Management of hemodialysis catheter-related bacteremia with an adjunctive antibiotic lock solution

BACKGROUND: Tunneled dialysis catheters are complicated by frequent systemic infections. Standard therapy of catheter-associated bacteremia involves both systemic antibiotics and catheter replacement. Recent data suggest that biofilms in the catheter lumen are responsible for the bacteremia, and that instillation of an antibiotic lock (highly concentrated antibiotic solution) into the catheter lumen after dialysis sessions can eradicate the biofilm. METHODS: We analyzed prospectively the efficacy of an antibiotic lock protocol, in conjunction with systemic antibiotics, for treatment of patients with dialysis catheter-associated bacteremia without catheter removal. Protocol success was defined as resolution of fever and negative surveillance cultures one week following completion of the protocol. Protocol failure was defined as persistence of fever or surveillance cultures positive for any pathogen. In addition, infection-free catheter survival was compared to that observed in institutional historical control patients treated with catheter replacement. RESULTS: Blood cultures were positive in 98 of 129 of episodes (76%) in which patients dialyzing with a catheter had fever or chills. Protocol success occurred in 40 of 79 infected patients (51%) treated with the antibiotic lock. Protocol failure occurred in 39 cases (49%): 7 had persistent fever, 15 had positive surveillance cultures (9 for Candida and 6 for bacteria), and 17 required catheter removal due to malfunction. Each of the pathogens in the surveillance cultures was different from the original pathogen in that patient. Eight of the 9 secondary Candida infections and all 6 secondary bacterial infections resolved after catheter exchange and specific antimicrobial treatment. Overall catheter survival with the antibiotic lock protocol was similar to that observed among patients managed with catheter replacement (median survival, 64 vs. 54 days, P = 0.24). CONCLUSIONS: Use of an antibiotic lock, in conjunction with systemic antibiotic therapy, can eradicate catheter-associated bacteremia while salvaging the catheter in about one half of cases. Moreover, this management approach offers clinical advantages over routine catheter exchange.     

Extended hepatectomy in patients with hepatobiliary malignancies with and without preoperative portal vein embolization

HYPOTHESIS: Preoperative portal vein embolization (PVE) allows potentially curative hepatic resection without additional morbidity or mortality in patients with hepatobiliary malignancies who are marginal candidates for resection based on small liver remnant size. DESIGN: A retrospective review of a consecutive series of patients in a multi-institutional database who underwent extended hepatectomy. SETTING: University-based referral centers. PATIENTS: Forty-two patients underwent preoperative determination of the future liver remnant (FLR) volume before extended hepatectomy (> or = 5 segments) for hepatobiliary malignancy without chronic underlying liver disease. Patients were stratified by treatment with or without preoperative PVE. INTERVENTION: Preoperative percutaneous PVE. MAIN OUTCOME MEASURES: Clinical characteristics, FLR volume, operative morbidity, and survival. RESULTS: There was no difference between the groups that did and did not undergo PVE for the number of tumors, tumor size, estimated blood loss, duration of the operation, complexity of resection, or surgical margins. The FLR at presentation was significantly smaller in patients who underwent PVE than in patients who did not undergo PVE (18% vs 23%; P<.001). After PVE, FLR volumes increased significantly (P =.003); preoperative FLR volumes were similar in both groups (patients who underwent PVE, 25%; and patients who did not undergo PVE, 23%). There was no perioperative mortality and no statistical difference in the incidence of perioperative complications between those who did and those who did not undergo PVE (5 [28%] of 18 patients vs 5 [21%] of 24 patients). The overall 3-year survival was 65% and the median survival duration was equivalent in the 2 groups (40 vs 52 months for those who did vs those who did not undergo PVE). CONCLUSION: Portal vein embolization enables safe and potentially curative extended hepatectomy in a subset of patients who would otherwise be marginal candidates for resection based on a small liver remnant size.     

Antimetastatic drugs in prostate cancer

Despite the benefits of local therapy with radical prostatectomy and radiation, many patients with prostate cancer require hormonal ablation. While chemotherapy has proven efficacy when the disease progresses to androgen-independent prostate cancer, patients ultimately succumb to the disease, thus the identification of other active therapies is needed. Future treatment modalities include molecular targeted therapies. Prostate cancer has been an ideal model to study the multiple steps required in the metastatic cascade. These steps have been utilized in the development of metastasis inhibitors. This review will present promising agents that have been tested preclinically or are undergoing clinical investigation for their abilities in preventing prostate cancer metastasis. Because prostate cancer metastasizes preferentially to the bone, special attention will be given to agents that interfere with this pattern of metastasis. Specifically, the efficacy of angiogenesis inhibitors, metalloproteinase inhibitors, inhibitors of prostate cancer cell- endothelial cell interactions, and bisphosphonates will be reported. In addition, the introduction of these novel agents has raised many questions as to the relevance and optimal utilization of current clinical trial designs. Issues regarding combination therapy with chemotherapy, optimal timing of treatment with metastatic inhibitors, and the need for surrogate endpoints for molecular targeted therapies will be discussed.     

医院应急危机处理

在当今资源紧张的医院管理中,优先考虑的是把有限的资源配置到最需要的地方。困难是哪些需要优先考虑的,哪些可以等到下一个预算周期。灾难医疗反应也是优先考虑的项目之一。如何最有效地应对这种可能性低但后果严重的威胁?     

Femoral venous flow during laparoscopic gynecologic surgery

The lower-limb venous return, assessed by the peak systolic venous velocities (PSVV) of the left common femoral vein, was recorded at different stages of operation for five patients undergoing major gynecologic operative laparoscopy. The average baseline PSVV was 23.1 cm/s. After positioning the patient in the Trendelenburg position, the PSVV increased to an average of 31.5 cm/s; this was a statistically significant increase. Creation of the pneumoperitoneum changed the waveform from a normal phasic pattern to a dampened, continuous, monophasic waveform. The average PSVV was reduced to 15.9 cm/s; this dampening was statistically significant. Further dampening was evident 1 hour intraoperatively, and the flow became intermittent, with cycles of dampened flow followed by periods of absent flow; these changes in PSVV were not statistically significant. Calf compressors did not increase the femoral PSVV at the beginning of operation, nor at I hour intraoperatively; the decrease was not statistically significant. After release of the pneumoperitoneum, the baseline waveform pattern and velocity returned. The Trendelenburg position used for gynecologic operative laparoscopy was associated with a statistically significant increase in the lower-limb PSVV. This increase did not fully counteract the dampening effect of a pneumoperitoneum on lower-limb PSVV. The authors' study did not support the benefit previously reported on the use of pneumatic calf compressors. The authors therefore recommend continuing the practice of antithrombotic measures for patients undergoing gynecologic operative laparoscopy.     

Chronic lung injury in preterm lambs: abnormalities of the pulmonary circulation and lung fluid balance

Chronic lung disease of early infancy, or bronchopulmonary dysplasia, is a frequent complication of prolonged mechanical ventilation after premature birth. Pulmonary hypertension and edema are common features of this condition, which is often attributed to long-term, repetitive overinflation of incompletely developed lungs. The overall objective of this work was to examine the effects on the pulmonary circulation and lung fluid balance of different ventilation strategies using large versus small inflation volumes in an animal model of bronchopulmonary dysplasia. We studied 16 newborn lambs that were delivered prematurely (124+/-3 d gestation, term = 147 d) by cesarean section and mechanically ventilated for 3 to 4 wk. Ten lambs were ventilated at 20 breaths/min, yielding a tidal volume of 15+/-5 mL/kg, and six lambs were ventilated at 60 breaths/min, yielding a tidal volume of 6+/-2 mL/kg. All lambs received surfactant at birth and had subsequent surgery for closure of the ductus arteriosus and catheter placement to allow serial measurements of pulmonary vascular resistance and lung lymph flow. Chronic lung injury, documented by serial chest radiographs and postmortem pathologic examination, developed in all lambs irrespective of the pattern of assisted ventilation. Pulmonary vascular resistance, which normally decreases during the month after birth at term, did not change significantly from the first to the last week of study. Lung lymph flow, an index of net transvascular fluid filtration, increased with time in lambs that were ventilated at 20 breaths/min, but not in lambs ventilated at 60 breaths/min. Lymph protein concentration decreased with time, indicative of increased fluid filtration pressure, without evidence of a change in lung vascular protein permeability. Postmortem studies showed interstitial lung edema, increased pulmonary arteriolar smooth muscle and elastin, decreased numbers of small pulmonary arteries and veins, and decreased capillary surface density in distal lung of chronically ventilated lambs compared with control lambs that were killed either 1 d (same postconceptional age) or 3 wk (same postnatal age) after birth at term. Thus, chronic lung injury from prolonged mechanical ventilation after premature birth inhibits the normal postnatal decrease in pulmonary vascular resistance and leads to lung edema from increased fluid filtration pressure. These abnormalities of the pulmonary circulation may contribute to the abnormal respiratory gas exchange that often exists in infants with bronchopulmonary dysplasia.     

Phage therapy: past history and future prospects

Bacterial viruses (bacteriophages, also called "phages") can be robust antibacterial agents in vitro. However, their use as therapeutic agents, during a number of trials from the 1920s to the 1950s, was greatly handicapped by a number of factors. In part, there were certain limitations inherent in phage physiology (e. g. narrow host range, and rapid clearance from the body); in part there were technological limitations in the era (e.g. lysogeny not yet discovered); but the greatest limitation was the highly inadequate scientific methodologies used by practitioners at the time (e.g., their failure to conduct placebo-controlled studies, to remove endotoxins from the preparations, and to re-confirm phage viability after adding sterilizing agents to the preparations). In recent years, well-controlled animal models have demonstrated that phages can rescue animals from a variety of fatal infections, while non-controlled clinical reports published in Eastern Europe have shown that phages can be effective in treating drug-resistant infections in humans. This encouraging data, combined with the fact that drug-resistant bacteria have become a global crisis, have created a window of opportunity for phage therapy to be tested anew, this time using modem technologies and placebo-controlled designs. If successful, it can be used as a stand-alone therapy when bacteria are fully resistant to antibiotics, and as a valuable adjunct to antibiotics when the bacteria are still susceptible.