Spin-Crossing in the (Z)-Selective Alkyne Semihydrogenation Mechanism Catalyzed by Mo3S4 Clusters: A Density Functional Theory Exploration.

Semihydrogenation of internal alkynes catalyzed by the air-stable imidazolyl amino [Mo3S4Cl3(ImNH2)3]+ cluster selectively affords the (Z)-alkene under soft conditions in excellent yields. Experimental results suggest a sulfur-based mechanism with the formation of a dithiolene adduct through interaction of the alkyne with the bridging sulfur atoms. However, computational studies indicate that this mechanism is unable to explain the experimental outcome: mild reaction conditions, excellent selectivity toward the (Z)-isomer, and complete deuteration of the vinylic positions in the presence of CD3OD and CH3OD. An alternative mechanism that explains the experimental results is proposed. The reaction begins with the hydrogenation of two of the Mo3(µ3-S)(µ-S)3 bridging sulfurs to yield a bis(hydrosulfide) intermediate that performs two sequential hydrogen atom transfers (HAT) from the S-H groups to the alkyne. The first HAT occurs with a spin change from singlet to triplet. After the second HAT, the singlet state is recovered. Although the dithiolene adduct is more stable than the hydrosulfide species, the large energy required for the subsequent H2 addition makes the system evolve via the second alternative pathway to selectively render the (Z)-alkene with a lower overall activation barrier.

Relationship between diabetic peripheral neuropathy and adherence to the Mediterranean diet in patients with type 2 diabetes mellitus: an observational study.

PURPOSE: The main study goal is to assess the relationship between adherence to the mediterranean diet (MD) and the presence of diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes mellitus (T2DM). METHODS: Observational pilot study of 174 patients diagnosed with T2DM. Sociodemographic and anthropometric variables, physical activity, smoking habits, blood biochemical parameters and comorbidities were recorded. The presence of alterations in sensitivity to pressure, pain, thermal and vibration was explored. Good MD adherence was a score ≥ 9 the 14-point MD adherence questionnaire (MEDAS-14). RESULTS: The study population consisted of 174 patients (61.5% men and 38.5% women), with a mean age of 69.56 ± 8.86 years; 19% of these patients adhered to the MD. The score obtained in the MEDAS-14 was higher in patients who did not present alterations in sensitivity to pressure (p = 0.047) or vibration (p = 0.021). The patients without diabetic peripheral neuropathy were more likely to comply with the MD and had a higher score on the MEDAS-14 (p = 0.047). However, multivariate analysis showed that only altered sensitivity to pressure was associated with adherence to the MD (altered sensitivity OR = 2.9; 95%CI 1.02-8.22; p = 0.045). CONCLUSIONS: Although the patients with DPN had lower scores on the MEDAS questionnaire and therefore poorer adherence to the mediterranean diet, the only parameter significantly associated with the MD was that of sensitivity to pressure (monofilament test).

Expression of 20 SCPP genes during tooth and bone mineralization in Senegal bichir.

The African bichir (Polypterus senegalus) is a living representative of Polypteriformes. P. senegalus possesses teeth composed of dentin covered by an enameloid cap and a layer of collar enamel on the tooth shaft, as in lepisosteids. A thin layer of enamel matrix can also be found covering the cap enameloid after its maturation and during the collar enamel formation. Teleosts fish do not possess enamel; teeth are protected by cap and collar enameloid, and inversely in sarcopterygians, where teeth are only covered by enamel, with the exception of the cap enameloid in teeth of larval urodeles. The presence of enameloid and enamel in the teeth of the same organism is an opportunity to solve the evolutionary history of the presence of enamel/enameloid in basal actinopterygians. In silico analyses of the jaw transcriptome of a juvenile bichir provided twenty SCPP transcripts. They included enamel, dentin, and bone-specific SCPPs known in sarcopterygians and several actinopterygian-specific SCPPs. The expression of these 20 genes was investigated by in situ hybridizations on jaw sections during tooth and dentary bone formation. A spatiotemporal expression patterns were established and compared with previous studies of SCPP gene expression during enamel/enameloid and bone formation. Similarities and differences were highlighted, and several SCPP transcripts were found specifically expressed during tooth or bone formation suggesting either conserved or new functions of these SCPPs.

Psychological impact after treatment in patients with head and neck cancer.

BACKGROUND: Cancer is the second cause of death all over the world and it causes considerable morbidity, disability, and treatment sequela, which often lead to post-treatment pain and disfigurement. This study aims to evaluate such physical sequelae, and their psychological, (cognitive and emotional), impact, in a cohort of patients treated for Head and Neck (HNC) cancer, in search for methods to help such patients deal effectively with the psychological effects of their cancer treatments adverse consequences. MATERIAL AND METHODS: The sample consists of 56 subjects, 47 men and 9 women, ranging from 47 years to 86 years of age, who were treated for head and neck cancers at Spanish Public General Hospital in the Otolaryngology Unit, Surgery Section. Two types of questionnaires were used in the study: the Questionnaire of Sequelae after Treatment of head and neck carcinoma and the State-Trait Anxiety Inventory (STAI-E and R). RESULTS: With respect to anxiety, the study found high levels of state anxiety which was significantly associated with the degree of perception of social stigma but was not associated with the post-treatment sequelae themselves nor with the level of discomfort that such symptomatic sequelae produced. The presence of a post-surgical stoma with cannula, increased patient's stigma (both components: external rejection and self-rejection) and state anxiety ratings, while there was no difference in state anxiety between cannulated and non-cannulated patients. There are few differences between men and women in terms of the presence of anxiety and their responses are similar in terms of the after-effects of surgery. CONCLUSIONS: Our study confirmed that current treatments for Head and Neck carcinoma generate adverse symptomatic sequela that impose significant psychological and physical burden for these patients. We will discuss the various pathways for preventive intervention that these findings open up.

Base-Free Catalytic Hydrogen Production from Formic Acid Mediated by a Cubane-Type Mo3S4 Cluster Hydride.

Formic acid (FA) dehydrogenation is an attractive process in the implementation of a hydrogen economy. To make this process greener and less costly, the interest nowadays is moving toward non-noble metal catalysts and additive-free protocols. Efficient protocols using earth abundant first row transition metals, mostly iron, have been developed, but other metals, such as molybdenum, remain practically unexplored. Herein, we present the transformation of FA to form H2 and CO2 through a cluster catalysis mechanism mediated by a cuboidal [Mo3S4H3(dmpe)3]+ hydride cluster in the absence of base or any other additive. Our catalyst has proved to be more active and selective than the other molybdenum compounds reported to date for this purpose. Kinetic studies, reaction monitoring, and isolation of the [Mo3S4(OCHO)3(dmpe)3]+ formate reaction intermediate, in combination with DFT calculations, have allowed us to formulate an unambiguous mechanism of FA dehydrogenation. Kinetic studies indicate that the reaction at temperatures up to 60 °C ends at the triformate complex and occurs in a single kinetic step, which can be interpreted in terms of statistical kinetics at the three metal centers. The process starts with the formation of a dihydrogen-bonded species with Mo-H···HOOCH bonds, detected by NMR techniques, followed by hydrogen release and formate coordination. Whereas this process is favored at temperatures up to 60 °C, the subsequent ß-hydride elimination that allows for the CO2 release and closes the catalytic cycle is only completed at higher temperatures. The cycle also operates starting from the [Mo3S4(OCHO)3(dmpe)3]+ formate intermediate, again with preservation of the cluster integrity, which adds our proposal to the list of the infrequent cluster catalysis reaction mechanisms.

Multiscale Modeling of Thiol Overoxidation in Peroxiredoxins by Hydrogen Peroxide.

In this work, we employ a multiscale quantum-classical mechanics (QM/MM) scheme to investigate the chemical reactivity of sulfenic acids toward hydrogen peroxide, both in aqueous solution and in the protein environment of the peroxiredoxin alkyl hydroperoxide reductase E from Mycobacterium tuberculosis (MtAhpE). The reaction of oxidation of cysteine with hydrogen peroxides, catalyzed by peroxiredoxins, is usually accelerated several orders of magnitude in comparison with the analogous reaction in solution. The resulting cysteine sulfenic acid is then reduced in other steps of the catalytic cycle, recovering the original thiol. However, under some conditions, the sulfenic acid can react with another equivalent of oxidant to form a sulfinic acid. This process is called overoxidation and has been associated with redox signaling. Herein, we employed a multiscale scheme based on density function theory calculations coupled to the classical AMBER force field, developed in our group, to establish the molecular basis of thiol overoxidation by hydrogen peroxide. Our results suggest that residues that play key catalytic roles in the oxidation of MtAhpE are not relevant in the overoxidation process. Indeed, the calculations propose that the process is unfavored by this particular enzyme microenvironment.

A clinically oriented computer model for radiofrequency ablation of hepatic tissue with internally cooled wet electrode.

PURPOSE: To improve the computer modelling of radiofrequency ablation (RFA) by internally cooled wet (ICW) electrodes with added clinically oriented features. METHODS: An improved RFA computer model by ICW electrode included: (1) a realistic spatial distribution of the infused saline, and (2) different domains to distinguish between healthy tissue, saline-infused tumour, and non-infused tumour, under the assumption that infused saline is retained within the tumour boundary. A realistic saline spatial distribution was obtained from an in vivo pig liver study. The computer results were analysed in terms of impedance evolution and coagulation zone (CZ) size, and were compared to the results of clinical trials conducted on 17 patients with the same ICW electrode. RESULTS: The new features added to the model provided computer results that matched well with the clinical results. No roll-offs occurred during the 4-min ablation. CZ transversal diameter (4.10 ± 0.19 cm) was similar to the computed diameter (4.16 cm). Including the tumour and saline infusion in the model involved (1) a reduction of the initial impedance by 10 - 20 Ω, (2) a delay in roll-off of 20 s and 70 - 100 s, respectively, and (3) 18 - 31% and 22 - 36% larger CZ size, respectively. The saline spatial distribution geometry was also seen to affect roll-off delay and CZ size. CONCLUSIONS: Using a three-compartment model and a realistic saline spatial distribution notably improves the match with the outcome of the clinical trials.

Analysis of the effectiveness of training school personnel in the management of food allergy and anaphylaxis.

BACKGROUND: Food allergy is a very frequent and increasingly common disease in children and adolescents. It affects quality of life and can even be life-threatening. Given that 10-18% of allergic/anaphylactic food reactions take place in schools, it is essential to provide school personnel with training on the management of reactions. METHODS: The Allergy Unit of Hospital Universitario de Fuenlabrada, Spain, organized a conference entitled "Management of Food Allergy in Children and Adolescents in School Centers" during which teachers, cooks, cafeteria monitors, and summer-camp leaders underwent a training course. Attendees filled out a questionnaire with eight questions before and after the course to assess their self-efficacy in management of food allergy and anaphylaxis. The results were compared. RESULTS: A total of 191 people participated (51% dining-room monitors, 24% teachers, 13% cooks, and 12% other professions). The areas in which the attendees presented the lowest confidence before receiving the course were recognition of symptoms and treatment of the reactions/anaphylaxis. The mean score for each of the eight concepts evaluated improved after the training course. This improvement was significant in the management of anaphylaxis. CONCLUSIONS: Our study demonstrates the usefulness of a self-efficacy scale in school personnel as a tool to assess the ability to manage food allergy and anaphylaxis. It can help to identify problem areas in which more specific training programs can be implemented.

Awareness of obstetric warning signs in Ecuador: a cross-sectional study.

OBJECTIVE: In Ecuador, the reported maternal death rate was 45.71 per 100,000 live births in 2013. This may be partly due to a lack of maternal knowledge of obstetric warning signs during pregnancy, delivery and the post-partum period. This study sought to evaluate awareness of obstetric warning signs among pregnant women in relation to individual demographic and area-level socio-economic indicators. STUDY DESIGN: We conducted a cross-sectional analysis of data collected by Ecuador's Ministry of Health at the conclusion of a national maternal health campaign (2014-2015). A nationally representative sample of 3435 pregnant women from the nine administrative zones completed surveys regarding basic demographics and their awareness of obstetric warning signs. METHODS: We defined eight obstetrical warning signs according to the literature and Ecuadorian practice that could occur during pregnancy, delivery and the post-partum period (severe headache, strong abdominal ache, bleeding or presence of malodorous secretion, rupture of the amniotic sac, high fever, abnormal presentation of the baby, decrease in baby's movements and delayed labour). A woman was considered 'aware' if she recognised at least four of the eight warning signs and stated she would seek immediate healthcare at their presentation. For each administrative zone, four socio-economic indicators (poverty, illiteracy, unemployment and subemployment) were obtained from the National Institute of Statistics and Census. Correlates of awareness of the obstetric warning signs were evaluated using hierarchical logistic models clustered by the administrative zone. RESULTS: Nationally, 86.9% of women were 'aware' of obstetric warning signs. After adjustment for age, socio-economic indicators and clustering, indigenous participants were 59% less likely to be aware of obstetric warning signs than mestizos (odds ratio [OR] = 0.41, 95% confidence interval [CI] = 0.28-0.59). For every 1% increase in area poverty, participants had a 5% decreased likelihood of being aware of obstetric warning signs (OR = 0.95, 95% CI = 0.93-0.96), adjusting for age, ethnicity and other socio-economic indicators. The most effective source of campaign information about obstetric warning signs was personal communication with a healthcare professional, as opposed to mass media advertisements (OR = 1.90, 95% CI = 1.34-2.71). CONCLUSIONS: A majority of Ecuadorian pregnant and post-partum women are aware of obstetric warning signs. Indigenous ethnicity and area-level poverty are associated with a lack of awareness. Personal communication with a healthcare professional was the most effective source of information. These findings have implications for improvement of maternal awareness of warning signs.

Pitfalls in the ABTS Peroxidase Activity Test: Interference of Photochemical Processes.

ABTS (2,2'-azinobis(3-ethylbenzothiazoline)-6-sulfonic acid) oxidation to form its radical cation in the presence of H2O2 is frequently used as a test for determining the peroxidase activity of enzyme mimics. Detailed studies using salen-type Mn(III) complexes show that photochemical processes involving H2O2, ABTS, and the complex itself can lead to erroneous results. The capability of the complexes to act as •OH scavengers can be also relevant when the mechanism of their biological activity is considered.

Comparison of two diagnostic techniques, skin-prick test and component resolved diagnosis in the follow-up of a cohort of paediatric patients with pollinosis. Multicentre pilot study in a highly exposed allergenic area.

BACKGROUND: Over the last years, different works have been published about the importance of incorporating new diagnosis techniques in allergic patients such as component-resolved diagnosis (CRD). The objective of this study is to compare the evolution of allergic sensitisation profiles by means of CRD and cutaneous tests (SPT) on pollen-allergic patients. METHODS: A total of 123 patients aged between 2 and 14 years were included in an open, prospective, multicentre study. All the children had symptoms suggestive of seasonal respiratory allergic disease, with the diagnosis confirmed by cutaneous tests. Specific-IgE to major pollen-allergens (CRD) and SPT were performed at basal and after three years of follow-up. RESULTS: Out of 123 patients included, a total of 85 were analysed. The mean age was 8±3 years. Significant changes in the allergic sensitisation profiles were observed for the most prevalent allergens (Olea and grass) but it is in grass, the most relevant allergen in terms of allergen pressure, where changes in both absolute and relative frequencies between SPT and CRD were more evident. CONCLUSION: CRD seems to be an essential tool to carry out an appropriate follow-up of patients with allergic respiratory disease, as well as to decide on the immunotherapy composition that best matches the allergic sensitisation profile of patients.

Antibiotic-associated diarrhea: Clinical characteristics and the presence of Clostridium difficile. / Diarrea asociada a antibióticos: características clínicas y presencia de Clostridium difficile.

INTRODUCTION AND AIMS: Evidence in Colombia and Latin America has been insufficient for establishing the clinical characteristics of patients with antibiotic-associated diarrhea (AAD). The present study attempts to describe the clinical characteristics of patients with AAD and to determine the presence of Clostridium difficile, utilizing the polymerase chain reaction (PCR) technique. MATERIALS AND METHODS: Forty-three patients with AAD, managed at the Hospital Universitario San Ignacio in Bogotá, Colombia, were evaluated. Prospective patient information was collected, with respect to demographic characteristics, profile of the antibiotic management received, clinical manifestations, risk factors, and paraclinical reports. In addition, the real time PCR test for Clostridium difficile (Cepheid Xpert®, Sunnyvale, CA, United States) was performed. RESULTS: Patient mean age was 58 years (19.31 SD). The majority of the patients received 2 or more antibiotics (62.9%) and the beta-lactams were the most frequently used. Hospital stay ranged from 2 to 104 days with a median of 10 days. The most frequent clinical manifestations were abdominal pain and bloating, followed by fever and tachycardia. At the time of diagnosis, 23 patients had noninflammatory results in the stool sample analyses and 18 had kidney failure. The mean level of albumin was 2.4mg/dl (0.7 SD). The presence of Clostridium difficile was documented through PCR in 6 patients (13.95% of the cases). CONCLUSIONS: AAD patients were characterized by a high frequency of severe comorbidities and prolonged hospital stay. The presence of Clostridium difficile in only 13.9% of the cases suggests that other causes of diarrhea in the hospitalized patient should be considered.

Kinetics Aspects of the Reversible Assembly of Copper in Heterometallic Mo3CuS4 Clusters with 4,4'-Di-tert-butyl-2,2'-bipyridine.

Treatment of the triangular [Mo3S4Cl3(dbbpy)3]Cl cluster ([1]Cl) with CuCl produces a novel tetrametallic cuboidal cluster [Mo3(CuCl)S4Cl3(dbbpy)3][CuCl2] ([2][CuCl2]), whose crystal structure was determined by X-ray diffraction (dbbpy = 4,4'-di-tert-butyl-2,2'-bipyridine). This species, which contains two distinct types of Cu(I), is the first example of a diimine-functionalized heterometallic M3M'S4 cluster. Kinetics studies on both the formation of the cubane from the parent trinuclear cluster and its dissociation after treatment with halides, supported by NMR, electrospray ionization mass spectrometry, cyclic voltammetry, and density functional theory calculations, are provided. On the one hand, the results indicate that addition of Cu(I) to [1]+ is so fast that its kinetics can be monitored only by cryo-stopped flow at -85 °C. On the other hand, the release of the CuCl unit in [2]+ is also a fast process, which is unexpectedly assisted by the CuCl2- counteranion in a process triggered by halide (X-) anions. The whole set of results provide a detailed picture of the assembly-disassembly processes in this kind of cluster. Interconversion between trinuclear M3S4 clusters and their heterometallic M3M'S4 derivatives can be a fast process occurring readily under the conditions employed during reactivity and catalytic studies, so their occurrence is a possibility that must be taken into account in future studies.

On the Critical Effect of the Metal (Mo vs. W) on the [3+2] Cycloaddition Reaction of M3 S4 Clusters with Alkynes: Insights from Experiment and Theory.

Whereas the cluster [Mo3 S4 (acac)3 (py)3 ](+) ([1](+) , acac=acetylacetonate, py=pyridine) reacts with a variety of alkynes, the cluster [W3 S4 (acac)3 (py)3 ](+) ([2](+) ) remains unaffected under the same conditions. The reactions of cluster [1](+) show polyphasic kinetics, and in all cases clusters bearing a bridging dithiolene moiety are formed in the first step through the concerted [3+2] cycloaddition between the C≡C atoms of the alkyne and a Mo(µ-S)2 moiety of the cluster. A computational study has been conducted to analyze the effect of the metal on these concerted [3+2] cycloaddition reactions. The calculations suggest that the reactions of cluster [2](+) with alkynes feature ΔG(≠) values only slightly larger than its molybdenum analogue, however, the differences in the reaction free energies between both metal clusters and the same alkyne reach up to approximately 10 kcal mol(-1) , therefore indicating that the differences in the reactivity are essentially thermodynamic. The activation strain model (ASM) has been used to get more insights into the critical effect of the metal center in these cycloadditions, and the results reveal that the change in reactivity is entirely explained on the basis of the differences in the interaction energies Eint between the cluster and the alkyne. Further decomposition of the Eint values through the localized molecular orbital-energy decomposition analysis (LMO-EDA) indicates that substitution of the Mo atoms in cluster [1](+) by W induces changes in the electronic structure of the cluster that result in weaker intra- and inter-fragment orbital interactions.

Mechanism of [3+2] cycloaddition of alkynes to the [Mo3 S4 (acac)3 (py)3 ][PF6 ] cluster.

A study, involving kinetic measurements on the stopped-flow and conventional UV/Vis timescales, ESI-MS, NMR spectroscopy and DFT calculations, has been carried out to understand the mechanism of the reaction of [Mo3 S4 (acac)3 (py)3 ][PF6 ] ([1]PF6 ; acac=acetylacetonate, py=pyridine) with two RCCR alkynes (R=CH2 OH (btd), COOH (adc)) in CH3 CN. Both reactions show polyphasic kinetics, but experimental and computational data indicate that alkyne activation occurs in a single kinetic step through a concerted mechanism similar to that of organic [3+2] cycloaddition reactions, in this case through the interaction with one Mo(µ-S)2 moiety of [1](+) . The rate of this step is three orders of magnitude faster for adc than that for btd, and the products initially formed evolve in subsequent steps into compounds that result from substitution of py ligands or from reorganization to give species with different structures. Activation strain analysis of the [3+2] cycloaddition step reveals that the deformation of the two reactants has a small contribution to the difference in the computed activation barriers, which is mainly associated with the change in the extent of their interaction at the transition-state structures. Subsequent frontier molecular orbital analysis shows that the carboxylic acid substituents on adc stabilize its HOMO and LUMO orbitals with respect to those on btd due to better electron-withdrawing properties. As a result, the frontier molecular orbitals of the cluster and alkyne become closer in energy; this allows a stronger interaction.

Synthesis and structure of trinuclear W3S4 clusters bearing aminophosphine ligands and their reactivity toward halides and pseudohalides.

The aminophosphine ligand (2-aminoethyl)diphenylphosphine (edpp) has been coordinated to the W3(µ-S)(µ-S)3 cluster unit to afford trimetallic complex [W3S4Br3(edpp)3](+) (1(+)) in a one-step synthesis process with high yields. Related [W3S4X3(edpp)3](+) clusters (X = F(-), Cl(-), NCS(-); 2(+)-4(+)) have been isolated by treating 1(+) with the corresponding halide or pseudohalide salt. The structure of complexes 1(+) to 4(+) contains an incomplete W3S4 cubane-type cluster unit, and only one of the possible isomers is formed: the one with the phosphorus atoms trans to the capping sulfur and the amino groups trans to the bridging sulphurs. The remaining coordination position on each metal is occupied by X. Detailed studies using stopped-flow, (31)P{(1)H} NMR, and ESI-MS have been carried out in order to understand the solution behavior and the kinetics of interconversion among species 1(+), 2(+), 3(+), and 4(+) in solution. Density functional theory (DFT) calculations have been also carried out on the reactions of cluster 1(+) with the different anions. The whole set of experimental and theoretical data indicate that the actual mechanism of substitutions in these clusters is strongly dependent on the nature of the leaving and entering anions. The interaction between an entering F(-) and the amino group coordinated to the adjacent metal have also been found to be especially relevant to the kinetics of these reactions.

Safe switching from a pdFIX (Immunine®) to a rFIX (Bax326).

The ability to switch between coagulation factors safely is of common interest to haemophilia patients and treating physicians. This is the first formal prospective comparative evaluation of safety, efficacy and incremental recovery of a plasma-derived FIX (pdFIX) and a recombinant FIX (rFIX) in the same haemophilia B patients following a switch from pdFIX Immunine® to a recently developed rFIX Bax326 product. Patients (aged <65 years) who completed a pretreatment study which prospectively documented the exposure to Immunine® and monitored FIX inhibitors while receiving prophylactic treatment were transitioned into pivotal (patients aged 12-65 years) and paediatric (patients aged <12 years) clinical studies investigating prophylaxis and treatment of bleeding episodes with Bax326. None of the 44 patients developed inhibitory or specific binding anti-FIX antibodies during the course of the studies. A total of 38 unrelated adverse events (AEs) were occurred in 20/44 (45.5%) subjects during the Immunine® study. Following a switch to Bax326, 51 AEs were reported in 25/44 (56.8%) subjects. The incidence of AEs related to Bax326 treatment (two episodes of dysgeusia in one patient) was low (2.3%); there were no serious adverse reactions. The comparison between Immunine® and Bax326 demonstrated analogous haemostatic characteristics and annualized bleeding rates. Overall, there is direct evidence indicating a safe and clinically effective transition from a pdFIX (Immunine®) to a newly developed rFIX (Bax326(1) ) for prophylaxis and treatment of bleeding in previously treated patients of all age cohorts with severe or moderately severe haemophilia B.

[Early source control of infection in patients seen in the emergency department: a systematic review]. / Control precoz del foco de infección en los pacientes atendidos en el servicio de urgencias: una revisión sistemática.

OBJECTIVE: The term source (or focus) control encompasses all those physical measures that can be used to reduce the inoculum and modify those factors in the infectious medium that promote microbial growth or foreign antimicrobial defenses of the host. The main objective of this systematic review (SR) is to know and compare whether early detection and control of the focus (in less than 6 hours) in adult patients treated in the ED for severe infection or sepsis, compared to not controlling the focus or delayed focus control (more than 12 hours) is more effective and safer (improves clinical evolution, mortality, complications, hospital stay or need for ICU admission). METHODS: A systematic review is carried out following the PRISMA regulations in the databases of PubMed, Web of Science, EMBASE, Lilacs, Cochrane, Epistemonikos, Tripdatabase and ClinicalTrials.gov from January 2000 to December 31, 2023 without language restrictions and using a combination of MESH terms: "Source Control", "Early" "Infection OR Bacterial Infection OR Sepsis", "Emergencies OR Emergency OR Emergency Department" and "Adults". Observational cohort studies were included. No meta-analysis techniques were performed, but results were compared narratively. RESULTS: A total of 1,658 articles were identified, of which 2 that met the inclusion criteria and were classified as high quality were finally analyzed. The included studies represent a total of 2,404 patients with 678 cases in which an intervention was performed to control the focus (28.20%). In the first study, 28-day mortality was lower in patients who underwent an intervention to control the focus (12.3% vs. 22.5%; P <0.001), with an adjusted HR of 0.538 (95% CI: 0.389-0.744; P<0.001). In the second, it was demonstrated that the time elapsed from when the patient was evaluated for the first time and was hemodynamically stabilized, until the start of surgery was associated with his survival at 60 days with an OR of 0.31 (95% CI: 0.19-0.45; P <0.0001). In fact, for each hour of delay an adjusted OR of 0.29 (95% CI: 0.16-0.47; P<0.0001) is established. So if the intervention is performed before 2 hours at 60 days, 98% of the patients are still alive, if it is performed between 2-4 hours it is reduced to 78%, if it is between 4-6 hours it drops to 55%, but if it is done for more than 6 hours there will be no survivors at 60 days. CONCLUSIONS: This review shows that source control carried out after the evaluation of patients attending the ED reduces short-term mortality (30-60 days) and that it would be advisable to implement any required source control intervention as soon as possible, ideally early (within 6 hours).

SER recommendations on treatment of refractory Behçet's syndrome.

OBJECTIVE: To develop multidisciplinary recommendations based on available evidence and expert consensus for the therapeutic management of patients with refractory Behçet's syndrome (BS) (difficult to treat, severe resistant, severe relapse) to conventional treatment. METHODS: A group of experts identified clinical research questions relevant to the objective of the document. These questions were reformulated in PICO format (patient, intervention, comparison and outcome). Systematic reviews of the evidence were conducted, the quality of the evidence was evaluated following the methodology of the international working group Grading of Recommendations Assessment, Development, and Evaluation (GRADE). After that, the multidisciplinary panel formulated the specific recommendations. RESULTS: 4 PICO questions were selected regarding the efficacy and safety of systemic pharmacological treatments in patients with BS with clinical manifestations refractory to conventional therapy related to mucocutaneous and/or articular, vascular, neurological parenchymal and gastrointestinal phenotypes. A total of 7 recommendations were made, structured by question, based on the identified evidence and expert consensus. CONCLUSIONS: The treatment of most severe clinical manifestations of BS lacks solid scientific evidence and, besides, there are no specific recommendation documents for patients with refractory disease. With the aim of providing a response to this need, here we present the first official Recommendations of the Spanish Society of Rheumatology for the management of these patients. They are devised as a tool for assistance in clinical decision making, therapeutic homogenisation and to reduce variability in the care of these patients.