Imported malaria in a cosmopolitan European city: A mirror image of the world epidemiological situation

© 2008 Millet et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

The HIV-1 reservoir landscape in persistent elite controllers and transient elite controllers.

BACKGROUNDPersistent controllers (PCs) maintain antiretroviral-free HIV-1 control indefinitely over time, while transient controllers (TCs) eventually lose virological control. It is essential to characterize the quality of the HIV reservoir in terms of these phenotypes in order to identify the factors that lead to HIV progression and to open new avenues toward an HIV cure.METHODSThe characterization of HIV-1 reservoir from peripheral blood mononuclear cells was performed using next-generation sequencing techniques, such as full-length individual and matched integration site proviral sequencing (FLIP-Seq; MIP-Seq).RESULTSPCs and TCs, before losing virological control, presented significantly lower total, intact, and defective proviruses compared with those of participants on antiretroviral therapy (ART). No differences were found in total and defective proviruses between PCs and TCs. However, intact provirus levels were lower in PCs compared with TCs; indeed the intact/defective HIV-DNA ratio was significantly higher in TCs. Clonally expanded intact proviruses were found only in PCs and located in centromeric satellite DNA or zinc-finger genes, both associated with heterochromatin features. In contrast, sampled intact proviruses were located in permissive genic euchromatic positions in TCs.CONCLUSIONSThese results suggest the need for, and can give guidance to, the design of future research to identify a distinct proviral landscape that may be associated with the persistent control of HIV-1 without ART.FUNDINGInstituto de Salud Carlos III (FI17/00186, FI19/00083, MV20/00057, PI18/01532, PI19/01127 and PI22/01796), Gilead Fellowships (GLD22/00147). NIH grants AI155171, AI116228, AI078799, HL134539, DA047034, MH134823, amfAR ARCHE and the Bill and Melinda Gates Foundation

Imported malaria among African immigrants: is there still a relationship between developed countries and their ex-colonies?

© 2009 Millet et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Genome-wide association analysis of dementia and its clinical endophenotypes reveal novel loci associated with Alzheimer's disease and three causality networks : The GR@ACE project

Introduction: Large variability among Alzheimer's disease (AD) cases might impact genetic discoveries and complicate dissection of underlying biological pathways. Methods: Genome Research at Fundacio ACE (GR@ACE) is a genome-wide study of dementia and its clinical endophenotypes, defined based on AD's clinical certainty and vascular burden. We assessed the impact of known AD loci across endophenotypes to generate loci categories. We incorporated gene coexpression data and conducted pathway analysis per category. Finally, to evaluate the effect of heterogeneity in genetic studies, GR@ACE series were meta-analyzed with additional genome-wide association study data sets. Results: We classified known AD loci into three categories, which might reflect the disease clinical heterogeneity. Vascular processes were only detected as a causal mechanism in probable AD. The meta-analysis strategy revealed the ANKRD31-rs4704171 and NDUFAF6-rs10098778 and confirmed SCIMP-rs7225151 and CD33-rs3865444. Discussion: The regulation of vasculature is a prominent causal component of probable AD. GR@ACE meta-analysis revealed novel AD genetic signals, strongly driven by the presence of clinical heterogeneity in the AD series

Postoperative blood salvage and reinfusion in spinal surgery: Blood quality, effectiveness and impact on patient blood parameters

Although reinfusion of salvaged shed blood has become popular in major orthopaedic procedures, this blood saving technique is still controversial. In an effort to assess the functional and metabolic status of shed blood erythrocytes and the impact of postoperative shed blood reinfusion on allogenic blood requirements and patient's blood parameters, analyses of perioperative blood samples were performed in 28 consecutive orthopaedic patients undergoing spinal fusion, in which postoperative shed blood was collected and reinfused with the ConstaVac CBC II device. In comparison with a previous series of 31 patients, this procedure reduced allogenic blood requirements by almost 30% (P < 0.05), without any increase in postoperative complications. Postoperative shed blood presented lower haematological values and higher plasma-free haemoglobin (PFHB) levels than preoperative blood, without any disturbance in morphology, median corpuscular fragility (MCF) or erythrocyte adenosine triphosphate (ATP) and diphosphoglycerate (DPG) content. Serum concentrations of enzymes - glutamate-oxalacetate aminotransferase (GOT), glutamate-piruvate aminotransferase (GPT), creatine kinase (CK), lactate dehydrogenase (LDH) - and inflammatory cytokines (IL-1β, IL-6) were elevated in shed blood. After reinfusion, there was no alteration in coagulation parameters or cytokine levels. Serum levels of some enzymes increased at the end of surgery and remained elevated at postoperative day 2 (CK) or 7 (GOT, LDH), with a higher increase if postoperative autotransfusion was used as a blood saving method. Therefore, caution should be taken when these serum enzyme levels are used for diagnosis. In conclusion, salvaged shed blood in orthopaedic procedures of the spine seems to be an excellent source of red cells which are not significantly damaged, keeping a normal functional and metabolic status, and reduces allogenic blood requirements without significant side effects

Autotransfusión en cirugía de columna lumbar

Objectives: An evaluation was made of the effectiveness of preoperative (preoperative autologous blood donation, PABD) and postoperative autologous blood salvage (shed blood salvage and reinfusion, PBSR) in reducing exposure to homologous blood transfusions (HBT) and transfusion-related complications in patients undergoing lumbar spine surgery. Patients and methods: The study population was a series of 122 consecutive patients who underwent instrumented lumbar spinal fusion (Allospine, Sulzer, Switzerland), divided into four groups depending on the transfusion regimen used. Group A (Control, homologous blood alone), Group B (PBSR), Group C (PABD), and Group D (PABD + PBSR). Shed blood was salvaged during the first 6 postoperative hours and reinfused using the ConstaVac CBCII device (Stryker, USA). The effectiveness (% of patients avoiding HBT) and use of autologous blood (% of collected autologous units reinfused) were evaluated, as well as the rate of postoperative complications. Results: Patients in group A (Control, n = 37) received only HBT (1.92 ± 0.2 U/pat), while those in group B (PBSR, n = 29) were reinfused 405 ± 29 ml/pat of shed blood (19 U, 74% of total postoperative blood loss) using the ConstaVac CBCII (Stryker). This reduced postoperative HBT requirements by 60% (0.28 vs. 0.67 U/pat, p < 0.05) and total HBT requirements by 20% (1.56 Vs 1.92 U/pat). Five patients in Group A and four in Group B did not receive HBT. The overall transfusion rate in Group B (2.25 ± 0.19) was not significantly different from that of Group A. In the next two groups, a 2 U/pat short-term PABD was obtained (7 days and 1 day before surgery) and used either alone (Group C, n = 24) or in combination with PBSR (Group D, n = 32). In group C, the transfusion requirement was 1.79 ± 0.1 U/pat, 83% of the PABD units was reinfused, and only two patients received HBT (effectiveness 93%). The patients in group D had the highest blood loss and lowest male/female ratio. In addition to 61 U of PABD (95%) and 24 U of PBSR (58% of total postoperative blood loss), 9 U of HBT were needed for 7 patients in Group D (effectiveness 78%), the mean transfusion rate being 3.03 ± 0.15 U/pat (p < 0.01). The overall effectiveness of the PABD program was 84% and only 11% of PABD units were not reinfused. There were no significant differences in preoperative, postoperative, and discharge hemoglobin levels, in the rate of infectious complications, or in the duration of hospitalization in the four groups. There were no clinically relevant adverse effects related to PABD or PBSR. Conclusions: Short-term PABD was found to be a safe and effective procedure for avoiding HBT in patients undergoing instrumented lumbar spinal surgery. The association of PBSR with PABD could be useful in patients who cannot donate the required number PABD units or when a large postoperative blood loss is anticipated

Acute phase response in patients undergoing lumbar spinal surgery: Modulation by perioperative treatment with naproxen and famotidine

In orthopaedic surgery, perioperative administration of nonsteroidal anti-inflammatory drugs has been shown to reduce postoperative pain and analgesic consumption. In addition, preoperative administration of ibuprofen has proved to reduce interleukin-6 (IL-6) release, while that of ranitidine reduced postoperative IL-6-induced C-reactive protein synthesis in patients undergoing abdominal surgery. However, it has not been established whether the preoperative administration of both types of drugs may reduced the postoperative inflammatory reaction after instrumented spinal surgery. Accordingly, our objective was to investigate the effects of preoperative treatment with naproxen plus famotidine on the postoperative systemic inflammatory reaction in patients undergoing instrumented lumbar spinal surgery. Forty consecutive patients scheduled for elective instrumented spinal fusion were alternately assigned to receive either naproxen (500 mg/day, p.o.) plus famotidine (40 mg/day, p.o.) for 7 days before operation, or no adjuvant treatment. Haematological parameters, acute phase proteins, complement fractions, immunoglobulins and cytokines were determined 7 days and immediately before surgery, and on days 0, 1, 2 and 7 after surgery. Haematological parameters, clinical data, duration of surgery, blood loss, perioperative blood transfusion and postoperative complications were similar in the two groups, although pretreated patients showed lower increases in body temperature and required less analgesic medication. Compared with preoperative levels, IL-6 levels were significantly increased postoperatively in all patients with no differences between groups. C-reactive protein, α1-acid-glycoprotein and haptoglobin levels were also significantly increased postoperatively in all patients; however, they were significantly lower in pretreated patients. In conclusion, perioperative treatment with naproxen plus famotidine was well tolerated and reduced the acute phase response after instrumented spinal surgery. However, further research is needed to determine the best dose and timing of preoperative treatment administration, and to correlate these changes with long-term clinical results

Transfusion of post-operative shed blood: Laboratory characteristics and clinical utility

Increased awareness of the potential hazards of allogenic blood transfusion, such as incompatibility reactions, metabolic and immunologic disorders, or transmission of viral diseases, has led to an emphasis on allogeneic blood alternatives. For orthopaedic surgery, several autologous transfusion modalities have emerged as alternatives to allogeneic blood transfusion, avoiding its immunomodulatory effects. Among them, transfusion or return of post-operative salvaged shed blood has become popular in major orthopaedic procedures. However, although the effectiveness of this blood-saving method is well documented, several authors have questioned its safety and recommended the use of washed blood. Therefore, this review analyses the haematologic characteristics of unwashed filtered shed blood, including metabolic status and survival of red blood cells, the components of the haemostatic system, the content of fat particles, bacterial and tumour cells and the possibility of their removal, the content of inflammatory mediators, and the effects on the patient's immune system. From data reviewed in this paper, it can be concluded that post-operative salvage of blood seems to be an excellent source of functional and viable red cells without many of the transfusion-related risks and with some immuno-stimulatory effects. In addition, from our experience, postoperative re-infusion of unwashed shed blood after major spine procedures has proved to reduce post-operative homologous transfusion requirements and to complement preoperative autologous blood donation, without any clinically relevant complication