Expert consensus and evidence-based recommendations for the assessment of flow-mediated dilation in humans.

Endothelial dysfunction is involved in the development of atherosclerosis, which precedes asymptomatic structural vascular alterations as well as clinical manifestations of cardiovascular disease (CVD). Endothelial function can be assessed non-invasively using the flow-mediated dilation (FMD) technique. Flow-mediated dilation represents an endothelium-dependent, largely nitric oxide (NO)-mediated dilatation of conduit arteries in response to an imposed increase in blood flow and shear stress. Flow-mediated dilation is affected by cardiovascular (CV) risk factors, relates to coronary artery endothelial function, and independently predicts CVD outcome. Accordingly, FMD is a tool for examining the pathophysiology of CVD and possibly identifying subjects at increased risk for future CV events. Moreover, it has merit in examining the acute and long-term impact of physiological and pharmacological interventions in humans. Despite concerns about its reproducibility, the available evidence shows that highly reliable FMD measurements can be achieved when specialized laboratories follow standardized protocols. For this purpose, updated expert consensus guidelines for the performance of FMD are presented, which are based on critical appraisal of novel technical approaches, development of analysis software, and studies exploring the physiological principles underlying the technique. Uniformity in FMD performance will (i) improve comparability between studies, (ii) contribute to construction of reference values, and (iii) offer an easy accessible and early marker of atherosclerosis that could complement clinical symptoms of structural arterial disease and facilitate early diagnosis and prediction of CVD outcomes.

Enhanced Tomographic Assessment to Detect Corneal Ectasia Based on Artificial Intelligence.

PURPOSE: To improve the detection of corneal ectasia susceptibility using tomographic data. DESIGN: Multicenter case-control study. METHODS: Data from patients from 5 different clinics from South America, the United States, and Europe were evaluated. Artificial intelligence (AI) models were generated using Pentacam HR (Oculus, Wetzlar, Germany) parameters to discriminate the preoperative data of 3 groups: stable laser-assisted in situ keratomileusis (LASIK) cases (2980 patients with minimum follow-up of 7 years), ectasia susceptibility (71 eyes of 45 patients that developed post-LASIK ectasia [PLE]), and clinical keratoconus (KC; 182 patients). Model accuracy was independently tested in a different set of stable LASIK cases (298 patients with minimum follow-up of 4 years) and in 188 unoperated patients with very asymmetric ectasia (VAE); these patients presented normal topography (VAE-NT) in 1 eye and clinically diagnosed ectasia in the other (VAE-E). Accuracy was evaluated with ROC curves. RESULTS: The random forest (RF) provided highest accuracy among AI models in this sample with 100% sensitivity for clinical ectasia (KC+VAE-E; cutoff 0.52), being named Pentacam Random Forest Index (PRFI). Considering all cases, the PRFI had an area under the curve (AUC) of 0.992 (94.2% sensitivity, 98.8% specificity; cutoff 0.216), being statistically higher than the Belin/Ambrósio deviation (BAD-D; AUC = 0.960, 87.3% sensitivity, 97.5% specificity; P = .006, DeLong's test). The optimized cutoff of 0.125 provided sensitivity of 85.2% for VAE-NT and 80% for PLE, with 96.6% specificity. CONCLUSION: The PRFI enhances ectasia diagnosis. Further integrations with corneal biomechanical parameters and with the corneal impact from laser vision correction are needed for assessing ectasia risk.

Validation of an Objective Scoring System for Forme Fruste Keratoconus Detection and Post-LASIK Ectasia Risk Assessment in Asian Eyes.

PURPOSE: To investigate the efficacy of the SCORE Analyzer (Bausch+Lomb TechnoLas, Germany) in detecting forme fruste keratoconus (FFKC) in Asian eyes and validate its usefulness as a risk assessment system for post-laser in situ keratomileusis (LASIK) keratectasia. METHODS: We retrospectively evaluated corneal topographies with the Orbscan IIz system and independently tested them with the SCORE Analyzer through masked investigators. Eyes were classified into 2 groups: (1) The FFKC group included clinically and topographically normal eyes with definite keratoconus in the contralateral eye. (2) The control group included normal preoperative topographies of patients with LASIK performed at least 4 years before with no resultant keratectasia. The main outcome measures were accuracy indicators: sensitivity, specificity, positive, and negative predictive values. Parameters in the calculation of the SCORE including irregularity at 3 mm, thinnest pachymetry, the difference between central and thinnest pachymetry (CP - TP), vertical decentration of the thinnest point, maximum posterior elevation, and anterior elevation of the thinnest point were compared in both groups. RESULTS: We analyzed 128 Orbscans of 128 Asian patients. There were 24 FFKC eyes and 104 control eyes. SCORE was negative in 7 eyes (false negative) in the FFKC group and was positive in 2 eyes in the control group (false positive). The sensitivity was 70.8%, specificity 98.1%, positive predictive value 89.5%, and negative predictive value 93.6%. Irregularity at 3 mm, thinnest pachymetry, CP - TP, thinnest point decentration, maximum posterior elevation, and anterior elevation of the thinnest point were significantly different in both groups. CONCLUSIONS: The SCORE Analyzer algorithm, developed and validated in eyes of white subjects, was found to be valid and consistent in Asian eyes, showing good sensitivity and specificity in FFKC detection, and to be useful in objectively identifying cases at risk of post-LASIK keratectasia.

Summary of recommendations for the haemodynamic and angiographic assessment of the pulmonary circulation. Joint statement of the Polish Cardiac Society's Working Group on Pulmonary Circulation and Association of Cardiovascular Interventions.

Right heart catheterisation (RHC) is the 'gold standard' for haemodynamic assessment of the pulmonary circulation. For the diagnosis of pulmonary hypertension (PH), the guidelines of the European Society of Cardiology require a mean pulmonary arterial pressure ≥ 25 mm Hg to be confirmed by direct haemodynamic measurement. Additionally, RHC provides a lot of valuable information about the differential diagnosis and severity of PH, and also helps determine the patient's prognosis. Acute vasoreactivity testing performed in patients with pulmonary arterial hypertension is intended to identify the group of patients who should be treated with calcium channel blockers. Patients referred for heart transplantation require advanced pulmonary vascular disease to be ruled out either on resting examination or during vasoreactivity testing. RHC is a component of such interventional procedures as balloon atrial septostomy, closure of intracardiac shunts in congenital heart and great vessel defects, valvuloplasty for pulmonary valve stenosis, and pulmonary angioplasty. Pulmonary angiography is an examination recommended when selecting patients for pulmonary endarterectomy or balloon pulmonary angioplasty in thromboembolic PH. Due to the dynamic growth in the number of patients diagnosed with and treated for PH in Poland, the Boards of the Polish Cardiac Society's Working Group on Pulmonary Circulation and Association of Cardiovascular Interventions have undertaken a joint project to develop recommendations to standardise guidelines for RHC procedure, acute vasoreactivity testing and pulmonary angiography at cardiac wards and haemodynamic laboratories in Poland. This document has been prepared by experts delegated by the Working Group on Pulmonary Circulation and the Association of Cardiovascular Interventions, and subsequently approved by the Boards of both organs of the Polish Cardiac Society.

Can neurophysiological assessment improve timing of intervention in posthaemorrhagic ventricular dilatation?

OBJECTIVE: Intraventricular haemorrhage is still the most common cause of brain lesion in preterm infants and development of a posthaemorrhagic ventricular dilatation (PHVD) can lead to additional neurological sequelae. Flash visual evoked potentials (fVEP) and amplitude-integrated electroencephalography (aEEG) are non-invasive neurophysiological monitoring tools. The aim of the study was to evaluate fVEPs and aEEGs in preterm infants with progressive PHVD prior to and after neurosurgical intervention for cerebrospinal fluid removal and to correlate the findings with severity of ventricular dilatation. DESIGN: fVEPs and aEEGs were performed weekly in infants with developing PHVD. As soon as the ventricular index reached the 97th percentile recordings were performed twice a week. METHODS: 17 patients admitted to the neonatal intensive care unit of the Medical University of Vienna who developed progressive PHVD were evaluated using fVEP and aEEG until and after reduction of intracranial pressure by placement of an external ventricular drainage. RESULTS: In all 17 cases (100%) wave latencies of fVEP increased above normal range and aEEG showed increased suppression in 13 patients (76%) with increasing ventricular dilatation. Both methods showed normalisation of patterns mostly within a week of successful therapeutic intervention (mean 8.5 days). Both changes in fVEP latencies and aEEG background patterns were detected before clinical signs of elevated intracranial pressure occurred. In only 10 patients (58.8%) ventricular width exceeded the 97th percentile+4 mm. CONCLUSIONS: fVEP and aEEG are useful additional tools for the evaluation of preterm infants with progressive PHVD.

Quantitative assessment of asymmetric aortic dilation with valve-related aortic disease.

RATIONALE AND OBJECTIVES: Previous work suggests that ascending aortic (AsAo) dilation can be asymmetric and is potentially related to valve-related blood flow abnormalities. The aim of this study was to investigate the relationship between the aortic valve and AsAo dilation using a quantitative, three-dimensional assessment of aortic shapes. MATERIALS AND METHODS: Computed tomographic and magnetic resonance images of the thorax were retrospectively reviewed. Four groups with aortic dilation were studied: those with tricuspid aortic valves (TAVs) with and without stenosis and those with bicuspid aortic valves (BAVs) with and without stenosis. Controls had either TAVs or BAVs but no aortic stenosis or dilation. In additional to standard orthogonal diameters, a unique measurement of AsAo asymmetry was used: the ratio of the greater to lesser curvatures measured using three-dimensional reformats in a "candy-cane" orientation. RESULTS: A total of 105 patients were identified. Ratios of greater to lesser curvature in patients with aortic dilation and nonstenotic TAVs were not significantly different from those in controls (1.69 vs 1.55, P > .20), but the asymmetry reflected by this ratio was markedly increased in patients with aortic dilation and stenotic TAVs (1.94, P < .001). Patients with aortic dilation and BAVs had significantly elevated ratios regardless of the status of the aortic valve (1.96 for nonstenotic and 2.05 for stenotic vs 1.53 for controls, P < .001). CONCLUSIONS: Asymmetric AsAo dilation with relative bulging of the greater curvature is linked to aortic stenosis, but it is also seen with nonstenotic BAVs. This suggests that the hemodynamic forces that contribute to aortic dilation are not fully revealed by conventional assessment of the aortic valve.

A complex case management system provides optimal care for all patients.

PURPOSE: To describe the complex case management system developed by Optical Express, a large corporate provider of laser vision correction, and to detail the benefits this system offers for managing the surgical complications of laser vision correction. METHODS: The classification scheme Optical Express uses to categorize surgical complications is described, and the various pathways patients can take through the complex case system are detailed. This process is illustrated with a case study describing the treatment of a patient with postoperative LASIK ectasia. The benefits of the complex case system are also discussed. RESULTS: A total of 1363 eyes were treated in the complex case management system during the 5-year period between January 1, 2004 and December 31, 2008. These 1363 eyes represent a small fraction (0.45%) of the approximately 300,000 eyes treated during this period. The Optical Express complex case management system organizes complications based on severity and urgency. Grade A complications (40 eyes, 2.9% of all complications) are the most serious and urgent, followed by grade B (327 eyes, 24.0%), and grade C (996 eyes, 73.1%). For each complication, the patient's journey through the complex case system starts with an evaluation by an optometrist. Depending on the severity of the complication, the patient may then be referred to the treating surgeon, a regional complex case surgeon, or an external consultant. A complex case manager coordinates care and logistics throughout this process. CONCLUSIONS: The complex case management system used by Optical Express provides clinical care and support for patients who experience a surgical complication.

Risk assessment for ectasia after corneal refractive surgery.

PURPOSE: To analyze the epidemiologic features of ectasia after excimer laser corneal refractive surgery, to identify risk factors for its development, and to devise a screening strategy to minimize its occurrence. DESIGN: Retrospective comparative and case-control study. PARTICIPANTS: All cases of ectasia after excimer laser corneal refractive surgery published in the English language with adequate information available through December 2005, unpublished cases seeking treatment at the authors' institution from 1998 through 2005, and a contemporaneous control group who underwent uneventful LASIK and experienced a normal postoperative course. METHODS: Evaluation of preoperative characteristics, including patient age, gender, spherical equivalent refraction, pachymetry, and topographic patterns; perioperative characteristics, including type of surgery performed, flap thickness, ablation depth, and residual stromal bed (RSB) thickness; and postoperative characteristics including time to onset of ectasia. MAIN OUTCOME MEASURES: Development of postoperative corneal ectasia. RESULTS: There were 171 ectasia cases, including 158 published cases and 13 unpublished cases evaluated at the authors' institution. Ectasia occurred after LASIK in 164 cases (95.9%) and after photorefractive keratectomy (PRK) in 7 cases (4.1%). Compared with controls, more ectasia cases had abnormal preoperative topographies (35.7% vs. 0%; P<1.0x10(-15)), were significantly younger (34.4 vs. 40.0 years; P<1.0x10(-7)), were more myopic (-8.53 vs. -5.09 diopters; P<1.0x10(-7)), had thinner corneas before surgery (521.0 vs. 546.5 microm; P<1.0x10(-7)), and had less RSB thickness (256.3 vs. 317.3 microm; P<1.0x10(-10)). Based on subgroup logistic regression analysis, abnormal topography was the most significant factor that discriminated cases from controls, followed by RSB thickness, age, and preoperative corneal thickness, in that order. A risk factor stratification scale was created, taking all recognized risk factors into account in a weighted fashion. This model had a specificity of 91% and a sensitivity of 96% in this series. CONCLUSIONS: A quantitative method can be used to identify eyes at risk for developing ectasia after LASIK that, if validated, represents a significant improvement over current screening strategies.

Differential diagnosis of the infundibular dilation and aneurysm of internal carotid artery: assessment with fusion imaging of 3D MR cisternography/angiography.

Fusion imaging of 3D MR cisternography/angiography was used for the assessment of the vascular bulging finding detected by MR angiography from the viewpoint of the outer wall configuration of the corresponding internal carotid artery depicted by MR cisternography. With a fusion image, useful information was obtained to distinguish an infundibular dilation and enlarged origin of the normal posterior communicating artery from an aneurysm. This imaging technique can be a feasible addition to a noninvasive screening of cerebrovascular lesions with MR angiography alone.

Assessment of vertebral scalloping in neurofibromatosis type 1 with plain radiography and MRI.

AIM: To evaluate vertebral scalloping in patients with neurofibromatosis type 1 (NF-1) and spinal deformity using plain radiographs and magnetic resonance imaging (MRI), and to determine the possible aetiological association with neurofibromas, dural ectasia and lateral meningocoeles. MATERIAL AND METHODS: Nineteen patients with NF-1, who had full spine radiographs and whole-spine MRI, were retrospectively reviewed. Dystrophic features and their relationship to the curve were recorded from radiographs. A comparison was then made between the dystrophic features evident on radiographs and adjacent soft-tissue abnormalities identified on MRI. RESULTS: Dystrophic changes were documented in 16 patients on plain radiographs and in all patients on MRI. Rib pencilling was the most common finding on radiographs. In 80% of the cases with scoliosis, scalloping was seen on the concavity of the curvature. In all patients with kyphoscoliosis, scalloping was contiguous to the apex of kyphosis. Twenty-four areas of scalloping were identified on MRI. Scalloping usually developed in the concavity of the scoliotic curve or at levels unrelated to the curve. Scalloping was evident in combination with dural ectasia or neurofibroma in 15 cases. The presence of dural ectasia was confirmed in 75% of the cases of posterior scalloping and in 25% of those of lateral scalloping. The presence of neurofibromas was recognized in 25% of the cases of anterior or lateral scalloping. Dural ectasia was identified in two patients without associated scalloping. Lateral meningocoeles were not related to the development of scalloping. CONCLUSION: Whereas posterior scalloping was commonly associated with dural ectasia, anterior and lateral scalloping were commonly the result of primary mesodermal dysplasia.

Importance of dural ectasia in phenotypic assessment of Marfan's syndrome.

BACKGROUND: Early identification of Marfan's syndrome is fundamental in the prevention of aortic dilatation, but the wide phenotypic expression of the disorder makes the clinical diagnosis very difficult. Dural ectasia has been classified as a major diagnostic criterion; however, its prevalence is not known. We aimed to identify the true prevalence of dural ectasia in Marfan's syndrome, and to investigate its relation to aortic pathology. METHODS: A magnetic-resonance-imaging (MRI) study of the thoracic aorta and of the lumbosacral spine was done in an inclusive series of 83 patients with Marfan's syndrome to assess the presence and degree of dural ectasia and aortic involvement; 12 patients were younger than 18 years. 100 individuals who underwent MRI of the lumbar spine for routine clinical indications represented the control group; none of them had any potential causes for dural ectasia. FINDINGS: Dural ectasia was identified in 76 (92%) patients and none of the control group. The severity of dural ectasia was related to age; the mean (SD) age of patients with mild dural ectasia was 26 years (14) whereas that of those with severe disease (meningocele) was 36 years (9) (p=0.038). 11 of 12 patients younger than 18 years had dural ectasia. No association was found between aortic dilatation and dural ectasia. INTERPRETATION: Dural ectasia is a highly characteristic sign of Marfan's syndrome, even at an early age.

Cardiac assessment of veteran endurance athletes: a 12 year follow up study.

OBJECTIVES: Sustained aerobic dynamic exercise is beneficial in preventing cardiovascular disease. The effect of lifelong endurance exercise on cardiac structure and function is less well documented, however. A 12 year follow up of 20 veteran athletes was performed, as longitudinal studies in such cohorts are rare. METHODS: Routine echocardiography was repeated as was resting, exercise, and 24 hour electrocardiography. RESULTS: Nineteen returned for screening. Mean (SD) age was 67 (6.2) years (range 56-83). Two individuals had had permanent pacemakers implanted (one for symptomatic atrial fibrillation with complete heart block, the other for asystole lasting up to 15 seconds). Only two athletes had asystolic pauses in excess of two seconds compared with seven athletes in 1985. Of these seven, five had no asystole on follow up. Two of these five had reduced their average running distance by about 15-20 miles a week. One athlete sustained an acute myocardial infarction during a competitive race in 1988. Three athletes had undergone coronary arteriography during the 12 years of follow up but none had obstructive coronary artery disease. Ten of 19 (53%) had echo evidence of left ventricular hypertrophy in 1997 but only two (11%) had left ventricular dilatation. Ten athletes had ventricular couplets on follow up compared with only two in 1985. CONCLUSIONS: Although the benefits of moderate regular exercise are undisputed, high intensity lifelong endurance exercise may be associated with altered cardiac structure and function. These adaptations to more extreme forms of exercise merit caution in the interpretation of standard cardiac investigations in the older athletic population. On rare occasions, these changes may be deleterious.

Idiopathic megarectum in adults. An assessment of manometric and radiologic variables.

Outlet obstruction is thought to be one of the major factors responsible for idiopathic constipation. However, outlet obstruction itself may be due to several mechanisms. Among these, the presence of a megarectum is a leading one. Pathophysiological studies in adult patients with idiopathic megarectum are scarce. We studied by manometric and defecographic means 15 adult subjects with idiopathic megarectum and severe chronic constipation. Twenty-five healthy volunteers of both sexes acted as controls. Manometric variables showed significant differences between patients and controls with respect to internal anal sphincter pressure (P = 0.02), minimum relaxation volume (P < 0.001), defecatory sensory threshold (P < 0.001), mean rectal tolerable volume (P < 0.001), and rectal compliance (P < 0.001). An altered response to straining was observed in 46.6% of patients and in 12% of controls (P < 0.04); the ability to expel a 50-ml balloon per anum was 13.3% in patients and 100% in controls (P < 0.001). Although all patients opened the anorectal angle and had descent of the pelvic floor, thereby confirming an adequate expulsion effort, evacuation of contrast material appeared extremely difficult. In fact, no subject was able to expel more than 30% of the rectal contents during fluoroscopic screening. These results confirm previous hypotheses that idiopathic megarectum displays features of a neuropathic process as an underlying mechanism. Further studies are needed that also take into consideration the muscle tone component of the rectum in these patients.

Fast imaging MR assessment of ureterohydronephrosis during pregnancy.

PURPOSE: to assess the value of the fast imaging sequence called RARE-MR-Urography (RMU) for the diagnosis of pathologic ureterohydronephrosis during pregnancy. MATERIALS AND METHODS: 15 pregnant women with an acute flank pain were examined with RMU. Results were compared with those of ultrasonography (US), X-rays, and the evolution of symptoms. RESULTS: the accuracy of RMU in the detection of urinary tract dilatation and the localization of the level of obstruction was excellent (100%). The determination of the type of obstruction, intrinsic vs. extrinsic, was always exact. RMU alone cannot specify the exact nature of the intrinsic obstruction. Ultrasonography gave less sensitive information in terms of level (60%) and type of obstruction (53%). CONCLUSION: RMU is able to differentiate a physiological from a pathologic ureterohydronephrosis during pregnancy. It could be considered as a procedure of choice for special cases when US failed to establish this differential diagnosis.

Neurosonographic assessment of twin pairs in the perinatal period.

Twins have higher rates of perinatal mortality, prematurity and its complications, low birth weight, intrauterine growth retardation, congenital anomalies and long-term developmental morbidity. In 31 twin pairs we evaluated the incidence and severity of peri-intraventricular hemorrhage (PIVH) and post-hemorrhagic ventricular dilatation. On ultrasonography minor PIVH (grades I and II) was observed in 26% of A twins and 25% of B twins (p less than 0.5). Major PIVH (grades III and IV) was less common, occurring in 3% of A twins and 6% of B twins (p less than 0.5). Ventriculomegaly, mostly regressive was equally distributed between the two groups of babies. From these results it can be concluded that with efficient antenatal care and skillful perinatal management of twin pregnancy, the incidence of major perinatal neurological complications such as PIVH and ventriculomegaly are not higher in the second-born twin.

Diuretic renography in the assessment of urinary tract dilatation in children.

We present our experience with diuretic renography in the evaluation of dilatation of the urinary tract in 27 children. The usefulness of this method along with its pitfalls are discussed.

Dilated episcleral arteries--a significant physical finding in assessment of patients with cerebrovascular insufficiency.

Dilated episcleral vessels associated with ipsilateral internal carotid artery occlusions have been previously reported though not widely appreciated. These ocular changes have been presumed to be manifestations of ocular ischemia. The authors have recently encountered this sign in seven patients and in none was there evidence of ocular ischemia. In addition to an ipsilateral internal carotid artery occlusion, arteriograms demonstrated that the major source of blood supply to the homolateral cerebral hemisphere was by retrograde flow through markedly enlarged ophthalmic arteries filled in retrograde fashion from dilated external carotid collateral channels in the orbit. This association of dilated episcleral arteries as a sign of increased orbital blood flow and the major source of collateral blood supply to the homolateral cerebral hemisphere has not been previously reported. We reemphasize the importance of a careful examination of the episcleral vessels in patients suspected of having internal carotid artery occlusions.