Randomized controlled trial of mechanical thrombectomy vs catheter-directed thrombolysis for acute hemodynamically stable pulmonary embolism: Rationale and design of the PEERLESS study.

BACKGROUND: The identification of hemodynamically stable pulmonary embolism (PE) patients who may benefit from advanced treatment beyond anticoagulation is unclear. However, when intervention is deemed necessary by the PE patient's care team, data to select the most advantageous interventional treatment option are lacking. Limiting factors include major bleeding risks with systemic and locally delivered thrombolytics and the overall lack of randomized controlled trial (RCT) data for interventional treatment strategies. Considering the expansion of the pulmonary embolism response team (PERT) model, corresponding rise in interventional treatment, and number of thrombolytic and nonthrombolytic catheter-directed devices coming to market, robust evidence is needed to identify the safest and most effective interventional option for patients. METHODS: The PEERLESS study (ClinicalTrials.gov identifier: NCT05111613) is a currently enrolling multinational RCT comparing large-bore mechanical thrombectomy (MT) with the FlowTriever System (Inari Medical, Irvine, CA) vs catheter-directed thrombolysis (CDT). A total of 550 hemodynamically stable PE patients with right ventricular (RV) dysfunction and additional clinical risk factors will undergo 1:1 randomization. Up to 150 additional patients with absolute thrombolytic contraindications may be enrolled into a nonrandomized MT cohort for separate analysis. The primary end point will be assessed at hospital discharge or 7 days post procedure, whichever is sooner, and is a composite of the following clinical outcomes constructed as a hierarchal win ratio: (1) all-cause mortality, (2) intracranial hemorrhage, (3) major bleeding, (4) clinical deterioration and/or escalation to bailout, and (5) intensive care unit admission and length of stay. The first 4 components of the win ratio will be adjudicated by a Clinical Events Committee, and all components will be assessed individually as secondary end points. Other key secondary end points include all-cause mortality and readmission within 30 days of procedure and device- and drug-related serious adverse events through the 30-day visit. IMPLICATIONS: PEERLESS is the first RCT to compare 2 different interventional treatment strategies for hemodynamically stable PE and results will inform strategy selection after the physician or PERT determines advanced therapy is warranted.

Characterizing left ventricular mechanical and electrical activation in patients with normal and impaired systolic function using a non-fluoroscopic cardiovascular navigation system.

PURPOSE: Cardiac disease frequently has a degenerative effect on cardiac pump function and regional myocardial contraction. Therefore, an accurate assessment of regional wall motion is a measure of the extent and severity of the disease. We sought to further validate an intra-operative, sensor-based technology for measuring wall motion and strain by characterizing left ventricular (LV) mechanical and electrical activation patterns in patients with normal (NSF) and impaired systolic function (ISF). METHODS: NSF (n = 10; ejection fraction = 62.9 ± 6.1%) and ISF (n = 18; ejection fraction = 35.1 ± 13.6%) patients underwent simultaneous electrical and motion mapping of the LV endocardium using electroanatomical mapping and navigational systems (EnSite™ NavX™ and MediGuide™, Abbott). Motion trajectories, strain profiles, and activation times were calculated over the six standard LV walls. RESULTS: NSF patients had significantly greater motion and systolic strains across all LV walls than ISF patients. LV walls with low-voltage areas showed less motion and systolic strain than walls with normal voltage. LV electrical dyssynchrony was significantly smaller in NSF and ISF patients with narrow-QRS complexes than ISF patients with wide-QRS complexes, but mechanical dyssynchrony was larger in all ISF patients than NSF patients. The latest mechanical activation was most often the lateral/posterior walls in NSF and wide-QRS ISF patients but varied in narrow-QRS ISF patients. CONCLUSIONS: This intra-operative technique can be used to characterize LV wall motion and strain in patients with impaired systolic function. This technique may be utilized clinically to provide individually tailored LV lead positioning at the region of latest mechanical activation for patients undergoing cardiac resynchronization therapy. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01629160.

Mapping-guided characterization of mechanical and electrical activation patterns in patients with normal systolic function using a sensor-based tracking technology.

AIMS: In times of evolving cardiac resynchronization therapy, intra-procedural characterization of left ventricular (LV) mechanical activation patterns is desired but technically challenging with currently available technologies. In patients with normal systolic function, we evaluated the feasibility of characterizing LV wall motion using a novel sensor-based, real-time tracking technology. METHODS AND RESULTS: Ten patients underwent simultaneous motion and electrical mapping of the LV endocardium during sinus rhythm using electroanatomical mapping and navigational systems (EnSite™ NavX™ and MediGuide™, SJM). Epicardial motion data were also collected simultaneously at corresponding locations from accessible coronary sinus branches. Displacements at each mapping point and times of electrical and mechanical activation were combined over each of the six standard LV wall segments. Mechanical activation timing was compared with that from electrical activation and preoperative 2D speckle tracking echocardiography (echo). MediGuide-based displacement data were further analysed to estimate LV chamber volumes that were compared with echo and magnetic resonance imaging (MRI). The lateral and septal walls exhibited the largest (12.5 [11.6-15.0] mm) and smallest (10.2 [9.0-11.3] mm) displacement, respectively. Radial displacement was significantly larger endocardially than epicardially (endo: 6.7 [5.0-9.1] mm; epi: 3.8 [2.4-5.6] mm), while longitudinal displacement was significantly larger epicardially (endo: 8.0 [5.0-10.6] mm; epi: 10.3 [7.4-13.8] mm). Most often, the anteroseptal/anterior and lateral walls showed the earliest and latest mechanical activations, respectively. 9/10 patients had concordant or adjacent wall segments of latest mechanical and electrical activation, and 6/10 patients had concordant or adjacent wall segments of latest mechanical activation as measured by MediGuide and echo. MediGuide's LV chamber volumes were significantly correlated with MRI (R2= 0.73, P < 0.01) and echo (R2= 0.75, P < 0.001). CONCLUSION: The feasibility of mapping-guided intra-procedural characterization of LV wall motion was established. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov; Unique identifier: CT01629160.

Three-Dimensional Cardiac Mapping Characterizes Ventricular Contractile Patterns during Cardiac Resynchronization Therapy Implant: A Feasibility Study.

BACKGROUND: Electroanatomic mapping systems track the position of electrodes in the heart. We assessed the feasibility of characterizing left ventricular (LV) performance during cardiac resynchronization therapy (CRT) implant utilizing an electroanatomic mapping system to track the motion of CRT lead electrodes, thus deriving ventricular contractility surrogates. METHODS: During CRT implant, atrial, right ventricular (RV), and LV leads were connected to the EnSite NavX™ mapping system (St. Jude Medical Inc., St. Paul, MN, USA). The relative displacement of electrodes was averaged over 10 cardiac cycles during RV, LV, and biventricular (BiV) pacing in DOO mode. Three contractility surrogates indicative of ventricular performance were extracted from the RV-LV distance waveform: systolic slope (SS), time to peak systolic contraction (TPSC), and fractional shortening (FS). RESULTS: In the 20 patients included, there were detectable differences in each of the three contractility surrogates responding to the different pacing configurations. Median SS varied 42%, median TPSC varied 35%, and median FS varied 19% across RV, LV, and BiV pacing interventions. The RV-LV distance waveform showed subtle sensitivity to varying pacing timing cycles when measured in a subset of patients. For all pacing configurations, RV-LV distance waveforms were stable during 2-minute recordings. CONCLUSIONS: Tracking the motion of CRT pacing electrodes with a mapping system to derive contractility surrogates during implant is feasible.

The freedom to heal: nonrigid immobilization by a halo orthosis.

Halo orthoses present a paradox. On the one hand, the nominally rigid immobilization they provide to the head aims to remove loads on the cervical spine following injury or surgery, and the devices are retightened routinely to maintain this. On the other hand, bone growth and remodeling are well known to require mechanical stressing. How are these competing needs balanced? To understand this trade-off in an effective, commercial halo orthosis, the authors quantified the response of a commercial halo orthosis to physiological loading levels, applied symmetrically about the sagittal plane. They showed for the first time that after a few cycles of loading analogous to a few steps taken by a patient, the support presented by a standard commercial halo orthosis becomes nonlinear. When analyzed through straightforward structural modeling, these data revealed that the nonlinearity permits mild head motion while severely restricting larger motion. These observations are useful because they open the possibility that halo orthosis installation could be optimized to transfer mild spinal loads that support healing while blocking pathological loads.

Spinal cord stimulation is safe and feasible in patients with advanced heart failure: early clinical experience.

AIMS: Pre-clinical work suggests that upper thoracic spinal cord stimulation (SCS) may have therapeutic effects in the treatment of heart failure (HF). We therefore aim to assess the safety and feasibility of SCS in HF patients. METHODS AND RESULTS: A prospective, randomized, double-blind, crossover pilot study was conducted in symptomatic HF patients receiving optimal medical therapy. Patients were implanted with an SCS system and randomized to an SCS-ACTIVE, delivered at 90% paraesthesia threshold, or an SCS-INACTIVE phase for 3 months, followed by a 1-month washout period and crossover to the alternative phase. The safety of SCS therapy was assessed by death and cardiac events. Implantable cardioverter defibrillator (ICD) function in the presence of SCS was tested by defibrillation testing during SCS system implant and review of real-time and stored electrograms during follow-up. The efficacy of SCS therapy was assessed by changes in patient symptoms, LV function, and BNP level. Nine patients were investigated. In all cases, ICD sensing, detection, and therapy delivery were unaffected by SCS. During follow-up, one patient died and one was hospitalized for HF while in the SCS-INACTIVE phase, and two patients had HF hospitalizations during the SCS-ACTIVE phase. Symptoms were improved in the majority of patients with SCS, while markers of cardiac structure and function were, in aggregate, unchanged. CONCLUSION: This study shows that an SCS system can be safely implanted in patients with advanced HF and that the SCS system does not interfere with ICD function.

A comparison of left ventricular endocardial, multisite, and multipolar epicardial cardiac resynchronization: an acute haemodynamic and electroanatomical study.

AIMS: Alternative forms of cardiac resynchronization therapy (CRT), including biventricular endocardial (BV-Endo) and multisite epicardial pacing (MSP), have been developed to improve response. It is unclear which form of stimulation is optimal. We aimed to compare the acute haemodynamic response (AHR) and electrophysiological effects of BV-Endo with MSP via two separate coronary sinus (CS) leads or a single-quadripolar CS lead. METHODS AND RESULTS: Fifteen patients with a previously implanted CRT system received a second temporary CS lead and left ventricular (LV) endocardial catheter. A pressure wire and non-contact mapping array were placed into the LV cavity to measure LVdP/dtmax and perform electroanatomical mapping. Conventional CRT, BV-Endo, and MSP were then performed (MSP-1 via two epicardial leads and MSP-2 via a single-quadripolar lead). The best overall AHR was found using BV-Endo pacing with a 19.6 ± 13.6% increase in AHR at the optimal endocardial site over baseline (P < 0.001). There was an increase in LVdP/dtmax with MSP-1 and MSP-2 compared with conventional CRT, but this was not statistically significant. Biventricular endocardial pacing from the optimal site was significantly superior to conventional CRT (P = 0.039). The AHR achieved when BV-Endo pacing was highly site specific. Within individuals, the best pacing modality varied and was affected by the underlying substrate. Left ventricular activation times did not predict the optimal haemodynamic configuration. CONCLUSION: Biventricular endocardial pacing and not MSP was superior to conventional CRT, but was highly site specific. Within individuals, however, different methods of stimulation are optimal and may need to be tailored to the underlying substrate.

Modeling dermatome selectivity of single-and multiple-current source spinal cord stimulation systems.

A recently published computational modeling study of spinal cord stimulation (SCS) predicted that a multiple current source (MCS) system could generate a greater number of central points of stimulation in the dorsal column (DC) than a single current source (1 CS) system. However, the clinical relevance of this finding has not been established. The objective of this work was to compare the dermatomal zone selectivity of MCS and 1 CS systems. A finite element method (FEM) model was built with a representation of the spinal cord anatomy and a 2 × 8 paddle electrode array. Using a contact configuration with two aligned tripoles, the FEM model was used to solve for DC field potentials across incremental changes in current between the two cathodes, modeling the MCS and 1 CS systems. The activation regions within the DC were determined by coupling the FEM output to a biophysical nerve fiber model, and coverage was mapped to dermatomal zones. Results showed marginal differences in activated dermatomal zones between 1 CS and MCS systems. This indicates that a MCS system may not provide incremental therapeutic benefit as suggested in prior analysis.

Computational modeling analysis of a spinal cord stimulation paddle lead reveals broad, gapless dermatomal coverage.

Spinal cord stimulation (SCS) is an effective therapy for treating chronic pain. The St. Jude Medical PENTA(TM) paddle lead features a 4 × 5 contact array for achieving broad, selective coverage of dorsal column (DC) fibers. The objective of this work was to evaluate DC activation regions that correspond to dermatomal coverage with use of the PENTA lead in conjunction with a lateral sweep programming algorithm. We used a two-stage computational model, including a finite element method model of field potentials in the spinal cord during stimulation, coupled to a biophysical cable model of mammalian, myelinated nerve fibers to determine fiber activation within the DC. We found that across contact configurations used clinically in the sweep algorithm, the activation region shifted smoothly between left and right DC, and could achieve gapless medio-lateral coverage in dermatomal fiber tract zones. Increasing stimulation amplitude between the DC threshold and discomfort threshold led to a greater area of activation and number of dermatomal zones covered on the left and/or right DC, including L1-2 zones corresponding to dermatomes of the lower back. This work demonstrates that the flexibility in contact selection offered by the PENTA lead may enable patient-specific tailoring of SCS.

Intraoperative characterization of interventricular mechanical dyssynchrony using electroanatomic mapping system--a feasibility study.

BACKGROUND: Interventricular mechanical dyssynchrony (VVMD) is a strong predictor of cardiac resynchronization therapy (CRT) response. However, no simple and reliable clinical method of measuring VVMD during CRT implant is currently available. We tested the hypothesis that the EnSite™ NavX™ system (St. Jude Medical, St. Paul, MN, USA) can be used intraoperatively to determine VVMD, thereby facilitating CRT optimization. METHODS: During CRT implant, the leads in the right atrium (RA), right ventricle (RV), and left ventricle (LV) were connected to the EnSite™ NavX™ system to record the real-time 3D motion of the lead electrodes. The distances from RA to RV lead electrodes (RA-RV) and RA to LV lead electrodes (RA-LV) were computed over ten cardiac cycles during each of RV pacing and biventricular (BiV) pacing, respectively. The degree of synchrony was computed from the distance waveforms between RA-RV and RA-LV by a cross-covariance method to characterize VVMD. Septal-to-posterior wall motion delay (SPWMD) from M-mode echocardiography (echo) was measured for reference at each pacing intervention. VVMD was present in all five patients undergoing CRT implant. RESULTS: Four of the five patients demonstrated clear improvement in EnSite™ NavX™-derived VVMD during BiV versus RV pacing, which corresponded to the SPWMD results by echo. CONCLUSIONS: It is feasible to characterize VVMD and resynchronization in CRT patients with the EnSite™ NavX™ system during implant, demonstrating its potential as a tool for intraoperative CRT optimization.

Spinal cord stimulation protects against atrial fibrillation induced by tachypacing.

BACKGROUND: Spinal cord stimulation (SCS) has been shown to modulate atrial electrophysiology and confer protection against ischemia and ventricular arrhythmias in animal models. OBJECTIVE: To determine whether SCS reduces the susceptibility to atrial fibrillation (AF) induced by tachypacing (TP). METHODS: In 21 canines, upper thoracic SCS systems and custom cardiac pacing systems were implanted. Right atrial and left atrial effective refractory periods were measured at baseline and after 15 minutes of SCS. Following recovery in a subset of canines, pacemakers were turned on to induce AF by alternately delivering TP and searching for AF. Canines were randomized to no SCS therapy (CTL) or intermittent SCS therapy on the initiation of TP (EARLY) or after 8 weeks of TP (LATE). AF burden (percent AF relative to total sense time) and AF inducibility (percentage of TP periods resulting in AF) were monitored weekly. After 15 weeks, echocardiography and histology were performed. RESULTS: Effective refractory periods increased by 21 ± 14 ms (P = .001) in the left atrium and 29 ± 12 ms (P = .002) in the right atrium after acute SCS. AF burden was reduced for 11 weeks in EARLY compared with CTL (P <.05) animals. AF inducibility remained lower by week 15 in EARLY compared with CTL animals (32% ± 10% vs 91% ± 6%; P <.05). AF burden and inducibility were not significantly different between LATE and CTL animals. There were no structural differences among any groups. CONCLUSIONS: SCS prolonged atrial effective refractory periods and reduced AF burden and inducibility in a canine AF model induced by TP. These data suggest that SCS may represent a treatment option for AF.

Attenuation of left ventricular adverse remodeling with epicardial patching after myocardial infarction.

BACKGROUND: Previous studies suggested that epicardial patch applied to the infarcted site after acute myocardial infarction (MI) can alleviate left ventricular (LV) remodeling and improve cardiac performance; however, the effects of regional epicardial patch on chronic phase of LV remodeling remain unclear. METHODS AND RESULTS: We studied 20 pigs with MI induced by distal embolization and impaired LV ejection fraction (LVEF < 45%) as detected by gadolinium-enhanced cardiac magnetic resonance imaging (MRI). Eight weeks post-MI, all animal underwent open chest procedure for sham surgery (control, n = 12) or patch implantation over the infarcted lateral LV wall (patch group, n = 12). In the patch group, +dP/dt increased and LV end-diastolic pressure decreased at 20 weeks compared with immediately post-MI and at 8 weeks (P < .05), but not in the control group (P > .05). As determined by cardiac MRI, LV end-diastolic and end-systolic volumes increased at 20 weeks compared with 8 weeks in both groups (P < .05). However, the increase in LV end-diastolic volume (+14.1 +/- 1.8% vs. +6.6 +/- 2.1%, P = .015) and LV end-systolic volume (+12.1 +/- 2.4% vs. -4.7 +/- 3.7%, P = .0015) were significantly greater in the control group compared with the patch group. Furthermore, the percentage increase in LVEF (+17.3 +/- 4.9% vs. +4.1 +/- 3.9%, P = .048) from 8 to 20 weeks was significantly greater in the patch group compared with the control group. Histological examination showed that LV wall thickness at the infarct region and adjacent peri-infarct regions were significantly greater in the patch group compared with the control group (P < .05). CONCLUSION: Regional application of a simple, passive synthetic epicardial patch increased LV wall thickness at the infarct region, attenuated LV dilation, and improved LVEF and +dP/dt in a large animal model of MI.

Simultaneous electrical and mechanical mapping using 3D cardiac mapping system: novel approach for optimal cardiac resynchronization therapy.

Cardiac resynchronization therapy (CRT) restores synchrony in heart failure patients. However, a significant proportion of patients implanted with CRT devices do not realize any benefit from CRT. Placing a left ventricular (LV) lead at the sites of electrical or mechanical delay has been advocated to maximize response to CRT, but there is currently no technique described to measure mechanical delay in real-time. We describe a novel technique that can be used intraoperatively to assess mechanical and electrical activation of the coronary sinus for guidance of LV pacing site optimization during CRT implantation.

Fast track open partial nephrectomy: reduced postoperative length of stay with a goal-directed pathway does not compromise outcome.

Introduction. The aim of this study is to examine the feasibility of reducing postoperative hospital stay following open partial nephrectomy through the implementation of a goal directed clinical management pathway. Materials and Methods. A fast track clinical pathway for open partial nephrectomy was introduced in July 2006 at our institution. The pathway has daily goals and targets discharge for all patients on the 3rd postoperative day (POD). Defined goals are (1) ambulation and liquid diet on the evening of the operative day; (2) out of bed (OOB) at least 4 times on POD 1; (3) removal of Foley catheter on the morning of POD 2; (4) removal of Jackson Pratt drain on the afternoon of POD 2; (4) discharge to home on POD 3. Patients and family are instructed in the fast track protocol preoperatively. Demographic data, tumor size, length of stay, and complications were captured in a prospective database, and compared to a control group managed consecutively immediately preceding the institution of the fast track clinical pathway. Results. Data on 33 consecutive patients managed on the fast track clinical pathway was compared to that of 25 control patients. Twenty two (61%) out of 36 fast track patients and 4 (16%) out of 25 control patients achieved discharge on POD 3. Overall, fast track patients had a shorter hospital stay than controls (median, 3 versus 4 days; P = .012). Age (median, 55 versus 57 years), tumor size (median, 2.5 versus 2.5 cm), readmission within 30 days (5.5% versus 5.1%), and complications (10.2% versus 13.8%) were similar in the fast track patients and control, respectively. Conclusions. In the present series, a fast track clinical pathway after open partial nephrectomy reduced the postoperative length of hospital stay and did not appear to increase the postoperative complication rate.

Phase I/II trial of docetaxel and concurrent radiation therapy in localized high risk prostate cancer (AGUSG 03-10).

PURPOSE: A Phase I/II trial was conducted to assess the radiosensitizer docetaxel administered weekly (20 mg/m(2)) with concurrent intensity modulated radiation therapy (72 Gy at 1.8 Gy/fraction) in high risk prostate cancer. PATIENTS AND METHODS: Patients with high risk prostate cancer (clinical stage > or = T3; Gleason score 8, 9, or 10; Gleason score 7 and PSA > 10) received IMRT (Clinac 600 CD with 6 MV photons and sliding window technique) and concurrent weekly docetaxel (20 mg/m(2)) as a continuous 30 minute infusion for 8 weeks. Patients desirous of concurrent androgen suppression were not excluded. RESULTS: Twenty men (median age: 64 years; range, 50-78 years) were enrolled in the chemoradiation protocol. Three patients experienced treatment interruptions: dehydration requiring inpatient hydration (n = 2); NSAID induced GI bleed (n = 1). An additional patient required outpatient hydration (<24 hours) with no treatment interruption. Overall, the most frequently observed toxicities were grade 2 diarrhea (40%), grade 2 fatigue (40%), grade 2 urinary frequency (35%), taste aversion (20%), grade 2 constipation (20%), and rectal bleeding (15%). No significant hematologic toxicity (grades 2-4) was encountered among the 20 patients. Although the follow-up interval was relatively short, no significant subacute gastrointestinal toxicities have been observed. At a median follow-up duration of 11.7 months, 17 patients were free of biochemical disease recurrence, and all patients are alive. CONCLUSION: The radiosensitizer docetaxel administered weekly (20 mg/m(2)) with concurrent IMRT is well tolerated with acceptable toxicity. Early oncologic outcomes in this challenging patient cohort are encouraging.

An interventional controlled trial comparing 2 management models for the treatment of tunneled cuffed catheter bacteremia: a collaborative team model versus usual physician-managed care.

BACKGROUND: The management of tunneled cuffed catheter (TCC)-associated bacteremias varies among nephrologists. To determine whether patient outcomes after TCC-associated bacteremia can be improved by modifying the management model, we performed an interventional controlled trial comparing a collaborative team model, intervention (INT), with the usual physician-managed model, usual care (UC). METHODS: INT consisted of an infection manager who worked closely with nephrologists and dialysis staff and made treatment recommendations using the available published guidelines at the time of the study's conception (Dialysis Outcomes Quality Initiative guideline no. 26, 1997) and additional literature-based recommendations. Nephrologists made the final treatment decisions. TCC-associated bacteremia was physician managed in the UC group. RESULTS: Two hundred twenty-three episodes of TCC-associated bacteremia occurred in 7 outpatient hemodialysis units during the 2-year study period. The INT was associated with a significantly lower incidence of recurrent bacteremia with the same organism (INT, 6% versus UC, 18%; odds ratio, 0.28; 95% confidence interval, 0.09 to 0.8; P = 0.015) and death from sepsis (INT, 0% versus UC, 6%; P < 0.02). In INT units, there was a 45% decrease in the practice of TCC salvage (TCC not removed; P = 0.05). Antibiotic prescribing practices (final antibiotic selection, dose, and duration of therapy) were improved in INT units compared with UC units. By using multivariate analysis, the INT was associated with a 73% decrease in the combined outcome of recurrent bacteremia or septic death (P < 0.02). CONCLUSION: Implementation of a collaborative team model for the management of TCC-associated bacteremic episodes is associated with improvement in the quality of heath care delivery and patient outcomes.

Tunnelled haemodialysis catheter bacteraemia: risk factors for bacteraemia recurrence, infectious complications and mortality.

BACKGROUND: Infection is a serious complication of tunnelled cuffed catheter (TCC) use and is associated with high complication and mortality rates. Although attempts at TCC salvage after bacteraemia have been associated with high rates of recurrent bacteraemia, there have been no large studies in which multivariate analysis has been performed to control for confounding factors such as infecting organisms, diabetes, etc. METHODS: A prospective observational study was performed in chronic HD patients dialyzing with a TCC at seven outpatient HD centers. All patients diagnosed with TCC bacteraemia were observed for 3 months following initial presentation and outcomes were recorded. RESULTS: During the 2.5 year study period, 226 patients had an episode of TCC bacteraemia that met inclusion criteria, and 3 month follow-up data were available in 219 episodes. Treatment failure, defined as recurrent TCC bacteraemia with the same organism or death from sepsis, occurred in 26 patients (12%). Infectious complications (such as endocarditis, osteomyelitis, etc.) occurred in 16 patients (7%), bacteraemia with a different organism occurred in 19 patients (9%), and death from sepsis occurred in eight patients (4%). Significant predictors of treatment failure (by univariate analysis) were TCC salvage, and infection with Staphylococcus aureus, (OR = 4.2, P = 0.002; and OR = 3.3, P = 0.02, respectively). TCC salvage, when used in episodes of S. aureus bacteraemia, was associated with an 8-fold higher risk of treatment failure (P = 0.001). The presence of an abnormal TCC exit site was associated with a significantly higher rate of death from sepsis, (OR = 7, P = 0.001). Outcomes (treatment failure and infectious complications) did not differ among bacteraemic episodes where the TCC was exchanged over a guidewire compared to those in which the TCC was immediately removed followed by delayed reinsertion. In the multivariate analysis, adjusted for potential confounding covariates, the only significant predictors of treatment failure after an episode of TCC bacteraemia were TCC salvage (OR = 5.4, P = 0.003), and S. aureus (OR = 4.2, P = 0.002). In a multivariate analysis, controlling for TCC management, the only variable that was significantly associated with the development of an infectious complication was infection with S. aureus (OR = 3.5, P = 0.02). CONCLUSIONS: We have shown, using multivariate analysis and adjusting for potential confounding factors, that the use of TCC salvage and S. aureus are independent risk factors for treatment failure after an episode of TCC bacteraemia, and that S. aureus is an independent risk factor for developing an infectious complication. An infected-appearing TCC exit site is associated with a higher mortality rate. Episodes of TCC bacteraemia treated using TCC salvage are associated with the highest treatment failure rates. TCC guidewire exchange can be an acceptable practice, unless severe exit site or tunnel infection is present.

Favourable outcomes in episodes of Pseudomonas bacteraemia when associated with tunnelled cuffed catheters (TCCs) in chronic haemodialysis patients.

BACKGROUND: Pseudomonas is regarded as a particularly lethal bacterial isolate. High mortality rates have been reported in episodes of Pseudomonas sepsis when associated with visceral infections as seen in immunosuppressed, hospitalized patients. In comparison, lower mortality rates have been reported with catheter-associated Pseudomonas bacteraemia in non-dialysis patients. The purpose of this study was to determine the risk factors and the outcomes for episodes of Pseudomonas bacteraemia associated with the use of tunnelled cuffed haemodialysis catheters (TCCs) in a chronic out-patient population. METHODS: We performed a prospective observational study in seven chronic haemodialysis units over a 2.5 year period. Patients who were diagnosed as having their initial TCC-associated bacteraemia within the study period were followed for 3 months. All episodes of Pseudomonas TCC bacteraemia were identified, and univariate analyses were performed to compare Pseudomonas bacteraemia with non-Pseudomonas bacteraemia. RESULTS: During the study period, 219 episodes of TCC bacteraemia were identified; 18 had a Pseudomonas isolate (8%). Pseudomonas bacteraemia episodes were associated with a significantly higher risk of not receiving appropriate initial antibiotics (odds ratio = 3.6, P = 0.02). There were no deaths in the Pseudomonas bacteraemia group, whereas 19% died in the non-Pseudomonas group. The TCC was removed in 89% of Pseudomonas bacteraemias. There were no significant risk factors for acquiring a Pseudomonas isolate, and no difference in recurrent bacteraemia or infectious complication rates between the groups. CONCLUSIONS: In haemodialysis patients with a TCC-associated Pseudomonas bacteraemia, outcomes are remarkably good. This may be because the source of Pseudomonas infection was removed in most cases. Initial antibiotic coverage lacking anti-Pseudomonas activity was not associated with increased mortality.

Sir William Osler's perceptions of urolithiasis and the case of the indigo calculus.

BACKGROUND: Sir William Osler published his textbook, The Principles and Practice of Medicine, in 1892. It became the definitive treatise on a wide variety of diseases. The section on nephrolithiasis clearly presents the etiology, pathology, symptoms, diagnosis, and treatments. What remains a mystery is the mention, under rare forms of human stones, of a type called "indigo." MATERIALS AND METHODS: A search of Index Medicus starting from 1909 backward to its inception in 1879 was performed for key words "indigo," "calculus," "renal" or "bladder stones" and "indicanuria." Twelve textbooks of urology published before 1940 were scrutinized for references to indigo calculi. RESULTS: Only two references to indigo were found, both related to its use for treating constipation (1887 and 1891). Of the 12 textbooks, only 4 make passing reference to "indigo stones." They all mention that such calculi are very rare, but direct references to cases are lacking. One textbook references a study of blue stones from Egyptian mummies. CONCLUSION: It is unlikely that Osler's reference to an indigo calculus was taken lightly during his writing of The Principles and Practice of Medicine. The case of the indigo calculus is fascinating and perhaps enlightening if only for the source of Osler's intrigue.