Angiographic demonstration of neoangiogenesis after intra-arterial infusion of autologous bone marrow mononuclear cells in diabetic patients with critical limb ischemia.

Critical limb ischemia in diabetic patients is associated with high rates of morbidity and mortality. Suboptimal responses to the available medical and surgical treatments are common in these patients, who also demonstrate limited vascular homeostasis. Neovasculogenesis induced by stem cell therapy could be a useful approach for these patients. Neovasculogenesis and clinical improvement were compared at baseline and at 3 and 12 months after autologous bone marrow-derived mononuclear cell (BMMNC) transplantation in diabetic patients with peripheral artery disease. We conducted a prospective study to evaluate the safety and efficacy of intra-arterial administration of autologous BMMNCs (100-400 × 10(6) cells) in 20 diabetic patients with severe below-the-knee arterial ischemia. Although the time course of clinical effects differed among patients, after 12 months of follow-up all patients presented a notable improvement in the Rutherford-Becker classification, the University of Texas diabetic wound scales, and the Ankle-Brachial Index in the target limb. The clinical outcome was consistent with neovasculogenesis, which was assessed at 3 months by digital subtraction angiography and quantified by MetaMorph software. Unfortunately, local cell therapy in the target limb had no beneficial effect on the high mortality rate in these patients. In diabetic patients with critical limb ischemia, intra-arterial perfusion of BMMNCs is a safe procedure that generates a significant increase in the vascular network in ischemic areas and promotes remarkable clinical improvement.

Neutrophil defensins: their possible role in allergic asthma.

BACKGROUND Neutrophil defensins, originally identified as broad-spectrum antimicrobial peptides, have been implicated in the regulation of inflammatory and immunological processes. OBJECTIVES To investigate whether the in vitro challenge of neutrophils from patients with bronchial asthma with allergens stimulated the release of alpha-defensins and whether levels released were dependent on lung infections. METHOD The neutrophils were cultivated with different agonists and the concentration of alpha-defensin in cell-free supernatant was measured with enzyme-linked immunosorbent assay (ELISA). RESULTS Neutrophils from allergic patients released alpha-defensins via an allergen-dependent mechanism. Our results indicate that the in vitro activation of neutrophils is highly allergen-specific. In this context, allergens other than those which produced clinical symptoms did not elicit alpha-defensin release, and allergens had no effect on neutrophils from healthy donors. However, neutrophils from both allergic patients and healthy controls were able to release alpha-defensins upon treatment with PMA. In the allergen-stimulated neutrophils, cells from asthmatic patients stimulated with a sensitizing allergen showed a significantly higher production of alpha-defensin under respiratory tract infection than cells from the same patients without such an infection. CONCLUSION Neutrophils from allergic patients release alpha-defensins via an allergen-dependent mechanism.

Impaired adipose tissue expandability and lipogenic capacities as ones of the main causes of metabolic disorders.

Obesity is considered a major health problem. However, mechanisms involved and its comorbidities are not elucidated. Recent theories concerning the causes of obesity have focused on a limit to the functional capacity of adipose tissue, comparing it with other vital organs. This assumption has been the central point of interest in our laboratory. We proposed that the failure of adipose tissue is initiated by the difficulty of this tissue to increase its cellularity due to excess in fat contribution, owing to genetic or environmental factors. Nevertheless, why the adipose tissue reduces its capacity to make new adipocytes via mesenchymal cells of the stroma has not yet been elucidated. Thus, we suggest that this tissue ceases fulfilling its main function, the storage of excess fat, thereby affecting some of the key factors involved in lipogenesis, some of which are reviewed in this paper (PPARγ, ROR1, FASN, SCD1, Rab18, BrCa1, ZAG, and FABP4). On the other hand, mechanisms involved in adipose tissue expandability are also impaired, predominating hypertrophy via an increase in apoptosis and a decrease in adipogenesis and angiogenesis. However, adipose tissue failure is only part of this great orchestra, only a chapter of this nightmare.

Transcatheter aortic valve implantation in very elderly patients: immediate results and medium term follow-up.

OBJECTIVE To evaluate immediate transcatheter aortic valve implantation (TAVI) results and medium-term follow-up in very elderly patients with severe and symptomatic aortic stenosis (AS). METHODS This multicenter, observational and prospective study was carried out in three hospitals. We included consecutive very elderly (> 85 years) patients with severe AS treated by TAVI. The primary endpoint was to evaluate death rates from any cause at two years. RESULTS The study included 160 consecutive patients with a mean age of 87 ± 2.1 years (range from 85 to 94 years) and a mean logistic EuroSCORE of 18.8% ± 11.2% with 57 (35.6%) patients scoring ≥ 20%. Procedural success rate was 97.5%, with 25 (15.6%) patients experiencing acute complications with major bleeding (the most frequent). Global mortality rate during hospitalization was 8.8% (n = 14) and 30-day mortality rate was 10% (n = 16). Median follow up period was 252.24 ± 232.17 days. During the follow-up period, 28 (17.5%) patients died (17 of them due to cardiac causes). The estimated two year overall and cardiac survival rates using the Kaplan-Meier method were 71% and 86.4%, respectively. Cox proportional hazard regression showed that the variable EuroSCORE ≥ 20 was the unique variable associated with overall mortality. CONCLUSIONS TAVI is safe and effective in a selected population of very elderly patients. Our findings support the adoption of this new procedure in this complex group of patients.

Riesgo de infección en pacientes de diálisis peritoneal: factores potencialmente relacionados

Comunicaciones Posters

Individualized Therapy with Ranibizumab in Wet Age-Related Macular Degeneration.

Individualized treatment regimens may reduce patient burden with satisfactory patient outcomes in neovascular age-related macular degeneration. Intravitreal anti-VEGF drugs are the current gold standard. Fixed monthly injections offer the best visual outcome but this regimen is not commonly followed outside clinical trials. A PRN regimen requires monthly visits where the patient is treated in the presence of signs of lesion activity. Therefore, an early detection of reactivation of the disease with immediate retreatment is crucial to prevent visual acuity loss. Several trials suggest that "treat and extend" and other proactive regimens provide a reasonable approach. The rationale of the proactive regimens is to perform treatment anticipating relapses or recurrences and therefore avoid drops in vision while individualizing patient followup. Treat and extend study results in significant direct medical cost savings from fewer treatments and office visits compared to monthly treatment. Current data suggest that, for one year, PRN is less expensive, but treat and extend regimen would likely be less expensive for subsequent years. Once a patient is not a candidate to continue with treatment, he/she should be sent to an outpatient unit with adequate resources to follow nAMD patients in order to reduce the burden of specialized ophthalmologist services.

Olfaction in eating disorders and abnormal eating behavior: a systematic review.

The study provides a systematic review that explores the current literature on olfactory capacity in abnormal eating behavior. The objective is to present a basis for discussion on whether research in olfaction in eating disorders may offer additional insight with regard to the complex etiopathology of eating disorders (ED) and abnormal eating behaviors. Electronic databases (Medline, PsycINFO, PubMed, Science Direct, and Web of Science) were searched using the components in relation to olfaction and combining them with the components related to abnormal eating behavior. Out of 1352 articles, titles were first excluded by title (n = 64) and then by abstract and fulltext resulting in a final selection of 14 articles (820 patients and 385 control participants) for this review. The highest number of existing literature on olfaction in ED were carried out with AN patients (78.6%) followed by BN patients (35.7%) and obese individuals (14.3%). Most studies were only conducted on females. The general findings support that olfaction is altered in AN and in obesity and indicates toward there being little to no difference in olfactory capacity between BN patients and the general population. Due to the limited number of studies and heterogeneity this review stresses on the importance of more research on olfaction and abnormal eating behavior.

Four main virotypes among extended-spectrum-β-lactamase-producing isolates of Escherichia coli O25b:H4-B2-ST131: bacterial, epidemiological, and clinical characteristics.

A total of 1,021 extended-spectrum-β-lactamase-producing Escherichia coli (ESBLEC) isolates obtained in 2006 during a Spanish national survey conducted in 44 hospitals were analyzed for the presence of the O25b:H4-B2-ST131 (sequence type 131) clonal group. Overall, 195 (19%) O25b-ST131 isolates were detected, with prevalence rates ranging from 0% to 52% per hospital. Molecular characterization of 130 representative O25b-ST131 isolates showed that 96 (74%) were positive for CTX-M-15, 15 (12%) for CTX-M-14, 9 (7%) for SHV-12, 6 (5%) for CTX-M-9, 5 (4%) for CTX-M-32, and 1 (0.7%) each for CTX-M-3 and the new ESBL enzyme CTX-M-103. The 130 O25b-ST131 isolates exhibited relatively high virulence scores (mean, 14.4 virulence genes). Although the virulence profiles of the O25b-ST131 isolates were fairly homogeneous, they could be classified into four main virotypes based on the presence or absence of four distinctive virulence genes: virotypes A (22%) (afa FM955459 positive, iroN negative, ibeA negative, sat positive or negative), B (31%) (afa FM955459 negative, iroN positive, ibeA negative, sat positive or negative), C (32%) (afa FM955459 negative, iroN negative, ibeA negative, sat positive), and D (13%) (afa FM955459 negative, iroN positive or negative, ibeA positive, sat positive or negative). The four virotypes were also identified in other countries, with virotype C being overrepresented internationally. Correspondingly, an analysis of XbaI macrorestriction profiles revealed four major clusters, which were largely virotype specific. Certain epidemiological and clinical features corresponded with the virotype. Statistically significant virotype-specific associations included, for virotype B, older age and a lower frequency of infection (versus colonization), for virotype C, a higher frequency of infection, and for virotype D, younger age and community-acquired infections. In isolates of the O25b:H4-B2-ST131 clonal group, these findings uniquely define four main virotypes, which are internationally distributed, correspond with pulsed-field gel electrophoresis (PFGE) profiles, and exhibit distinctive clinical-epidemiological associations.

Use of Granada medium to detect group B streptococcal colonization in pregnant women.

Direct inoculation onto Granada medium (GM) in plates and tubes was compared to inoculation into a selective Todd-Hewitt broth (with 8 microg of gentamicin per ml and 15 microg of nalidixic acid per ml) for detection of group B streptococci (GBS) in pregnant women with 800 vaginal and 450 vaginoanorectal samples. Comparatively, GM was found to be as sensitive as the selective broth for the detection of GBS in vaginal specimens and more sensitive than selective broth for the detection of GBS in vaginoanorectal samples (96 versus 82%). The use of GM improved the time to reporting of a GBS-positive result by at least 24 h and reduced the direct cost of screening. We have also found that the inconvenience of anaerobic incubation of GM plates can be avoided when a cover slide is placed upon the inoculum, because aerobic incubation in GM plates with cover slides causes GBS to develop the same pigmentation that it develops with incubation under anaerobic conditions. These data support the routine use of GM plates or tubes as a more accurate, easier, and cheaper method of identification of GBS-colonized women compared to the enrichment broth technique.

Endocarditis caused by nonhemolytic group B streptococcus.

We report a case of bacterial endocarditis caused by nonhemolytic group B streptococcus (GBS) in a 67-year-old man with no predisposing risk factors. Nonhemolytic GBS strains rarely cause illness and are usually detected in perinatal infections. We believe this to be the first reported case of endocarditis caused by a nonhemolytic strain of GBS.

Análisis de anticuerpos antifosfolipídicos y cistatina C en pacientes con esclerosis múltiple

Cystatin C is considered the most important physiological inhibitor of endogenous cysteine proteases; the role of cystatin C is believed to be to modulate the activity of proteases secreted or released from damaged cells or in the process of necrosis, therefore cystatins being fundamental regulatory processes and a potential prevention of local proteolytic damage. Antiphospholipid antibodies are used to clarify the diagnosis of diseases like multiple sclerosis (MS) and other pathologies could present similar symptoms or paraclinical findings. The objective of the present work is to analyze the concentration of cystatin C and the presence or absence of antiphospholipid antibodies in patients diagnosed with relapsing remitting multiple sclerosis (RRMS) as markers of demyelization. This work was carried out jointly by the Vascular Risk Laboratory, the Laboratory of Autoimmunity and Multiple Sclerosis Unit, Hospital Universitario Virgen Macarena in Seville in one year. Two types of people were selected: Group 1 (n = 30) RRMS group and a control group, n = 30. Cystatin C and antiphospholipid antibodies IgG and IgM, IgG and IgM anticardiolipin, β2 glycoprotein IgG and IgM were determined. Patients showed negative titers of antiphospholipid antibodies IgG and IgM, IgG and IgM anticardiolipin, β2 glycoprotein IgG and IgM. Cystatin C concentration is lower in the group of patients diagnosed with MS, which could give rise to a decrease in the modulation of endogenous cysteine proteases. This would exacerbate the progress of demyelization in MS.

Natalizumab-related anaphylactoid reactions in MS patients are associated with HLA class II alleles.

OBJECTIVES We aimed to investigate potential associations between human leukocyte antigen (HLA) class I and class II alleles and the development of anaphylactic/anaphylactoid reactions in patients with multiple sclerosis (MS) treated with natalizumab. METHODS HLA class I and II genotyping was performed in patients with MS who experienced anaphylactic/anaphylactoid reactions and in patients who did not develop infusion-related allergic reactions following natalizumab administration. RESULTS A total of 119 patients with MS from 3 different cohorts were included in the study: 54 with natalizumab-related anaphylactic/anaphylactoid reactions and 65 without allergic reactions. HLA-DRB1*13 and HLA-DRB1*14 alleles were significantly increased in patients who developed anaphylactic/anaphylactoid reactions (p M-H = 3 × 10(-7); odds ratio [OR]M-H = 8.96, 95% confidence interval [CI] = 3.40-23.64), with a positive predictive value (PPV) of 82%. In contrast, the HLA-DRB1*15 allele was significantly more represented in patients who did not develop anaphylactic/anaphylactoid reactions to natalizumab (p M-H = 6 × 10(-4); ORM-H = 0.2, 95% CI = 0.08-0.50), with a PPV of 81%. CONCLUSIONS HLA-DRB1 genotyping before natalizumab treatment may help neurologists to identify patients with MS at risk for developing serious systemic hypersensitivity reactions associated with natalizumab administration.

Management of bleeding following major trauma: an updated European guideline.

INTRODUCTION Evidence-based recommendations are needed to guide the acute management of the bleeding trauma patient, which when implemented may improve patient outcomes. METHODS The multidisciplinary Task Force for Advanced Bleeding Care in Trauma was formed in 2005 with the aim of developing a guideline for the management of bleeding following severe injury. This document presents an updated version of the guideline published by the group in 2007. Recommendations were formulated using a nominal group process, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) hierarchy of evidence and based on a systematic review of published literature. RESULTS Key changes encompassed in this version of the guideline include new recommendations on coagulation support and monitoring and the appropriate use of local haemostatic measures, tourniquets, calcium and desmopressin in the bleeding trauma patient. The remaining recommendations have been reevaluated and graded based on literature published since the last edition of the guideline. Consideration was also given to changes in clinical practice that have taken place during this time period as a result of both new evidence and changes in the general availability of relevant agents and technologies. CONCLUSIONS This guideline provides an evidence-based multidisciplinary approach to the management of critically injured bleeding trauma patients.

Capsule endoscopy in the small bowel Crohn's disease.

CD is a chronic inflammatory disorder associated to mucosal and transmural inflammation of the bowel wall. It is well known that CD can affect the entire gastrointestinal. Therefore, ileocolonoscopy and biopsies of the terminal ileum as well as of each colonic segment to look for microscopic evidence of CD are the first-line procedures to establish the diagnosis. However, it has been observed that up to 30% of the patients have only small bowel involvement. Evaluation of the small bowel has been made with radiological procedures, barium radiography, and abdominal computed tomography or by ileocolonoscopy or enteroscopy, but they have many recognized limitations. CE is undoubtedly a very useful diagnostic tool proposed to observe small-bowel lesions undetectable by conventional endoscopy or radiologic studies. We review different studies that have been published reporting the use of CE in suspected and evaluation of the extension or the recurrence in CD and also its use in pediatric population and its complications.