Clinical impact of positive Propionibacterium acnes cultures in orthopedic surgery.

BACKGROUND: The clinical significance of a positive culture to Propionibacterium acnes in orthopedic specimens remains unclear, whether about its role as a contaminant or a pathogen, or its impact as a coinfectant. Therefore, we performed a retrospective study to provide a more accurate description of the clinical impact of P. acnes in an orthopedic population aiming to determine: 1) if there is a clinical difference between P. acnes infection and contamination? 2) If there is a clinical difference between P. acnes monoinfection, and coinfection. HYPOTHESIS: There is a clinical difference between P. acnes infection and contamination. MATERIALS AND METHODS: Patients were selected over a five-year period, and those with a minimum of one positive culture for P. acnes, from any intraoperative orthopedic tissue sample, were included in the study. P. acnes infection was defined as the isolation of P. acnes from≥2 specimens, or in only one specimen, in the presence of typical perioperative findings and/or local signs of infection. RESULTS: A total of 68 patients had a positive P. acnes culture, 35 of which were considered to be infected. The infections affected mostly males (29/35-83%), occurred mostly in shoulders (22/35-63%), and at a site already containing an orthopedic implant (32/35-91%). Local inflammatory signs were present in half of the cases when an infection was diagnosed. Coinfection with other pathogens was present in 31% of patients (11/35). When comparing patients coinfected with P. acnes, and those who were monoinfected, the latter presented less often with local inflammatory signs. Recurrence rate was 24% (8/35) and the only risk factor for recurrence was the presence of a monoinfection. DISCUSSION: This study confirms the pathogenicity of P. acnes in an orthopedic population, as it is present in multiple samples in the same patient, and because it is present in cultures from cases with clinical recurrence. Our study showed that monoinfections differ from coinfections mainly by their higher risk of recurrence. LEVEL OF EVIDENCE: Level IV retrospective case series.

The role of defensive ecological interactions in the evolution of conotoxins.

Venoms comprise of complex mixtures of peptides evolved for predation and defensive purposes. Remarkably, some carnivorous cone snails can inject two distinct venoms in response to predatory or defensive stimuli, providing a unique opportunity to study separately how different ecological pressures contribute to toxin diversification. Here, we report the extraordinary defensive strategy of the Rhizoconus subgenus of cone snails. The defensive venom from this worm-hunting subgenus is unusually simple, almost exclusively composed of αD-conotoxins instead of the ubiquitous αA-conotoxins found in the more complex defensive venom of mollusc- and fish-hunting cone snails. A similarly compartmentalized venom gland as those observed in the other dietary groups facilitates the deployment of this defensive venom. Transcriptomic analysis of a Conus vexillum venom gland revealed the αD-conotoxins as the major transcripts, with lower amounts of 15 known and four new conotoxin superfamilies also detected with likely roles in prey capture. Our phylogenetic and molecular evolution analysis of the αD-conotoxins from five subgenera of cone snails suggests they evolved episodically as part of a defensive strategy in the Rhizoconus subgenus. Thus, our results demonstrate an important role for defence in the evolution of conotoxins.

Methodology for AACT evidence-based recommendations on the use of intravenous lipid emulsion therapy in poisoning

Intravenous lipid emulsion (ILE) therapy is a novel treatment that was discovered in the last decade. Despite unclear understanding of its mechanisms of action, numerous and diverse publications attested to its clinical use. However, current evidence supporting its use is unclear and recommendations are inconsistent. To assist clinicians in decision-making, the American Academy of Clinical Toxicology created a workgroup composed of international experts from various clinical specialties, which includes representatives of major clinical toxicology associations. Rigorous methodology using the Appraisal of Guidelines for Research and Evaluation or AGREE II instrument was developed to provide a framework for the systematic reviews for this project and to formulate evidence-based recommendations on the use of ILE in poisoning. Systematic reviews on the efficacy of ILE in local anesthetic toxicity and non-local anesthetic poisonings as well as adverse effects of ILE are planned. A comprehensive review of lipid analytical interferences and a survey of ILE costs will be developed. The evidence will be appraised using the GRADE system. A thorough and transparent process for consensus statements will be performed to provide recommendations, using a modified Delphi method with two rounds of voting. This process will allow for the production of useful practice recommendations for this therapy.(AU)

Extracorporeal treatment for acetaminophen poisoning: recommendations from the EXTRIP workgroup.

BACKGROUND: The Extracorporeal Treatments in Poisoning (EXTRIP) workgroup was created to provide evidence-based recommendations on the use of extracorporeal treatments (ECTR) in poisoning and the results are presented here for acetaminophen (APAP). METHODS: After a systematic review of the literature, a subgroup selected and reviewed the articles and summarized clinical and toxicokinetic data in order to propose structured voting statements following a pre-determined format. A two-round modified Delphi method was chosen to reach a consensus on voting statements, and the RAND/UCLA Appropriateness Method was used to quantify disagreement. Following discussion, a second vote determined the final recommendations. RESULTS: Twenty-four articles (1 randomized controlled trial, 1 observational study, 2 pharmacokinetic studies, and 20 case reports or case series) were identified, yielding an overall very low quality of evidence for all recommendations. Clinical data on 135 patients and toxicokinetic data on 54 patients were analyzed. Twenty-three fatalities were reviewed. The workgroup agreed that N-acetylcysteine (NAC) is the mainstay of treatment, and that ECTR is not warranted in most cases of APAP poisoning. However, given that APAP is dialyzable, the workgroup agreed that ECTR is suggested in patients with excessively large overdoses who display features of mitochondrial dysfunction. This is reflected by early development of altered mental status and severe metabolic acidosis prior to the onset of hepatic failure. Specific recommendations for ECTR include an APAP concentration over 1000 mg/L if NAC is not administered (1D), signs of mitochondrial dysfunction and an APAP concentration over 700 mg/L (4630 mmol/L) if NAC is not administered (1D) and signs of mitochondrial dysfunction and an APAP concentration over 900 mg/L (5960 mmol/L) if NAC is administered (1D). Intermittent hemodialysis (HD) is the preferred ECTR modality in APAP poisoning (1D). CONCLUSION: APAP is amenable to extracorporeal removal. Due to the efficacy of NAC, ECTR is reserved for rare situations when the efficacy of NAC has not been definitively demonstrated.

Successful prevention of respiratory syncytial virus nosocomial transmission following an enhanced seasonal infection control program.

Respiratory syncytial virus (RSV) infections can be serious in severely immunocompromised patients. Use of a targeted infection control program (TICP) has been shown to reduce RSV nosocomial transmission. We evaluated the impact of an enhanced seasonal infection control program (ESICP) vs standard TICP in a hematology-oncology ward. TICP was applied from 1999 to 2001 and ESICP applied from 2001 to 2003. ESICP consisted of strict isolation for all patients admitted on the ward during the RSV season. We prospectively evaluated the incidence, related morbidity and mortality of nosocomial RSV in both field interventions. A total of 40 hospitalized RSV infections were documented. The cumulative incidence of nosocomial RSV during TICP and ESICP was respectively of 42.8 and 3.9 cases/1000 admissions (relative risk = 0.09). ESICP needed to be implemented on 26 admitted patients on our ward to prevent one RSV nosocomial case. Furthermore, implementation of ESICP prevented four pneumonias and two deaths per RSV season. We conclude that ESICP is significantly more efficient than TICP to reduce the occurrence of nosocomial RSV infections and its related morbidity and mortality in patients with hematological malignancy and recipients of hematopoietic SCT.

Successful hemodialysis in a phenytoin overdose: case report and review of the literature.

We describe the case of a 42-year-old female who presented to our care 1 hour after ingesting 3.6 g of phenytoin. She was stuporous 48 hours after admission despite supportive therapy. She was treated with hemodialysis (HD) for nearly 6 hours in order to remove phenytoin. Her level of consciousness improved markedly during the procedure. During HD, phenytoin levels decreased by 47% and measured half-life was 6.8 hours as compared to 116 hours when not on HD. Finally, we were able to remove 547 mg of phenytoin (directly measured from the dialysate), representing approximately a third of estimated body stores. The use of extracorporeal therapy in phenytoin overdose is reviewed here. We believe that in severe cases of phenytoin intoxication, hemodialysis can be used to accelerate total body burden of the drug, even if protein binding is significant.

[Treatment of growth hormone deficiencies with growth hormone releasing hormone. Current status and perspectives]. / Traitement des déficits en hormone de croissance par le facteur hypothalamique de libération de l'hormone de croissance. Etat actuel et perspectives.

Results of clinical trials performed with human hypothalamic growth hormone releasing factor (GRF) are conflicting, but rather disappointing for most of them. Pulsatile administration of GRF has been found to increase growth hormone secretion as well as growth velocity, but is not convenient for practical use. All other routes and rhythms of administration lead only to sub-optimal results, and generally does not seem to procure an appropriate GRF bio-availability. Improvements are possible, particularly the development of agonists and new galenic forms with sustained release. Therapeutic approach with hexapeptides, or hexapeptides analogs, looks promising, but could be more complementary than competitive.

Double blind placebo controlled multicentre study of ginkgolide B in treatment of acute exacerbations of multiple sclerosis. The Ginkgolide Study Group in multiple sclerosis.

After an open labelled pilot study of ginkgolide B, a potent inhibitor of platelet activating factor, in the treatment of acute exacerbations of multiple sclerosis, a randomised double blind placebo controlled study was undertaken. One hundred and four patients were enrolled in the study: for seven days 43 received placebo, 29 received 240 mg/day ginkgolide B and 32 received 360 mg/day ginkgolide B. There was no statistical difference between the three groups for changes in Rankin, Kurtzke expanded disability status scale (EDSS), and Hauser ambulation index (AI) scores. Although there was a trend in favour of groups treated with ginkgolide for a change of Rankin and AI scores, it is concluded that ginkgolide B is not an effective treatment of exacerbations of multiple sclerosis.