = 0.036). CONCLUSIONS: The attitude of LA citizens residing in Spain was favorable both toward related LKD and unrelated living donation.

Validation and cross-cultural adaptation of the 'Fibromyalgia Participation Questionnaire' to the Spanish population: study protocol.

There are few high-quality instruments to evaluate the participation and social functioning of fibromyalgia patients. The Fibromyalgia Participation Questionnaire (FPQ) is a questionnaire that evaluates these aspects with high reliability and validity in its German original version. The aim of this work was to describe the translation and cross-cultural adaptation process of the FPQ into Spanish and its validation to ensure the equivalence against the original version. The questionnaire will be translated according to the FACIT methodology, and it will be tested in the Clinical Management Unit of North Almeria Health Area. This methodology includes several stages: double forward translation, reconciled version, back-translation, review of the previous versions and development of the prefinal version for the pretest. Once the pretest ends, the final version of the questionnaire will be developed, which will be subjected to a validation process to study its psychometric properties. Reliability will be studied by internal consistency and test-retest reliability through Cronbach's alpha and Pearson's correlation coefficient, respectively. External and construct validity will be analysed using correlation coefficients, content validity with an empirical analysis, and a differential item functioning analysis will be employed to measure discriminative validity. The presence of ceiling and floor effects will be calculated too. The validation of the FPQ into different languages will allow better evaluation and treatment based on the observed limitations fibromyalgia patients suffer from, as well as bringing the possibility to compare between other countries and generalize its use in the scientific community.

[Renal replacement therapy in Intensive Care Units in Catalonia (Spain)]. / Utilización de las terapias de depuración extracorpórea en los Servicios de Medicina Intensiva de Cataluña (España).

OBJECTIVE: To assess the indications, settings and techniques used in renal replacement therapy (RRT) in Intensive Care Units (ICUs). STUDY DESIGN: A prospective, multicenter observational study was carried out. SETTING: Intensive Care Units. PATIENTS: All patients admitted to ICUs during the two-month study period in 2011 who required RRT. INTERVENTIONS: None. VARIABLES OF INTEREST: Patient demographic characteristics, baseline clinical data, RRT technique and materials used. RESULTS: Thirty-three patients were analyzed. RRT was started within the first 24hours after ICU admission in 17 of the 33 patients (52%). At the start of RRT, 18% of the patients (n=6) presented grade R on the RIFLE acute kidney injury (AKI) scale. The most common disorder associated with AKI was multiple organ dysfunction syndrome (64%; n=21). At the start of RRT, most patients (76%; n=25) presented hemodynamic instability, while the remaining 24% (n=8) were considered hemodynamically stable. The most common RRT technique in hemodynamically stable patients was continuous renal replacement therapy (CRRT) (63%; n=5). CRRT was the technique of choice in all 25 of the hemodynamically unstable patients (100%). Anticoagulation was used in 55% (n=18) of the patients. In most cases (61%, n=20), RRT was administered through the right femoral vein. In 84% (n=28) of the patients, the ultrafiltration effluent flow rate was ≤ 35ml/kg/h. CONCLUSIONS: The ICU physicians in this study followed current RRT guidelines. CRRT was preferred over intermittent renal replacement therapy, regardless of patient hemodynamic status.

Renal replacement therapy in the critical patient: treatment variation over time.

OBJECTIVES: To analyze the evolution of patients subjected to renal replacement therapy (RRT), and to determine risk factors associated with mortality and the recovery of renal function. DESIGN: A prospective, observational study of critically ill patients. SETTING: Clinical-surgical Intensive Care Unit (ICU) of Sabadell Hospital (Spain). PATIENTS: Inclusion of all patients treated in our Unit due to acute renal failure (ARF) requiring RRT. PRIMARY VARIABLES OF INTEREST: We recorded epidemiological data, severity using the APACHE II score, days of the technique, ICU mortality, and renal function recovery. The study period was divided into 2 parts: part 1 (2000-2004) and part 2 (2005-2009). The 2 periods were compared using the Student t-test for continuous variables and the chi-squared test for categorical variables. Multiple regression analysis was performed to determine the risk factors for mortality and recovery of renal function. RESULTS: A total of 304 patients were treated. Sepsis was the main etiology of ARF (61%), involving principally respiratory and abdominal foci. In the second period the convective technique and community-acquired ARF were far more prevalent than in the first period. There were fewer days of therapy in the second period (19.7 versus 12.3 days; P=.015). Total ICU mortality was 52.3%, with a decrease in the last period (61.9% to 45.5%: P=.003). The risk factors associated to mortality were creatinine upon admission (odds ratio [OR] 0.77; 95% confidence interval [95%CI] 0.61-0.97) and treatment with IHD alone (OR 0.37, 95%CI 0.16-0.87). Survivors had normal renal function at ICU discharge in 56.7% of the cases in the second period, vs in 72.9% in the first period, with more patients subjected to IHD in the second period (10.4% versus 26.8%). The factors related to the recovery of renal function were creatinine upon admission (OR 1.98, 95%CI 1.12-3.48), acute renal failure (OR 0.11, 95%CI 0.04-0.34) and treatment with continuous techniques (OR 0.18, 95%CI 0.03-0.85). CONCLUSIONS: Mortality among critically ill patients subjected to RRT has improved in recent years.

Xenotransplantation and Risks: The Opinion of Veterinary Students at Spanish Universities.

BACKGROUND: Understanding the perception of the risks associated with xenotransplant, especially among professionals who will contribute to the care of the animals, is important for xenotransplant to become a clinical reality. The objective of this study was to analyze opinions regarding the risks of organ xenotransplant among veterinary university students in Spain. METHODS: The study population was 2683 veterinary students from different courses and universities in Spain. Instrument valuation: Validated self-administered questionnaire completed anonymously (PCID-XENOTx-Ríos). Consent to collaborate in the study was requested. Variables for the study: attitude toward xenotransplant and risks (infectious, immunologic, ethical/moral, philosophical, religious, other unspecified risks). STATISTICS: descriptive analysis, Student t test, χ2 test, and Fisher exact test. RESULTS: Of the total number of respondents, 2646 students answered this question, with a completion rate of 98.6%. They considered immunologic risk 78.4% (n = 2074), infectious risk 48.6% (n = 1286), ethical/moral risk 10.7% (n = 284), philosophical risk 5.2% (n = 137), religious risk 1.5% (n = 40), and other risks 3.9% (n = 104). Significant relationships were observed between immunologic risks (P < .001), ethical/moral risks (P < .001), and other risks (P = .002). CONCLUSIONS: Despite the consideration of different types of risks, the favorable attitude toward xenotransplant among veterinary students at Spanish universities is highly prevalent, and evidence-based information campaigns on the different risks associated with xenotransplant are important.

[Neurologic complications of central neuraxial blocks]. / Complicaciones neurológicas en los bloqueos centrales.

Central neuraxial blocks, which are associated with a low incidence of complications, are safe. When complications do occur, however, the resulting morbidity and mortality is considerable. The reported incidence of complications in all series is under 4 per 10000 patients, but given the absence of formal registries and notification procedures, which have legal implications, the real rate of occurrence of these rare events is uncertain. We searched the literature through PubMed and the Cochrane Plus Library for a 5-year period, using the search terms epidural anesthesia AND safety, spinal anesthesia AND safety, complications AND epidural anesthesia, complications AND spinal anesthesia, neurologic complications AND epidural anesthesia, and neurologic complications AND spinal anesthesia. Neuraxial injury after a central blockade may be the result of anatomical and/or physiological lesions affecting the spinal cord, spinal nerves, nerve roots, or blood supply. The pathophysiology of neuraxial injury may be related to mechanical, ischemic, or neurotoxic damage or any combination. When a complication occurs, factors related to the technique will have interacted with pre-existing patient-related conditions. Various scientific societies have published guidelines for managing the complications of regional anesthesia. Recently published clinical practice guidelines recommend ultrasound imaging as a useful tool in performing a central neuraxial block.

Clinical risk factors for early mortality in patients with community-acquired septic shock. The importance of adequate source control.

OBJECTIVE: To evaluate the incidence and risk factors for early mortality (EM) in the ICU in patients with community-acquired septic shock (CASS). DESIGN: A retrospective cohort study of patients with CASS admitted to the ICU (2003-2016). SETTING: ICU at a University Hospital in Spain. PATIENTS: All consecutive patients admitted to the ICU with CASS. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: CASS was defined according to the Sepsis-3 definitions. EM were defined as occurring within of 72h following ICU admission. A multinomial logistic regression analysis was performed to identify the risk factors associated with early deaths. RESULTS: During the study period, 625 patients met the Sepsis-3 criteria and admitted with CASS. 14.4% of all patients died within the first 72h. Of 161 patients who died in the ICU, 90 (55.9%) died within the first 72h. The percentage of early and late mortality did not vary significantly during the study period. The need and adequacy of source control were significantly lower in patients with EM. In the multivariate analysis, ARDS, non-respiratory infections, bacteremia and severity at admission were variables independently associated with EM. The only factor that decreased EM was adequate source control in patients with infections amenable to source control. CONCLUSIONS: The incidence of EM has remained stable over time, which means that more than half of the patients who die from CASS do so within the first 72h. Infections where adequate source control can be performed have lower EM.

Long-term corticosteroid-induced chronic glaucoma model produced by intracameral injection of dexamethasone-loaded PLGA microspheres.

PURPOSE: To evaluate a new chronic glaucoma model produced by intracameral injection of dexamethasone-loaded poly lactic-co-glycolic acid microspheres (Dex-PLGA-Ms) over six months. METHODS: Healthy rats received two injections (at baseline and Week 4) of Dex-PLGA-Ms into the anterior chamber of the right eye. Clinical signs and intraocular pressure (IOP) were weekly recorded. The structure of the retina and optic nerve was in vivo evaluated using optical coherence tomography (OCT) every two weeks and functionally using dark- and light-adapted electroretinography at 0-12-24 weeks. Histological studies were also performed. RESULTS: IOP progressively increased up to hypertension (23.22 ± 3.63 mmHg) in both eyes but did so later in left eyes. OCT quantified a decrease in full-thickness retina posterior pole (R), retinal-nerve-fiber layer (RNFL), and ganglion-cell layer (GCL) thickness up to 24 weeks. Right eyes showed higher neuroretinal thickness loss up to week 8. RNFL experienced the highest percentage thickness loss at the inferior-superior axis, while in GCL the inner sectors of the horizontal axis (Nasal-Temporal) suffered the greatest decrease in thickness. Retinal ganglion cell, photoreceptor, and intermediate cell functionality decreased over time. Increased deposition of collagen IV was also found in zonular fibers and the ciliary body. CONCLUSIONS: This work shows the usefulness of drug delivery systems, not to treat pathology but to induce it. Only two injections of Dex-PLGA-Ms in the anterior chamber of rat eyes were enough to progressively create ocular hypertension and subsequent functional and structural neuroretinal degeneration, at least over 6 months.

Clinical risk factors for early mortality in patients with community-acquired septic shock. The importance of adequate source control.

OBJECTIVE: To evaluate the incidence and risk factors for early mortality (EM) in the ICU in patients with community-acquired septic shock (CASS). DESIGN: A retrospective cohort study of patients with CASS admitted to the ICU (2003-2016). SETTING: ICU at a University Hospital in Spain. PATIENTS: All consecutive patients admitted to the ICU with CASS. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: CASS was defined according to the Sepsis-3 definitions. EM were defined as occurring within of 72h following ICU admission. A multinomial logistic regression analysis was performed to identify the risk factors associated with early deaths. RESULTS: During the study period, 625 patients met the Sepsis-3 criteria and admitted with CASS. 14.4% of all patients died within the first 72h. Of 161 patients who died in the ICU, 90 (55.9%) died within the first 72h. The percentage of early and late mortality did not vary significantly during the study period. The need and adequacy of source control were significantly lower in patients with EM. In the multivariate analysis, ARDS, non-respiratory infections, bacteremia and severity at admission were variables independently associated with EM. The only factor that decreased EM was adequate source control in patients with infections amenable to source control. CONCLUSIONS: The incidence of EM has remained stable over time, which means that more than half of the patients who die from CASS do so within the first 72h. Infections where adequate source control can be performed have lower EM.