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.

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. 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.

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.

Adenocarcinoma of the stomach. Changing patterns over the last 4 decades.

A retrospective study was performed on 255 consecutive patients admitted to a single hospital from 1953-1983 with a follow-up of 100%. The number of proximal esophagogastric junction and fundus tumors increased significantly over the last 4 decades from 21% to 44% (p less than 0.001), accompanied by a significant decrease in antral carcinomas from 60% to 33% (p less than 0.01). Patients with proximal neoplasms were significantly more likely to be white (71% vs. 29%, p less than 0.001), whereas patients with antral cancer were significantly more likely to be black (64% vs. 36%, p less than 0.001). There were no significant differences in nodal status, presence of distant metastases, or the overall 5-year survival rate between these two sites. The 5-year survival rate for the entire group was 6%. Sixty-five patients (30%) underwent curative resection, and the 5-year survival rate in this group was 24%, which was significantly better than palliative procedures. The 5-year survival rate was strongly influenced by TNM stage, local invasiveness, nodal status, and presence or absence of distal metastases (p less than 0.001). Although the overall survival rate has not changed over the past 30 years, there were definite epidemiologic differences between proximal and antral lesions, which suggest that new treatment protocols should be designed to include the location of the neoplasm.

Effect of cyclosporine on bile secretion in rats.

Short-term effects of cyclosporine were studied in the isolated perfused rat liver model. Bile flow was inhibited by cyclosporine in 2 mg/kg and 20 mg/kg doses but not by a 0.2 mg/kg dose. Cholestasis was accompanied by a decrease in bile acid secretion, indicating an inhibitory effect on the bile acid-dependent fraction of bile flow. Perfusate bilirubin levels increased threefold in rat livers given 20 mg/kg of cyclosporine, but did not change in control animals. Alkaline phosphatase and transaminase levels did not differ from those of control animals. The isolated perfused rat liver was able to excrete cyclosporine, as demonstrated by a continual decrease in perfusate cyclosporine levels. No light microscopic evidence of cholestasis or hepatocellular damage was demonstrated on histologic staining. Our model appears to be a good one for the study of altered hepatic physiologic characteristics caused by administration of cyclosporine.

Inhibition of bile flow by intravenous arginine hydrochloride.

One proposed mechanism for the cholestasis associated with total parenteral nutrition is infusion of amino acids. Arginine, 19 mumol/kg/min, was infused for a short time in healthy dogs with a biliary fistula to test the effect of endogenous hormone release on bile flow and composition. Both plasma glucagon and blood glucose levels increased. Despite the release of the choleretic hormone, glucagon, bile flow decreased 30%. The suppression of bile flow was attributed to a decrease in the bile acid-dependent fraction of bile flow. Bile acid, cholesterol, and phospholipid output were all depressed.

Successful management of late-onset primary lymphatic hypoplasia.

Primary lymphedema of the extremities, abdomen, or chest is an unusual and difficult clinical problem with few guidelines for management. A case is reported of lymphedema acquired at the age of 61 years, with associated massive chylous ascites and chylothorax. No underlying condition was discovered and the patient was found to have hypoplastic lymphatics by lymphangiography. Initial management consisted of extremity elevation, diuresis, and repeated paracenteses and thoracenteses. A peritoneojugular shunt provided temporary relief. Surgical pleurodesis combined with intensive diuresis has given prolonged relief of his symptoms allowing him to return to a functional life. Diagnostic and therapeutic guidelines for the management of this unusual condition are suggested.