Likert vs PI-RADS v2: a comparison of two radiological scoring systems for detection of clinically significant prostate cancer.

OBJECTIVE: To compare the clinical validity and utility of Likert assessment and the Prostate Imaging Reporting and Data System (PI-RADS) v2 in the detection of clinically significant and insignificant prostate cancer. PATIENTS AND METHODS: A total of 489 pre-biopsy multiparametric magnetic resonance imaging (mpMRI) scans in consecutive patients were subject to prospective paired reporting using both Likert and PI-RADS v2 by expert uro-radiologists. Patients were offered biopsy for any Likert or PI-RADS score ≥4 or a score of 3 with PSA density ≥0.12 ng/mL/mL. Utility was evaluated in terms of proportion biopsied, and proportion of clinically significant and insignificant cancer detected (both overall and on a 'per score' basis). In those patients biopsied, the overall accuracy of each system was assessed by calculating total and partial area under the receiver-operating characteristic (ROC) curves. The primary threshold of significance was Gleason ≥3 + 4. Secondary thresholds of Gleason ≥4 + 3, Ahmed/UCL1 (Gleason ≥4 + 3 or maximum cancer core length [CCL] ≥6 or total CCL≥6) and Ahmed/UCL2 (Gleason ≥3 + 4 or maximum CCL ≥4 or total CCL ≥6) were also used. RESULTS: The median (interquartile range [IQR]) age was 66 (60-72) years and the median (IQR) prostate-specific antigen level was 7 (5-10) ng/mL. A similar proportion of men met the biopsy threshold and underwent biopsy in both groups (83.8% [Likert] vs 84.8% [PI-RADS v2]; P = 0.704). The Likert system predicted more clinically significant cancers than PI-RADS across all disease thresholds. Rates of insignificant cancers were comparable in each group. ROC analysis of biopsied patients showed that, although both scoring systems performed well as predictors of significant cancer, Likert scoring was superior to PI-RADS v2, exhibiting higher total and partial areas under the ROC curve. CONCLUSIONS: Both scoring systems demonstrated good diagnostic performance, with similar rates of decision to biopsy. Overall, Likert was superior by all definitions of clinically significant prostate cancer. It has the advantages of being flexible, intuitive and allowing inclusion of clinical data. However, its use should only be considered once radiologists have developed sufficient experience in reporting prostate mpMRI.

Autonomic regulation of systemic inflammation in humans: A multi-center, blinded observational cohort study.

OBJECTIVE: Experimental animal models demonstrate that autonomic activity regulates systemic inflammation. By contrast, human studies are limited in number and exclusively use heart rate variability (HRV) as an index of cardiac autonomic regulation. HRV measures are primarily dependent on, and need to be corrected for, heart rate. Thus, independent autonomic measures are required to confirm HRV-based findings. Here, the authors sought to replicate the findings of preceding HRV-based studies by using HRV-independent, exercise-evoked sympathetic and parasympathetic measures of cardiac autonomic regulation to examine the relationship between autonomic function and systemic inflammation. METHODS: Sympathetic function was assessed by measuring heart rate changes during unloaded pedaling prior to onset of exercise, divided into quartiles; an anticipatory heart rate (AHRR) rise during this period is evoked by mental stress in many individuals. Parasympathetic function was assessed by heart rate recovery (HRR) 60s after finishing cardiopulmonary exercise testing, divided into quartiles. Parasympathetic dysfunction was defined by delayed heart rate recovery (HRR) ≤12.beats.min-1, a threshold value associated with higher cardiovascular morbidity/mortality in the general population. Systemic inflammation was primarily assessed by neutrophil-lymphocyte ratio (NLR), where a ratio >4 is prognostic across several inflammatory diseases and correlates strongly with elevated plasma levels of pro-inflammatory cytokines. High-sensitivity C-reactive protein (hsCRP) was also measured. RESULTS: In 1624 subjects (65±14y; 67.9% male), lower HRR (impaired vagal activity) was associated with progressively higher NLR (p=0.004 for trend across quartiles). Delayed HRR, recorded in 646/1624 (39.6%) subjects, was associated with neutrophil-lymphocyte ratio >4 (relative risk: 1.43 (95%CI: 1.18-1.74); P=0.0003). Similar results were found for hsCRP (p=0.045). By contrast, AHRR was not associated with NLR (relative risk: 1.24 (95%CI: 0.94-1.65); P=0.14). CONCLUSIONS: Delayed HRR, a robust measure of parasympathetic dysfunction, is independently associated with leukocyte ratios indicative of systemic inflammation. These results further support a role for parasympathetic modulation of systemic inflammation in humans.

The Use of a Polyetheretherketone (PEEK) Implant to Reconstruct the Midface Region.

A good functional and cosmetic result after midfacial reconstructive surgical procedures is of paramount importance. We describe the use of a Polyetheretherketone (PEEK) implant to reconstruct the midface area, after extensive mutilating surgery due to an infiltrative skin tumor. A 67-year-old male patient underwent multiple and extensive surgeries to the left cheek and lower lid because of a highly aggressive metatypical basal cell carcinoma. Complete resection of the recurrent tumor resulted in a cosmetically evident absent cheek contour and facial deformity. The PEEK implant was used to restore the bony cheek contour, with good aesthetic outcome and restoration of the facial symmetry. Preoperative planning with 3-dimensional CT scans allow for customization of the implant. PEEK implants have been scantily described in the periorbital region. The material has a very low reported morbidity and also has the advantage of improving intraoperative predictability and reducing surgical time in complex reconstructive procedures.

Psycho-social factors associated with type two diabetes remission through lifestyle intervention: A scoping review.

OBJECTIVES: There is growing evidence that type 2 diabetes (T2D) can be put into remission through lifestyle intervention. Current focus on remission in terms of physiological considerations and biomedical scales, means there is limited understanding of the role psycho-social factors play in moderating the efficacy of lifestyle interventions for T2D remission. In the current review we aimed to synthesise the emerging literature on psycho-social factors associated with T2D remission, specifically from lifestyle interventions. METHODS: Five databases (EMBASE, MEDLINE, CINAHL ultimate, PsychINFO and PsycArticles) were searched to identify studies from 2009 onwards that reported remission outcomes from lifestyle interventions in participants ≥ 18years old, with a clinical diagnosis of T2D. Studies included were of an interventional or observational design and restricted to English language. Screening and data extraction was performed independently by two reviewers using prespecified criteria. RESULTS: In total 6106 studies were screened, 36 studies meeting the inclusion criteria were included. Studies were globally diverse, with 30 (83%) being published ≥ 2017. Psycho-social scales were under-utilised with 22 (67%) of studies failing to include any psycho-social measures. Single arm, prospective studies were most frequently utilised, however study quality was perceived to be heterogeneous. Further disparity in the quality, content and delineation of the psycho-social interventions was also identified. Education and self-monitoring interventions were the most frequently incorporated. Self-monitoring was also identified as an important facilitator to remission, in addition to social support. CONCLUSIONS: Our findings indicate that psycho-social factors in T2D remission are under-explored. We have identified a number of methodological issues (comparability, conflicting remission criteria and poorly defined psycho-social interventions) suggesting knowledge gaps which could inform the methodology of future research design. There is significant opportunity for future research to incorporate the social model of disease, conceptualise remission more holistically, and build a more comprehensive evidence base to guide clinical practice.

Salvage antegrade visceral revascularization and antegrade aortic stenting for type I and III endoleaks after fenestrated juxtarenal aneurysm repair.

A 73-year-old man developed type I and III endoleaks from a fractured right renal stent with downward migration of a fenestrated endograft, 6 years after endovascular repair of a juxtarenal aneurysm. Endovascular treatment attempts were unsuccessful. He underwent aortic debranching and antegrade visceral artery revascularization via a left thoracolaparotomy incision and an extraperitoneal approach to the visceral aorta. An antegrade aortic stent covered the endoleak, with technical and clinical success at 9 months. Failure of complex endografts presents particular problems, potentially not amenable to totally endovascular repair. Continued surveillance is mandated as late, asymptomatic sac expansion can occur.

Effects of Electrical Stimulation of NAc Afferents on VP Neurons' Tonic Firing.

Afferents from the nucleus accumbens (NAc) are a major source of input into the ventral pallidum (VP). Research reveals that these afferents are GABAergic, however, stimulation of these afferents induces both excitatory and inhibitory responses within the VP. These are likely to be partially mediated by enkephalin and substance P (SP), which are also released by these afferents, and are known to modulate VP neurons. However, less is known about the potentially differential effects stimulation of these afferents has on subpopulations of neurons within the VP and the cellular mechanisms by which they exert their effects. The current study aimed to research this further using brain slices containing the VP, stimulation of the NAc afferents, and multi-electrode array (MEA) recordings of their VP targets. Stimulation of the NAc afferents induced a pause in the tonic firing in 58% of the neurons studied in the VP, while 42% were not affected. Measures used to reveal the electrophysiological difference between these groups found no significant differences in firing frequency, coefficient of variation, and spike half-width. There were however significant differences in the pause duration between neurons in the dorsal and ventral VP, with stimulation of NAc afferents producing a significantly longer pause (0.48 ± 0.06 s) in tonic firing in dorsal VP neurons, compared to neurons in the ventral VP (0.21 ± 0.09 s). Pauses in the tonic firing of VP neurons, as a result of NAc afferent stimulation, were found to be largely mediated by GABAA receptors, as the application of picrotoxin significantly reduced their duration. Opioid agonists and antagonists were found to have no significant effects on the pause in tonic activity induced by NAc afferent stimulation. However, NK-1 receptor antagonists caused significant decreases in the pause duration, suggesting that SP may contribute to the inhibitory effect of NAc afferent stimulation via activation of NK-1 receptors.

Correction: Heart rate recovery and morbidity after noncardiac surgery: Planned secondary analysis of two prospective, multi-centre, blinded observational studies.

[This corrects the article DOI: 10.1371/journal.pone.0221277.].

Heart rate recovery and morbidity after noncardiac surgery: Planned secondary analysis of two prospective, multi-centre, blinded observational studies.

BACKGROUND: Impaired cardiac vagal function, quantified preoperatively as slower heart rate recovery (HRR) after exercise, is independently associated with perioperative myocardial injury. Parasympathetic (vagal) dysfunction may also promote (extra-cardiac) multi-organ dysfunction, although perioperative data are lacking. Assuming that cardiac vagal activity, and therefore heart rate recovery response, is a marker of brainstem parasympathetic dysfunction, we hypothesized that impaired HRR would be associated with a higher incidence of morbidity after noncardiac surgery. METHODS: In two prospective, blinded, observational cohort studies, we established the definition of impaired vagal function in terms of the HRR threshold that is associated with perioperative myocardial injury (HRR ≤ 12 beats min-1 (bpm), 60 seconds after cessation of cardiopulmonary exercise testing. The primary outcome of this secondary analysis was all-cause morbidity three and five days after surgery, defined using the Post-Operative Morbidity Survey. Secondary outcomes of this analysis were type of morbidity and time to become morbidity-free. Logistic regression and Cox regression tested for the association between HRR and morbidity. Results are presented as odds/hazard ratios [OR or HR; (95% confidence intervals). RESULTS: 882/1941 (45.4%) patients had HRR≤12bpm. All-cause morbidity within 5 days of surgery was more common in 585/822 (71.2%) patients with HRR≤12bpm, compared to 718/1119 (64.2%) patients with HRR>12bpm (OR:1.38 (1.14-1.67); p = 0.001). HRR≤12bpm was associated with more frequent episodes of pulmonary (OR:1.31 (1.05-1.62);p = 0.02)), infective (OR:1.38 (1.10-1.72); p = 0.006), renal (OR:1.91 (1.30-2.79); p = 0.02)), cardiovascular (OR:1.39 (1.15-1.69); p<0.001)), neurological (OR:1.73 (1.11-2.70); p = 0.02)) and pain morbidity (OR:1.38 (1.14-1.68); p = 0.001) within 5 days of surgery. CONCLUSIONS: Multi-organ dysfunction is more common in surgical patients with cardiac vagal dysfunction, defined as HRR ≤ 12 bpm after preoperative cardiopulmonary exercise testing. CLINICAL TRIAL REGISTRY: ISRCTN88456378.

Dichotomous Dopaminergic Control of Ventral Pallidum Neurons.

The ventral pallidum (VP) is crucially involved in reward processing. Dopaminergic afferents reach the VP from the ventral tegmental area (VTA). Recent in vivo studies suggest dopamine application increase the firing in the VP. However, little is known about the cellular effects of dopamine within the VP. We aimed to address this paucity of data using brain slices containing the VP and multi-electrode array recordings. Dopamine significantly affected firing in 86% of spontaneously active VP neurons. Among the affected neurons, 84% were excited, while 16% were inhibited. The selective D1-like receptor agonist SKF81297 also had modulatory effects on the majority of VP neurons, but its effects were universally excitatory. On the other hand, the D2-like receptor agonist quinpirole had modulatory effects on 87% of VP neurons studied. It caused significant inhibitory effects in 33% of the cases and excitatory effects in the remaining 67%. The effects of D1-like receptor activation were presynaptic as blocking synaptic transmission with low Ca2+ abolished the effects of SKF81297 application. Furthermore, SKF81297 effects were abolished by blocking ionotropic glutamate receptors, suggesting that D1-like receptors boost glutamate release, which in turn excites VP neurons through postsynaptic glutamate receptors. Effects caused by D2-like receptor activation were found to involve pre and postsynaptic mechanisms, as low Ca2+ abolished the excitatory effects of quinpirole but not the inhibitory ones. Increases in firing frequency (ff) to quinpirole application were abolished by a group 2/3 mGluR antagonist, suggesting that D2-like receptors cause presynaptic inhibition of glutamate release, resulting in reduced postsynaptic activation of inhibitory mGluRs. Conversely, the inhibitory effects of quinpirole persisted in low Ca2+ and therefore can be attributed to postsynaptic D2-like receptor activation. VP neurons excited by dopamine had shorter spike half-widths and are excited by D1-like receptors (presynaptically) and by D2-like receptors (postsynaptically). VP neurons inhibited by dopamine have longer spike half-widths and while D1-like receptor activation has a presynaptic excitatory influence on them, D2-like receptor activation has a postsynaptic inhibitory effect that prevails, on balance. These data provide novel insights into the cellular mechanisms by which dopamine controls information processing within the VP.

Antibiotic Susceptibility Monitoring of Neisseria gonorrhoeae in Bacolod City, Philippines.

A local study was conducted to monitor the antibiotic susceptibility of N. gonorrhoeae in Bacolod City, Philippines. A total of 88 isolates were taken during the period of 1 January 2015 to 30 June 2017, from male patients ages 12 to 72 years. The highest incidence of gonorrhea infection was in the group aged 20⁻24 years (34.09%). The susceptibility pattern to antibiotics was as follows: ceftriaxone 100%, cefixime 82.6%, spectinomycin 92.1%, ciprofloxacin 4.9%, tetracycline 5.1%, and penicillin G with 0%. All isolates were noted to produce beta-lactamase, which can be attributed to plasmid-mediated penicillin resistance. These findings indicate that the resistance rates of N. gonorrhoeae to most commonly-used antibiotics are increasing, and that ceftriaxone remains an effective antibiotic in treating gonorrhea infections locally.

A systematic review of the quality of genetic association studies in human sepsis.

OBJECTIVE: Epidemiological studies demonstrate that inherited factors play a major role in the development and prognosis of sepsis. However, genetic association studies in sepsis have produced contradictory evidence of an effect from individual polymorphisms. Major methodological flaws have been reported in a number of genetic association studies in non-septic populations, relating to problems with experimental design, statistical analysis, study size, power and replication. We hypothesised that genetic association studies investigating sepsis suffer from similar problems, and that this explains the lack of consistent evidence for an effect from polymorphisms. DESIGN: A systematic review was conducted of published genetic association studies in sepsis from 1996-2005 using a newly devised scoring system for study quality and rigour. A Bayesian statistical analysis was also carried out to assess the false-positive report probability of identified studies. MEASUREMENTS AND RESULTS: Study quality was assessed using a 10-point scoring system designed from published reporting guidelines. The majority of studies were of low to intermediate quality, with deficiencies in control group selection, genetic assay technique, study blinding, statistical interpretation, study replication, study size and power. Bayesian analysis indicated that many of the studies reporting a positive association between a genetic polymorphism and sepsis were likely to represent false-positive associations. CONCLUSIONS: The quality and size of genetic association studies in septic patients needs to improve if advances in identifying genetic effects in sepsis are to occur. Investigators should, as a minimum, follow recommended guidelines when designing studies.

Using preoperative imaging for intraoperative guidance: a case of mistaken identity.

BACKGROUND: Surgical image guidance systems to date have tended to rely on reconstructions of preoperative datasets. This paper assesses the accuracy of these reconstructions to establish whether they are appropriate for use in image guidance platforms. METHODS: Nine raters (two experts in image interpretation and preparation, three in image interpretation, and four in neither interpretation nor preparation) were asked to perform a segmentation of ten renal tumours (four cystic and six solid tumours). These segmentations were compared with a gold standard consensus segmentation generated using a previously validated algorithm. RESULTS: Average sensitivity and positive predictive value (PPV) were 0.902 and 0.891, respectively. When assessing for variability between raters, significant differences were seen in the PPV, sensitivity and incursions and excursions from consensus tumour boundary. CONCLUSIONS: This paper has demonstrated that the interpretation required for the segmentation of preoperative imaging of renal tumours introduces significant inconsistency and inaccuracy. Copyright © 2015 John Wiley & Sons, Ltd.

Hospital planning: challenges or opportunities?

The quality and suitability of the hospital environment is a key contributor to the patient experience. Although major improvements have been made to NHS hospitals in England over the past 20 years, a significant proportion of the estate remains unfit for purpose. Affording investment in capital schemes will be increasingly challenging for NHS trusts and foundation trusts given the projected financial constraints facing the NHS; robust and effective planning is needed more than ever to ensure that any capital funding available delivers tangible benefits to patient care. Early and consistent clinical engagement is vital to enable true alignment of clinical services and facilities. It is essential that the planning of hospital facilities responds to changing models of care and is undertaken through a genuine 'whole system' approach. Providing a fit for purpose patient environment across the health economy must be a key target for all commissioners and providers alike.

Complex thoracoabdominal aortic aneurysms: endovascular exclusion with visceral revascularization.

OBJECTIVE: We review our ongoing experience with a transabdominal stent repair of complex thoracoabdominal aneurysms (Crawford type I, II, and III) with surgical revascularization of visceral and renal arteries. METHODS: A retrospective review was conducted of prospectively collected data from 29 consecutive patients who underwent an attempted visceral hybrid procedure between January 2002 and April 2005. Twenty-two patients were elective, four were urgent (symptomatic), and three were emergent (true rupture). The median patient age was 74 years (range, 37 to 81 years). The aneurysms were Crawford type I in 3, type II in 18, type III in 7, and type IV in 1. Previous aortic surgery had been performed in 13 (45%) of 29 and included aortic valve and root replacement in 3, TAA repair in 1, type I repair in 1), type IV repair in 3, type B dissection in 2, infrarenal aneurysm in 5, and right common iliac aneurysm in 1. Severe preoperative comorbidity was present in 23 (80%) of 29: chronic renal impairment in 5, severe chronic obstructive pulmonary disease in 6, myocardial disease in 11 at New York Heart Association grade II (6) and grade III (5), and Marfan's syndrome in 6. Twenty-six patients (90%) had a completed procedure. In two patients, myocardial instability prevented completion of the procedure despite extensive preoperative cardiac assessment, and in one, poor flow in the true lumen of a chronic type B dissection prevented anastomosis of the revascularization grafts. Exclusion of the full thoracoabdominal aorta was achieved in all 26 completed procedures and extended to include the iliac arteries in four, with revascularization of coeliac in 26, superior mesenteric artery in 26, left renal artery in 21, and right renal artery in 21). RESULTS: There was no paraplegia < or =30 days or during inpatient admission, and elective and urgent mortality was 13% (3/23). All of the patients with ruptured thoracoabdominal aneurysms died < or =30 days. Major complications included prolonged respiratory support (>5 days) in 9, inotropic support in 4, renal impairment requiring temporary support in 2 and not requiring support in 2, prolonged ileus in 2, resolved left hemispheric stroke in 1, and resection of an ischemic left colon in 1. Median blood loss was 3.9 liters (range, 1.2 to 13 liters). The median ischemia time was 15 minutes (range, 13 to 27 minutes) for the superior mesenteric and coeliac arteries and 15 minutes for the renal arteries (range, 13 to 21 minutes). The median hospital stay was 27 days (range, 16 to 84 days). Follow-up was a median of 8 months (range, 2 to 31 months), with 92 of 94 grafts patent. Six patients were found to have a type I endoleak. In four, this was a proximal leak, and stent extension in three reduced, but did not cure, the endoleak. One patient with a distal type I endoleak was successfully treated by embolization. Four type II endoleaks resolved without intervention, and one was treated by occlusion coiling of the origin of the left subclavian artery. A single late type III endoleak was found. CONCLUSION: Early results of visceral hybrid stent-grafts for types I, II, and III thoracoabdominal aneurysms are encouraging, with no paraplegia in this particularly high-risk group of patients. These results have encouraged us to perform the new procedure, in preference to open surgery, in Crawford type I, II, and III thoracoabdominal aortic aneurysms.

DNA damage uncouples the mitogenic response to IGF-I in MCF-7 malignant breast cancer cells by switching the roles of PI3 kinase and p21WAF1/Cip1.

In addition to its mitogenic and survival actions, recent evidence indicates that IGF-I can enhance DNA repair, implying IGF activity may limit the efficacy of many therapeutic strategies that rely on induction of DNA damage. Although the individual pathways by which DNA damage and IGF-I act are well understood, the cross-talk between these signaling events is not well defined. We examined the effects of DNA damage on the IGF-I response of MCF-7 breast cancer cells. Cells were exposed to the UV mimetic, 4-NQO, or the gamma-irradiation mimetic and chemotherapeutic drug, bleomycin; cellular proliferation was assessed by cell counting, tritiated thymidine incorporation and FACS cell cycle analysis. Although IGF-I acutely suppressed the p53 response to both agents, it subsequently enhanced the chronic increase in p53 and p21(WAF1/Cip1), resulting in cell cycle arrest; however, no apoptosis was observed. Use of specific inhibitors demonstrated that PI3 kinase was utilized with p38 MAPK to induce the p53 response to DNA damage, but was also utilized by IGF-I to diminish the acute p53 response. In addition, p21WAF1/Cip1 was increased by IGF-I, which has previously been shown to contribute to the mitogenic response. Here we demonstrate that with DNA damage IGF-I can also enhance the chronic p53-dependent increase in p21WAF1/Cip1, culminating in growth arrest. Overall, we have shown that PI3 kinase and p21WAF1/Cip1 play dual roles in mediating the mitogenic response to IGF-I, but these are both switched by cellular DNA damage to mediate a growth arrest.

Transoesophageal echocardiogram identifying the source of endoleak after combined open/endovascular repair of a type 3 thoracoabdominal aortic aneurysm.

Open repair of thoracic aortic aneurysms is associated with significant morbidity and mortality. The introduction of endovascular repair has reduced both the morbidity and mortality. However, endovascular stent repair can be complicated by endoleaks. We report here the successful treatment of a type 2 endoleak following endovascular repair of a thoracoabdominal aortic aneurysm, using transesophageal echocardiography to assist in the localization of the thoracic endoleak.

Development and validation of a high-performance liquid chromatography assay for voriconazole.

An analytical method for the determination of voriconazole (UK-109,496; Pfizer) in plasma was developed and validated. The method utilizes solid-phase extraction technology and high-performance liquid chromatography. The lower limit of quantitation is 0.2 microg/ml, and the range of linearity tested was 0.2 to 10 microg/ml.

Relationship of matrix metalloproteinases and macrophages to embolization during endoluminal carotid interventions.

PURPOSE: To investigate if relationships exist among macrophage infiltration, plasma matrix metalloproteinase (MMP) levels, and the number of emboli generated during endoluminal carotid interventions. METHODS: Carotid endarterectomy specimens excised as intact cylinders (n=27) were subjected to a standardized angioplasty procedure under radiological guidance in an ex vivo pulsatile flow model. Emboli collected in distal filters were counted and sized using microscopy. Preoperative plasma gelatinase activity was determined by gelatin zymography and quantified using image analysis software. Levels of tissue inhibitors of metalloproteinases (TIMP) 1 and 2 were determined by ELISA. Macrophages within postangioplasty plaques were analyzed using immunohistochemical staining for CD68 antigen and graded by a blinded examiner. Statistical analysis was performed using Spearman's rank correlation. RESULTS: The median number of emboli recorded during angioplasty was 104 (interquartile range 33.75-242.5, absolute range 13-1090). Plasma MMP-9 and MMP-2 levels correlated with emboli number (r=0.544 [p=0.003] and r=0.412, [p=0.033], respectively), while TIMP-1 and TIMP-2 levels did not. Macrophage infiltration within the plaques correlated with emboli number (r=0.722, p<0.001) and the plasma MMP-9 level (r=0.489, p=0.010). CONCLUSIONS: These data indicate that plaque macrophage infiltration may play a role in the generation of emboli during endoluminal carotid intervention, possibly via modulation of protease activity.

Tesio-Caths provide effective and safe long-term vascular access.

BACKGROUND: Vascular access is judged on its ability to provide good dialysis adequacy, its durability and complication rates. Formation of a functional arteriovenous fistula is desirable but difficult to achieve in a significant proportion of patients. We report the large-scale use of Tesio-Caths, a twin-line single-lumen central venous catheter, to maximize dialysis adequacy where formation of an arteriovenous fistula was not possible. METHODS: All patients who had Tesio-Caths inserted between 1 January 1999 and 1 October 2002 were studied. RESULTS: Six hundred and twenty-three Tesio-Caths were inserted from 1 January 1999 to 1 October 2002 in 435 patients, generating 7464 patient months of follow-up. Five hundred and ninety-four out of 623 (95.3%) Tesio-Caths were immediately functional. Mean dialysis adequacy measured by single-pool Kt/V was 1.5+/-0.3 for all Tesio-Caths for the entire period of study, with 68% of Tesio-Caths delivering a Kt/V >1.4. Cumulative functional Tesio-Cath survival to final failure was 77.8 and 44% at 1 and 3 years, respectively. Cumulative patient survival was 84.7, 71.4 and 63% at 1, 2 and 3 years, respectively. Access-related infection accounted for 0.28 admissions/1000 catheter days, and the death rate from access-related sepsis was 9.6 deaths/1000 patient years at risk. The admission rate for access dysfunction was 0.33/1000 patient years at risk. CONCLUSION: Tesio-Caths provide good dialysis adequacy for patients in whom an arteriovenous fistula cannot be formed. Patient and functional access survival for this group was comparable with current European data irrespective of vascular access type. Complication rates were acceptably low.