Excimer laser technology in percutaneous coronary interventions: Cardiovascular laser society's position paper.

Excimer Laser Coronary Atherectomy (ELCA) is a well-established therapy that emerged for the treatment of peripheral vascular atherosclerosis in the late 1980s, at a time when catheters and materials were rudimentary and associated with the most serious complications. Refinements in catheter technology and the introduction of improved laser techniques have led to their effective use for the treatment of a wide spectrum of complex coronary lesions, such as thrombotic lesions, severe calcific lesions, non-crossable or non-expandable lesions, chronic occlusions, and stent under-expansion. The gradual introduction of high-energy strategies combined with the contrast infusion technique has enabled us to treat an increasing number of complex cases with a low rate of periprocedural complications. Currently, the use of the ELCA has also been demonstrated to be effective in acute coronary syndrome (ACS), especially in the context of large thrombotic lesions.

The Kenya cancer research and control stakeholder program: Evaluating a bilateral partnership to strengthen national cancer efforts.

Background: In response to a growing cancer burden and need for improved coordination among stakeholders in Kenya, the US National Cancer Institute and the Kenya Ministry of Health collaboratively hosted a stakeholder meeting in 2014 which identified four priority areas of need (research capacity building, pathology and cancer registries, cancer awareness and education, and health system strengthening) and developed corresponding action plans. Methods: Surveys were conducted with participants to collect input on the progress and impact of the 2014 stakeholder meeting. Findings: Of 69 eligible participants, 45 responded from academia, healthcare institutions, civil society, government, and international agencies. Of the four technical focus areas, three have continued to conduct working group meetings and two have conducted in-person meetings to review and update their respective action plans. Accomplishments linked to or enhanced by t meeting include: Kenyan and international support for expansion of population-based cancer registries, increased availability of prioritized diagnostic tests in selected regional referral hospitals, a greater focus on development of a national cancer research agenda, strategic planning for a community education strategy for cancer awareness, and improved coordination of partners through in-country technical assistance. Interpretation: The Stakeholder Program has successfully united individuals and organizations to improve cancer control planning in Kenya, and has enhanced existing efforts and programs across the country. This model of partners working in parallel on prioritized track activities has supported development of long term coordination of cancer research and control activities sustainable by the Kenyan government and Kenyan institutions.

Phosphate balance in ESRD: diet, dialysis and binders against the low evident masked pool.

Phosphate metabolism is crucial in the pathophysiology of secondary hyperparathyroidism and vascular calcification. High phosphate levels have been consistently associated with unfavorable outcomes in dialysis patients, but several limitations are still hampering a resolutive definition of the optimal targets of phosphate serum levels to be achieved in this cohort. Nonetheless, hyperphosphatemia is a late marker of phosphate overload in humans. Clinical nephrologists routinely counteract the positive phosphate balance in dialysis patients through nutritional counseling, stronger phosphate removal by dialysis and prescription of phosphate binders. However, the superiority against placebo of phosphate control by diet, dialysis or binders in terms of survival has never been tested in dedicated randomized controlled trials. The present review discusses this conundrum with particular emphasis on the rationale supporting the value of a simultaneous intervention against phosphate overload in dialysis patients via the improvement of dietary intakes, dialysis efficiency and an individualized choice of phosphate binders.

Does cone beam CT actually ameliorate stab wound analysis in bone?

This study aims at verifying the potential of a recent radiological technology, cone beam CT (CBCT), for the reproduction of digital 3D models which may allow the user to verify the inner morphology of sharp force wounds within the bone tissue. Several sharp force wounds were produced by both single and double cutting edge weapons on cancellous and cortical bone, and then acquired by cone beam CT scan. The lesions were analysed by different software (a DICOM file viewer and reverse engineering software). Results verified the limited performances of such technology for lesions made on cortical bone, whereas on cancellous bone reliable models were obtained, and the precise morphology within the bone tissues was visible. On the basis of such results, a method for differential diagnosis between cutmarks by sharp tools with a single and two cutting edges can be proposed. On the other hand, the metrical computerised analysis of lesions highlights a clear increase of error range for measurements under 3 mm. Metric data taken by different operators shows a strong dispersion (% relative standard deviation). This pilot study shows that the use of CBCT technology can improve the investigation of morphological stab wounds on cancellous bone. Conversely metric analysis of the lesions as well as morphological analysis of wound dimension under 3 mm do not seem to be reliable.

Retrograde approach for revascularization of coronary chronic total occlusion.

Retrograde approach via collateral channels in coronary angioplasty for chronic total occlusion (CTO) can improve recanalization success rate. Most interventionalists will meet few cases where the retrograde approach will provide unequaled advantages, but many are held back from taking retrograde approach by lack of proper equipment and expertise. In this article, we give detailed description of all techniques to traverse the collateral channels, and to cross the CTO by retrograde approach. We also illustrate the difficulties in collateral channel crossing with different examples providing a basic guide for case selection purposes.

Modulation of the platelet serotonin transporter by thermal balneotherapy: a study in healthy subjects.

BACKGROUND: Although the beneficial effects of balneotherapy have been recognized since a long time, a few information is available on the biological mechanisms underlying them and the subjective feelings of increased well-being and mood. AIM: The links between the serotonin (5-HT) system and mood prompted us to investigate the 5-HT platelet transporter (SERT), which is considered a reliable, peripheral marker of the same structure present in presynaptic neurons, in 30 healthy volunteers before (t0) and 30 minutes after (t1) thermal balneotherapy with ozonized water, as compared with a similar group who underwent a bath in non-mineral water. MATERIALS AN METHODS: The SERT was evaluated by means of the specific binding of 3H-paroxetine (3H-Par) to platelet membranes. Equilibrium-saturation binding data, the maximal binding capacity (Bmax) and the dissociation constant (Kd), were obtained by means of the Scatchard analysis. RESULTS: The results showed that, while Bmax values did not change in both groups, the Kd values decreased significantly at t1 only in those subjects who bathed in ozonized water. CONCLUSIONS: The results of this study, while showing a decrease of the dissociation constant (Kd) which is the inverse of affinity constant, of 3H-Par binding to SERT in all subjects after balneotherapy and not in those bathing in normal water, suggest that SERT modifications may be related to a specific effect of ozonized water and, perhaps, also to the increased sense of well-being.

Clinical significance of FGF-23 measurement in dialysis patients.

AIMS: Considering the growing relevance of fibroblast growth factor-23 (FGF-23) in the pathogenesis of chronic kidney disease bone and mineral disorder (CKD-MBD), an analysis was performed to determine the relative importance of C-terminal (cFGF-23) and intact (iFGF-23) assays in assessing CKD-MBD status in the first place and the relationship between FGF-23 and mortality as a secondary aim. METHODS: In 77 patients (15 peritoneal dialysis and 62 hemodialysis), levels of calcium, phosphate, parathyroid hormone (PTH), 25-hydroxyvitamin- D (25D), 1,25D, FGF-23 (C-terminal and intact molecule) were measured and their correlations were analyzed. The relationship between FGF-23 levels and patient survival was also analyzed. RESULTS: A significant correlation was found between cFGF-23 and 1,25D, PTH and 25D while iFGF-23 was significantly correlated with phosphate, 25D and PTH. PTH and 1,25D were independent predictors of cFGF-23, while for iFGF-23 independent predictors were phosphate and 25D. No significant relationship was found between FGF-23 and mortality. CONCLUSIONS: C-terminal or intact FGF-23 levels are weakly correlated and thus not clearly indicative of FGF-23 effects on PTH, P and vitamin D metabolism in dialysis patients. Assays for cFGF-23 and iFGF-23 showed a good correlation, but the intact molecule was not superior in defining interactions with CKD-MBD molecules. Measuring FGF-23 on a regular basis with the current assays in CKD and dialysis patients does not yet seem clinically useful.

[The first anthropological study of the victims of World War I]. / Studio antropologico dei resti scheletrici risalenti alla grande guerra: tra storia, medicina e antropologia.

In Italy many hundreds of victims of both armies who fought WWI still attend to be recovered and, if possible, identified and given back to their relatives. This study has as its objective to carry out a correct recovery, anthropological analysis and possible identification of these soldiers. Our plan has been elaborated so that it may involve various experts of different disciplines (archeologists, historians, antropologists, but also genetists and entomologists). So far, in this research project, 35 recovered skeletons have been studied. Thus the biological profile was defined (sex, age, stature and ancestry) then pathologies as well as trauma. The first results show the presence of adult men but also of adolescents. The subjects show diseases of a degenerative type (arthrosis, reumatoide arthritis), as well as perimortal lesions linked to blunt trauma, explosions, or due bullet wounds.

Impaired brachial artery endothelial flow-mediated dilation and orthostatic stress in hemodialysis patients.

PURPOSE: Chronic kidney disease (CKD) is associated with an impaired endothelial function, which may contribute to cardiovascular events. Whether impairment in endothelial function is involved in the circulatory response to orthostatic stress is unknown. We assessed endothelial function via brachial artery flow-mediated dilation (BAFMD), an index of endothelial-dependent vasodilation. METHODS: We measured changes in brachial artery diameter (BAD) and blood flow by Doppler ultrasound in 35 CKD patients on hemodialysis, 37 young healthy controls (HC) and 50 non-uremic matched controls (MC), in the supine position and after 60 degrees head-up tilting (HUT). RESULTS: In the supine position, endothelial flow-mediated BAD was significantly increased in HC (p<0.001) and MC (p<0.01) while no significant changes were detected in CKD. Mean percent blood flow changes were HC+323.5%, MC+195.1% and CKD+158.8% (HC vs. CKD p<0.001; HC vs. MC p<0.001; MC vs. CKD p=0.04). Similarly, during HUT mean BAD and blood flow increases were significantly impaired in CKD patients. CONCLUSION: In CKD patients, an impaired response in the physiologic vascular reactivity, suggesting endothelial dysfunction, was found in the supine position and after orthostasis by BAFMD. Our results are in favor of a possible adjunctive role of uremia in the abnormal brachial artery response.

[The bone-vasculature-axis interaction: new insights into the pathogenesis of vascular calcification.]. / Interazione citochinica tra tessuto osseo e vasi: prospettive patogenetiche sul processo di calcificazione vascolare.

It is commonly accepted that the first cause of morbidity and mortality in chronic kidney disease (CKD) is the cardiovascular (CV) disease, in which vascular calcification (VC) plays a central pathogenetic role. In CKD population, mineral metabolism disorders have been recently investigated not only as key factors on renal osteodystrophy but also as inducing players on extra-skeletal calcification. Clearly, either high phosphate (P) or high calcium (Ca) concentration induce vascular smooth muscle cells mineralization in vitro studies. In fact, VC is induced by a cell-mediated process, which actively accompanies the traditional and passive Ca-P deposition in arterial walls. Interestingly, lack of inhibitory proteins, such as fetuin-A (alpha2-HS glycoprotein, AHSG), matrix GLA protein (MGP), osteoprotegerin (OPG), and bone morphogenetic protein 7 (BMP-7) are the regulatory key factors in preventing VC in uremic conditions.

[New insights in the pathogenesis of secondary hyperparathyroidism]. / Nuove acquisizioni nella patogenesi dell'iperparatiroidismo secondario.

Parathyroid gland growth is a major cause of secondary hyperparathyroidism in renal failure. It is well known that high serum phosphate levels, low serum calcium levels and vitamin D deficiency are the three promoters of parathyroid hyperplasia in renal failure. Recent studies have investigated in depth the potential role of growth factors (transforming growth factor alpha) and their receptors (epidermal growth factor receptor) in the pathogenesis of parathyroid cell hyperplasia in chronic renal failure. The identification of molecular mechanisms involved in calcium, phosphate and vitamin D manipulations in an experimental renal failure model could help design more effective therapy for secondary hyperparathyroidism in uremic patients.

Facial changes in adult uremic patients on chronic dialysis: possible role of hyperparathyroidism.

BACKGROUND: Uremic patients on regular dialytic treatment (RDT) are often affected by a complex metabolic syndrome leading to osteodystrophy. Bone changes are primarily due to high bone turnover, often combined with a mineralization defect leading to increased bone fractures and bone deformities. Although rarely considered, the craniofacial skeleton represents one of the peculiar targets of this complex metabolic disease whose more dramatic pattern is a form of leontiasis ossea. This complication, although described, has never been evaluated in depth nor quantitatively assessed. In order to assess facial deformities in uremic conditions and to understand the possible relation with hyperparathyroidism, we undertook a quantitative evaluation of soft facial structures in a cohort of uremic patients undergoing RDT. METHODS: The three-dimensional coordinates of 50 soft-tissue facial landmarks were obtained by an electromagnetic digitizer in 10 male and 10 female patients with chronic renal insufficiency aged 53-81 years, and in 34 healthy individuals of the same age, ethnicity and sex. Uremic patients were enrolled according to hyperparathyroid status (PTH < 300 pg/mL and PTH > 500 pg/mL). From the landmarks, facial distances, angles and volumes were calculated according to a geometrical face model. RESULTS: Overall, the uremic patients had significantly larger facial volumes than the reference subjects. The effect was particularly evident in the facial middle third (maxilla), leading to an inversion of the mandibular-maxillary ratio. Facial dimensions were increased in all three spatial directions: width (skull base, mandible, nose), length (nose, mandible), and depth (mid face, mandible). The larger maxilla was accompanied by a tendency to more prominent lips (reduced interlabial angle). Some of the facial modifications (nose, lips, mandible) were significantly related to the clinical characteristics of the patients (age, duration of renal insufficiency and PTH levels). CONCLUSIONS: This report, the first in the literature, shows that facial structures of uremic patients are enlarged in comparison with matched normal subjects and that increased bone turnover could be responsible--at least in part--for facial bone changes.

[Prevention of extraskeletal calcifications in uremia]. / Prevenzione delle calcificazioni extrascheletriche nel paziente uremico.

Secondary hyperparathyroidism (HPTH) is a common feature in end-stage renal disease (ESRD) patients. The three main factors involved in secondary HPTH pathogenesis are high phosphate levels, hypocalcemia and vitamin D deficiency. Recently, many studies demonstrated a strong association between bone disease and cardiovascular events in chronic kidney disease patients. In addition, cardiovascular events are the most frequent cause of death in patients with chronic renal failure. Increased levels of serum phosphorus and calcium-phosphate product are directly involved in the pathogenesis of extraskeletal calcifications (blood vessels, soft tissues, etc) in dialyzed patients compared to the non-uremic population. Recent studies suggested that vascular calcification is due not only to a passive calcium-phosphate deposition on atherosclerotic arteries, but also to active mechanisms regulated by bone-associated genes. In particular, fetuin and matrix Gla-protein are two 'protective' proteins associated with reduced vascular calcification and could be the regulatory keys in preventing this process in renal failure. The limitations of calcium salts as phosphate-binders in patients with advanced renal failure have been thoroughly evaluated in the last 5 yrs. New phosphate binders, which do not contain aluminum or calcium, have been developed to reduce the risk of extraskeletal calcifications in ESRD.

[Mechanism of uremic osteodystrophy and prevention of hyperparathyroidism in the uremic patient]. / Meccanismi dell'osteodistrofia uremica e prevenzione dell'iperparatiroidismo del soggetto uremico.

The management of secondary hyperparathyroidism is of crucial importance in the treatment of end stage renal disease (ESRD) patients. In particular, hypercalcemia, hyperphosphatemia, and elevated calcium x phosphate (Ca x P) product should be taken into consideration during administration of vitamin D metabolites for the control of PTH secretion. During the last 10 years, many authors have been studying the efficacy of new non-calcemic vitamin D analogs on suppressing secondary hyperparathyroidism in ESRD patients. In this brief review, we analyzed three new vitamin D analogs: 22-oxacalcitriol (Maxacalcitriol), 19-nor-1a, 25(OH)2D2 (Paracalcitriol), and 1a (OH)2D2 (Doxacalciferol). In addition, calcimimetic agents may represent a new pharmacologic choice to the treatment of secondary hyperparathyroidism, binding parathyroid calcium sensing receptors (CaSR) and reducing PTH secretion. These compounds may represent an important tool for the treatment of both secondary hyperparathyroidism and soft tissue calcifications in ESRD patients. In conclusion, a combined use of non calcemic phosphate binders, new vitamin D analogs and calcimimetics should be seriously considered to further improve the already known therapy of secondary hyperparathyroidism in ESRD patients.

Incremental prognostic value of technetium-99m-tetrofosmin exercise myocardial perfusion imaging for predicting outcomes in patients with suspected or known coronary artery disease.

Technetium-99m (Tc-99m)-tetrofosmin is a radio isotope that has been shown to be an accurate alternative to thallium-201 for detecting coronary artery disease. However, its prognostic value is less well determined. To this end, 459 consecutive patients (mean age 58 +/- 10 years) with suspected or known coronary artery disease underwent exercise single-photon emission tomography Tc-99m-tetrofosmin scintigraphy. Follow-up, defined as the time from scanning until a soft event (revascularization procedures), a hard event (myocardial infarction and cardiac death), or patient response, lasted up to 78 months (median 38). An ischemic scintigraphic perfusion score, which takes into account both the extent and severity of reversible perfusion defects, was calculated to estimate the severity of perfusion abnormalities. Patients with normal scans were at low risk of events (yearly hard event rate 0.5% and soft event rate 0.9%). The rate of outcomes increased significantly with abnormal scans (yearly hard event rate 4.9% and soft event rate 10.3%). Statistical analysis using the Kaplan-Meyer survival curves showed a significant difference in event-free survival between patients with normal and abnormal scans. With use of Cox proportional-hazards analysis, after adjusting for prescan information, nuclear data provided incremental prognostic value for hard events (clinical and exercise data vs nuclear data; chi-square = 15.5 vs 33.4, p <0.001). Exercise single-photon emission tomographic scintigraphy using Tc-99m-tetrofosmin provides significant independent information on the subsequent risk of hard and soft events. The annual event rate for hard and soft events is <1% for patients with a normal scan. Furthermore, this tracer yields incremental prognostic information in addition to that provided by clinical and exercise data for hard events.

Long-term angiographic follow-up after successful repeat balloon angioplasty for in-stent restenosis.

BACKGROUND: Coronary stent implantation is associated with improved angiographic short-term and mid-term clinical outcome. However, restenosis rate still remains between 20 and 30%. HYPOTHESIS: The purpose of the study, performed as a prospective angiographic follow-up to detect restenosis, was to evaluate the immediate and the 6-month angiographic results of repeat balloon angioplasty for in-stent restenosis. METHODS: From April 1996 to September 1997, 335 stenting procedures performed in 327 patients underwent prospectively 6-month control angiography. Of the 96 lesions that showed in-stent restenosis (> 50% diameter stenosis) (29%), 72 underwent balloon angioplasty. RESULTS: The primary success rate was 100%. Follow-up angiogram at a mean of 6.9 +/- 2.4 months was obtained in 54 patients. Recurrent restenosis was observed in 24 of the 55 stents (44%). Repeat intervention for diffuse and body location in-stent restenosis before repeat intervention was associated with significantly higher rates of recurrent restenosis (p < 0.001 and p < 0.05, respectively). Of the 19 patients who underwent further balloon angioplasty (100% success rate), coronary angiography was performed in 18 (95%) at a mean of 8.2 +/- 2.0 months and showed recurrent restenosis in 12 patients (67%). Further repeat intervention for diffuse and severe in-stent restenosis before the second repeat intervention was associated with significantly higher rates of further recurrent restenosis (p < 0.05 and p < 0.005, respectively). CONCLUSIONS: Although balloon angioplasty can be safely, successfully, and repeatedly performed after stent restenosis, it carries a progressively high recurrence of angiographic restenosis rate during repeat 6-month follow-ups. The subgroup of patients with diffuse, severe, and/or body location in-stent restenosis proved to be at higher risk of recurrent restenosis.

Usefulness of glycoprotein IIb/IIIa inhibitors in unstable angina due to small vessel disease.

We describe the role of abciximab in unstable angina due to small vessel disease in a 58-year-old patient who was submitted to percutaneous transluminal coronary angioplasty and stenting of an occluded venous graft.