Sepsis Mortality Prediction Based on Predisposition, Infection and Response

OBJECTIVE: To empirically test, based on a large multicenter, multinational database, whether a modified PIRO (predisposition, insult, response, and organ dysfunction) concept could be applied to predict mortality in patients with infection and sepsis. DESIGN: Substudy of a multicenter multinational cohort study (SAPS 3). PATIENTS: A total of 2,628 patients with signs of infection or sepsis who stayed in the ICU for >48 h. Three boxes of variables were defined, according to the PIRO concept. Box 1 (Predisposition) contained information about the patient's condition before ICU admission. Box 2 (Injury) contained information about the infection at ICU admission. Box 3 (Response) was defined as the response to the infection, expressed as a Sequential Organ Failure Assessment score after 48 h. INTERVENTIONS: None. MAIN MEASUREMENTS AND RESULTS: Most of the infections were community acquired (59.6%); 32.5% were hospital acquired. The median age of the patients was 65 (50-75) years, and 41.1% were female. About 22% (n=576) of the patients presented with infection only, 36.3% (n=953) with signs of sepsis, 23.6% (n=619) with severe sepsis, and 18.3% (n=480) with septic shock. Hospital mortality was 40.6% overall, greater in those with septic shock (52.5%) than in those with infection (34.7%). Several factors related to predisposition, infection and response were associated with hospital mortality. CONCLUSION: The proposed three-level system, by using objectively defined criteria for risk of mortality in sepsis, could be used by physicians to stratify patients at ICU admission or shortly thereafter, contributing to a better selection of management according to the risk of death.

The Role of the Humoral Immune Response in the Molecular Evolution of the Envelope C2, V3 and C3 Regions in Chronically HIV-2 Infected Patients

BACKGROUND: This study was designed to investigate, for the first time, the short-term molecular evolution of the HIV-2 C2, V3 and C3 envelope regions and its association with the immune response. Clonal sequences of the env C2V3C3 region were obtained from a cohort of eighteen HIV-2 chronically infected patients followed prospectively during 2-4 years. Genetic diversity, divergence, positive selection and glycosylation in the C2V3C3 region were analysed as a function of the number of CD4+ T cells and the anti-C2V3C3 IgG and IgA antibody reactivity RESULTS: The mean intra-host nucleotide diversity was 2.1% (SD, 1.1%), increasing along the course of infection in most patients. Diversity at the amino acid level was significantly lower for the V3 region and higher for the C2 region. The average divergence rate was 0.014 substitutions/site/year, which is similar to that reported in chronic HIV-1 infection. The number and position of positively selected sites was highly variable, except for codons 267 and 270 in C2 that were under strong and persistent positive selection in most patients. N-glycosylation sites located in C2 and V3 were conserved in all patients along the course of infection. Intra-host variation of C2V3C3-specific IgG response over time was inversely associated with the variation in nucleotide and amino acid diversity of the C2V3C3 region. Variation of the C2V3C3-specific IgA response was inversely associated with variation in the number of N-glycosylation sites. CONCLUSION: The evolutionary dynamics of HIV-2 envelope during chronic aviremic infection is similar to HIV-1 implying that the virus should be actively replicating in cellular compartments. Convergent evolution of N-glycosylation in C2 and V3, and the limited diversification of V3, indicates that there are important functional constraints to the potential diversity of the HIV-2 envelope. C2V3C3-specific IgG antibodies are effective at reducing viral population size limiting the number of virus escape mutants. The C3 region seems to be a target for IgA antibodies and increasing N-linked glycosylation may prevent HIV-2 envelope recognition by these antibodies. Our results provide new insights into the biology of HIV-2 and its relation with the human host and may have important implications for vaccine design.

Perinatal Ischemic Stroke: a Five-Year Retrospective Study in a Level-III Maternity

Objective To study the incidence, clinical presentation, risk factors, imaging diagnosis, and clinical outcome of perinatal stroke. Methods Data was retrospectively collected from full-term newborns admitted to the neonatal unit of a level III maternity in Lisbon with cerebral stroke, from January 2007 to December 2011. Results There were 11 cases of stroke: nine were arterial ischemic stroke and two were cerebral venous sinus thrombosis. We estimated an incidence of arterial ischemic stroke of 1.6/5,000 births and of cerebral venous sinus thrombosis of 7.2/100,000 births. There were two cases of recurrent stroke. Eight patients presented with symptoms while the remaining three were asymptomatic and incidentally diagnosed. The most frequently registered symptoms (8/11) were seizures; in that, generalized clonic (3/8) and focal clonic (5/8). Strokes were more commonly left-sided (9/11), and the most affected artery was the left middle cerebral artery (8/11). Transfontanelle ultrasound was positive in most of the patients (10/11), and stroke was confirmed by cerebral magnetic resonance in all patients. Electroencephalographic recordings were carried out in five patients and were abnormal in three (focal abnormalities n=2, burst-suppression pattern n=1). Eight patients had previously identified risk factors for neonatal stroke which included obstetric and neonatal causes. Ten patients were followed up at outpatients setting; four patients developed motor deficits and one presented with epilepsy. Conclusions Although a modest and heterogeneous sample, this study emphasizes the need for a high level of suspicion when it comes to neonatal stroke, primarily in the presence of risk factors. The prevalence of neurological sequelae in our series supports the need of long-term follow-up and early intervention strategies.

Recommendations for Vaccination in Adult Patients with Systemic Inflammatory Rheumatic Diseases from the Portuguese Society of Rheumatology

Serious infections are a major cause of morbidity and mortality in systemic inflammatory rheumatic disease (SIRD) patients. Although vaccination may prevent numerous infections, vaccination uptake rates are low in this group of patients. OBJECTIVES: To develop evidence-based recommendations for vaccination in SIRD patients. METHODS: We searched MEDLINE (until 31 October 2014) and EMBASE (until 14 December 2014) databases, as well as the ACR and EULAR congress abstracts (2011-2014). Patients with any systemic inflammatory rheumatic disease were included and all vaccines were considered. Any safety and efficacy outcomes were admitted. Search results were submitted to title and abstract selection, followed by detailed review of suitable studies. Data were subsequently pooled according to the type of vaccine and the SIRD considered. Results were presented and discussed by a multidisciplinary panel and systematic literature review (SLR)-derived recommendations were voted according to the Delphi method. The level of agreement among rheumatologists was assessed using an online survey. RESULTS: Eight general and seven vaccine-specific recommendations were formulated. Briefly, immunization status should routinely be assessed in all SIRD patients. The National Vaccination Program should be followed and some additional vaccines are recommended. To maximize the efficacy of vaccination, vaccines should preferably be administered 4 weeks before starting immunosuppression or, if possible when disease activity is controlled. Non-live vaccines are safe in SIRD, including immunosuppressed patients. The safety of live attenuated vaccines in immunosuppressed patients deserves further ascertainment, but might be considered in particular situations. DISCUSSION: The present recommendations combine scientific evidence with the multidisciplinary expertise of our taskforce panel and attained desirable agreement among Portuguese rheumatologists. Vaccination recommendations need to be updated on a regular basis, as more scientific data regarding vaccination efficacy and safety, emergent infectious threats, new vaccines as well as new immunomodulatory therapies become available.