Epidemiology and outcome of fungemia in a cancer Cohort of the Infectious Diseases Group (IDG) of the European Organization for Research and Treatment of Cancer (EORTC 65031).

BACKGROUND: Anti-cancer treatment and the cancer population have evolved since the last European Organisation for Research and Treatment of Cancer (EORTC) fungemia survey, and there are few recent large epidemiological studies. METHODS: This was a prospective cohort study including 145 030 admissions of patients with cancer from 13 EORTC centers. Incidence, clinical characteristics, and outcome of fungemia were analyzed. RESULTS: Fungemia occurred in 333 (0.23%; 95% confidence interval [CI], .21-.26) patients, ranging from 0.15% in patients with solid tumors to 1.55% in hematopoietic stem cell transplantation recipients. In 297 evaluable patients age ranged from 17 to 88 years (median 56 years), 144 (48%) patients were female, 165 (56%) had solid tumors, and 140 (47%) had hematological malignancies. Fungemia including polymicrobial infection was due to: Candida spp. in 267 (90%), C. albicans in 128 (48%), and other Candida spp. in 145 (54%) patients. Favorable overall response was achieved in 113 (46.5%) patients by week 2. After 4 weeks, the survival rate was 64% (95% CI, 59%-70%) and was not significantly different between Candida spp. Multivariable logistic regression identified baseline septic shock (odds ratio [OR] 3.04, 95% CI, 1.22-7.58) and tachypnoea as poor prognostic factors (OR 2.95, 95% CI, 1.66-5.24), while antifungal prophylaxis prior to fungemia (OR 0.20, 95% CI, .06-.62) and remission of underlying cancer (OR, 0.18; 95% CI, .06-.50) were protective. CONCLUSIONS: Fungemia, mostly due to Candida spp., was rare in cancer patients from EORTC centers but was associated with substantial mortality. Antifungal prophylaxis and remission of cancer predicted better survival.

Infectiologie et postulats de Koch: tourner la page [Infectious diseases and Koch's postulates: turning the page].

The thoracolumbar junctional region (T10-L1) of the spine is a transitional zone, where more than half of the thoracic and lumbar fractures occur. In this presentation the origin of the pathoanatomical changes in the thoracolumbar junctional region of the spine is discussed in view of the previous studies. These studies refer to a torsional force contributing to the formation of the degenerative changes, especially in the facet joints. Degenerative changes anteriorly and posteriorly do not concur in the thoracolumbar junctional region. Only a weak concurrence is found between disc degeneration and spondylosis, which refer to differences in their pathomechanisms. A strong concurrence between the degenerative changes at different levels, especially anteriorly, reflects factors causing overall degeneration in the thoracolumbar junctional region.

Signs of a vector's adaptive choice: on the evasion of infectious hosts and parasite-induced mortality

Laboratory and field experiments have demonstrated in many cases that malaria vectors do not feed randomly, but show important preferences either for infected or non-infected hosts. These preferences are likely in part shaped by the costs imposed by the parasites on both their vertebrate and dipteran hosts. However, the effect of changes in vector behaviour on actual parasite transmission remains a debated issue. We used the natural associations between a malaria-like parasite Polychromophilus murinus, the bat fly Nycteribia kolenatii and a vertebrate host the Daubenton's bat Myotis daubentonii to test the vector's feeding preference based on the host's infection status using two different approaches: 1) controlled behavioural assays in the laboratory where bat flies could choose between a pair of hosts; 2) natural bat fly abundance data from wild-caught bats, serving as an approximation of realised feeding preference of the bat flies. Hosts with the fewest infectious stages of the parasite were most attractive to the bat flies that did switch in the behavioural assay. In line with the hypothesis of costs imposed by parasites on their vectors, bat flies carrying parasites had higher mortality. However, in wild populations, bat flies were found feeding more based on the bat's body condition, rather than its infection level. Though the absolute frequency of host switches performed by the bat flies during the assays was low, in the context of potential parasite transmission they were extremely high. The decreased survival of infected bat flies suggests that the preference for less infected hosts is an adaptive trait. Nonetheless, other ecological processes ultimately determine the vector's biting rate and thus transmission. Inherent vector preferences therefore play only a marginal role in parasite transmission in the field. The ecological processes rather than preferences per se need to be identified for successful epidemiological predictions.

Consultations infectiologiques ambutatoires non VIH: analyse d'un centre universitaire sur cinq ans [Non-HIV infectious disease outpatient consultations: a 5-year study in a Swiss University Hospital].

Few studies have examined the workload or clinical spectrum of non-HIV infectious diseases outpatient consultations (IDOC). This retrospective study aims to describe IDOC referrals over the past 5 years. In total, 483 patients were referred (with an increase of 63% between 2009 and 2013). Most referrals were received from primary care clinicians (45%). Median patient age was 47 years, 57% of patients were men and 17% were immunosuppressed. Of the diagnoses retained, 74% were infectious, 20% were non-infectious and 6% were of unknown aetiology. Two community outbreaks were identified (tattoo-related mycobacterial infection and Q fever). In conclusion, the infectious diseases outpatient clinic, which has expanded progressively in the past 5 years, provides a specialised service for primary health clinicians and for public health.

Sobrecarga de ferro transfusional em portadores de anemia falciforme: comparação entre ressonância magnética e ferritina sérica

OBJETIVO: Identificar variáveis preditoras de sobrecarga de ferro em portadores de anemia falciforme e correlacionar indicadores bioquímicos e imaginológicos. MATERIAiS E MÉTODOS: Foi realizado estudo transversal envolvendo 32 portadores de anemia falciforme, que foram submetidos a dosagem sérica de ferro, ferritina e a ressonância magnética do fígado. Foram realizadas cinco sequências gradiente-eco e uma spin-eco. A intensidade de sinal foi obtida em cada sequência pelas médias das regiões de interesse no fígado e musculatura paravertebral para obter a razão da intensidade de sinal (RIS) fígado/músculo. A partir da RIS foi obtida a concentração hepática estimada de ferro (CHEF) pela fórmula: e[5,808 - (0,877 × T2*) - (1,518 × PI)], onde T2* é a RIS na sequência com TE de 13 ms e PI é a RIS da sequência com ponderação intermediária. Os pacientes foram agrupados segundo o regime de transfusão de hemácias (regulares mensais versus esporádicas). RESULTADOS: Os grupos transfusionais foram comparados pelas variáveis clínico-laboratoriais, sendo significativas as diferenças entre RIS, CHEF e ferritina sérica: o grupo que recebeu transfusões regulares apresentou sobrecarga de ferro hepático mais intensa. CONCLUSÃO: A ressonância magnética foi ferramenta eficiente para avaliação de sobrecarga hepática de ferro em portadores de anemia falciforme.

Pancytopénie avec anémie hémolytique et schizocytes: une approche pragmatique [Pancytopenia, Hemolytic Anemia and Schizocytes: a Pragmatic Approach].

ous discutons le cas d'une femme de 58 ans qui présente une asthénie progressive et une dyspnée ainsi que des paresthésies des membres. On découvre une pancytopénie avec des neutrophiles hypersegmentés, une anémie macrocytaire hyporégénérative et des éléments d'hémolyse (forte augmentation des LDH). Cette constellation doit faire suspecter une carence en vitamine B12 qui est confirmée chez notre patiente par un dosage de la cobalamine indétectable. Le bilan étiologique montre des anticorps anti-cellules pariétales gastriques positifs à 1/640, diagnostiques d'une maladie de Biermer. A 58 year old woman presents with a progressive fatigue and dyspnea associated with paresthesia. Laboratory tests show pancytopenia with hypersegmented neutrophiles, macrocytic hyporegenerative anemia and arguments for hemolysis, in particular highly increased LDH. This constellation strongly suggests vitamin B12 deficiency, which was confirmed with an undetectable cobalamine concentration in the blood of our patient. The etiologic work up shows the presence of anti-parietal cells antibodies at a titer of 1/640, diagnostic of Biermer anemia.

Two-photon excitation fluorometry in detection of infectious diseases

Because of the heavily overlapping symptoms, pathogen-specific diagnosis and treatment of infectious diseases is difficult based on clinical symptoms alone. Therefore, patients are often treated empirically. More efficient treatment and management of infectious diseases would require rapid point-of-care compatible in vitro diagnostic methods. However, current point-of-care methods are unsatisfactory in performance and in cost structure. The lack of pointof- care methods results in unnecessary use of antibiotics, suboptimal use of virus-specific drugs, and compromised patient care. In this thesis, the applicability of a two-photon excitation fluorometry is evaluated as a tool for rapid detection of infectious diseases. New separation-free immunoassay methodologies were developed and validated for the following application areas: general inflammation markers, pathogen-specific antibodies, pathogen-specific antigens, and antimicrobial susceptibility testing. In addition, dry-reagent methodology and nanoparticulate tracers are introduced in context to the technique. The results show that the new assay technique is a versatile tool for rapid detection of infectious diseases in many different application areas. One particularly attractive area is rapid multianalyte testing of respiratory infections, where the technique was shown to allow simple assay protocols and comparable performance to the state-of-the-art laboratory methods. If implemented in clinical diagnostic use, the new methods could improve diagnostic testing routines, especially in rapid testing of respiratory tract infections.

TCDI vs TCD for stroke risk prevention in children with sickle cell anemia: a cross-sectional study

Children with sickle cell anemia (SCA) are at increased risk of stroke. Elevated blood-flow velocities in the middle cerebral artery detected by Transcranial Doppler (TCD) are a good predictor of stroke risk in these children. Velocities obtained by TCD are measured by using a specific parameter, the time-averaged mean of the maximum velocity (TAMM). Children with TAMM velocities ≥200 cm/sec are at high risk of stroke, and transfusions as primary prevention might be done. Transcranial Doppler-imaging (TCDI) is now widely available and it allows the visualization of intracranial vessels.Few studies have compared the TAMM in TCD and TCDI, and no studies have established a cutoff point for TAMM in TCDI equivalent to the STOP criteria of “normal”, “conditional” and “abnormal”, which could predict a high risk of stroke in children with SCAObjectives: To compare the TAMM velocity obtained by TCDI with the TAMM velocity obtained with TCD in the middle cerebral artery, and to determine a cutoff point for TAMM in TCDI that could predict a high risk of stroke in children with SCAMethods: This study is a cross-sectional study of a diagnostic test. 78 children with sickle cell anemia between 2 to 16 years will be evaluated with both TCD and TCDI in order to determinate the TAMM with the two devices. Velocities obtained with both Doppler techniques will be compared using an intraclass correlation coefficient

Anemia falciforme: desafios e avanços na busca de novos fármacos

Sickle Cell Disease (SCD) is a disease characterized by a punctual mutation (GTG - GAG) in the sixth codon of the gamma globin gene leading to a substitution of glutamic acid by a valine in the β chain of hemoglobin. Despite the huge progress on the molecular knowledge of the disease in recent years, few therapeutic resources were developed. Currently, the treatment is mainly done with the anticancer agent hydroxyurea. This review summarizes current knowledge about possible targets and new approaches to the discovery new compounds to treat the symptoms of SCD.

Avaliação da Velocidade Média na Aorta Torácica Descendente em Fetos com Anemia

Objetivo: verificar se existe correlação significativa entre a velocidade média na dopplerfluxometria da artéria aorta torácica descendente e o grau de anemia fetal. Métodos: estudo prospectivo, transversal, no qual foram analisados 66 fetos de gestantes isoimunizadas, em que se realizou a cordocentese para a realização de transfusões intra-uterinas pela via intravascular (66,7%). Nos fetos que foram submetidos à transfusão intra-uterina pela via intraperitoneal, ou naqueles casos em que não houve necessidade de tratamento intra-uterino (33,3%), a determinação da concentração de hemoglobina do cordão foi realizada pela punção do cordão umbilical, no momento da interrupção da gestação. Neste grupo de fetos estudados, foi realizado exame dopplerfluxométrico da artéria aorta torácica descendente, sendo calculada a velocidade média de fluxo. Foi realizado estudo de associação entre as variáveis. Foram também calculados os valores de sensibilidade, especificidade, valores preditivos positivo e negativo. Resultados: observou-se correlação significativa e inversa entre a velocidade média na artéria aorta torácica descendente e o nível de hemoglobina fetal. A velocidade média na dopplerfluxometria da artéria aorta torácica descendente apresentou sensibilidade de 47,5% para anemia fetal moderada (Hg<10 g/dL), com o teste exato de Fisher apresentando valor de p<0,01, e de 54,5% para anemia fetal grave (Hg<7,0 g/dL), com um valor de p=0,01. Conclusões: houve associação significativa entre a velocidade média na aorta torácica descendente e o grau de diagnóstico de anemia fetal.