Late-onset sepsis and mortality among neonates in a Brazilian Intensive Care Unit: a cohort study and survival analysis.

A cohort study was performed from January 2014 to December 2016 in a Brazilian neonatal intensive care unit, including neonates with high risk for infection and death. We estimated bloodstream infection (BSI) incidence and conducted a survival analysis, considering the time to death and to the first episode of BSI as outcomes, comparing very low birth weight (VLBW) neonates with the remaining neonates. An extended Cox model was performed and the hazard ratio (HR) was calculated for different time periods. The study had 1560 neonates included, the incidence and the incidence density of BSI was 22% and 18.6 per 1000 central venous catheter-days, respectively. Considering VLBW neonates as the reference group, the HR for time to death was 4.06 (95% CI 2.75-6.00, P < 0.01) from day 0 to 60 and for time to the first episode of BSI was 1.76 (95% CI 1.31-2.36, P < 0.01) from day 0 to 36. Having the heavier neonates group as reference, the HR for time to the first episode of BSI was 2.94 (95% CI 1.92-4.34, P < 0.01) from day 37 to 90. Late-onset neonatal sepsis prevention measures should consider the differences in risk during time, according to neonates' birth weight.

Reseña actualizada de ingeniería tisular en disciplinas odontológicas / An updated review of tissue engineering in dental disciplines

La ingeniería tisular (IT) ha sido considerada un campo interdisciplinario, aplicando los principios de ciencias de ingeniería y biología para el desarrollo de sustitutos biológicos que restauran, mantienen o mejoran la función tisular. Se basa en el entendimiento de losprincipios del crecimiento tisular, y su aplicación, para producir reemplazo de tejidos para uso clínico. Se consideran determinantes para el éxito de la IT las Stem Cells (células madre), morfógenos y las “scaffolds” (constructos). Poner en práctica dicha disciplina requiere elempleo de estrategias terapéuticas biológicas que apuntan a reemplazar, reparar, mantener y/o mejorar la función tisular. El objetivo de este trabajo, ha sido realizar una actualización sobre nuevos conocimientos emergentes de las últimas publicaciones científicas realizadas en el ámbito de esta nueva disciplina. Para ello se realizó una exhaustiva búsqueda de información en la base de datos de Pubmed. Actualmente, la IT concentra sus esfuerzos en lograr la regeneración de tejidos dentarios y para dentarios, así como en lograr la obtención de una pieza dental completa. Su avance clínico ha sido notable. Se han reportado artículos publicados que ya evidencian su aplicación en periodoncia, cirugía, implantología, rehabilitación oral y endodoncia. Si bien, estrategias de la IT ya se utilizan clínicamente en odontología, su rápido desarrollo se convierte entonces en un gran desafío e incógnita tanto para quienes ejercen la profesión en la actualidad, como para aquellos que se encuentran en plena formación académica. Tomar conocimiento de logros y avances resulta entonces fundamental, ya que podría convertirse en un futuro próximo, en una herramienta de uso habitual.

Tissue engineering (TE) is considered an interdisciplinary field, and applies principles of engineering and biology to develop biologicalsubstitutes that restore, maintain, or improve tissue function. It is based on the application of the principles of tissue growth to producetissue replacement for clinical use. Stem cells, morphogens, and scaffolds are determinant to the success of TE. Implementation of TErequires the use of biological therapeutic strategies aiming to replace, repair, maintain, and/or improve tissue function. The objective ofthe present work was to perform an update of new knowledge presented in recent scientific publications in this field. For this purpose, weconducted an extensive search for information on Pubmed. At present, TE focuses on achieving regeneration of dental and para-dentaltissues, as well as on obtaining a whole tooth. There have been outstanding clinical advances in this field. There are reports showingsuccessful application of TE in periodontics, surgery, implantology, oral rehabilitation and endodontics. Although TE strategies arealready used in dentistry, their rapid development poses a great challenge both to current practitioners and to those who are in the midst oftheir academic training. Gaining an awareness of the achievements and advances in TE is therefore essential, since it could become widelyapplied in the near future.

Relapse rates in chronic hepatitis B naïve patients after discontinuation of antiviral therapy with entecavir.

Registration studies show entecavir (ETV) to be effective and safe in NUC-naïve patients with chronic hepatitis B, but relapse rates after treatment discontinuation have not been well established. Relapse rates and predictors of relapse were evaluated in naïve HBeAg-positive and HBeAg-negative patients treated with ETV. Treatment duration was defined according to international guidelines. Virological relapse was defined as reappearance in serum of hepatitis B virus (HBV) DNA to >2000 IU/mL after discontinuation of treatment. A hundred and sixty-nine consecutive patients were treated for a median 181 weeks. 61% were HBeAg positive, 23% had cirrhosis, and mean HBV DNA level was 6.88 ± 1.74 log10 IU/mL. Ninety-two per cent became HBV DNA negative; 71% of HBeAg+ve patients became HBeAg negative and 68% anti-HBe positive; 14% became HBsAg negative and 13% anti-HBs positive. At the end of the study, 36 patients discontinued treatment: one due to breakthrough associated with resistant variants and 35 (20%) due to sustained virological response; 33 of these patients developed HBeAg seroconversion and 18 HBsAg seroconversion. Median off-treatment time was 69 weeks. Nine patients (26%), all HBeAg positive at baseline, developed virological relapse after a median 48 weeks off-treatment, 3 of them showed HBeAg reversion and 4 lost anti-HBe. No patient with HBsAg seroconversion relapsed. HBeAg clearance after week 48 of treatment was associated with an increase risk of relapse. After ETV discontinuation, HBsAg seroconversion was maintained in 100% of the patients, HBeAg seroconversion maintained in 90%, and virological relapse rate was 24%.

Nucleation and growth kinetics of electrodeposited sulfate-doped polypyrrole: determination of the diffusion coefficient of SO(4)(2-) in the polymeric membrane.

A kinetic study for the electrosynthesis of polypyrrole (Ppy) doped with SO(4)(2-) ions is presented. Ppy films were electrochemically polymerized onto a graphite-epoxy resin electrode. Experimental current density transients (j-t) were obtained for three different potentiometric behaviors: anionic, cationic, and a combination. Theoretical models were used to fit the experimental j-t data to determine the nucleation and growth processes controlling the polymer synthesis. It was encountered that, in all cases, pyrrole electropolimerization involves two concomitant processes, namely, a Ppy diffusion limited multiple 3D nucleation and growth and pyrrole electro-oxidation on the growing surface of the Ppy nuclei. SEM analysis of the electrodes surfaces reveals that Ppy deposition occurred over most of the electrode surface by multiple nucleation of hemispheres, as the theoretical model used for the analysis of the current transients required. Hemispherical particles formed the polymeric film displaying different sizes. The order for the particle size was as follows: anionic > anionic-cationic > cationic. These results are congruent with those obtained by theoretical analysis of the corresponding current transients. Analysis of the impedance measurements recorded on the anionic Ppy film, immersed in an aqueous solution with different sulfate ion concentrations evidenced that SO(4)(2-) ions diffuse through the Ppy film provoking a decrease of its electrical resistance and an increase of its dielectric constant. From the Warburg impedance coefficient, the sulfate coefficient of diffusion in the Ppy film was 1.38 x 10(-9) cm(2) s(-1).

The rarity of infection with Leishmania (Viannia) braziliensis among patients from the Manaus region of Amazonas state, Brazil, who have cutaneous leishmaniasis.

The frequency of Leishmania ( Viannia) braziliensis infection was assessed in 79 of the 138 patients with cutaneous leishmaniasis who attended a reference outpatient unit in Manaus, Amazonas state, between the August and December of 1997. The disease was characterized by one or more cutaneous ulcers, the skin lesions being frequently associated with satellite lymph-node enlargement. All parasite isolates were identified using monoclonal antibodies and enzyme electrophoresis. Only two (2.8%) of the 71 patients from whom parasites were successfully isolated were found to be infected with L. ( V.) braziliensis, the other 69 isolates being identified, from their isoenzyme profiles, as L. ( V.) guyanensis. In the Manaus region, therefore, almost all human cutaneous leishmaniasis is the result of infection with L. (V.) guyanensis, and L. ( V.) braziliensis is a relatively rare cause of the disease.

Comparison of cutaneous leishmaniasis due to Leishmania (Viannia) braziliensis and L. (V.) guyanensis in Brazil: therapeutic response to meglumine antimoniate.

We conducted a quasi-experimental study to compare the response to meglumine antimoniate in patients with localized cutaneous leishmaniasis from two endemic areas of Brazil that were infected by two Leishmania species. Sixty-one were infected by Leishmania (Viannia) braziliensis (group B) and 57 by L. (V.) guyanensis (group G). All had a parasitologically proven diagnosis and were treated with 20 mg of pentavalent antimonial (SbV)/kg/day given intravenously or intramuscularly for 20 days. Main outcomes were diagnosed using clinical criteria three months after treatment and patients were followed for six months. Intention-to-treat analysis showed a higher failure rate in group G (relative risk [RR] = 1.5, 95% confidence interval [CI] = 1.1-2.0, chi2 = 7.44, P = 0.006). The analysis using an explanatory approach including 52 patients from group B and 49 from group G, who were regularly treated and followed for six months, showed a low cure rate (50.8% in group B and 26.3% in group G) with a greater risk of failure in the latter group (RR = 1.7, 95% CI = 1.2-2.5, chi2 = 8.56, P = 0.003). The effect of the etiologic agent remained significant after adjusting for age, disease duration, and site and number of lesions that were identified as predictors of failure in a logistic regression model. We concluded that Leishmania species constitute an important factor in predicting the outcome of cutaneous leishmaniasis treated with a pentavalent antimonial.

Sensitivity of the polymerase chain reaction for the diagnosis of cutaneous leishmaniasis due to Leishmania (Viannia) guyanensis.

The sensitivity of the polymerase chain reaction (PCR) in 35 consecutive outpatients with cutaneous leishmaniasis caused by Leishmania (Viannia) guyanensis was evaluated using, as gold standard, the in vitro isolation of the parasite through culture of aspirates of the cutaneous ulcers. All isolates were identified using electrophoretic enzyme analysis. Patients were mainly young males with recent onset disease without prior specific treatment. PCR was performed using DNA extracted from fresh frozen biopsies of cutaneous ulcers. The reaction used a pair of oligonucleotides that amplify the conserved region of the minicircle molecule. PCR showed 100% sensitivity (95% CI from 90.0 to 100.0). These results were similar to the visualization of amastigotes in imprint preparations of cutaneous biopsy tissue and the inoculation of biopsy material in golden hamsters. Despite the high sensitivity of the PCR, in this particular clinical setting of cutaneous leishmaniasis caused by L. (V.) guyanensis in the Brazilian Amazon, it appears that the method of choice for diagnosis should be the direct visualization of amastigotes using imprint preparations and the PCR reserved for those patients with negative imprint results.

Comparison of cutaneous leishmaniasis due to Leishmania (Viannia) braziliensis and L. (V.) guyanensis in Brazil: clinical findings and diagnostic approach.

We compared the clinical findings and diagnostic methods for 66 patients with cutaneous leishmaniasis in the state of Bahia, Brazil, who were infected by Leishmania (Viannia) braziliensis (group A), with those for 68 patients in the state of Amazonas, Brazil, who were mainly infected by Leishmania (Viannia) guyanensis (group B). Differences were observed with regard to number, size, and location of skin lesions and to the pattern of lymphatic involvement. Patients in group B had smaller and more numerous lesions, which were frequently located above the waist, versus the larger but less numerous lesions among patients in group A, which were usually located on the lower limbs. Lymphatic involvement was present in 55 (83.3%) of the 66 patients in group A and in 42 (61.8%) of the 68 patients in group B (P=0.005). The positivity rates of imprints and skin culture procedures were higher in group B. Sensitivity of in vitro culture of skin aspirates was 47.0% and 91.2% for groups A and B, respectively (P<.001). Although hamster inoculation showed similar results in both groups, the interval before development of disease was shorter in group B. Our data provide substantial evidence that indicate that the disease caused by these species differs with regard to clinical presentation and diagnostic approach.

[Comparative study between sodium stibogluconate BP 88 and meglumine antimoniate in cutaneous leishmaniasis treatment. II. Biochemical and cardiac toxicity]. / Estudo comparativo entre estibogluconato de sódio BP 88 e antimoniato de meglumina no tratamento da leishmaniose cutânea. II. Toxicidade bioquímica e cardíaca.

Toxicity of two antimonial pentavalents were evaluated in 111 patients with cutaneous leishmaniasis. Forty-seven patients received meglumine antimoniate (Group I) and 64 patients, sodium stibogluconate BP 88 (Group II), 20 mg Sbv/kg/day for 20 days. Evaluation of aminotransferases, alkaline phosphatase, amilase, creatinine, urea, urine analysis and electrocardiogram were performed at baseline, on the tenth and twentieth day of treatment. Greater frequency of aminotransferase abnormal levels were observed on the tenth and twentieth days in group II (p < 0.001) and a greater proportion of amilase abnormal levels at the tenth day in the same group (p < 0.001). There was a greater variation of aminotransferases, alkaline phosphatase and amilase in the first ten days of treatment in group II (p < 0.01). On the twentieth day there was a greater variation of aminotransferase levels in group II (p = 0.02 and p = 0.03, respectively). Forty-three percent of group I and 54% of group II showed electrocardiographic abnormalities (p = 0.30).

[Clinical study of falciparum malaria in children in Manaus, AM, Brazil]. / Estudo clínico da malária falciparum em crianças em Manaus, AM, Brasil.

The clinical characteristics of falciparum malaria were studied among 61 children, aged 0 to 14 treated at a reference center in Manaus, from October to December 1997. The symptoms observed were fever (98.4%), headache (80.3%), chills (68.9%), perspiration (65. 6%), myalgia (59.0%), nausea (54.1%), lumbar pain (49.2%), vomiting (49.2%), cough (45.9%), arthralgia (31.1%), diarrhea (34.4%), dyspnea (8.2%), convulsions (8.2%) and dizziness (4.9%). Pallor and anaemia were found more frequently in children under five years old. Anaemia was associated with high levels of parasitaemia. Fifty-eight (91.5%) patients had uncomplicated malaria, 3 (4.9%) had severe malaria and the lethality was 1.6%.

[RIII mefloquine resistance in children with falciparum malaria in Manaus, AM, Brazil]. / Resistência à mefloquina do tipo RIII em crianças com malária falciparum em Manaus, AM, Brasil.

We report the occurrence of resistance to mefloquine 20mg/day in 51 children with falciparum malaria treated, at reference center of Manaus, Brazil, from October to December 1997. All children were evaluated at day 3, 5, 7, 14, 21, 28 and 35 of treatment. Clinical and parasitological cure criteria were adopted. The incidence of RIII mefloquine resistance was 5.9% (IC 95% 1.5-17.2). The cure/resistance proportion was 20:1 and cure/severity was 62:1. These findings suggest the importance of mefloquine resistance within this group of children.

[A comparative study between sodium stibogluconate BP 88R and meglumine antimoniate in the treatment of cutaneous leishmaniasis. I. The efficacy and safety]. / Estudo comparativo entre estibogluconato de sódio BP 88R e antimoniato de meglumina no tratamento da leishmaniose cutânea: I. Eficácia e segurança.

Efficacy and safety of meglumine antimoniate and sodium stibogluconate BP 88R were compared in cutaneous leishmaniasis treatment in Corte de Pedra, Bahia, an endemic area of leishmaniasis due to Leishmania (Viannia) braziliensis. An open trial was developed with one hundred twenty seven patients who were diagnosed based on clinical criteria and Montenegro's skin test. Fifty eight patients were treated with meglumine antimoniate and 69 received sodium stibogluconate. Both groups received 20 mg/Sbv/kg/day for 20 days. Patients were followed every ten days during treatment and every month thereafter for three months. Sixty two percent patients cured with meglumine antimoniate and 55% cured with sodium stibogluconate (p = 0.42). Headache was more frequent during the first half of treatment in patients receiving sodium stibogluconate (p = 0.026). During the second half, patients treated with sodium stibogluconate showed a greater frequency of myalgia/arthralgia (p = 0.004) and abdominal pain/anorexia (p = 0.004). Three patients treated with sodium stibogluconate had severe side effects.

Sensitivity of a vacuum aspiratory culture technique for diagnosis of localized cutaneous leishmaniasis in an endemic area of Leishmania (Viannia) braziliensis transmission.

Sixty eight patients with localized cutaneous leishmaniasis from an area with Leishmania (Viannia) braziliensis transmission had cultures performed with a modified Marzochís vacuum aspiratory puncture technique to establish sensitivity and contamination rate with this new method. Overall sensitivity of three aspirates was 47.1%; (CI95% 39.4; 59.4) significantly greater than the sensitivity of a single one aspirate. Fungal contamination was observed in 6/204 (2.9%) inoculated culture tubes. We recommend that this useful technique should be adopted as routine for primary isolation of L. (V.) braziliensis from localized cutaneous ulcers.

Sensitivity of lymph node aspiration in localized cutaneous leishmaniasis due to Leishmania (Viannia) braziliensis.

Twenty nine patients with localized cutaneous leishmaniasis had lymph node and skin ulcer aspirations for culture of Leishmania with the modified Marzochís vacuum aspiratory technique. Sensitivity of lymph node aspiration was 58.6% and 34.5% for skin ulcer aspiration (P=0.06). Combined sensitivity of the two methods was 79.3%. There was no agreement between methods (Kappa Index = -0.084; CI95% -0,45; 0,28) showing the potential complementary roles in diagnostic approach.

[Treatment of mucosal leishmaniasis with aminosidine sulfate: results of two year follow-up]. / Tratamento da leishmaniose mucosa com sulfato de aminosidine: resultados de dois anos de acompanhamento.

In 1996, 20 of 21 patients with mucosal leishmaniasis, treated in 1994 with aminosidine sulfate, 16mg/kg/day salt, by intramuscular injection for 20 days, were clinically evaluated. One patient died due to disease not related to mucosal leishmaniasis. Seven of 14 patients (66.7% N = 21) who achieved complete remission three months after treatment remained clinically cured 24 months later and seven relapsed in the same period (50% N = 14). Sorological follow-up showed poor correlation with the results of clinical examination.

Tratamento da leishmaniose mucosa com sulfato de aminosidine: resultados de dois anos de acompanhamento / Treatment of mucosal leishmaniasis with aminosidine sulfate: results of two year follow-up

In 1996, 20 of 21 patients with mucosal leishmaniasis, treated in 1994 with aminosidine sulfate, 16mg/kg/day salt, by intramuscular injection for 20 days, were clinically evaluated. One patient died due to disease not related to mucosal leishmaniasis. Seven of 14 patients (66.7% N = 21) who achieved complete remission three months after treatment remained clinically cured 24 months later and seven relapsed in the same period (50% N = 14). Sorological follow-up showed poor correlation with the results of clinical examination.

Em 1996 foram avaliados clinicamente 20 dos 21 pacientes com leishmaniose mucosa, tratados em 1994 com sulfato de aminosidine 16mg do sal/kg/dia, intramuscular, por 20 dias. Um paciente foi a óbito por causas não relacionadas com a leishmaniose mucosa. Dos 14 pacientes (66,7% N = 21) que inicialmente alcançaram a remissão completa dos sinais e sintomas durante os três primeiros meses de seguimento, sete (50% N = 14) permaneceram livres de doença por 24 meses e sete pacientes apresentaram recidiva neste período. O acompanhamento sorológico mostrou pobre correlação com a avaliação clínica.

Clinical observations of unresponsive mucosal leishmaniasis.

We report the long-term clinical follow-up of two patients with unresponsive mucosal leishmaniasis due to Leishmania (Viannia) braziliensis from the Três Braços area in Bahia State, Brazil. Both were agricultural male workers with extensive upper respiratory mucosal involvement that was not cured with conventional and experimental therapy.

[Open therapeutic study with aminosidine sulfate in mucosal leishmaniasis caused by Leishmania (Viannia) braziliensis]. / Estudo terapêutico aberto com sulfato de aminosidine na leishmaniose mucosa causada por Leishmania (Viannia) braziliensis.

From September to November 1994. 21 patients with active mucosal leishmaniasis were treated with aminosidine sulphate 16 mg/kg/day by intramuscular injection for 20 days. They were principally adult male agricultural workers. Thirteen patients had not received specific treatment and eight had failed to respond to Glucantime therapy. Diagnosis was based on clinical and epidemiological observations, a search for the parasite, leishmanin skin sensitivity and indirect fluorescent antibody serological tests. Sixty seven percent of patients had leishmania parasites isolated from inoculated hamsters or visualized in imprints or histopathological sections. The mean follow-up period was 12.6 months. All patients completed treatment. Side effects were pain at the injection site (86%); mild proteinuria (24%), elevated serum creatinine (.5%) and subclinical bearing loss in one of two patients who did audiometric tests. Clinical cure was achieved in 48% and the accumulated relapse rate was 29% (4/14).