Effects on cerebral blood flow after single doses of the ß2 agonist, clenbuterol, in healthy volunteers and patients with mild cognitive impairment or Parkinson's disease.

AIMS: Cerebral hypometabolism occurs years prior to a diagnosis of neurodegenerative diseases and coincides with reduced cerebral perfusion and declining noradrenergic transmission from the locus coeruleus. In pre-clinical models, ß-adrenoceptor (ß-AR) agonists increase cerebrocortical glucose metabolism, and may have therapeutic potential for neurodegenerative diseases. This study investigated the safety and effects on regional cerebral blood flow (rCBF) of the oral, brain-penetrant ß2-AR agonist, clenbuterol, in healthy volunteers (HV) and patients with mild cognitive impairment (MCI) or Parkinson's disease (PD). METHODS: This study evaluated the safety and effects on cerebral activity of the oral, brain-penetrant, ß2-AR agonist clenbuterol (20-160 µg) in healthy volunteers and patients with MCI or PD. Regional CBF, which is tightly coupled to glucose metabolism, was measured by arterial spin labelling MRI in 32 subjects (25 HV and 8 MCI or PD) across five cohorts. In some cohorts, low doses of nadolol (1-5 mg), a ß-AR antagonist with minimal brain penetration, were administered with clenbuterol to control peripheral ß2-AR responses. RESULTS: Significant, dose-dependent increases in rCBF were seen in multiple brain regions, including hippocampus, amygdala and thalamus, following the administration of clenbuterol to HVs (mean changes from baseline in hippocampal rCBF of -1.7%, 7.3%, 22.9%, 28.4% 3 h after 20, 40, 80 and 160 µg clenbuterol, respectively). In patients with MCI or PD, increases in rCBF following 80 µg clenbuterol were observed both without and with 5 mg nadolol (in hippocampus, 18.6%/13.7% without/with nadolol). Clenbuterol was safe and well-tolerated in all subjects; known side effects of ß2-agonists, including increased heart rate and tremor, were mild in intensity and were blocked by low-dose nadolol. CONCLUSIONS: The effects of clenbuterol on rCBF were evident both in the absence and presence of low-dose nadolol, suggesting central nervous system (CNS) involvement. Concomitant inhibition of the peripheral effects of clenbuterol by nadolol confirms that meaningful ß2-AR antagonism in the periphery was achieved without interrupting the central effects of clenbuterol on rCBF.

Glucagon receptor antagonist volagidemab in type 1 diabetes: a 12-week, randomized, double-blind, phase 2 trial.

Hyperglucagonemia contributes to hyperglycemia in patients with type 1 diabetes (T1D); however, novel therapeutics that block glucagon action could improve glycemic control. This phase 2 study evaluated the safety and efficacy of volagidemab, an antagonistic monoclonal glucagon receptor (GCGR) antibody, as an adjunct to insulin therapy in adults with T1D. The primary endpoint was change in daily insulin use at week 12. Secondary endpoints included changes in hemoglobin A1c (HbA1c) at week 13, in average daily blood glucose concentration and time within target range as assessed by continuous blood glucose monitoring (CGM) and seven-point glucose profile at week 12, incidence of hypoglycemic events, the proportion of subjects who achieve HbA1c reduction of ≥0.4%, volagidemab drug concentrations and incidence of anti-drug antibodies. Eligible participants (n = 79) were randomized to receive weekly subcutaneous injections of placebo, 35 mg volagidemab or 70 mg volagidemab. Volagidemab produced a reduction in total daily insulin use at week 12 (35 mg volagidemab: -7.59 units (U) (95% confidence interval (CI) -11.79, -3.39; P = 0.040 versus placebo); 70 mg volagidemab: -6.64 U (95% CI -10.99, -2.29; P = 0.084 versus placebo); placebo: -1.27 U (95% CI -5.4, 2.9)) without meeting the prespecified significance level (P < 0.025). At week 13, the placebo-corrected reduction in HbA1c percentage was -0.53 (95% CI -0.89 to -0.17, nominal P = 0.004) in the 35 mg volagidemab group and -0.49 (95% CI -0.85 to -0.12, nominal P = 0.010) in the 70 mg volagidemab group. No increase in hypoglycemia was observed with volagidemab therapy; however, increases in serum transaminases, low-density lipoprotein (LDL)-cholesterol and blood pressure were observed. Although the primary endpoint did not meet the prespecified significance level, we believe that the observed reduction in HbA1c and tolerable safety profile provide a rationale for further randomized studies to define the long-term efficacy and safety of volagidemab in patients with T1D.

Determinación de anticuerpos antidiarrea viral bovina (DVB) en vacas lecheras de un municipio de Boyacá (Colombia) / Determination of Antibodies against Bovine Viral Diarrhea (BVD) in Diry Cows in a Municipality of Boyacá (Colombia)

Resumen La diarrea viral bovina (DVB) es una patología infecciosa generada por un pestivirus de distribución mundial, causante de problemas reproductivos y pérdidas económicas. El objetivo del presente estudio fue establecer la positividad al virus de diarrea viral bovina (vDVB) en vacas del municipio de Tuta (Boyacá, Colombia), y analizar los grupos etarios, raciales y las variables reproductivas y de manejo como posibles factores de riesgo. Se tomaron 374 muestras de sangre, a las cuales se les realizó la prueba ELISA indirecta, implementando el kit Serelisa® BVD p80 Ab Mono Blocking; los datos se procesaron con EpiInfo®. Se encontró una seroprevalencia del 41,7 %. Los cruces raciales y los bovinos >4 años presentaron la seroprevalencia más alta. Los animales >4 años (p= 0,0000001922) presentaron asociación estadística con la presencia de la enfermedad, y se consideró factor de riesgo para vDVB. Se deben establecer programas de control y prevención que dificulten su diseminación en la zona.

Abstract Bovine viral diarrhea (BVD) is an infectious pathology generated by a pestivirus of worldwide distribution, which causes reproductive problems and economic losses. The objective of this study was to establish bovine viral diarrhea virus (BVDV) positivity in cows from the municipality of Tuta (Boyacá, Colombia), and to analyze age and racial groups and reproductive and management variables as possible risk factors. A total of 374 blood samples were taken and the indirect ELISA test was performed using the Serelisa® BVD p80 Ab Mono Blocking kit; the data were processed with EpiInfo®. A seroprevalence of 41.7% was found. Crossbreds and cattle >4 years had the highest seroprevalence. Animals >4 years old (p= 0.0000001922) were statistically associated with the presence of the disease and were considered a risk factor for BVDV. Control and prevention programs should be established to hinder its dissemination in the area.

Safety and immunogenicity of Px563L, a recombinant anthrax vaccine candidate, in a two-dose regimen for post-exposure prophylaxis in healthy adults.

Px563L is a next-generation anthrax vaccine candidate consisting of a protein subunit, mutant recombinant protective antigen SNKE167-ΔFF-315-E308D (mrPA), and liposome-embedded monophosphoryl lipid A (MPLA) adjuvant. Px563L has the potential to deliver an improved safety and immunogenicity profile relative to the currently licensed vaccine, which is produced from filtered B. anthracis culture supernatants. We conducted a Phase 1, double-blind, placebo-controlled, dose-escalation study in 54 healthy subjects to evaluate Px563L at 3 dose levels of mrPA (10, 50, and 80 mcg). For each dose level, 18 subjects were randomized in an 8:8:2 ratio to Px563L (mrPA with adjuvant), RPA563 (mrPA only) or placebo (saline). Each subject received an intramuscular (IM) injection on Day 0 and Day 28. Primary safety and immunogenicity analysis was conducted after all subjects completed the Day70 visit, a duration deemed clinically relevant for post-exposure prophylaxis. Long-term safety was assessed through Day 393. Vaccinations with Px563L at all dose levels were well-tolerated. There were no serious adverse events or adverse events (AE) leading to early withdrawal. In all treatment groups, most AEs were due to injection site reactions, and all AEs at the 10 and 50 mcg dose levels were mild. For the primary immunogenicity endpoint (protective toxin neutralizing antibody 50% neutralization factor [TNA NF50]), titers started to increase significantly after the second administration of Px563L, from Day35 through Day70, with the geometric mean and lower bound of the 95% confidence interval exceeding 0.56, a threshold correlating with significant survival in animal models of anthrax exposure. In conclusion, Px563L, administered as two IM doses 28 days apart, was well-tolerated and elicited a protective antibody response starting at seven days after the second vaccination. These findings support the continued development of Px563L in a two-dose regimen for anthrax post-exposure prophylaxis. ClinicalTrials.gov identifier NCT02655549.

Seroprevalence of bovine viral diarrhea virus (BVDV) in cattle from Sotaquirá, Colombia.

Worldwide distributed Bovine Viral Diarrhea Virus (BVDV) represents a high risk of infection in most bovine farms, in which it is associated with gastrointestinal, respiratory, and reproductive diseases. The purpose of this research was to establish the seroprevalence and the main risk factors associated with the presentation of BVDV in the municipality of Sotaquirá, Colombia. Samples were taken from 1000 cattle of Holstein, Ayrshire, Jersey, Normande Gyr and Holstein x Gyr. Epidemiological surveys were implemented, reproductive and management variables were taken into consideration. Indirect ELISA was performed to detect specific antibodies against BVDV using the commercial kit SERELISA® BVD p80 Ab Mono Blocking. The overall seroprevalence of antibodies against BVDV was 42.5% (425/1000), where the Gyr breed (59.1% apparent prevalence (AP); 60.3% real prevalence (PR)) and the age group > 4 years (53.0% PA; 54.4% PR) presented the highest seroprevalences. A significant statistical association was found for the breed, age, management practices evaluated and the presentation of PI3 (p ≤ 0.05). Age group > 4 years, Normande breed, presentation of PI3 and grazing lease were established as risk factors associated with BVDV in the herds. These infections are mainly associated with dairy cattle and herds with many animals, so it is important to consider vaccination plans as a preventive system and follow up on the most common diseases.

Bacteria-immune cells dialog and the homeostasis of the systems.

The dialog between microbes and immune cells is critical for the establishment and maintenance of immune homeostasis. Bacterial-derived metabolites or structural components initiate immune signaling pathways and transcriptional factors, inducing a broad range of specificities and functional repertoires of the immune cells. Conversely, the immune system regulates the composition and function of bacterial communities. Elements of the adaptive immunity, including maternal antibodies and mucosal antibody responses, play crucial roles in protecting the hosts from pathogens in addition to promoting colonization of symbiotic bacteria at mucosal surfaces. The complex interactions set from an early stage in life between the microbiota and adaptive immunity, impact other major physiological systems. In this review, we summarize recent advances in our understanding of how gut bacteria regulate systemic homeostasis by highlighting the finely orchestrated interactions between gut bacteria, immune responses and the nervous system.

Mucosal and systemic immune responses to Aujeszky's disease virus (ADV) in early vaccinated piglets.

Newborn humans and animals are highly susceptible to viral infections. The Aujeszky´s disease virus (ADV) is a porcine herpes virus 1 which infects the respiratory tract and is lethal during the first weeks of life. Current intramuscular vaccines, applied at weaning, induce poor mucosal immunity and frequently fail to prevent and control the disease. Additionally, early vaccination has not been studied thoroughly. Therefore, we studied a systemic/mucosal route of immunization using an inactivated ADV vaccine in two-and fourteen-day-old groups of unweaned SPF miniature Vietnamese pigs, measuring the anti ADV antibody (ELISA) and cytokine (qPCR) responses in systemic and mucosal samples. The results showed that the serum ADV-specific IgG response was higher in the 14-day groups. However, the nasal IgA responses were similar in immunized groups, although the response in saliva was higher in the 2-day old group. Moreover, in vitro ADV stimulated peripheral blood mononuclear cells and lung cells from immunized pigs showed higher IFN-γ mRNA production in the 14-day old group than in younger animals and similar levels of IL-4 and IL-10 transcripts. Our data suggest that early mucosal immunization induce humoral and cellular systemic and mucosal immune responses against ADV in young pigs and younger animals may have compensatory mechanisms to overcome early immaturity and maternal-driven immune interference. Therefore, early protection in susceptible animals could be induced using this immunization protocol, opening the possibility for its application against other viral pathogens of pigs and for traslational studies in humans.

Effect of a glucagon receptor antibody (REMD-477) in type 1 diabetes: A randomized controlled trial.

The aim of the current study (Clinical trial reg. no. NCT02715193, clinicaltrials.gov) was to study the efficacy and safety of REMD-477, a glucagon receptor antagonist, in type 1 diabetes. This was a randomized controlled trial in which 21 patients with type 1 diabetes were enrolled. Glycaemic control and insulin use were evaluated in outpatient and inpatient settings, before and after a single 70-mg dose of REMD-477 (half-life 7-10 days) or placebo. Inpatient insulin use was 26% (95% CI, 47%, 4%) lower 1 day after dosing with REMD-477 than with placebo (P = .02). Continuous glucose monitoring during post-treatment days 6 to 12 showed that average daily glucose was 27 mg/dL lower (P < .001), percent time-in-target-range (70-180 mg/dL) was ~25% greater (~3.5 h/d) (P = .001), and percent time-in-hyperglycaemic-range (> 180 mg/dL) was ~40% lower (~4 h/d) (P = .001) in the REMD-477 group than in the placebo group, without a difference in percent time-in-hypoglycaemic-range (<70 mg/dL). No serious adverse events were reported. Glucagon receptor antagonism decreases insulin requirements and improves glycaemic control in patients with type 1 diabetes.

Phase I, Randomized, Double-blind, Placebo-controlled, Single-dose, and Multiple-dose Studies of Erenumab in Healthy Subjects and Patients With Migraine.

Monoclonal antibodies (mAbs) targeting calcitonin gene-related peptide (CGRP) signaling are being explored as prophylactic treatments for migraine. Erenumab (AMG 334) is the first potent, selective, and competitive human mAb antagonist of the CGRP receptor. We report the data from two phase I studies assessing the safety, pharmacokinetics (PK), and pharmacodynamics of single and multiple administrations of erenumab in healthy subjects and patients with migraine. The results indicate that the PK profile of erenumab is nonlinear from 1 mg to 70 mg and the linear portion of the clearance from 70 mg to 210 mg is consistent with other human immunoglobulin G2 antibodies. Single doses of erenumab resulted in >75% inhibition of capsaicin-induced dermal blood flow, with no apparent dose-dependency for erenumab ≥21 mg. Erenumab was generally well tolerated, with an acceptable safety profile, supporting further clinical development of erenumab for migraine prevention.

Grupo de trabajo para la revisión, modificación y desarrollo de indicadores de calidad para unidades de cuidados intensivos respiratorios en México / No disponible

No disponible

Obesity and pro-inflammatory mediators are associated with acute kidney injury in patients with A/H1N1 influenza and acute respiratory distress syndrome.

BACKGROUND: The obesity has been shown to increase the severity of A/H1N1 infection and the development of acute respiratory distress syndrome (ARDS) and organ involvement. METHODS: Circulating levels of C-peptide, insulin, glucagon, leptin, acute phase reactants (procalcitonin, C-reactive protein, tissue plasminogen activator, and serum amyloids A and P), were measured in samples from 32 critically ill patients with A/H1N1 virus infection, 17 of whom had ARDS complicated by acute kidney injury (AKI) and 15 of whom had ARDS but did not develop AKI. RESULTS: Patients with ARDS and AKI (ARDS/AKI) had higher BMI and higher levels of C-peptide, insulin, leptin, procalcitonin and serum amyloid A compared to those ARDS patient who did not develop AKI. Adjusting for confounding variables using logistic regression analysis, higher levels of C-peptide (>0.75 ng/mL) (OR=64.8, 95% CI = 2.1-1980, p = 0.0006) and BMI>30 Kg/m(2) (OR = 42.0, 95% CI = 1.2-1478, p = 0.04) were significantly associated with the development of AKI in ARDS patients. CONCLUSION: High levels of C-peptide and BMI>30 kg/m(2) were associated with the development of AKI in ARDS patients due to A/H1N1 infection. These metabolic/obesity indicators, together with the profiles of pro-inflammatory acute phase proteins, may be important links between obesity and poor outcomes in A/H1N1 09 infection.

Effects of an anti-TSLP antibody on allergen-induced asthmatic responses.

BACKGROUND: Thymic stromal lymphopoietin (TSLP) is an epithelial-cell-derived cytokine that may be important in initiating allergic inflammation. AMG 157 is a human anti-TSLP monoclonal immunoglobulin G2λ that binds human TSLP and prevents receptor interaction. METHODS: In this double-blind, placebo-controlled study, we randomly assigned 31 patients with mild allergic asthma to receive three monthly doses of AMG 157 (700 mg) or placebo intravenously. We conducted allergen challenges on days 42 and 84 to evaluate the effect of AMG 157 in reducing the maximum percentage decrease in the forced expiratory volume in 1 second (FEV1). We also measured the fraction of nitric oxide in exhaled air, blood and sputum eosinophils, and airway hyperresponsiveness. The primary end point was the late asthmatic response, as measured 3 to 7 hours after the allergen challenge. RESULTS: AMG 157 attenuated most measures of allergen-induced early and late asthmatic responses. The maximum percentage decrease in the FEV1 during the late response was 34.0% smaller in the AMG-157 group than in the placebo group on day 42 (P=0.09) and 45.9% smaller on day 84 (P=0.02). In addition, patients receiving AMG 157 had significant decreases in levels of blood and sputum eosinophils before and after the allergen challenge and in the fraction of exhaled nitric oxide. There were 15 adverse events in the AMG-157 group, as compared with 12 in the placebo group; there were no serious adverse events. CONCLUSIONS: Treatment with AMG 157 reduced allergen-induced bronchoconstriction and indexes of airway inflammation before and after allergen challenge. These findings are consistent with a key role for TSLP in allergen-induced airway responses and persistent airway inflammation in patients with allergic asthma. Whether anti-TSLP therapeutics will have clinical value cannot be determined from these data. (Funded by Amgen; ClinicalTrials.gov number, NCT01405963.).

Effect of age and maternal antibodies on the systemic and mucosal immune response after neonatal immunization in a porcine model.

Newborn mammals are highly susceptible to respiratory infections. Although maternal antibodies (MatAb) offer them some protection, they may also interfere with their systemic immune response to vaccination. However, the impact of MatAb on the neonatal mucosal immune response remains incompletely described. This study was performed to determine the effect of ovalbumin (OVA) -specific MatAb on the anti- OVA antibody response in sera, nasal secretions and saliva from specific pathogen-free Vietnamese miniature piglets immunized at 7 or 14 days of age. Our results demonstrated that MatAb increased antigen-specific IgA and IgG responses in sera, and transiently enhanced an early secretory IgA response in nasal secretions of piglets immunized at 7 days of age. In contrast, we detected a lower mucosal (nasal secretion and saliva) anti- OVA IgG response in piglets with MatAb immunized at 14 days of age, compared with piglets with no MatAb, suggesting a modulatory effect of antigen-specific maternal factors on the isotype transfer to the mucosal immune exclusion system. In our porcine model, we demonstrated that passive maternal immunity positively modulated the systemic and nasal immune responses of animals immunized early in life. Our results, therefore, open the possibility of inducing systemic and respiratory mucosal immunity in the presence of MatAb through early vaccination.

Gene expression profiles normalized in psoriatic skin by treatment with brodalumab, a human anti-IL-17 receptor monoclonal antibody.

The IL-17 pathway is an established driver of psoriasis pathogenesis. We examined the detailed molecular and cellular effects of blockade of IL-17 signaling in human psoriatic skin before and following treatment with brodalumab, a competitive inhibitor of the IL-17 Receptor A subunit. Thousands of aberrantly expressed genes in lesional skin normalized within 2 weeks following brodalumab treatment, with conversion of the lesional psoriasis transcriptome to resemble that seen in nonlesional skin. Keratinocyte-expressed genes appeared to normalize rapidly, whereas T cell-specific normalization occurred over six weeks. The three IL-17 ligand genes that are upregulated in lesional skin, IL17A, IL17C, and IL17F, were all downregulated in a dose-dependent manner following brodalumab treatment. Cellular measures also showed a similar pattern with dramatic decreases in keratinocyte hyperplasia within one week, and decreases in infiltrating leukocytes occurred over a longer timescale. Individuals with the highest brodalumab exposure showed normalization of both IL-17-responsive genes and the psoriasis transcriptome, whereas subjects with lower exposures showed transient or incomplete molecular responses. Clinical and molecular response appeared dependent on the extent of brodalumab exposure relative to the expression of IL-17 ligand genes, and reduction of IL-17 signaling into the nonlesional range was strongly correlated with normalization of the psoriasis transcriptome. These data indicate that blockade of IL-17 signaling in psoriatic skin leads to rapid transcriptomal changes initially in keratinocyte-expressed genes, followed by normalization in the leukocyte abnormalities, and demonstrates the essential role of the IL-17R on keratinocytes in driving disease pathogenesis.

Angiogenic and inflammatory markers in acute respiratory distress syndrome and renal injury associated to A/H1N1 virus infection.

Acute kidney injury (AKI) is often associated to acute respiratory distress syndrome (ARDS) due to influenza A/H1N1 virus infection. The profile of angiogenic and inflammatory factors in ARDS patients may be relevant for AKI. We analyzed the serum levels of several angiogenic factors, cytokines, and chemokines in 32 patients with A/H1N1 virus infection (17 with ARDS/AKI and 15 ARDS patients who did not developed AKI) and in 18 healthy controls. Significantly higher levels of VEGF, MCP-1, IL-6, IL-8 and IP-10 in ARDS/AKI patients were detected. Adjusting by confusing variables, levels of MCP-1 ≥150 pg/mL (OR=12.0, p=0.04) and VEGF ≥225 pg/mL (OR=6.4, p=0.03) were associated with the development of AKI in ARDS patients. Higher levels of MCP-1 and IP-10 were significantly associated with a higher risk of death in patients with ARDS (hazard ratio (HR)=10.0, p=0.02; HR=25.5, p=0.03, respectively) even taking into account AKI. Patients with influenza A/H1N1 infection and ARDS/AKI have an over-production of MCP-1, VEGF and IP-10 possibly contributing to kidney injury and are associated to a higher risk of death.

Potentially-toxic and essential elements profile of AH1N1 patients in Mexico City.

During spring of 2009, a new influenza virus AH1N1 spread in the world causing acute respiratory illness and death, resulting in the first influenza pandemic since 1968. Blood levels of potentially-toxic and essential elements of 40 pneumonia and confirmed AH1N1 were evaluated against two different groups of controls, both not infected with the pandemic strain. Significant concentrations of potentially-toxic elements (lead, mercury, cadmium, chromium, arsenic) along with deficiency of selenium or increased Zn/Cu ratios characterized AH1N1 cases under study when evaluated versus controlled cases. Deficiency of selenium is progressively observed from controls I (influenza like illness) through controls II (pneumonia) and finally pneumonia-AH1N1 infected patients. Cases with blood Se levels greater than the recommended for an optimal cut-off to activate glutathione peroxidase (12.5 µg/dL) recovered from illness and survived. Evaluation of this essential element in critical pneumonia patients at the National Institutes is under evaluation as a clinical trial.

Does anticoagulation in Eisenmenger syndrome impact long-term survival?

OBJECTIVE: To determine the impact of anticoagulation on survival in Eisenmenger syndrome. BACKGROUND: The use of anticoagulation for primary prevention of adverse events in patients with Eisenmenger syndrome has been proposed but not studied. Strong arguments have been made both for and against anticoagulation based on the known risk of hemoptysis and pulmonary vascular thrombosis. DESIGN AND SETTING: Retrospective cohort study at a tertiary referral hospital. PATIENTS AND INTERVENTIONS: One hundred forty-four patients with established Eisenmenger physiology all underwent initial laboratory, echocardiographic, and catheterization evaluation after initial referral. We retrospectively identified patients who were started on anticoagulation (AC) and compared them to patients who did not receive anticoagulation therapy (non-AC). Baseline variables were compared between groups, as well as between survivors and nonsurvivors. Analyses of prognostic factors and survival were done using Cox and Kaplan-Meier methods. OUTCOME MEASURES: The primary outcome was death since time of baseline evaluation. RESULTS: We identified 48 anticoagulated and 44 non-anticoagulated patients with Eisenmenger physiology (oxygen saturation 82 ± 9%, PaO(2) 48 ± 8 mm Hg, hemoglobin 18.6 ± 4 g/dL). More atrial septal defect patients were in the AC group, but there were no other baseline differences in clinical, functional, or hemodynamic data. After mean follow-up of 7 ± 5.4 years (range 1-31), 11 patients died in the AC and 10 died in the non-AC group. There was no survival difference between groups (log rank test = 1.78; P is not significant). For the entire cohort, mortality was significantly associated with New York Heart Association class 3-4 (hazard ratio = 4.2), evidence of right heart failure (hazard ratio = 13.6), and a mean corpuscular volume <80 fL (hazard ratio = 3.8). Use of anticoagulation did not impact survival. Bleeding complications occurred in seven (16%) of AC patients, including two fatalities. CONCLUSIONS: Anticoagulation had no impact on long-term survival in this limited study. These data may be useful in considering future studies addressing this question.

[The response of the intensive care units during the influenza A H1N1 pandemic: the experience in Chiapas, Mexico]. / La respuesta de la unidades de terapia intensiva frente a la pandemia de influenza AH1N1 2009: la experiencia en Chiapas, México.

Respiratory virus epidemics had highlighted the importance of the Intensive Care Unit (ICU) to save life of severe cases. ICU functioning and outcomes depends on infrastructure and trained healthcare personnel. In Chiapas, a Southern state in Mexico,an area to care for severe H1N1 cases on respiratory distress during the second H1N1-2009 outbreak, had to be habilitated.This had to be done without sufficient equipment and ICU un-experienced healthcare workers. It was possible to improve its performance through training and standardizing attention care processes for critically ill patients. In preparation for the next pandemic it is essential to designate hospitals with preexistent ICU where to refer severe cases and avoid improvisations.The experience in Chiapas showed that standardization of medical care processes are clue and in case of an overwhelming emergency it is possible to habilitate an ICU although it is imperative to take advantage from installed facilities in each city with the official authority.