The Impact of Kidney/Pancreas Transplantation on Peripheral Arterial Disease.

INTRODUCTION: It is unclear whether kidney/pancreas (KP) transplantation will prevent the progression of peripheral arterial disease (PAD) in patients with insulin dependent diabetes (IDDM) and end-stage renal disease. We sought to determine the pre- and posttransplant prevalence of symptomatic PAD and changes in carotid artery intima-media thickness (IMT) in KP recipients. METHODS: In this single center study, outcomes were compared between KP recipients with and without a history of PAD. A subset of recipients underwent pre- and posttransplant IMT measurements. RESULTS: Among the study group (N = 107), 18 (17%) recipients admitted to a pretransplant history of symptomatic PAD, comprised 11 foot infections and 7 amputations (5 minor and 2 major). Baseline characteristics of age, gender, race, years of diabetes, dialysis history, smoking history, years of hypertension, and history of coronary artery disease (CAD) were equivalent between PAD and non-PAD cohorts. At a median follow-up of 60 months (IQR: 28, 110), 16 (15%) KP recipients had suffered a PAD event. In multivariate analysis, a pretransplant history of PAD (hazard ratio [HR] 9.66, p < 0.001) and CAD (HR 3.33, p = 0.04) were independent predictors of posttransplant PAD events. Among a subset of 20 recipients (3 with PAD), mean IMT measurements pretransplant and at a median of 24 (range 18-24) months posttransplant, showed no evidence of disease progression. CONCLUSION: Based on IMT measurements and clinical results, KP transplantation stabilized PAD in most patients, but did not alter outcomes of symptomatic PAD recipients. A pretransplant history of PAD and CAD was an independent predictor of posttransplant PAD events.

Laterality of deep white matter hyperintensities correlates with basilar artery bending and vertebral artery dominance.

AIM: To investigate whether vertebrobasilar geometry contributes to the presence, severity, and laterality of white matter hyperintensities (WMH). METHODS: We retrospectively reviewed 290 cerebral scans of patients who underwent time-of-flight and fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) between 2017 and 2018. WMH were counted, localized, and grouped according to laterality on the FLAIR sequence. A 3D mesh of the posterior circulation was reconstructed (with ITK SNAP software) and the morphology of the vertebrobasilar system analyzed with an in-house software written in Python. RESULTS: Patients were assigned into a group with WMH (n=204) and a group without WMH (n=86). The severity of WMH burden was mainly affected by age and hypertension, while the localization of the WMH (or laterality) was mainly affected by the vertebrobasilar system morphology. Basilar artery morphology only affected the parieto-occipital region significantly if both posterior communicating arteries were hypoplastic or absent. The dominant vertebral artery and basilar artery curve had an opposite directional relationship. CONCLUSIONS: An unequal vertebral artery flow is an important hemodynamic contributor to basilar bending. Increased basilar artery curvature and increased infratentorial WMH burden may signal inadequate blood flow and predict cerebrovascular events.

Ultrasound and dynamic functional imaging in vascular cognitive impairment and Alzheimer's disease.

BACKGROUND: The vascular contributions to neurodegeneration and neuroinflammation may be assessed by magnetic resonance imaging (MRI) and ultrasonography (US). This review summarises the methodology for these widely available, safe and relatively low cost tools and analyses recent work highlighting their potential utility as biomarkers for differentiating subtypes of cognitive impairment and dementia, tracking disease progression and evaluating response to treatment in various neurocognitive disorders. METHODS: At the 9th International Congress on Vascular Dementia (Ljubljana, Slovenia, October 2015) a writing group of experts was formed to review the evidence on the utility of US and arterial spin labelling (ASL) as neurophysiological markers of normal ageing, vascular cognitive impairment (VCI) and Alzheimer's disease (AD). Original articles, systematic literature reviews, guidelines and expert opinions published until September 2016 were critically analysed to summarise existing evidence, indicate gaps in current knowledge and, when appropriate, suggest standards of use for the most widely used US and ASL applications. RESULTS: Cerebral hypoperfusion has been linked to cognitive decline either as a risk or an aggravating factor. Hypoperfusion as a consequence of microangiopathy, macroangiopathy or cardiac dysfunction can promote or accelerate neurodegeneration, blood-brain barrier disruption and neuroinflammation. US can evaluate the cerebrovascular tree for pathological structure and functional changes contributing to cerebral hypoperfusion. Microvascular pathology and hypoperfusion at the level of capillaries and small arterioles can also be assessed by ASL, an MRI signal. Despite increasing evidence supporting the utility of these methods in detection of microvascular pathology, cerebral hypoperfusion, neurovascular unit dysfunction and, most importantly, disease progression, incomplete standardisation and missing validated cut-off values limit their use in daily routine. CONCLUSIONS: US and ASL are promising tools with excellent temporal resolution, which will have a significant impact on our understanding of the vascular contributions to VCI and AD and may also be relevant for assessing future prevention and therapeutic strategies for these conditions. Our work provides recommendations regarding the use of non-invasive imaging techniques to investigate the functional consequences of vascular burden in dementia.

Environmental Factors Responsible for Variability of Hepatic Vein Flow: A Doppler Assessment in Healthy Twins.

Doppler interrogation studies of the liver blood flow indicate altered hepatic vein waveforms in association with impaired hepatocellular function. However, little is known about the mechanisms responsible for variations of these parameters in the absence of disease. We aimed to investigate the contribution of heritable and environmental factors to the physiological variability of hepatic vein flow in a twin cohort. Two hundred twenty-eight healthy adult Hungarian twins (69 monozygotic, 45 same-sex dizygotic pairs) underwent Doppler sonography of the hepatic vein. Age- and sex-adjusted heritability of the highest velocity (amplitude of S wave) of hepatic vein flow was negligible. Shared environment contributed to 33% (95% CI, 16%-51%), and unshared environment was responsible for the largest portion (67%; 95% CI, 49%-84%) of the variance. Duration of sports activities was significantly (P < 0.05) related to the magnitude of hepatic vein flow, while other risk factors and lifestyle characteristics had no significant influence. The data suggest that genetic factors have little impact on the parameters of hepatic venous blood flow. The variability observed in healthy twins by the Doppler interrogation can be explained by the effect of unshared environmental components primarily related to regular physical activity. These findings underscore the importance of unique environments in physiological variations of hepatic venous blood flow.

Modest genetic influence on bronchodilator response: a study in healthy twins.

AIM: To determine the reasons for large standard deviation of bronchodilator response (BDR) and establish whether there is a potential heritable component in healthy subjects. METHODS: 67 monozygotic and 42 dizygotic adult twin pairs were assessed for bronchodilator response (% change in FEV1 after inhaling 400 µg salbutamol). Univariate quantitative genetic modeling was performed. RESULTS: Multiple regression modeling showed a significant association between BDR and sex and baseline FEV1 (P<0.05), while no association was found with smoking habits, body mass index, or age. Within pair correlation in monozygotic twins was modest (0.332), but higher than in dizygotic twins (0.258). Age-, sex-, and baseline FEV1-adjusted genetic effect accounted for 14.9% (95% confidence interval, CI 0%-53.1%) of the variance of BDR, shared environmental effect for 18.4% (95% CI 0%-46.8%), and unshared environmental effect for 66.8% (95% CI 46.8%-88.7%). CONCLUSION: Our twin study showed that individual differences in BDR can be mostly explained by unshared environmental effects. In addition, it is the first study to show low, insignificant hereditary influences, independently from sex, age, and baseline FEV1.

Heritability of venous biomechanics.

OBJECTIVE: Altered venous biomechanics may contribute to the pathogenesis of venous diseases, and their heritability is less known. METHODS AND RESULTS: Seventy-eight monozygotic twin pairs (aged 42.4 ± 16.8 years) and 24 same-sex dizygotic twin pairs (aged 50.5 ± 16.1 years) were examined. Anteroposterior and mediolateral diameters of the common femoral vein were measured by ultrasonography. Measurements were made both in supine and in standing body positions, with or without controlled forced expiration (Valsalva test). High correlation of diameter, capacity, and distensibility values was found between twin pairs. The univariate heritability (A), shared (C), and unshared (E) environmental effects model has shown 39.3% genetic component of the variance of low pressure, 37.9% of high-pressure venous capacity, and 36.4% of maximal capacity changes, even after elimination of sex, age, and body weight effects. Bivariate Cholesky analysis revealed substantial covariance of inherited body weight and venous capacity components (57.0%-81.4%). CONCLUSIONS: Femoral vein capacity and elasticity depend ≈30% to 40% on genetic factors, and this value in the standing body position can reach 50%. A relatively high genetic covariance was found between weight and femoral vein capacity and elasticity. Our work might yield some new insights into the inheritance of venous diseases that are associated with altered venous biomechanics and help elucidate the involved genes.

Blood flow velocity changes in anterior cerebral arteries during cognitive tasks performance.

OBJECTIVE: Transcranial Doppler sonography (TCD) enables monitoring of blood flow velocities (BFVs) in basal cerebral arteries during different cognitive tasks performance with great temporal resolution. So far, BFVs changes during mental activity were monitored primarily in middle cerebral arteries (MCAs) and little is known about these changes in anterior cerebral arteries (ACAs). AIM: To determine the effect of different cognitive tasks performance on BFV changes and hemispheric dominance in ACAs and to assess the most suitable activation test for monitoring of BFV changes in ACAs. METHODS: Fourteen right-handed, healthy subjects aged 20-26 were included in the study. BFVs in both ACAs were recorded simultaneously during performance of cognitive tasks designed to activate frontal lobes: phonemic verbal fluency test (pVFT), Stroop tests and Trail Making Tests (TMTs). RESULTS: A statistically significant BFV increase was recorded in both ACAs during performance of all cognitive tasks. Statistically significant right ACA dominance was found during performance of pVFT and TMTB. The most significant BFV increase was obtained during performance of TMTB. CONCLUSION: Our result addressed cognitive tests with great activation potential for monitoring of ACAs that might be used in distinguishing of healthy individuals and patients with neurovascular or neurodegenerative diseases.

Genetic influence on capillary oxygen saturation: a twin study.

BACKGROUND: While heritability has been shown for daytime sleepiness, the heritability of daytime capillary oxygen saturation (SpO(2)) has not been described in detail. Our aim was to estimate the role of genes and environmental factors--both shared and unshared--in the variation of daytime SpO(2). METHODS: A total of 193 adult healthy twin pairs (138 monozygotic, 55 dizygotic) were recruited in Hungary and in the United States [age = 43.6 ± 15.6 years (mean ± SD)]. SpO(2) was measured by pulse oximetry. Univariate quantitative genetic modeling was performed to decompose the phenotypic variance of the considered parameter into heritability (A), shared (C), and unshared (E) environmental effects. RESULTS: SpO(2) twin correlation in monozygotic twins was stronger than in dizygotic twins (0.30 and -0.15, respectively, p < 0.05). Age-, sex-, country-, and body mass index-adjusted genetic effects accounted for 26 % (95 % CI 10, 45 %) of the variance of SpO(2), and the unshared environmental component explained the remaining 74 % (95 % CI 59, 89 %). No shared environmental influence on SpO(2) was detected. The heritability of SpO(2) was not different between smokers and nonsmokers. CONCLUSION: In summary, individual differences in daytime SpO(2) are explained by genetic and unshared environmental effects. The strong unshared environmental influence highlights the role of prevention of known environmental risk factors.

Unusual Evidence of Fat Embolism in the Subclavian Vein Detected by High-Intensity Transient Signals.

Fat emboli may occur in patients after traumatic fractures or orthopedic procedures; however, their clinical detection is a very rare finding. Here, we describe a 77-year-old female who was admitted to the emergency department with a fracture of the right humerus. We diagnosed fat embolism after an ultrasound of the right subclavian vein. The embolism was detected by high-intensity transient signals present on the spectral Doppler. While these signals are well known for microembolization in transcranial Doppler, to our knowledge this is the first case report in the medical literature to observe and describe high-intensity transient signals seen in the upper extremities by spectral Doppler. Although it is unusual to detect a fat embolism in transit, we believe clinicians should be aware of this finding, particularly when evaluating high-risk patients.

Internal Carotid Artery Hypoplasia Misidentified as Internal Carotid Artery Dissection.

Agenesis or hypoplasia of the internal carotid artery (ICA) may easily be confused with dissection or occlusion. We report a case of a 24-year-old female with complaint of acute left-hand hypoesthesia and a history of occasional intermittent numbness of her right hand with myoclonic jerking. Because previous imaging studies over 2 years were interpreted as occlusion of the left ICA secondary to carotid dissection, the treating physician had prescribed anticoagulant therapy. During transcranial Doppler (TCD) examination, the spectral waveform was unexpectedly normal, prompting a repeat review of all imaging due to the TCD results. Magnetic resonance angiography (MRA) revealed the same "flame-like" appearance of the ICA origin. Late-phase digital subtraction angiography showed a small caliber cervical ICA (occluded at the skull base). Computed tomography demonstrated absence of the carotid canal, confirming an absent intracranial portion of the ICA and establishing a correct diagnosis of left internal carotid hypoplasia. Vascular ultrasound and TCD examinations are noninvasive and inexpensive tools that can improve the interpretation and understanding of the clinical significance of other "static" radiographic tests (MRA, digital subtraction angiography ). An accurate diagnosis is essential to avoid risky, aggressive treatment, such as anticoagulation for an "absent" dissection.

The intracranial effects of flow reversal during transcarotid artery revascularization.

Background: This study aimed to assess intraoperative cerebral hemodynamic responses and embolic events during transcarotid artery revascularization via transcranial Doppler, near-infrared spectroscopy, and bispectral index monitoring. Methods: Twelve patients (7 males, 5 females; mean age: 72.8±9.0 years; range, 63 to 91 years) undergoing transcarotid artery revascularization with simultaneous transcranial Doppler, near-infrared spectroscopy, and bispectral index monitoring were analyzed in this retrospective study between September 2017 and December 2019. The mean flow velocity and pulsatility index of the middle cerebral artery, alongside near-infrared spectroscopy and bispectral index values, before flow reversal, during flow reversal, and after flow reversal phases were investigated. The presence and frequency of high-intensity transient signals were recorded to evaluate embolic incidents. Results: Significant reductions in middle cerebral artery mean flow velocity were noted during flow reversal (40.58±10.57 cm/sec to 20.58±14.34 cm/sec, p=0.0004), which subsequently returned to and exceeded baseline values after flow reversal cessation (53.33±17.69 cm/sec, p=0.0005). Near-infrared spectroscopy (71±4.4% to 66±6.2%) and bispectral index (45.71±8.5 to 40.14±8.1) values mirrored these hemodynamic changes, with notable decreases during flow reversal, and recoveries after flow reversal. The highest concentration of high-intensity transient signals was observed during stent deployment, signifying a critical embolic phase. No perioperative neurological complications or other significant adverse events were documented. Conclusion: Transcranial Doppler, near-infrared spectroscopy, and bispectral index effectively monitor cerebral hemodynamics and embolic potential during transcarotid artery revascularization, providing real-time data crucial for optimizing perioperative management. These findings underscore the clinical value of multimodal monitoring in improving patient outcomes in transcarotid artery revascularization procedures.

Genetic and environmental variance of renal parenchymal thickness: a twin study.

AIM: To estimate heritability and environmental effects on renal parenchymal thickness. METHODS: In this twin study, renal parenchymal thickness of 98 Hungarian healthy adult twin pairs (68 monozygotic, 30 dizygotic) without kidney disease was measured bilaterally using renal ultrasound with Esaote MyLab 70X ultrasound machine with low-frequency curved transducers (1-8 MHz). RESULTS: In both monozygotic and dizygotic group there were more women (76.5%). Mean right and left renal parenchymal thickness was 1.32±0.33 cm and 1.62±0.31 cm, respectively. Age- and sex-adjusted heritability of renal parenchymal thickness was 0.0% (95% confidence interval, 0.0 to 50.2%), shared and unshared environmental factor was 30.2% (4.1 to 55.9%) and 69.8% (45.8 to 89.5%), respectively. CONCLUSION: This study shows a negligible role of heritability and an important role of environmental effects in developing renal parenchymal thickness, emphasizing the importance of lifestyle for primary prevention.

Evidence for a strong genetic influence on carotid plaque characteristics: an international twin study.

BACKGROUND AND PURPOSE: Few family studies reported moderate genetic impact on the presence and scores of carotid plaques. However, the heritability of carotid plaque characteristics remains still unclear. Twin studies more reliably estimate the relative contribution of genes to these traits in contrast to family study design. METHODS: One hundred ninety-two monozygotic and 83 dizygotic adult twin pairs (age 49±15 years) from Italy, Hungary, and the United States underwent B-mode and color Doppler ultrasound of bilateral common, internal, and external carotid arteries. RESULTS: Age-, sex-, and country-adjusted heritability was 78% for the presence of carotid plaque (95% CI, 55%-90%), 74% for plaque echogenicity (hypoechoic, hyperechoic, or mixed; 95% CI, 38%-87%), 69% for plaque size (area in mm2 in longitudinal plane; 50 percentile; 95% CI, 16%-86%), 74% for plaque sidedness (unilateral or bilateral; 95% CI, 25%-90%), 74% for plaque numerosity (95% CI, 26%-86%), 68% (95% CI, 40%-84%), and 66% (95% CI, 32%-90%) for the presence of plaque in carotid bulbs and proximal internal carotid arteries. No role of shared environmental factors was found. Unique environmental factors were responsible for the remaining variance (22%-34%). Controlling for relevant covariates did not change the results significantly. CONCLUSIONS: The heritability of ultrasound characteristics of carotid plaque is high. Unshared environmental effects account for a modest portion of the variance. Our findings should stimulate the search for genes responsible for these traits.

The argatroban and tissue-type plasminogen activator stroke study: final results of a pilot safety study.

BACKGROUND AND PURPOSE: Argatroban is a direct thrombin inhibitor that safely augments recanalization achieved by tissue-type plasminogen activator (tPA) in animal stroke models. The Argatroban tPA Stroke Study was an open-label, pilot safety study of tPA plus Argatroban in patients with ischemic stroke due to proximal intracranial occlusion. METHODS: During standard-dose intravenous tPA, a 100-µg/kg bolus of Argatroban and infusion for 48 hours was adjusted to a target partial thromboplastin time of 1.75× baseline. The primary outcome was incidence of significant intracerebral hemorrhage defined as either symptomatic intracerebral hemorrhage or Parenchymal Hematoma Type 2. Recanalization was measured at 2 and 24 hours by transcranial Doppler or CT angiography. RESULTS: Sixty-five patients were enrolled (45% men, mean age 63±14 years, median National Institutes of Health Stroke Scale=13). The median (interquartile range) time tPA to Argatroban bolus was 51 (38-60) minutes. Target anticoagulation was reached at a median (interquartile range) of 3 (2-7) hours. Significant intracerebral hemorrhage occurred in 4 patients (6.2%; 95% CI, 1.7-15.0). Of these, 3 were symptomatic (4.6%; 95% CI, 0.9-12.9). Seven patients (10%) died in the first 7 days. Within the 2-hour monitoring period, transcranial Doppler recanalization (n=47) occurred in 29 (61%) patients: complete in 19 (40%) and partial in another 10 (21%). CONCLUSIONS: The combination of Argatroban and intravenous tPA is potentially safe in patients with moderate neurological deficits due to proximal intracranial arterial occlusions and may produce more complete recanalization than tPA alone. Continued evaluation of this treatment combination is warranted. CLINICAL TRIAL REGISTRATION: URL: www.clinicaltrials.gov. Unique identifier: NCT00268762.

Endovascular management of carotid artery stenosis secondary to sclerosing mediastinitis.

Sclerosing mediastinitis is a rare, progressive condition characterized by extensive fibrotic reaction. We report the first known case of symptomatic, extrinsic compression of the carotid artery by fibrotic extension of sclerosing mediastinitis. A 54-year-old woman began experiencing neurologic symptoms from extension of a known mediastinal mass resulting in 70% to 79% stenosis of the right internal carotid artery. The stenosis was treated with endovascular stenting. Completion angiogram revealed a good result with <10% residual stenosis. At 18-month follow-up, the patient was symptom free without evidence of re-stenosis. Endovascular therapy provides a novel and durable solution in the midterm to this very rare problem.

Heritability of non-alcoholic fatty liver disease and association with abnormal vascular parameters: a twin study.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has been linked to increased cardiovascular morbidity. However, genetic factors have an unclear role in this condition. AIMS: To analyse heritability of NAFLD and its association with abnormal vascular parameters in a large twin cohort. METHODS: Anthropometric and lipid metabolic parameters were obtained from 208 adult Hungarian twins (63 monozygotic and 41 dizygotic pairs; 58 men and 150 women; age 43.7 ± 16.7 years). B-mode ultrasonography was performed to detect steatosis and categorize severity. Brachial and aortic augmentation indices and aortic pulse wave velocity were assessed using oscillometry (TensioMed Arteriograph). Carotid intima media thickness (IMT) was measured using ultrasonography on the proximal common, distal common and internal carotid arteries. RESULTS: NAFLD was identified in 47 subjects (22.6%), of which 44 (93.6%) had mild and 3 (6.4%) had moderate steatosis. These subjects were older (age: 50.9 ± 14.3 vs. 41.5 ± 16.7 years, P < 0.001) and had a higher body mass index (BMI; 30.1 ± 5.2 vs. 24.6 ± 4.1 km/m(2) , P < 0.001) than non-NAFLD twins. Based on 91 same-sex twin pairs, heritability analysis indicated no discernible role for genetic components in the presence of NAFLD (95% confidence interval, 0.0-36.0%), while shared and unshared environmental effects accounted for 74.2% and 25.8% of variations adjusted for age and BMI. Augmentation indices and carotid IMT in twins with NAFLD were increased at most examined locations (P < 0.05-P < 0.001). CONCLUSION: These findings do not support heritability of NAFLD, although it coexists with vascular parameters linked to increased cardiovascular risk, underscoring the importance and value of prevention in this very common disorder.

[Characteristics of smoking and secondhand smoke exposure in monozygotic and dizygotic twins: results from an international twin study]. / Egy- és kétpetéju ikrek aktív és passzív dohányzási szokásai: nemzetközi ikervizsgálat eredményei.

INTRODUCTION: Zygosity differences in smoking exposure are unclear in twins. AIMS: To assess smoking and secondhand smoke exposure characteristics in twins. METHODS: 151 monozygotic and 62 dizygotic Hungarian and American adult twin pairs (age 43.8±16.5 years, mean±SD) participated in the study. RESULTS: Monozygotic twins started smoking 1.8 years earlier compared to dizygotic twins (p = 0.08). Dizygotic twins smoked longer (p<0.01) and suffered more parental smoke exposure during childhood (p<0.05). Monozygotic twins reported stricter smoking restrictions at home and workplaces (p<0.005) and less smoke exposure in indoor public places (p<0.01). 85.7% of monozygotic twins were ex or active smokers, while only 69.5% of the dizygotics (p<0.01). Lesser difference was observed in the self-reported smoke exposure rate in monozygotic compared to dizygotic pairs concerning restaurants and cafés (p<0.05) which was not present regarding bars, pubs and transportation facilities. CONCLUSIONS: Different psychological family orientation may be present across zygosity. Preventive parental care is warranted in twin families exposed to smoking.

Ultrasound during neck rotation to reveal a case of positional occlusion of the internal carotid artery.

Positional occlusion of the internal carotid artery is an unusual phenomenon. Reports are scarce in the literature and generally related to compression by external agents when the head is rotated. Cases with no extrinsic etiology are even more uncommon and require high suspicion to avoid misdiagnosis. We present a case of a patient with intermittent internal carotid occlusion depending on the position of the head with no external agent identified. Due to the dynamic characteristics of this presentation, diagnostic tests yielded contradictory results. Carotid ultrasound during neck rotation revealed the positional occlusion. Ultrasound is a versatile technique to explore the carotid arteries in different angles of the neck, useful if positional pathology is suspected.

Endovascular ascending aortic pseudoaneurysm repair under image fusion guidance and transcranial Doppler monitoring.

We describe a 78-year-old woman with a large ascending aortic pseudoaneurysm who underwent thoracic endovascular aortic repair under intraoperative image fusion guidance and real-time transcranial Doppler (TCD) monitoring. TCD monitoring revealed a total of 419 microembolic signals throughout the procedure, with the majority occurring as the first stent graft crossed the ascending aorta. Two days later, she underwent endovascular repair of a graft type IA endoleak. We highlight the role of image fusion guidance and TCD monitoring in enabling successful thoracic endovascular aortic repair in an elderly woman and in identifying procedural areas of improvement to minimize stroke risk.