A randomized placebo-controlled phase II study of a Pseudomonas vaccine in ventilated ICU patients.

BACKGROUND: Currently, no vaccine against Pseudomonas is available. IC43 is a new, recombinant, protein (OprF/I)-based vaccine against the opportunistic pathogen, Pseudomonas aeruginosa, a major cause of serious hospital-acquired infections. IC43 has proven immunogenicity and tolerability in healthy volunteers, patients with burns, and patients with chronic lung diseases. In order to assess the immunogenicity and safety of IC43 in patients who are most at risk of acquiring Pseudomonas infections, it was evaluated in mechanically ventilated ICU patients. METHODS: We conducted a randomized, placebo-controlled, partially blinded study in mechanically ventilated ICU patients. The immunogenicity of IC43 at day 14 was determined as the primary endpoint, and safety, efficacy against P. aeruginosa infections, and all-cause mortality were evaluated as secondary endpoints. Vaccinations (100 µg or 200 µg IC43 with adjuvant, or 100 µg IC43 without adjuvant, or placebo) were given twice in a 7-day interval and patients were followed up for 90 days. RESULTS: Higher OprF/I IgG antibody titers were seen at day 14 for all IC43 groups versus placebo (P < 0.0001). Seroconversion (≥4-fold increase in OprF/I IgG titer from days 0 to 14) was highest with 100 µg IC43 without adjuvant (80.6%). There were no significant differences in P. aeruginosa infection rates, with a low rate of invasive infections (pneumonia or bacteremia) in the IC43 groups (11.2-14.0%). Serious adverse events (SAEs) considered possibly related to therapy were reported by 2 patients (1.9%) in the group of 100 µg IC43 with adjuvant. Both SAEs resolved and no deaths were related to study treatment. Local tolerability symptoms were mild and rare (<5% of patients), a low rate of treatment-related treatment-emergent adverse events (3.1-10.6%) was observed in the IC43 groups. CONCLUSION: This phase II study has shown that IC43 vaccination of ventilated ICU patients produced a significant immunogenic effect. P. aeruginosa infection rates did not differ significantly between groups. In the absence of any difference in immune response following administration of 100 µg IC43 without adjuvant compared with 200 µg IC43 with adjuvant, the 100 µg dose without adjuvant was considered for further testing of its possible benefit of improved outcomes. There were no safety or mortality concerns. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00876252 . Registered on 3 April 2009.

La importancia de declarar un conflicto de intereses en las revistas médicas / The relevance of declaring an interest conflict in medical journals

Medical journals are often at risk of difussinng research articles, reviews, position articles, editorials or letters ubose message has been influenced by a conflict of interest. The readers may then be induced to accept conclusions and recommendations based on bisaaed protocols or an unwarranted interpretation of the results. Financial support or professional links witb pharmaceutical companies or other supporting agencies are the most common sources of conflict of interests, often difficult to detect. Similarly, reviews of manuscripts can be biassed by personal relationsbips (good or bad) between reviewers and autbors, by academic competition or intellectual passion, becoming otber sources of conflict of interest. Even uben a potential conflict of interest exists, it may not necessarily bave influenced the manuscript or its review but in order to defend the transparency of the editorial process, from submission to publication, authors, reviewers and editors sbould declare any conflict of interest they may have and allou others to decide whether the action has been biassed or not. In the present issue of Revista Médica de Chile, and updated text of the Instructions to Authors establishes that all autbors should sign a statement of habing or not a conflict of interest, clarifying which aspects of the work might have been affected by it

Actualización de los criterios de autoría en las publicaciones biomédicas / Update in authorship criteria in biomedical articles

In the year 2000, a previous Editorial in this journal reviewed the criteria for authorship as defined by experienced authors and editors, discussed in selected references from the biomedical literature. An emphasis was given to the definition of authorship stated in the available 1997 version of the "Uniform Requirements for Manuscripts Submitted to Biomedical Journals". After that Editorial was published, an updated version of the "Uniform Requirements" established important changes in their criteria; eg. Participation of each author in the work should permit them to take public responsibility for "appropiate portions of the content"; and acquisition of data was added as an acceptable alternative in the first requisite for authorship. These and other changes should be difussed to prospective authors, particularly in multicentric studies usually leading to multiauthorship. This new Editorial and a translation into Spanish of the authorship criteria contained in an updated (2001) version of the "Uniform Requirements" are included in this issue of Revista Médica de Chile with the purpose of stimulating authors and readers to think in their implications

Vibrio vulnificus: una causa infrecuente de shock séptico / Septic shock caused by vibrio vulnificus: report of 1 case

Vibrio vulnificus is a lactose positive Gram negative rod that lives in warm seas and can infect wounds and produce sepsis. Its infection is acquired after eating oysters or other filtering marine organisms. We report a 53 years old diabetic male who started with fever after a voyage to Central America. He was admitted febrile, hipotense, dehydrated and polypneic. Painful erythematous lesions and lumps were observed in his upper and lower limbs. After 72 hours of evolution, the lesions became violaceous, with crepitating vesicles full of hemorrhagic exudate. He developed a renal failure and a disseminated intravascular coagulation. Blood cultures demonstrated the presence of Vibrio vulnificus and the patient died 68 hours after admission

Estudio de la cinética de citoquinas en sepsis grave y su relación con mortalidad y score de disfunción orgánica / Cytokine kinetics in severe sepsis: its relationship with mortality and organic dysfunction

Background: The Infectious Systemic Inflammatory Response syndrome and multiple organic dysfunction have common physiopathological mechanisms. Multiple organic dysfunction can be assessed using severity scores. Aim: To relate cytokine kinetics with a multiple organic dysfunction score during sepsis. Material and methods : Tumor necrosis factor a (TNFa) and interleukin 6 (IL6) kinetics were studied in 25 patients with severe sepsis with less than 48 h of evolution and interleukin 1ß (ILß) kinetics was studied in 13 patients. Measurements were made at 0, 12, 24 and 48 hours after admission to the study, using an ELISA technique. These parameters were correlated with the Marshall multiple organic dysfunction score and survival. Results: Mean age of study subjects was 70 years, the APACHE II score was 16.9ñ6 and the Marshall score was 6.8ñ3.6. Sepsis was of pulmonary origin in 56 percent of patients and intra abdominal in 32 percent. Mortality was 36 percent. TNFa increased during the study period (24.1 pg/ml initially and 37.8 pg/ml at 24 hours, with a slight posterior reduction, p<0.02). These levels had no association with mortality or organic dysfunction. IL6 remained elevated during the first hours and had a tendency to decrease thereafter. Deceased patients had higher values than survivors (306 pg/ml and 55.4 pg/ml respectively, p=0.011). Its values were tightly correlated with Marshall score, with the number of failing organs, with the presence of shock and with probability of dying during hospitalization. IL1ß remained low and was not associated with clinical parameters. Conclusions: There is a tight correlation between the elevation of IL6 and the severity of the Systemic Inflammatory Response and mortality in these patients with sepsis

El Comité Asesor Internacional / The International Advisory Committee

The Editors of Revista Médica de Chile are taking steps aimed to improve the "visibility" of this journal and to stimulate local and foreign authors to submit better original articles, appealing to a broader and international readership. Until now, the journal's editorial policy has been to stress its educational role, focused in Chilean readers and authors. In the recent years, an increasing number of research articles is being received, including manuscripts from North America, Europe and other Latinamerican countries. This is explainable, in part, by the fact that this journal is indexed in MEDLINE, ISI (Current Contents/Clinical Medicine) and several other major databases. The Revista is also one of the oldest medical journals in the world, published since 1872. In this issue of the Revista we welcome the new members of an "International Advisory Committee", with prominent physicians, scientists and teachers from the U.S.A. and Europe. They accepted to advise the Editors in their task, to submit review articles, state-of-the-art or position papers on topics of their own interest, and to help in the assessment of some manuscripts. We thank them warmly for their enthusiastic response to our invitation

Necrólisis epidérmica tóxica: terapia en UCI con inmunoglobulinas intravenosas en un caso / Toxic epidermal necrolysis: report of 1 case treated with intravenous immunoglobulins

We report a 27 years old homosexual male with AIDS that was admitted to the ICU dehydrated, with fever and severe malaise. He had irregular bullae, an extensive purpuric exanthema and a zone of epidermic detachment in the right arm. A toxic epidermal necrolysis was diagnosed and therapy with i.v. immunoglobulins was started. After four days of treatment, bullous lesions disappeared and the extension of exanthema decreased. Toxic epidermal necrolysis is a potentially fatal disease and the use of intravenous immunoglobulins for this condition has been reported as successful

La autoría en los manuscritos publicados en revistas biomédicas / Authorship in manuscripts published in biomedical journals

Multiauthorship shows an increasing trend in biomedical and other scientific journals. A main concern for editors, reviewers and readers is to find out whether all individuals enlisted as authors actually fulfill criteria for authorship as defined in the document "Uniform Requirements for Manuscripts Submitted to Biomedical Journals". Revista MÄdica de Chile is addressing this relevant topic with a combined strategy: (1) A retrospective analysis of the manuscripts published in the recent decades in the Revista will quantify and illustrate the local trend in multiauthorship; (2) A "Statement of accountability": signed by all authors in manuscripts submitted to the Revista, is in use since 1997; and (3) A new form of this "Statement of accountability" requests all authors to identify their personal involvement in the work represented by the manuscript. This information will be available to every person participating in the editorial assessment of the manuscript (editors and external reviewers) but during a trial period of six months authors will be allowed to object the publication of this data, stating the reasons for this objection. After six months the editors will evaluate the information collected and the self-declared role of every author enlisted. The terms "Authors" and "Main author" will continue being used to designate participants because "contributor" (replacement alternative proposed by Rennie et al., currently in use by several leading general medical journals) has a different main meaning in Spanish than in English and it might have a negative effect

Artículos de investigación / Research articles

Since 1973, Revista Médica de Chile has classified biomedical and clinical prospective research papers in a Section named Research Articles, while purely clinical and retrospective studies were classified into another Section, named Clinical Experiences. This distinction seems no longer necessary, because both types of manuscripts are subjected to a uniform external peer-review system and their intrinsic quality is not a distinctive feature. Furthermore, the name of Sections where similar papers are classified by the major general clinical medicine journals is clearly non-uniform. Therefore, Research Articles and Clinical Experiences will from now on be included into a single Section: Research Articles

Necrólisis epidérmica tóxica (NET) una entidad de alta morbimortalidad: a propósito de cuatro casos clínicos / Toxic epidermal necrolysis an entity of high morbimortality: a proposal of 4 clinical cases

La necrolisis epidérmica tóxica (NET) es una severa reacción cutánea caracterizada por la pérdida de grandes áreas de epidermis, producida principalmente por drogas. Poco se sabe en cuanto a la fisiopatología de esta enfermedad, involucrándose factores inmunológicos, infecciosos y genéticos. Al mismo tiempo, se desconoce un tratamiento específico para esta entidad, limitándose a cuidados generales, comparables a los de un gran quemado, y al uso de corticosteroides sistémicos, con resultados controversiales. En esta revisión discutiremos, a propósito de cuatro casos manejados en nuestro Hospital, la situación actual fisiopatológica y terapéutica de esta entidad nosológica. La necrolisis epidérmica tóxica, o síndrome de Lyell, es una severa reacción cutánea producida por drogas en una alta proporción de casos (80 por ciento), pero también por infecciones por gérmenes como mycoplasma pneumoniae y herpes simplex, inmunizaciones y aditivos de alimentos, en la cual se produce una eritrodermia descamativa aguda con necrosis epidérmica y destrucción de la unión dermoepidérmica, originando ampollas flácidas (que dan la apariencia de piel escaldada), generada por apoptosis de los queratinocitos. Tiene una incidencia de 0,4 a 1,2 casos por millón, y ocurre con mayor frecuencia por el uso de sulfonamidades, anticonvulsivantes y antiinflamatorios no esteroidades. Es un cuadro de alta mortalidad reportada, no conociéndose aún tratamiento específico (1,2)

Síndrome de respuesta inflamatoria sistémica severa: ¿es comparable a la sepsis severa? / Systemic inflammatory response syndrome: is it similar to severe sepsis?

Background: in 1992, a consensus conference defined the terms systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis and septic shock. Since then, numerous reports have validated the prognostic usefulness of these operative definitions. Aim: to evaluate if sepsis severity criteria, as defined by the Consensus Conference, can be applied to noninfectious SIRS. Patients and methods: five hundred eighteen patients admitted to 5 intensive care units (ICU) from 4 hospitals were prospectively evaluated during a 3 months period. Patients that met at least one severity criteria were included. SIRS etiology, organ dysfunction and evolution were recorded in each patient. Results: One hundred two patients were included: 79 with sepsis (group I) and 23 with noninfectious SIRS (group II). ICU and hospital mortality were comparable (43 and 48 percent in sepsis compared to 43 and 51 percent in non infectious SIRS). The most common sources of sepsis were pneumonia and peritonitis. Group II patients had a wide variety of diseases. ICU stay, APACHE score and number of organs with dysfunction were not different among groups. Only the incidence of renal dysfunction was higher in the septic group. Conclusions: The Consensus sepsis severity criteria can be applied to noninfectious SIRS, defining a population subset with similar high mortality and organ dysfunction incidence, although with greatly heterogeneous etiologies

¿Es la metodología de nuestros trabajos de investigación esencialmente inferior a la de estudios similares en revistas que se publican en inglés? / Is methodology in our original articles essentially inferior to similar papers published in english-speaking journals?

Randomised controlled trials reported in languages other than English are generally excluded from systematic reviews. This exclusion is often based in the biased opinion that the strictness of methodology and the quality of assessment of the results are essentially inferior to similar articles reported in English. A study published in 1996 in The Lancet compared completeness of reporting, design characteristics, and analytical approaches of 229 randomised controlled trials published in English, French, German, Italian or Spanish, between 1989 and 1994. Eight of those trials had been published in Revista MÄdica de Chile. No significant differences were found in any single item analysed, between trials published in English and in other languages. The peer review system applied by a journal and the editorial selection of original articles to be published are crucial determinants of the overall quality of its publications. The role of local journals that publish in languages other than English is most important for the communities they are intended to serve and their contribution to disseminating scientific and other important aspects of medicine should be acknowledged and considered by readers, authors and editors in English-speaking countries, especially when these local journals belong to the mainstream literature included in the major international indexing services

Flebitis séptica: origen de cuadros sépticos graves / Septic phlebitis: report of two cases

We report two patients, an 82 yeers old female and a 71 years old male, who bad a severe sepis with positive blood cultures for Staphylococcus aureis and a superficial phlebitis as the only probable focus. In both, the diagnosis of septic phlebitis was reached and an emergency phlebotomy was performed under local anaesthesia. The clinical response was satÝsfactory and the pathological examination of excised veins showed an acute exudative leukocytic thrombophlebitis

Instrucciones a los autores de manuscritos que se someterán a publicación en la Revista Médica de Chile / Instructions to authors of manuscripts to be submitted to Revista Médica de Chile

Instructions to authors of manuscripts to be submitted to this journal are published in the Junuary and July issue. These instructions consider the scope of the journal, the experience acquired along two decades applying the peer review system, and the most recent edition (Junary 1997) of the "Uniform Requirements for Manuscripts Submitted to Biomedical Journal". All articles are published in Spanish but each one starts with an abstract in English. The most common errors detected in formal presentation or in contents are briefly reminded in these instructions. A free translation of paragraphs chosen from the "Uniform Requirements..." allows the editors to emphasize some statements added to (or expanded in) this document: "Redundant or duplicate publication" and "Protection of patients' rights". Authors are requested to study the "Uniform Requirements..." and the specific "Instructions to the Authors" when preparing their manuscripts for submission to this journal