Controlling intrathoracic hemorrhage on ECMO: help from Factor VIIa and Virchow.

OBJECTIVE: Thoracentesis with chest tube placement is often needed to decompress a clinically significant pneumothorax or pleural effusion. The risks of such a procedure may be considered too great to perform on a systemically anticoagulated patient supported by extracorporeal membrane oxygenation (ECMO). RESULTS: An 8-year-old child with respiratory failure due to necrotizing pneumonia and autoimmune vasculitis, on veno-venous ECMO, developed a severe tension pneumothorax that required emergent decompression with a chest tube. Post-procedure, the patient developed a hemothorax that was approaching non-sustainability. We developed a strategy based on Virchow's triad to favor homeostasis in the patient while avoiding thrombosis in the ECMO circuit. We employed selective lung ventilation, passive pleural drainage, high flow ECMO, and aggressive coagulation cascade control, including the use of aminocaproic acid and activated factor VIIa. Following this strategy, the hemorrhage was controlled and, later, the patient was able to successfully come off ECMO. CONCLUSIONS: With careful coagulation cascade manipulation, complete lung rest for the affected lung, control of ECMO blood flow, and prudent hemothorax drainage, we were able to facilitate hemostasis that was required for the successful recovery of our patient while avoiding critical ECMO circuit thrombosis. Even with today's highly advanced medical technologies, centuries-old basic medical principles can still assist in the care of our sickest and most complex patients. Chest tube placement while on ECMO is rare and, although necessary, may be a risky procedure. With precise coagulation control, it can be a successful procedure on ECMO.

No increase in adverse events with lateral extra-articular tenodesis augmentation of anterior cruciate ligament reconstruction - Results from the stability randomized trial.

OBJECTIVES: Results from the Stability Study suggest that adding a lateral extra-articular tenodesis (LET) to a hamstring tendon autograft reduces the rate of anterior cruciate ligament reconstruction (ACLR) failure in high-risk patients. The purpose of this study is to report adverse events over the 2-year follow-up period and compare groups (ACLR alone vs. ACLR + LET). METHODS: Stability is a randomized clinical trial comparing hamstring tendon ACLR with and without LET. Patients aged 14-25 years with an ACL deficient knee were included. Patients were followed and adverse events documented (type, actions taken, resolution) with visits at 3, 6, 12, and 24 months postoperatively. Adverse events were categorized as none, minor medical, minor surgical, contralateral ACL rupture, or graft rupture. Patient reported outcome measures (PROMs) collected at each visit included the Knee Injury and Osteoarthritis Outcome Score (KOOS), International Knee Documentation Committee Score (IKDC), and ACL Quality of Life Questionnaire (ACL-QOL). RESULTS: In total, 618 patients were randomized (mean age 18.9 years, 302 (49%) male). Forty-five patients (7%) suffered graft rupture; 34 (11%) in the ACLR group compared to 11 (4%) in the ACLR + LET group (RRR = 0.67, 95% CI 0.36 to 0.83, p < 0.001). There were no differences in effusion or infection rates between groups. The ACLR + LET group experienced an increased number of hardware removals (10 vs. 4). Overall, the rate of minor medical events (11%), minor surgical events (7%), and ipsilateral or contralateral ACL tears (10%) were low considering the high-risk patient profile. Increasing severity of adverse events was associated with lower PROMs at 24 months post-operative. Patients in the ACLR + LET group reported greater degree of pain at 3 months only. There were no clinically significant differences in range of motion between groups. CONCLUSIONS: The addition of LET to hamstring tendon autograft ACLR in young patients at high risk of re-injury resulted in a statistically significant reduction in graft rupture. While the addition of LET may increase rates of hardware irritation, there was no significant increase in overall rates of minor medical adverse events, minor surgical events, or overall re-operation rates. The concerns regarding complications associated with a LET did not materialize in this study. LEVEL OF EVIDENCE: Level I.

Bumble bee species' responses to a targeted conservation measure depend on landscape context and habitat quality.

The global decline of insect pollinators, especially bees, is cause for concern, and there is an urgent need for cost-effective conservation measures in agricultural landscapes. While landscape context and habitat quality are known to influence species richness and abundance of bees, there is a lack of evidence from manipulative field experiments on bees' responses to adaptive management across differently structured landscapes. We present the results of a large-scale study that investigated the effects of a targeted agri-environment scheme (AES) on bumble bees (Bombus spp.) over three years in the United Kingdom. Forage patches of different sizes were sown with a conservation flower mixture across eight sites covering a broad range of agricultural land use types. Species richness and worker densities (especially of the longer-tongued Bombus species for which the mixture was targeted) were significantly higher on sown forage patches than on existing non-crop control habitats throughout the three-year study, but the strength of this response depended on both the proportions of arable land and abundance of herbaceous forb species in the surrounding landscape. The size of sown patches also affected worker density, with smaller patches (0.25 ha) attracting higher densities of some species than larger patches (1.0 ha). Our models show that a targeted AES can deliver greater net benefits in more intensively farmed areas, in terms of the number and species richness of bumble bees supported, than in heterogeneous landscapes where other foraging habitats exist. These findings serve to strengthen the evidence base for extending agri-environment schemes to boost declining pollinator populations to a larger number of agricultural landscapes across the globe.

Ban on triazine herbicides likely to reduce but not negate relative benefits of GMHT maize cropping.

The UK Farm-Scale Evaluations (FSE) compared the effects on biodiversity of management of genetically modified herbicide-tolerant (GMHT) spring-sown crops with conventional crop management. The FSE reported larger weed abundance under GMHT management for fodder maize, one of three crops studied. Increased seed production may be important for the long-term persistence of these arable weeds and may benefit invertebrates, small mammals and seed-eating birds. In three-quarters of FSE maize fields, growers used atrazine on the conventionally managed half, reflecting contemporary commercial practice. Withdrawal of the triazine herbicides atrazine, simazine and cyanazine from approved lists of EU chemicals could therefore reduce or even reverse the reported benefits of GMHT maize. Here we analyse effects of applications of triazine herbicides in conventional maize regimes on key indicators, using FSE data. Weed abundances were decreased greatly relative to all other regimes whenever atrazine was applied before weeds emerged. Here, we forecast weed abundances in post-triazine herbicide regimes. We predict weed abundances under future conventional herbicide management to be considerably larger than that for atrazine used before weeds emerged, but still smaller than for the four FSE sites analysed that used only non-triazine herbicides. Our overall conclusion is that the comparative benefits for arable biodiversity of GMHT maize cropping would be reduced, but not eliminated, by the withdrawal of triazines from conventional maize cropping.

[Risk announcement in paediatric cancerology: strengthen the therapeutic alliance]. / L'annonce des risques en cancérologie pédiatrique: consolider l'alliance thérapeutique.

Although announcement of the risks related to treatment has become a general rule in the healthcare relationship, doctors, nurses and parents of severely ill children tend to feel uncomfortable in relation to this mandatory information. The work conducted by the AP-HP Espace éthique working party in collaboration with parents, healthcare personnel and a philosopher demonstrates the need to announce these risks, even beyond the legal framework, while bearing in mind the difficulties and hazards inherent to changes in legislation and by observing the philosophical values that subtend this legislation. Faced with the broad range of diverse and complex risks, the working party proposes a classification of risks and hierarchisation of the difficulties encountered by the doctor during this announcement, which is difficult to make, and difficult to hear, as intimately related to the child's quality of life. The very concept of the probability of a risk raises concepts that are difficult to accept: chance, randomness, and uncertainty. Informing the patient involves hearing as much as talking, listening as much as explaining and requires availability, time, space and an ability to listen to the patient. This article proposes several good practice guidelines designed to consolidate the therapeutic alliance by sharing the uncertainty of the risk and allowing the various partners to remain actors. Nonconfiscation of knowledge by doctors does not lead to a loss or transfer of their responsibility, but allows decisions to be taken in the context of the alliance, while taking the risks into account.

[End of life and clinical research in pediatric oncology]. / Fin de vie de l'enfant et recherche clinique en cancérologie pédiatrique.

The objective of a phase I trials in paediatrics is to determine the recommended dose of a new treatment in children while evaluating its toxicity. These trials are proposed when no effective curative treatment is available. The probability of a benefit in terms of disease control is certainly very low, but greater than zero. On the basis of the work conducted by an Assistance publique-Hôpitaux de Paris Espace éthique group in collaboration with parents, healthcare personnels and a philosopher, phase I therapeutic trials can be considered to be an ethically acceptable proposal provided the criteria and risks of inclusion in such a trial are clearly defined. This article discusses the main elements of this process and is designed to provide guidelines for healthcare personnel and parents. The need for an information provided gently but honestly, the importance of a sufficient time to think about the proposed trial, a two-sided dialogue and partnership between the various actors, and the priority given to the child's best interest, as should always be the case, constitute the decisive elements to guide the proposed inclusion in a phase I trial. These conditions help to ensure that a decision is reached which appears to be morally founded for all parties, while allowing the child to remain alive up until the end, i.e. a human being capable of relating. This decision allows parents and healthcare personnel to retain a good self-image; if the child dies, it is by keeping their self-esteem that parents can live with their bereavement and healthcare personnel can reinvest in other patients.

Country-specific effects of neonicotinoid pesticides on honey bees and wild bees.

Neonicotinoid seed dressings have caused concern world-wide. We use large field experiments to assess the effects of neonicotinoid-treated crops on three bee species across three countries (Hungary, Germany, and the United Kingdom). Winter-sown oilseed rape was grown commercially with either seed coatings containing neonicotinoids (clothianidin or thiamethoxam) or no seed treatment (control). For honey bees, we found both negative (Hungary and United Kingdom) and positive (Germany) effects during crop flowering. In Hungary, negative effects on honey bees (associated with clothianidin) persisted over winter and resulted in smaller colonies in the following spring (24% declines). In wild bees (Bombus terrestris and Osmia bicornis), reproduction was negatively correlated with neonicotinoid residues. These findings point to neonicotinoids causing a reduced capacity of bee species to establish new populations in the year following exposure.

Successful primary use of VVDL+V ECMO with cephalic drain in neonatal respiratory failure.

OBJECTIVE: To describe the use of double-lumen venovenous (VVDL) extracorporeal membrane oxygenation (ECMO) with cephalic draining cannula (VVDL+V) as a primary approach for all neonatal respiratory diagnoses and to compare our single-center experience with data as collected in the Extracorporeal Life Support Organization (ELSO) database. STUDY DESIGN: We retrospectively reviewed all cases of ECMO for neonatal respiratory failure performed in the neonatal intensive-care unit at a large referral children's hospital, the Children's Healthcare of Atlanta at Egleston (CHOA-E). Comparisons were then made to neonatal respiratory ECMO data retrieved from the ELSO database. RESULTS: At CHOA-E 162 of 189 cases were completed with the VVDL+V approach. Survival in the VVDL+V cohort was 89.1% versus 68.7% from ELSO, P<0.001. For those complications considered, the overall risk of complication favored the CHOA-E VVDL+V group as compared with ELSO (odds ratio (OR) 0.71 (0.52-0.7)) as did the risk of neurologic complications (OR 0.29, (0.15-0.58)), including intracranial hemorrhage (OR 0.39 (0.18-0.97), P=0.011). CONCLUSION: The VVDL+V approach can be used successfully as the primary approach for ECMO for neonatal respiratory failure of various etiologies and in this single-center cohort this approach was associated with improved survival and lower rates of complication as compared with the ELSO database.

Extending standard testing period in honeybees to predict lifespan impacts of pesticides and heavy metals using dynamic energy budget modelling.

Concern over reported honeybee (Apis mellifera spp.) losses has highlighted chemical exposure as a risk. Current laboratory oral toxicity tests in A. mellifera spp. use short-term, maximum 96 hour, exposures which may not necessarily account for chronic and cumulative toxicity. Here, we use extended 240 hour (10 day) exposures to examine seven agrochemicals and trace environmental pollutant toxicities for adult honeybees. Data were used to parameterise a dynamic energy budget model (DEBtox) to further examine potential survival effects up to 30 day and 90 day summer and winter worker lifespans. Honeybees were most sensitive to insecticides (clothianidin > dimethoate ≫ tau-fluvalinate), then trace metals/metalloids (cadmium, arsenic), followed by the fungicide propiconazole and herbicide 2,4-dichlorophenoxyacetic acid (2,4-D). LC50s calculated from DEBtox parameters indicated a 27 fold change comparing exposure from 48 to 720 hours (summer worker lifespan) for cadmium, as the most time-dependent chemical as driven by slow toxicokinetics. Clothianidin and dimethoate exhibited more rapid toxicokinetics with 48 to 720 hour LC50s changes of <4 fold. As effects from long-term exposure may exceed those measured in short-term tests, future regulatory tests should extend to 96 hours as standard, with extension to 240 hour exposures further improving realism.

Determinants of species richness in the Park Grass Experiment.

The Park Grass Experiment at Rothamsted in southeast England was started in 1856, making it the longest-running experiment in plant ecology anywhere in the world. Experimental inputs include a range of fertilizers (nitrogen, phosphorus, potassium, and organic manures) applied annually, with lime applied occasionally, and these have led to an increase in biomass and, where nitrogen was applied in the form of ammonium sulfate, to substantial decreases in soil pH. The number of species per plot varies from three to 44 per 200 m(2), affording a unique opportunity to study the determinants of plant species richness and to estimate the effect sizes attributable to different factors. The response of species richness to biomass depends on the amount and type of nitrogen applied; richness declined monotonically with increasing biomass on plots receiving no nitrogen or receiving nitrogen in the form of sodium nitrate, but there was no relationship between species richness and biomass on plots acidified by ammonium sulfate application. The response to lime also depended on the type of nitrogen applied; there was no relationship between lime treatment and species richness, except in plots receiving nitrogen in the form of ammonium sulfate, where species richness increased sharply with increasing soil pH. The addition of phosphorus reduced species richness, and application of potassium along with phosphorus reduced species richness further, but the biggest negative effects were when nitrogen and phosphorus were applied together. The analysis demonstrates how multiple factors contribute to the observed diversity patterns and how environmental regulation of species pools can operate at the same spatial and temporal scale as biomass effects.

A randomized trial of intravenous heparin in conjunction with anistreplase (anisoylated plasminogen streptokinase activator complex) in acute myocardial infarction: the Duke University Clinical Cardiology Study (DUCCS) 1.

OBJECTIVES: We designed a randomized trial to evaluate the effects of heparin administration in conjunction with anistreplase (anisoylated plasminogen streptokinase activator complex [APSAC]) on arterial patency and clinical end points. BACKGROUND: The role of conjunctive intravenous heparin therapy with APSAC has not been tested despite the recommendations that intravenous heparin should be used. METHODS: Four hours after APSAC administration, 250 patients with acute myocardial infarction were randomly assigned to receive 325 mg of either aspirin alone or aspirin and a continuous infusion of heparin (15 IU/kg body weight per h). Clinical ischemic events and bleeding complications were monitored. On hospital day 5, coronary arteriography and left ventriculography were performed. RESULTS: The primary end point of the trial (the combined outcome of death, reinfarction, recurrent ischemia and occlusion of the infarct-related artery) occurred in 42% of the heparin-treated group versus 43% of the group treated without heparin (p = 0.94). A patent infarct-related artery was present in 80% of the patients treated with heparin and in 73% of those treated without heparin (p = 0.26). Left ventricular function, as measured by ejection fraction, was well preserved in both groups (52% vs. 50.5%, respectively, p = 0.29). The overall bleeding rate was higher in patients with (32%) than without (17.2%) heparin (p = 0.006). CONCLUSIONS: Weight-adjusted intravenous heparin therapy after APSAC in acute myocardial infarction does not reduce the combined incidence of death, reinfarction, recurrent ischemia and occlusion of the infarct-related artery. Furthermore, withholding intravenous heparin therapy is associated with a 46% reduction in bleeding complications. Our findings do not support the addition of intravenous heparin after APSAC therapy, as currently recommended, and suggest that a strategy of withholding heparin is simpler and safer and does not place the patient at increased risk for ischemic complications after myocardial infarction.

Sulbactam/ampicillin versus cefoxitin for uncomplicated and complicated acute pelvic inflammatory disease.

In this study, 17 women were treated for uncomplicated acute pelvic inflammatory disease requiring hospitalisation for therapy, and 5 women were treated for the same infection complicated by pelvic abscesses. Treatment regimens were sulbactam 1g plus ampicillin 2g (14 women) or cefoxitin 2g (8 women) given by intravenous infusion every 6 hours. On the third day of therapy, a rash developed in 1 woman who was being successfully treated for uncomplicated disease with sulbactam/ampicillin. The other 21 women were cured. No other adverse clinical reactions and no significant abnormal laboratory results were observed with either regimen. Bacteriological efficacy, 98% for sulbactam/ampicillin and 94% for cefoxitin, closely paralleled clinical efficacy. Sulbactam, a suicide-type beta-lactamase inhibitor, appears to have restored and expanded the antibacterial activity of ampicillin.

Cefazolin for hysterectomy prophylaxis.

Efficacy data for single-dose cefazolin prophylaxis at hysterectomy are meager, and there are none evaluating the impact of route of administration on efficacy. For these reasons, 772 women undergoing elective abdominal or vaginal hysterectomy for benign diseases were given 1 g cefazolin either intramuscularly or intravenously in a randomized clinical trial. Preoperative diagnoses and clinical, surgical, and outcome variables were similar by route of administration for each surgical approach. Risk factors for infection after abdominal hysterectomy included younger age, lower postoperative hemoglobin concentration, and pelvic hematoma; women who developed infection after vaginal hysterectomy were heavier than those who remained uninfected and were more likely to have a pelvic hematoma. The overall incidence of major operative site infection requiring parenteral antimicrobial therapy in evaluable women was 7.2%: 7.6% for 539 women undergoing abdominal hysterectomy and 6.3% for 207 women undergoing vaginal hysterectomy. Postoperative infection was unrelated to route of cefazolin administration.

Alterations in lower reproductive tract flora after single-dose piperacillin and triple-dose cefoxitin at vaginal and abdominal hysterectomy.

There are no current data regarding the effect of a newer, broad-spectrum penicillin on lower reproductive flora at hysterectomy. To identify any existing differential effect on species and their susceptibilities, we obtained pre- and postoperative lower reproductive tract culture material from 209 women who were given single-dose piperacillin, then placebo or triple-dose cefoxitin, intravenously for prophylaxis at vaginal and abdominal hysterectomy in a prospective, randomized, blinded clinical trial. Significantly more preoperative endocervical bacteria were susceptible to piperacillin. Piperacillin caused less alteration in the numbers of lower reproductive tract flora when preoperative species were compared with postoperative species. More resistance to cefoxitin was identified postoperatively in bacteria recovered from the vaginal cuff of women who remained uninfected.

Single-dose cefoxitin prophylaxis for premenopausal women undergoing vaginal hysterectomy.

A prospective randomized blinded study was conducted comparing a single 2-g preoperative dose of cefoxitin with three 2-g doses of cefoxitin over 12 hours given to premenopausal women scheduled for vaginal hysterectomy in Parkland Memorial Hospital. The incidence of major pelvic infection in 58 women given one dose was 1.7%, and it was 3.7% for 54 women given three doses. The mean hospital stay (4.5 days) was similar for both regimens; for those who developed major infection it was eight days. More aerobic bacteria with altered species dominance and fewer anaerobic bacteria were recovered from the vaginal cuff at discharge from the hospital when compared with those recovered from the endocervix preoperatively. There was a trend toward increasing minimal inhibitory concentrations to cefoxitin in bacteria isolated after surgery, which was more frequent in women given three doses. There was not a statistically significant intergroup difference in the recovery of bacteria resistant to cefoxitin in vitro after surgery. A single preoperative dose of cefoxitin was as effective in preventing major infection as were three perioperative doses, while providing other real and theoretic benefits.

Bacteriology and treatment of malodorous lower reproductive tract in gynecologic cancer patients.

OBJECTIVE: To determine the bacteriology of lower genital tract cancers to direct potential treatment modalities and to determine the impact of treatment on quality of life. METHODS: Gram stain, saline preparations, tumor pH determinations, and anaerobic and aerobic tumor cultures were obtained from 13 consecutive patients with malodorous gynecologic cancers and 13 patients (controls) with nonmalodorous tumors. All patients with odor were treated with topical metronidazole for 7 days. Odor assessment questionnaires were administered daily in the treatment group. Quality-of-life evaluation was assessed using the Functional Assessment of Cancer Therapy questionnaire before and after treatment. RESULTS: Cancer of the cervix (n = 21) was the most common primary site and accounted for 81% (95% confidence interval 61%, 93%) of malodorous gynecologic cancers. Eight of 13 (62%) patients with malodorous tumors had bacterial vaginosis compared with four of 13 (31%) of those without odor (P =.11). Aerobic and anaerobic bacteria were isolated with equal frequency from malodorous gynecologic cancers. Results of odor assessment questionnaires showed a graded improvement with topical antibiotic therapy (P <.001). The Functional Assessment of Cancer Therapy questionnaire indicated improved quality of life after therapy (P =.02). CONCLUSION: Most patients with odor had bacterial vaginosis and had an improvement in odor with topical metronidazole. Therefore, this treatment might be useful for patients with malodorous pelvic tumors.

Cefotaxime sodium therapy for endomyometritis following cesarean section: dose-finding and comparative studies.

One hundred eighteen women who developed endomyometritis after cesarean section in Parkland Memorial Hospital were treated with parenteral cefotaxime sodium. The requirement for additional antimicrobial therapy was significantly higher at an initial daily dose of 3 g/day (16.4%) than when the dose was 6 g/day (4.8%) (P less than .05). The latter clinical efficacy and the observed in vitro susceptibility of 88% of isolates indicate that cefotaxime is well suited for single-agent parenteral therapy for this polymicrobial pelvic infection. Subsequently, 120 women with the same diagnosis were randomly treated with cefotaxime or clindamycin and gentamicin. Patient populations, surgical variables, in vitro microbiologic data, and side effects were similar for both groups. Clinical success observed was also similar: it was 97.5% for women given cefotaxime and 95% for women given clindamycin and gentamicin.

Cefoperazone and cefoxitin prophylaxis for abdominal hysterectomy.

One hundred one women undergoing elective abdominal hysterectomy were given perioperative cefoperazone or cefoxitin in a prospective randomized blinded study. Both regimens were well tolerated and no significant toxic or allergic manifestations were observed. Interrelationships between antimicrobial concentration in serum and pelvic tissues, intraoperative cardinal ligament cultures, febrile morbidity, and major postoperative infection were determined. At uterine removal, mean cefoperazone concentrations in serum (56.1 micrograms/mL) and pelvic tissues (18.6 micrograms/g) were significantly higher than mean concentrations of cefoxitin, ie, 16.1 micrograms/mL and 8.1 micrograms/g, respectively (P less than .001). The incidence of major postoperative infection was 6% or less with both regimens. Perioperative prophylaxis significantly reduced the incidence of this infection. When it did develop, however, it continued to cause significant morbidity, prolonging hospital stay a mean of more than four days (P less than .001) and increasing the hospital bill a mean of almost $1500 (P less than .001).

Interrelationships between toxins: studies on the cross-reactivity between bacterial or animal toxins and monoclonal antibodies to two jellyfish venoms.

Affinity chromatography on columns of immobilized anti-Chrysaora and anti-Physalia monoclonal antibodies can be an effective purification tool for animal and bacterial toxins. Furthermore, the fact that specific fractions of a given species obtained from immunochromatography columns prepared with either monoclonal antibody possessed identical protein bands, were quantitatively similar in in vitro cardiotoxicity and bound like amounts of antibody, as indicated by the enzyme-linked immunosorbent assay, suggested that antigenic targets of the two monoclonal antibodies are cross-reactive and/or are located on the same molecule. Additional enzyme-linked immunosorbent assays were conducted using non-coelenterate toxins. The significant binding of brown recluse spider venom and purified cholera toxin to both our monoclonal antibodies indicated that these toxic substances shared a common or cross-reacting antigenic site(s) with some coelenterate venoms.