Safety and Effectiveness of two treatment regimes with tranexamic acid to minimize inflammatory response in elective cardiopulmonary bypass patients: a randomized double-blind, dose-dependent, phase IV clinical trial

<p>Abstract</p> <p>Background</p> <p>In cardiopulmonary bypass (CPB) patients, fibrinolysis may enhance postoperative inflammatory response. We aimed to determine whether an additional postoperative dose of antifibrinolytic tranexamic acid (TA) reduced CPB-mediated inflammatory response (IR).</p> <p>Methods</p> <p>We performed a randomized, double-blind, dose-dependent, parallel-groups study of elective CPB patients receiving TA. Patients were randomly assigned to either the single-dose group (40 mg/Kg TA before CPB and placebo after CPB) or the double-dose group (40 mg/Kg TA before and after CPB).</p> <p>Results</p> <p>160 patients were included, 80 in each group. The incident rate of IR was significantly lower in the double-dose-group TA2 (7.5% vs. 18.8% in the single-dose group TA1; <it>P </it>= 0.030). After adjusting for hypertension, total protamine dose and temperature after CPB, TA2 showed a lower risk of IR compared with TA1 [OR: 0.29 (95% CI: 0.10-0.83), (<it>P </it>= 0.013)]. Relative risk for IR was 2.5 for TA1 (95% CI: 1.02 to 6.12). The double-dose group had significantly lower chest tube bleeding at 24 hours [671 (95% CI 549-793 vs. 826 (95% CI 704-949) mL; <it>P </it>= 0.01 corrected-<it>P </it>significant] and lower D-dimer levels at 24 hours [489 (95% CI 437-540) vs. 621(95% CI: 563-679) ng/mL; <it>P </it>= 0.01 corrected-<it>P </it>significant]. TA2 required lower levels of norepinephrine at 24 h [0.06 (95% CI: 0.03-0.09) vs. 0.20(95 CI: 0.05-0.35) after adjusting for dobutamine [F = 6.6; <it>P </it>= 0.014 corrected-<it>P </it>significant].</p> <p>We found a significant direct relationship between IL-6 and temperature (rho = 0.26; <it>P </it>< 0.01), D-dimer (rho = 0.24; <it>P </it>< 0.01), norepinephrine (rho = 0.33; <it>P </it>< 0.01), troponin I (rho = 0.37; <it>P </it>< 0.01), Creatine-Kinase (rho = 0.37; <it>P </it>< 0.01), Creatine Kinase-MB (rho = 0.33; <it>P </it>< 0.01) and lactic acid (rho = 0.46; <it>P </it>< 0.01) at ICU arrival. Two patients (1.3%) had seizure, 3 patients (1.9%) had stroke, 14 (8.8%) had acute kidney failure, 7 (4.4%) needed dialysis, 3 (1.9%) suffered myocardial infarction and 9 (5.6%) patients died. We found no significant differences between groups regarding these events.</p> <p>Conclusions</p> <p>Prolonged inhibition of fibrinolysis, using an additional postoperative dose of tranexamic acid reduces inflammatory response and postoperative bleeding (but not transfusion requirements) in CPB patients. A question which remains unanswered is whether the dose used was ideal in terms of safety, but not in terms of effectiveness.</p> <p>Current Controlled Trials number</p> <p>ISRCTN: <a href="http://www.controlled-trials.com/ISRCTN84413719">ISRCTN84413719</a></p

The Impact of IFN-g; Receptor on SLPI Expression in Active Tuberculosis: Association with Disease Severity

Interferon (IFN)-g displays a critical role in tuberculosis (TB), modulating the innate and adaptive immune responses. Previously, we reported that secretory leukocyte protease inhibitor (SLPI) is a pattern recognition receptor with anti-mycobacterial activity against Mycobacterium tuberculosis (Mtb). Herein, we determined whether IFN-g modulated the levels of SLPI in TB patients. Plasma levels of SLPI and IFN-g were studied in healthy donors (HDs) and TB patients. Peripheral blood mononuclear cells from HDs and patients with TB or defective IFN-g receptor 1* were stimulated with Mtb antigen and SLPI, and IFN-gR expression levels were measured. Both SLPI and IFN-g were significantly enhanced in plasma from those with TB compared with HDs. A direct association between SLPI levels and the severity of TB was detected. In addition, Mtb antigen stimulation decreased the SLPI produced by peripheral blood mononuclear cells from HDs, but not from TB or IFN-gR patients. Neutralization of IFN-g reversed the inhibition of SLPI induced by Mtb antigen in HDs, but not in TB patients. Furthermore, recombinant IFN-g was unable to modify the expression of SLPI in TB patients. Finally, IFN-gR expression was lower in TB compared with HD peripheral blood mononuclear cells. These results show that Mtb-induced IFN-g down-modulated SLPI levels by signaling through the IFNgR in HDs. This inhibitory mechanism was not observed in TB, probably because of the low expression of IFN-gR detected in these individuals. (Am J Pathol 2014, 184: 1e6Fil: Tateosian, Nancy Liliana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos; Argentina; ArgentinaFil: Pasquinelli, Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires; ArgentinaFil: Hernández Del Pino, Rodrigo Emanuel. Universidad de Buenos Aires; ArgentinaFil: Ambrosi, Nella Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos; Argentina; ArgentinaFil: Guerrieri, Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos; Argentina; ArgentinaFil: Pedraza Sánchez, Sigifredo. Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; MéxicoFil: Santucci, Natalia Estefanía. Universidad Nacional de Rosario; ArgentinaFil: D'attilio, Luciano David. Universidad Nacional de Rosario; ArgentinaFil: Pellegrini, Joaquín Miguel. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Araujo Solis, María A.. Instituto Mexicano del Seguro Social; MéxicoFil: Musella, Rosa M.. Hospital "F. J. Muñiz"; ArgentinaFil: Palmero, Domingo J.. Hospital "F. J. Muñiz"; ArgentinaFil: Hernandez Pando, Rogelio. Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; MéxicoFil: Garcia, Veronica Edith. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Chuluyan, Hector Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos; Argentina; Argentin

Multidrug resistant pulmonary tuberculosis treatment regimens and patient outcomes: an individual patient data meta-analysis of 9,153 patients.

Treatment of multidrug resistant tuberculosis (MDR-TB) is lengthy, toxic, expensive, and has generally poor outcomes. We undertook an individual patient data meta-analysis to assess the impact on outcomes of the type, number, and duration of drugs used to treat MDR-TB

Time-related improvement of survival in resectable gastric cancer: the role of Japanese-style gastrectomy with D2 lymphadenectomy and adjuvant chemotherapy

BACKGROUND: We investigated the change of prognosis in resected gastric cancer (RGC) patients and the role of radical surgery and adjuvant chemotherapy. METHODS: We retrospectively analyze the outcome of 426 consecutive patients from 1975 to 2002, divided into 2 time-periods (TP) cohort: Before 1990 (TP1, n = 207) and 1990 or after (TP2; n= 219). Partial gastrectomy and D1-lymphadenetomy was predominant in TP1 and total gastrectomy with D2-lymphadenectomy it was in TP2. Adjuvant chemotherapy consisted of mitomycin C (MMC), 10–20 mg/m2 iv 4 courses or MMC plus Tegafur 500 mg/m2 for 6 months. RESULTS: Positive nodes were similar in TP2/TP1 patients with 56%/59% respectively. Total gastrectomy was done in 56%/45% of TP2/TP1 respectively. Two-drug adjuvant chemotherapy was administered in 65%/18% of TP2/TP1 respectively. Survival at 5 years was 66% for TP2 versus 42% for TP1 patients (p < 0.0001). Survival by stages II, IIIA y IIIB for TP2 versus TP1 patients was 70 vs. 51% (p = 0.0132); 57 vs. 22% (p = 0.0008) y 30 vs. 15% (p = 0.2315) respectively. Multivariate analysis showed that age, stage of disease and period of treatment were independent variables. CONCLUSION: The global prognosis and that of some stages have improved in recent years with case RGC patients treated with surgery and adjuvant chemotherapy

Impacts of Use and Abuse of Nature in Catalonia with Proposals for Sustainable Management

This paper provides an overview of the last 40 years of use, and in many cases abuse, of the natural resources in Catalonia, a country that is representative of European countries in general, and especially those in the Mediterranean region. It analyses the use of natural resources made by mining, agriculture, livestock, logging, fishing, nature tourism, and energy production and consumption. This use results in an ecological footprint, i.e., the productive land and sea surface required to generate the consumed resources and absorb the resulting waste, which is about seven times the amount available, a very high number but very similar to other European countries. This overexploitation of natural resources has a huge impact on land and its different forms of cover, air, and water. For the last 25 years, forests and urban areas have each gained almost 3% more of the territory at the expense of agricultural land; those municipalities bordering the sea have increased their number of inhabitants and activity, and although they only occupy 6.7% of the total surface area, they account for 43.3% of the population; air quality has stabilized since the turn of the century, and there has been some improvement in the state of aquatic ecosystems, but still only 36% are in good condition, while the remainder have suffered morphological changes and different forms of nonpoint source pollution; meanwhile the biodiversity of flora and fauna remains still under threat. Environmental policies do not go far enough so there is a need for revision of the legislation related to environmental impact and the protection of natural areas, flora, and fauna. The promotion of environmental research must be accompanied by environmental education to foster a society which is Land 2021, 10, 144 3 of 53 more knowledgeable, has more control and influence over the decisions that deeply affect it. Indeed, nature conservation goes hand in hand with other social and economic challenges that require a more sustainable vision. Today’s problems with nature derive from the current economic model, which is environmentally unsustainable in that it does not take into account environmental impacts. Lastly, we propose a series of reasonable and feasible priority measures and actions related to each use made of the country’s natural resources, to the impacts they have had, and to their management, in the hope that these can contribute to improving the conservation and management of the environment and biodiversity and move towards sustainability.info:eu-repo/semantics/publishedVersio

Coxitis due to multidrug-resistant mycobacterium tuberculosis in an HIV negative patient

Se presenta el caso de una paciente HIV negativa con artritis coxofemoral de etiología tuberculosa, cepa multirresistente, y colagenopatía asociada en tratamiento con glucocorticoides. Fue medicada con cicloserina, ácido p-aminosalicílico, etambutol y ofloxacina, mostrando regresión de sus lesiones articulares. Se efectúa una revisión de la literatura sobre el tema.A case of an HIV negative female patient with coxofemoral arthritis of tuberculous etiology, multidrugresistant strain, and connective tissue disease associated to glucocorticoid therapy is reported. The patient was treated with cycloserine, ethambutol, p-aminosalicylic acid and ofloxacin, with improvement of the joint lesions. Previous publications on this subject are reviewed.Fil: Palmero, Domingo J. Hospital F.J. Muñiz. Sala 19; Argentina.Fil: Simboli, Norberto. ANLIS Dr.C.G.Malbrán. Laboratorio de Micobacterias; Argentina.Fil: Alberti, Federico. Hospital F.J. Muñiz. Sala 19; Argentina.Fil: Francos, José L. Hospital F.J. Muñiz. Sala 19; Argentina.Fil: Guemes Gurtubay, Jose L. Hospital F.J. Muñiz. Sala 19; Argentina.Fil: Ochoa, Elio J. Hospital F.J. Muñiz. Sala 19; Argentina.Fil: Cardozo, Leonor. Hospital Argerich. Bacteriología; ArgentinaFil: Waisman, Jaime L. Hospital F.J. Muñiz. Sala 19; Argentina

Coxitis due to multidrug-resistant mycobacterium tuberculosis in an HIV negative patient

Se presenta el caso de una paciente HIV negativa con artritis coxofemoral de etiología tuberculosa, cepa multirresistente, y colagenopatía asociada en tratamiento con glucocorticoides. Fue medicada con cicloserina, ácido p-aminosalicílico, etambutol y ofloxacina, mostrando regresión de sus lesiones articulares. Se efectúa una revisión de la literatura sobre el tema.A case of an HIV negative female patient with coxofemoral arthritis of tuberculous etiology, multidrugresistant strain, and connective tissue disease associated to glucocorticoid therapy is reported. The patient was treated with cycloserine, ethambutol, p-aminosalicylic acid and ofloxacin, with improvement of the joint lesions. Previous publications on this subject are reviewed.Fil: Palmero, Domingo J. Hospital F.J. Muñiz. Sala 19; Argentina.Fil: Simboli, Norberto. ANLIS Dr.C.G.Malbrán. Laboratorio de Micobacterias; Argentina.Fil: Alberti, Federico. Hospital F.J. Muñiz. Sala 19; Argentina.Fil: Francos, José L. Hospital F.J. Muñiz. Sala 19; Argentina.Fil: Guemes Gurtubay, Jose L. Hospital F.J. Muñiz. Sala 19; Argentina.Fil: Ochoa, Elio J. Hospital F.J. Muñiz. Sala 19; Argentina.Fil: Cardozo, Leonor. Hospital Argerich. Bacteriología; ArgentinaFil: Waisman, Jaime L. Hospital F.J. Muñiz. Sala 19; Argentina