Mortality of Adult Critically Ill Subjects With Cancer.

BACKGROUND: Cancer patients may require intensive care support for postoperative care, complications associated with underlying malignancy, or toxicities related to cancer therapy. The higher mortality rates found in this population than in the population of ICU patients without cancer may be attributable to confounding due to a higher prevalence of multiple organic dysfunctions at ICU admission in patients with malignancy; however, data regarding this hypothesis are scarce. Accordingly, we performed the present study to compare the crude and propensity score-matched mortality rates between adult subjects with and without cancer admitted to a mixed medical-surgical ICU. METHODS: We conducted a retrospective analysis of a comprehensive longitudinal ICU database in a tertiary referral hospital in Southern Brazil. All adult subjects who were admitted to the ICU from January 2008 to December 2014 were evaluated. Crude and propensity score-matched all-cause 30-d mortality rates of critically ill subjects with cancer were compared with those of critically ill subjects without cancer. RESULTS: A total of 4,221 subjects were evaluated. The survival analysis revealed that the crude mortality rate was higher among subjects with cancer than among subjects without cancer (18.7% vs 10.2%, P < .001). However, after matching by propensity score, the 30-d mortality rates of subjects with and without cancer were similar (18.5% vs 15.2%, P = .17). CONCLUSIONS: The present study failed to show an association between malignancy and all-cause 30-d mortality rate in adult subjects admitted to a mixed medical-surgical ICU. The propensity score-matched analysis showed no evidence of excessive mortality due to cancer diagnosis.

Safety of a training program for ultrasound-guided internal jugular vein catheterization in critically ill patients.

OBJECTIVES: Evaluate the safety and effectiveness of a training program for performing ultrasound-guided internal jugular vein cannulation in critically ill patients. METHODS: Cohort prospective study, evaluating adult patients admitted in a teaching intensive care unit (ICU). Catheter placement was performed by an ICU medical resident. The patient's baseline characteristics, vessel's position and operator experience were the evaluated variables. The main outcomes were cannulation success rate and incidence of major complications. RESULTS: A total of 118 consecutive patients were enrolled between May 2008 and November 2009. The success rate of ultrasound guided catheter placement was 90% (106/118), 77% in the first attempt. Major complications occurred in 4% of the cases (n = 5) and were not associated with the analyzed variables. Inability to place the guide wire was the reason for 58% (7/12) of the failures. Operators with more than 15 previous ultrasound guided cannulations had an increased success rate (95% vs. 79%, p = 0.01) and increased failure was related to previous catheterization (26% vs. 7%, p = 0.02). CONCLUSION: Learning ultrasound guidance for IJV vein cannulation was safe and feasible in ICU patients. This process was not associated to complications and better results were achieved across the spectrum of operator experience.

Evaluación de modalidades de intervención en el ámbito público para población con trastorno de pánico / Assessment of intervention modalities in the public sphere for population with panic disorder

Se presentan los resultados de un proyecto de investigación clínica desarrollado en la Dirección General de Salud y Asistencia Social, UBA, que evaluó la eficacia terapéutica en el tratamiento del ataque de pánico. Para ello se compararon dos modalidades terapéuticas: Psicoterapia Focal de Orientación Psicoanalítica (POP) y Tratamiento Combinado (TC) -POP y Tratamiento Psicofarmacológico-. La muestra fue constituida por 55 sujetos con trastorno de pánico, según los criterios del DSM-IV TR, que recibieron aleatoriamente uno u otro tratamiento durante 12 sesiones a razón de una sesión semanal. Los resultados obtenidos demostraron que POP y el TC constituyen modalidades de intervención eicaces en el tratamiento del trastorno de pánico permitiendo reducir la sintomatología del mismo, mejorar la calidad de vida del paciente y mantener los resultados en el largo plazo. POP favorece la adherencia al tratamiento farmacológico. El TC no mostró diferencias significativas respecto de POP con relación a su eficacia.

We are presenting the conclusions of a clinical research project developed by the General Directorate for Health and Social Assistance, UBA, which assessed the therapeutic eficacy in the treatment of a panic attack. The results were based on the comparison of two therapeutic modalities: Focal Psychoanalytically Oriented Psychotherapy (POP) and Combined Treatment (TC) - POP and Psychopharmacological Treatment. The sample group was comprised of 55 subjects with panic disorder (based on DSM-IV TR panic disorder diagnosis) who randomly received one or another weekly treatment during a period of 12 weeks (one session per week). The results showed that POP and the TC are effective intermission methods for the treatment of panic disorder, the ability to reduce the symptoms, improve the quality of life of the patient, and maintain long term results. POP favors adherence to pharmacological treatment. The TC showed no significant differences with regard to POP with relation to its eficacy.

Kinetic and mechanistic characterization of Mycobacterium tuberculosis glutamyl-tRNA synthetase and determination of its oligomeric structure in solution.

Mycobacterium tuberculosis glutamyl-tRNA synthetase (Mt-GluRS), encoded by Rv2992c, was overproduced in Escherichia coli cells, and purified to homogeneity. It was found to be similar to the other well-characterized GluRS, especially the E. coli enzyme, with respect to the requirement for bound tRNA(Glu) to produce the glutamyl-AMP intermediate, and the steady-state kinetic parameters k(cat) (130 min(-1)) and K(M) for tRNA (0.7 microm) and ATP (78 microm), but to differ by a one order of magnitude higher K(M) value for L-Glu (2.7 mm). At variance with the E. coli enzyme, among the several compounds tested as inhibitors, only pyrophosphate and the glutamyl-AMP analog glutamol-AMP were effective, with K(i) values in the mum range. The observed inhibition patterns are consistent with a random binding of ATP and L-Glu to the enzyme-tRNA complex. Mt-GluRS, which is predicted by genome analysis to be of the non-discriminating type, was not toxic when overproduced in E. coli cells indicating that it does not catalyse the mischarging of E. coli tRNA(Gln) with L-Glu and that GluRS/tRNA(Gln) recognition is species specific. Mt-GluRS was significantly more sensitive than the E. coli form to tryptic and chymotryptic limited proteolysis. For both enzymes chymotrypsin-sensitive sites were found in the predicted tRNA stem contact domain next to the ATP binding site. Mt-GluRS, but not Ec-GluRS, was fully protected from proteolysis by ATP and glutamol-AMP. Small-angle X-ray scattering showed that, at variance with the E. coli enzyme that is strictly monomeric, the Mt-GluRS monomer is present in solution in equilibrium with the homodimer. The monomer prevails at low protein concentrations and is stabilized by ATP but not by glutamol-AMP. Inspection of small-angle X-ray scattering-based models of Mt-GluRS reveals that both the monomer and the dimer are catalytically active. By using affinity chromatography and His(6)-tagged forms of either GluRS or glutamyl-tRNA reductase as the bait it was shown that the M. tuberculosis proteins can form a complex, which may control the flux of Glu-tRNA(Glu) toward protein or tetrapyrrole biosynthesis.

Eosinophilic globules in bronchoalveolar lavage fluid of patients with systemic sclerosis-related interstitial lung disease: a diagnostically useful, previously unreported finding in a retrospective and prospective study, including differential diagnosis with other idiopathic and secondary interstitial lung diseases.

Bronchoalveolar lavage (BAL) is a minimally invasive method possibly representing a diagnostic tool in the evaluation of interstitial lung diseases (ILDs) of different causes. We first describe herein the morphologic, histochemical, and immunohistochemical features of previously unreported eosinophilic globular deposits of acellular amorphous material of uncertain nature in a relatively large series of 227 BAL samples obtained from patients with various ILDs. Overall, eosinophilic globules were detected in 18 cases (7.9%), 16 of which were in patients with systemic sclerosis (SSc)-related ILD (16/50 [32%]) and in 2 cases of apparently idiopathic usual interstitial pneumonia. Apart from the possible diagnostic information of this finding, in patients with SSc, the globules were significantly related to BAL neutrophilia or eosinophilia and extensive ILD in high-resolution computed tomography (P < .0001). Differential diagnosis with other types of acellular globular materials observed in BAL samples is also discussed.

Safety of a training program for ultrasound-guided internal jugular vein catheterization in critically ill patients / Segurança de um programa de treinamento para punção de veia jugular interna guiada por ultrassom em pacientes críticos

OBJECTIVES: Evaluate the safety and effectiveness of a training program for performing ultrasound-guided internal jugular vein cannulation in critically ill patients. METHODS: Cohort prospective study, evaluating adult patients admitted in a teaching intensive care unit (ICU). Catheter placement was performed by an ICU medical resident. The patient's baseline characteristics, vessel's position and operator experience were the evaluated variables. The main outcomes were cannulation success rate and incidence of major complications. RESULTS: A total of 118 consecutive patients were enrolled between May 2008 and November 2009. The success rate of ultrasound guided catheter placement was 90 percent (106/118), 77 percent in the first attempt. Major complications occurred in 4 percent of the cases (n = 5) and were not associated with the analyzed variables. Inability to place the guide wire was the reason for 58 percent (7/12) of the failures. Operators with more than 15 previous ultrasound guided cannulations had an increased success rate (95 percent vs. 79 percent, p = 0.01) and increased failure was related to previous catheterization (26 percent vs. 7 percent, p = 0.02). CONCLUSION: Learning ultrasound guidance for IJV vein cannulation was safe and feasible in ICU patients. This process was not associated to complications and better results were achieved across the spectrum of operator experience.

OBJETIVO: Avaliar a segurança e efetividade de um programa de treinamento para cateterização da veia jugular interna guiada por ultrassom em pacientes críticos. MÉTODOS: Estudo de coorte prospectivo, avaliando pacientes adultos internados em uma unidade de terapia intensiva com programa de ensino. Os médicos residentes do serviço realizaram as punções de veia jugular interna guiadas por ultrassom. Foram avaliadas as características de base dos pacientes, sintopia dos vasos e experiência dos operadores. Os desfechos primários foram a taxa de sucesso da cateterização e a incidência de complicações graves. RESULTADOS: No período entre maio de 2008 e novembro de 2009 foram avaliados 118 pacientes. A taxa de sucesso da punção guiada por ultrassom foi 90 por cento (106/118), 77 por cento dessas na primeira tentativa. Complicações graves ocorreram em 4 por cento dos casos (n = 5) e não foram associadas às variáveis analisadas. Incapacidade de progredir o fio-guia foi a razão de 58 por cento (7/12) das falhas. Operadores com mais de 15 punções guiadas por ultrassom obtiveram uma maior taxa de sucesso (95 por cento vs. 79 por cento, p = 0,01) e pacientes com cateterização prévia apresentaram um maior número de falhas (26 por cento vs. 7 por cento, p = 0,02). CONCLUSÃO: O aprendizado da técnica de punção de veia jugular interna guiada por ultrasssom é seguro e efetivo em pacientes críticos. Este processo não esteve associado a um aumento da taxa de complicações e melhores resultados são obtidos à medida que aumenta a experiência do operador.

The unexpected structural role of glutamate synthase [4Fe-4S](+1,+2) clusters as demonstrated by site-directed mutagenesis of conserved C residues at the N-terminus of the enzyme beta subunit.

Azospirillum brasilense glutamate synthase (GltS) is a complex iron-sulfur flavoprotein whose catalytically active alphabeta protomer (alpha subunit, 162kDa; beta subunit, 52.3 kDa) contains one FAD, one FMN, one [3Fe-4S](0,+1), and two [4Fe-4S](+1,+2) clusters. The structure of the alpha subunit has been determined providing information on the mechanism of ammonia transfer from L-glutamine to 2-oxoglutarate through a 30 A-long intramolecular tunnel. On the contrary, details of the electron transfer pathway from NADPH to the postulated 2-iminoglutarate intermediate through the enzyme flavin co-factors and [Fe-S] clusters are largely indirect. To identify the location and role of each one of the GltS [4Fe-4S] clusters, we individually substituted the four cysteinyl residues forming the first of two conserved C-rich regions at the N-terminus of GltS beta subunit with alanyl residues. The engineered genes encoding the beta subunit variants (and derivatives carrying C-terminal His6-tags) were co-expressed with the wild-type alpha subunit gene. In all cases the C/A substitutions prevented alpha and beta subunits association to yield the GltS alphabeta protomer. This result is consistent with the fact that these residues are responsible for the formation of glutamate synthase [4Fe-4S](+1,+2) clusters within the N-terminal region of the beta subunit, and that these clusters are implicated not only in electron transfer between the GltS flavins, but also in alphabeta heterodimer formation by structuring an N-terminal [Fe-S] beta subunit interface subdomain, as suggested by the three-dimensional structure of dihydropyrimidine dehydrogenase, an enzyme containing an N-terminal beta subunit-like domain.

Properties of the recombinant ferredoxin-dependent glutamate synthase of Synechocystis PCC6803. Comparison with the Azospirillum brasilense NADPH-dependent enzyme and its isolated alpha subunit.

The properties of the recombinant ferredoxin-dependent glutamate synthase of Synechocystis PCC6803 were determined by means of kinetic and spectroscopic approaches in comparison to those exhibited by the bacterial NADPH-dependent enzyme form. The ferredoxin-dependent enzyme was found to be similar to the bacterial glutamate synthase alpha subunit with respect to cofactor content (one FMN cofactor and one [3Fe-4S] cluster per enzyme subunit), overall absorbance properties, and reactivity of the FMN N(5) position with sulfite, as expected from the similar primary structure of ferredoxin-dependent glutamate synthase and of the bacterial NADPH-dependent glutamate synthase alpha subunit. The ferredoxin- and NADPH-dependent enzymes were found to differ with respect to the apparent midpoint potential values of the FMN cofactor and of the [3Fe-4S] cluster, which are less negative in the ferredoxin-dependent enzyme form. This feature is, at least in part, responsible for the efficient oxidation of L-glutamate catalyzed by this enzyme form, but not by the bacterial NADPH-dependent counterpart. At variance with earlier reports on ferredoxin-dependent glutamate synthase, in the Synechocystis enzyme the [3Fe-4S] cluster is not equipotential with the flavin cofactor. The present studies also demonstrated that binding of reduced ferredoxin to ferredoxin-dependent glutamate synthase is essential in order to activate reaction steps such as glutamine binding, hydrolysis, or ammonia transfer from the glutamine amidotransferase site to the glutamate synthase site of the enzyme. Thus, ferredoxin-dependent glutamate synthase seems to control and coordinate catalytic activities taking place at its subsites by regulating the reactions of the glutamine amidotransferase site. Association with reduced ferredoxin appears to be necessary, but not sufficient, to trigger the required activating conformational changes.

Necrose digital em paciente com lúpus eritematoso sistêmico e esclerose sistêmica tratada com inibidores da fosfodiesterase / Digital necrosis treated with phosphodiesterase inhibitors in a patient with connective tissue disease

Os inibidores da fosfodiesterase têm sido introduzidos, nos últimos anos, como novos agentes farmacológicos no tratamento dos pacientes com fenômeno de Raynaud e isquemia digital. Será descrito o caso de uma paciente com lúpus eritematoso sistêmico e esclerose sistêmica limitada apresentando fenômeno de Raynaud grave e necrose digital refratária à terapia. A paciente obteve excelente resposta à associação de imunossupressão e sildenafil.

The phosphodiesterase inhibitors have been used recently for the treatment of Raynaud's phenomenon and digital ischaemia. We report the case of a patient affected by systemic lupus erythematosus and limited systemic sclerosis who presented severe Raynaud's phenomenon with digital necrosis despite treatment. The patient presented an excellent response to the association of immunosuppressant therapy and sildenafil.