Effects of elutriates from contaminated coastal sediments on different life cycle phases of planktonic diatoms.

We assessed the effects of elutriates from sediments collected at three stations in the polluted Bay of Bagnoli-Coroglio along the Campania coast (Tyrrhenian Sea, Italy) using three planktonic diatoms regularly occurring in the area, Pseudo-nitzschia multistriata, P. arenysensis and Chaetoceros socialis. Specifically, we tested the production of sexual stages in the heterothallic Pseudo-nitzschia species with the hypothesis that pollutants could impair sexual reproduction. We also tested the seeding capacity of spores of C. socialis after up to six months of storage in elutriates, assuming that pollutants could affect the capability of resting stages to germinate. Elutriate from station 56, with the highest concentrations of pollutants, impaired growth, sexual reproduction and spore germination. Elutriates from stations 25 and 84 caused moderate enhancement of growth and sexual reproduction in Pseudo-nitzschia as compared with control conditions, and also had intermediate effect on spore seeding capacity.

Ventilator-associated pneumonia and bloodstream infections in intensive care unit cancer patients: a retrospective 12-year study on 3388 prospectively monitored patients.

PURPOSE: Some publications suggest high rates of healthcare-associated infections (HAIs) and of nosocomial pneumonia portending a poor prognosis in ICU cancer patients. A better understanding of the epidemiology of HAIs in these patients is needed. METHODS: A retrospective analysis of all the patients hospitalized for ≥ 48 h during a 12-year period in the 12-bed ICU of the Gustave Roussy hospital, monitored prospectively for ventilator-associated pneumonia (VAP) and bloodstream infection (BSI) and for use of medical devices. RESULTS: During 3388 first stays in the ICU, 198 cases of VAP and 103 primary, 213 secondary, and 77 catheter-related BSIs were recorded. The VAP rate was 24.5/1000 ventilator days (95% confidence interval [CI] 21.2-28.0); the catheter-related BSI rate was 2.3/1000 catheter days (95% CI 1.8-2.8). The cumulative incidence during the first 25 days of exposure was 58.8% (95% CI 49.1-66.6%) for VAP, 8.9% (95% CI, 6.2-11.5%) for primary, 15.1% (95% CI 11.6-18.5%) for secondary and 5.0% (95% CI 3.2-6.8%) for catheter-related BSIs. VAP or BSIs were not associated with a higher risk of ICU mortality. CONCLUSIONS: This is the first study to report HAI rates in a large cohort of critically ill cancer patients. Although both the incidence of VAP and the rate of BSI are higher than in general ICU populations, this does not impact patient outcomes. The occurrence of device-associated infections is essentially due to severe medical conditions in patients and to the characteristics of malignancy.

Update of survival and cost of metastatic melanoma with new drugs: Estimations from the MelBase cohort.

PURPOSE: Since 2011, significant progress was observed in metastatic melanoma (MM), with the commercialisation of seven immunotherapies or targeted therapies, which showed significant improvement in survival. In France, in 2004, the cost of MM was estimated at €1634 per patient; this cost has not been re-estimated since. This study provided an update on survival and cost in real-life clinical practice. METHODS: Clinical and economic data (treatments, hospitalisations, radiotherapy sessions, visits, imaging and biological exams) were extracted from the prospective MelBase cohort, collecting individual data in 955 patients in 26 hospitals, from diagnosis of metastatic disease until death. Survival was estimated by the Kaplan-Meier method. Costs were calculated from the health insurance perspective using French tariffs. For live patients, survival and costs were extrapolated using a multistate model, describing the 5-year course of the disease according to patient prognostic factors and number of treatment lines. RESULTS: Since the availability of new drugs, the mean survival time of MM patients has increased to 23.6 months (95%confidence interval [CI] :21.2;26.6), with 58% of patients receiving a second line of treatment. Mean management costs increased to €269,682 (95%CI:244,196;304,916) per patient. Drugs accounted for 80% of the total cost. CONCLUSION: This study is the first that evaluated the impact of immunotherapies and targeted therapies both on survival and cost in real-life conditions. Alongside the introduction of breakthrough therapies in the first and subsequent lines, MM has been associated with a significant increase in survival but also in costs, raising the question of financial sustainability.

Statistical controversies in clinical research: prognostic gene signatures are not (yet) useful in clinical practice.

With the genomic revolution and the era of targeted therapy, prognostic and predictive gene signatures are becoming increasingly important in clinical research. They are expected to assist prognosis assessment and therapeutic decision making. Notwithstanding, an evidence-based approach is needed to bring gene signatures from the laboratory to clinical practice. In early breast cancer, multiple prognostic gene signatures are commercially available without having formally reached the highest levels of evidence-based criteria. We discuss specific concepts for developing and validating a prognostic signature and illustrate them with contemporary examples in breast cancer. When a prognostic signature has not been developed for predicting the magnitude of relative treatment benefit through an interaction effect, it may be wishful thinking to test its predictive value. We propose that new gene signatures be built specifically for predicting treatment effects for future patients and outline an approach for this using a cross-validation scheme in a standard phase III trial. Replication in an independent trial remains essential.

Adjuvant cisplatin-based chemotherapy in nonsmall-cell lung cancer: new insights into the effect on failure type via a multistate approach.

BACKGROUND: Adjuvant cisplatin-based chemotherapy has become the standard therapy against resected nonsmall-cell lung cancer (NSCLC). Because of variable results on its late effect, we reanalyze the long-term data of the International Adjuvant Lung Cancer Trial (IALT) to describe in details the role of adjuvant chemotherapy. PATIENTS AND METHODS: In the IALT, 1867 patients were randomized between adjuvant cisplatin-based chemotherapy and control, who were followed up for a median of 7.5 years. Of these, 1687 patients were enrolled from 132 centers accepting to report the times to cancer events. We used event history methodology to estimate the effects of adjuvant chemotherapy on the risks of local relapse, distant metastasis, and death. RESULTS: Adjuvant chemotherapy was highly effective against local relapses [HR = 0.73; 95% confidence interval (CI) 0.60-0.90; P = 0.003] and nonbrain metastases (HR = 0.79; 95% CI 0.66-0.94; P = 0.008) but not against brain metastases (HR = 1.1; 95% CI 0.82-1.4; P = 0.61). The effect on noncancer mortality was nonsignificant during the first 5 years (HR = 1.1; 95% CI 0.81-1.5; P = 0.29), whereas the risk of noncancer mortality was subsequently higher with treatment (HR = 3.6; 95% CI 2.2-5.9; P < 0.001). This harmful effect, however, potentially concerned only about 2% of the patients at 8 years. CONCLUSION: Adjuvant cisplatin-based chemotherapy reduced the risk of local relapse and of nonbrain metastasis, thereby improving survival. This treatment exerted no residual effect on mortality during the first 5 years, but a higher risk of noncancer mortality was found thereafter. Detailed long-term follow-up is strongly recommended for all patients in randomized trials evaluating adjuvant treatments in NSCLC.

[16-MDCT angiography coronary artery in the emergency department for patients with acute coronary syndrome (NSTEMI-UA)]. / La 16-MDCT delle arterie coronarie eseguita in urgenza nei pazienti affetti da sindrome coronarica acuta (NSTEMI-UA).

AIM: The diagnosis of acute coronary syndrome (ACS), non-ST-elevation myocardial infarction and unstable angina in the emergency department (ED) remains a challenge. The aim of our study was to investigate quality and the diagnostic accuracy of 16-MDCT coronary angiography, detecting coronary artery lesions in patients with suspected ACS presented in ED. MATERIALS AND METHODS: We studied with 16-MDCT (Sensation 16, Siemens, Forchleim, Germania) and coronary angiography 37 patients with the following inclusion criteria: chest pain compatible with myocardial ischemia, normal or no-diagnostic ECG changes and initial concentrations of serum troponin-I < or =1 ng/ml. The 16-MDCT was performed with ECG-gated technique after the intravenous administration of 90-100 ml of iodinated contrast material followed by a saline bolus. The scan parameters were: 120 kV, 650-720 mAs, 16 x 0.75mm collimation, 0.42s rotation time, 3 mm (pitch 0.25) feed/rot, B30f kernel. We evaluated for each patient: image quality and different artefacts, plaques identification and characterization. RESULTS: The evaluation of the image quality was based on a total of 453 segments, of which 415 segments (92.2%) were considered to have diagnostic image quality. MDCT correctly detected 15 patients with at least 1 stenosis >50% and correctly ruled out significant coronary artery disease in 19 patients with 1 FP and 2 FN: sensitivity 88%, specificity 95%, PPV 94%, NPV 90%. The plaques were hard in 6 cases, mixt in 16 cases and soft in 14 cases, respectively. CONCLUSIONS: Our results point-out that 16-MDCT in ED has the real ability to detect and rule out significant coronary stenoses in patients with ACS.

Fournier gangrene associated with Crohn disease.

A 17-year-old boy presented with Fournier gangrene associated with previously undiagnosed Crohn ileocolitis. Fournier gangrene was managed by débridement, broad-spectrum antibiotics, and hyperbaric oxygen. A diverting ileostomy was performed before skin grafting and scrotal reconstruction. Microscopy of a full-layer surgical sample from the terminal ileum revealed granulomas with multinucleated histiocytes, consistent with Crohn disease. Crohn disease was treated with mesalamine, metronidazole, 6-mercaptopurine, and infliximab. The patient was discharged on hospital day 32. At 6-month follow-up, reconstruction of his scrotum had completely healed. Ostomy output was normal.

Long-term results of surgery for the treatment of sustentacular fractures of the calcaneus.

The authors reviewed 55 sustentacular fractures of the calcaneus treated between 1979 and 1988. Our therapeutic objective was that of reconstructing the subtalar joint. This purpose was always achieved in a short amount of time; nonetheless, there were some cases of secondary unreduction in time (13% poor results in 4.5 years). Essex-Lopresti closed surgery was used to treat fractures with limited damage of the joint surface; open osteosynthesis with associated grafting was used to treat fractures with more than one fragment.

Grosse Kempf locked intramedullary nailing in the treatment of diaphyseal fractures of the lower limb. A case review.

After a review of the cases (57 between 1981 and 1988) the authors present the results of treatment of diaphyseal fractures of the lower limb by Grosse Kempf locked intramedullary nailing. The advantages and the effectiveness of the method are emphasized; the method has obtained brilliant results in complex and "boundary" fractures of the femur and tibia; furthermore, some suggestions are made with regard to surgery.

Intramedullary osteosynthesis 3. Küntscher nailing in the humerus.

With regard for the principles that govern the correct application of intramedullary osteosynthesis in the long bones of the lower limb, the authors also support its use in the humerus. After an exhaustive survey of the specific problems at this site, a critical review of 130 cases observed over the last 15 years is reported. Extremely favourable results emerged in the treatment of the humerus with this means of synthesis, thanks to its surgical, mechanical and biological advantages.

Intramedullary osteosynthesis. 4. Küntscher nailing in the ulna.

Intramedullary osteosynthesis with Küntscher nailing is an appropriate and extremely effective operation in the treatment of diaphyseal fractures of the ulna. Like the other long bones of the limbs (femur, humerus, tibia), in the ulna, as well, the advantages of the method, particularly when performed in closed surgery, are undeniable, so much so that this bone has a shape which is particularly favourable to nailing. The authors present and discuss their personal series of cases reporting results which are excellent. Thus, once again, the great reliability of this simple means of synthesis, in use for more than 20 years, is emphasised, and the subject is completed with a series of previous technical suggestions on how to obtain the best results.

Intramedullary osteosynthesis. 1. Küntscher nailing in the femur.

Based on more than 20 years experience, the authors support the effectiveness of intramedullary nailing in the treatment of diaphyseal fractures of the femur. They review the history and advantages of this method and discuss the biomechanical principles on which it is based. Recent advances in technique have made it possible to secure proximal and distal anchorage in cancellous bone. This allows the method to be extended to more proximal and distal fractures than in the traditional method which is applicable only to the middle third. It also facilitates progressive axial compression, early loading and early mobilisation of the limb, thus creating the optimum biological conditions for consolidation and joint function. The closed method also reduces blood loss and the risk of infection. The techniques adopted to deal with more complex situations are described. These include moderately comminuted oblique and spiral fractures and certain bifocal fractures. Finally, the results of treating 450 cases are reviewed, with a longterm analysis of 198 patients.

The association of two or more surgical methods in the tibia.

The authors propose the association of two or more surgical methods in the treatment of aseptic pseudarthrosis of the tibia with the object of increasing the probability of union and reducing the period of disability. Based on the anatomo-pathological features of the pseudarthrosis, methods aimed at obtaining mechanical stability (fibula pro tibia, Küntscher) and methods which stimulate biological repair (decortication, transplants) are associated. The results obtained confirm the theoretical presuppositions, revealing a relatively short amount of time required for healing.

Intramedullary osteosynthesis. 2. Küntscher nailing in fractures of the tibia.

The purpose of this study is to discuss diaphyseal fractures of the tibia treated by intramedullary Küntscher nailing. This is based on 368 cases treated over the last 20 years. Closed intramedullary osteosynthesis favours the healing process, resulting in the early formation of callus which is of good quality and abundant. A careful review of the cases showed a 93.7% incidence of good results.

Long-term results of intersomatic lumbar fusion with a posterior approach.

The authors discuss the advantages of using intersomatic lumbar fusion with a posterior approach for the treatment of low back pain due to discopathy or grade I spondylolisthesis. After a description of the surgical method used, the long-term results obtained in 16 cases are presented. The clinical and radiographic results are good in cases of discopathy, while in those of spondylolisthesis there is disagreement between the clinical evaluation, which is generally satisfactory, and the radiographic evaluation which is not quite as satisfactory.

Osteosynthesis of fractures of the femoral neck by nail-plate, screws and valgus osteotomy.

The authors describe the method used for the treatment of subcapital fractures of the femoral neck in younger subjects. This method associates intertrochanteric osteotomy with osteosynthesis using one or two spongy bone screws and a nail plate. The series includes 26 patients followed up both clinically and radiographically. The results were very good, with 100% union and only 4 cases of ischaemic necrosis (15%).

Regulation of biliary protein secretion in dogs.

The biliary secretion of protein in response to bile acids and other agents known to increase bile flow was examined in a chronic bile fistula dog model. Infusion of 25, 50, or 75 mumole/kg/hr sodium taurocholate after 3 hr of bile fistulization increased biliary protein output significantly by 52, 86, and 108% respectively compared to preinfusion values. A proportionate increase in biliary albumin output during taurocholate choleresis was demonstrated. Protein outputs during bile fistulization without taurocholate replacement were unchanged. The non-micelle-forming bile acid dehydrocholate markedly increased bile flow but did not change protein output. Similarly, the hormonal choleretics glucagon and secretin caused significant decreases in biliary protein concentration but no change in protein output. These data indicate a correlation between biliary protein secretion and bile acid-dependent bile flow. It is likely that regulation of certain proteins is dependent on the micelle-forming properties of bile acids.