Pilot study on the effect of flavonoids on arterial stiffness and oxidative stress in chronic kidney disease.

BACKGROUND: Flavonoids, the main class of polyphenols, exhibit antioxidant and antihypertensive properties. AIM: To prospectively investigate the impact of flavonoids on arterial stiffness in patients with chronic kidney disease (CKD) stages I-IV. METHODS: In this prospective, single-arm study, CKD patients with arterial hypertension and diabetes mellitus were enrolled. Baseline demographic, clinical, and laboratory variables were recorded. Patients received daily treatment with a phenol-rich dietary supplement for 3 months. Blood pressure, arterial stiffness (carotid-femoral pulse wave velocity, central pulse pressure), and oxidative stress markers (protein carbonyls, total phenolic compound, total antioxidant capacity) were measured at baseline and at study end. RESULTS: Sixteen patients (mean age: 62.5 years, 87.5% male) completed the study. Following intervention, peripheral systolic blood pressure decreased significantly by 14 mmHg (P < 0.001). Carotid-femoral pulse wave velocity decreased from 8.9 m/s (baseline) to 8.2 m/s (study end) (P < 0.001), and central pulse pressure improved from 59 mmHg to 48 mmHg (P = 0.003). Flavonoids also reduced oxidative stress markers including protein carbonyls (P < 0.001), total phenolic compound (P = 0.001), and total antioxidant capacity (P = 0.013). CONCLUSION: Flavonoid supplementation in CKD patients shows promise in improving blood pressure, arterial stiffness, and oxidative stress markers.

Recent advances in proteomic analysis to study carotid artery plaques.

Objective: We sought to identify differentially expressed proteins in serum, plasma, and plaque samples of patients with carotid atherosclerotic lesions. Methods: We performed a systematic review of the proteomic profile of serum, plasma, and plaque samples of patients with carotid artery disease. We included full-length peer-reviewed studies of adult humans and reported them using PRISMA guidelines. The quality of the design and content of the articles included in the review was assessed using the Newcastle-Ottawa scale. Results: We included six peer-reviewed articles reporting protein expression in serum, plasma, or plaque samples from patients with carotid atherosclerosis. Three were single-center cross-sectional studies, two were single-center case-control studies, and one was a single-center cohort study. Thirty-six proteins were found to be expressed differentially when comparing samples from healthy subjects and individuals with diseased carotid vessels and between patients with symptomatic and asymptomatic carotid artery atherosclerotic lesions. Some of these were shown to be related to inflammatory or anti-inflammatory pathways in atherogenesis. CD5L and S100A12 were both found to be upregulated in patients with unstable plaque, the former owing to its anti-inflammatory properties and the latter for its pro-oxidant effects in atherosclerosis. ACTB is involved in cellular structure and integrity and was found to be downregulated in patients with ruptured carotid plaques. Conclusions: Atherosclerotic carotid disease places the patient at increased risk of ischemic neurological events. Proteomics may help to understand their pathophysiological processes and can identify differential protein expression in blood samples from healthy subjects and patients with carotid artery plaques. This patient-centered approach will allow for the timely identification of individuals at higher risk of experiencing stroke.

Cerebral perfusion in patients with unilateral internal carotid artery occlusion by dual post-labeling delays arterial spin labeling imaging.

BACKGROUND: Global and regional cerebral blood flow (CBF) changes in patients with unilateral internal carotid artery occlusion (ICAO) are unclear when the dual post-labeling delays (PLD) arterial spin labeling (ASL) magnetic resonance imaging (MRI) technique is used. Manual delineation of regions of interest for CBF measurement is time-consuming and laborious. AIM: To assess global and regional CBF changes in patients with unilateral ICAO with the ASL-MRI perfusion technique. METHODS: Twenty hospitalized patients with ICAO and sex- and age-matched controls were included in the study. Regional CBF was measured by Dr. Brain's ASL software. The present study evaluated differences in global, middle cerebral artery (MCA) territory, anterior cerebral artery territory, and Alberta Stroke Program Early Computed Tomography Score (ASPECTS) regions (including the caudate nucleus, lentiform nucleus, insula ribbon, internal capsule, and M1-M6) and brain lobes (including frontal, parietal, temporal, and insular lobes) between ICAO patients and controls at PLD 1.5 s and PLD 2.5 s. RESULTS: When comparing CBF between ICAO patients and controls, the global CBF in ICAO patients was lower at both PLD 1.5 s and PLD 2.5 s; the CBF on the occluded side was lower in 15 brain regions at PLD 1.5 s, and it was lower in 9 brain regions at PLD 2.5 s; the CBF in the contralateral hemisphere was lower in the caudate nucleus and internal capsule at PLD 1.5 s and in M6 at PLD 2.5 s. The global CBF in ICAO patients was lower at PLD 1.5 s than at PLD 2.5 s. The ipsilateral CBF at PLD 1.5 s was lower than that at PLD 2.5 s in 15 regions, whereas the contralateral CBF was lower at PLD 1.5 s than at PLD 2.5 s in 12 regions. The ipsilateral CBF was lower than the contralateral CBF in 15 regions at PLD 1.5 s, and in M6 at PLD 2.5 s. CONCLUSION: Unilateral ICAO results in hypoperfusion in the global and MCA territories, especially in the ASPECTS area. Dual PLD settings prove more suitable for accurate CBF quantification in ICAO.

Adherence to Dietary Patterns and Cardiovascular Disease Risk: A Cross-Sectional Study of Total Carotid Plaque Area in Argentina.

Objective: Assessing subclinical atherosclerosis (sAT) is crucial for preventing cardiovascular disease. The Mediterranean diet is considered the gold standard for cardiovascular protection, but cultural and economic barriers can hinder adherence to it. The prudent dietary pattern (DP) has been associated with protective effects against chronic diseases. However, its impact on primary cardiovascular prevention remains uncertain. This study examined adherence to various DPs and their effect on sAT, measured by total carotid plaque area (TPA). Methods: This cross-sectional study included 116 adults enrolled in a cardiovascular prevention program. Demographic, clinical, laboratory, and TPA data were collected. Adherence to DPs was assessed using a food frequency questionnaire. Participants were categorized according to their adherence to 4 mutually exclusive DPs: prudent, traditional, sweet, and mixed. Generalized linear models were used to assess the effect of DPs on TPA, adjusting for relevant cardiovascular variables. Results: The traditional, sweet, and mixed DPs were associated with higher TPA values than the prudent DP, with medians (interquartile range) of 27 (99), 39 (49), 27.5 (58), and 0 (36) mm2, respectively. Gamma regression analysis found that the beta exponents for the traditional, sweet, and mixed DPs versus the prudent DP were 3.78 (p=0.046); 3.73 (p=0.013), and 2.20 (p=0.072), respectively. Systolic blood pressure values were higher for the sweet and mixed DPs than for the prudent DP (133.9±11.7; 132.5±13.9 and 122.7±8.8 mmHg, respectively; p<0.05). Conclusion: These findings underscore the importance of additional research and targeted interventions to promote healthier DPs to promote improvements in cardiovascular health.

Resistance- and endurance-trained young men display comparable carotid artery strain parameters that are superior to untrained men.

PURPOSE: Central arterial stiffness, a predictor of cardiovascular risk, attenuates with endurance-exercise in ageing populations. However, in young individuals, this effect is inconsistent and emerging evidence suggests resistance-exercise may increase arterial stiffness. Two-dimensional (2D)-Strain imaging of the common carotid artery (CCA) is more sensitive at detecting endurance-training induced alterations in CCA stiffness than conventional methods, but has not been used to examine CCA stiffness in young resistance-trained individuals. Therefore, we compared CCA 2D-Strain parameters at rest, during acute exercise and recovery between resistance-trained, endurance-trained, and untrained young men. METHODS: Short-axis CCA ultrasound images were obtained from 12 endurance-trained [27yrs (95%CI; 24-29)], 14 resistance-trained [24yrs (23-26)] and 12 untrained [23yrs (22-24] men at rest, during isometric handgrip (IHG) exercise and recovery. 2D-Strain analysis quantified CCA peak circumferential strain (PCS) and systolic (S-SR) and diastolic (D-SR) strain rates. Conventional stiffness indices included aortic pulse-wave velocity, CCA ß-stiffness (ß1) and Petersons elastic modulus (Ep). RESULTS: Resting conventional stiffness indices were not different between groups (P > 0.05). Resting PCS and S-SR were comparable between resistance- [11.6% (10.6-12.5) and 1.46 s-1 (1.37-1.55), respectively] and endurance-trained [11.4% (10.7-12.2) and 1.5 s-1 (1.38-1.62)] men and superior to untrained men [9.5% (9.19-9.9); P < 0.004 and 1.24 s-1 (1.17 - 1.31); P < 0.018)]. Both trained groups displayed comparable reductions in PCS and S-SR during IHG, which returned to resting values during recovery (P < 0.001), whereas these parameters remained unchanged in untrained men. D-SR decreased during IHG in all groups (P < 0.001), but to a lesser extent in endurance-trained men (P < 0.023), whereas ß1 and Ep increased to a similar magnitude in all groups and returned to resting values during recovery (P < 0.001). CONCLUSION: Resistance- and endurance-trained men display comparable CCA 2D-Strain parameters that are superior to untrained men, which contends previous reports that resistance-training increases CCA stiffness.

Relationships of Leg Ischemia Symptoms and Carotid Artery Atherosclerosis with Hypertensive-Disorders-of-Pregnancy-Associated Peptides in Patients with Lower Extremity Arterial Disease.

Objectives: We have proposed seven peptides with low molecular weights in blood as biomarkers for the diagnosis of hypertensive disorders of pregnancy (HDP). The purpose of this cross-sectional study was to investigate the relationships of the HDP-associated peptides with symptoms of leg ischemia and degree of atherosclerosis in patients with lower extremity arterial disease (LEAD). Methods: The subjects were 165 outpatients with LEAD (145 men and 20 women aged 74.3 ± 8.1 years [47-93 years]). Their symptoms of leg ischemia, leg arterial flow, and degree of atherosclerosis were evaluated using the Rutherford classification of Clinical Ischemia Category, ankle-brachial index (ABI) and the intima-media thickness (IMT) of carotid arteries, respectively. Serum concentrations of the HDP-related peptides were measured by mass spectrometry. Results: The grade of the Rutherford classification was positively associated with levels of the peptides with m/z 2091 and 2378 and was inversely associated with levels of the peptide with m/z 2081. The category of the Rutherford classification was inversely associated with ABI. There were no HDP-associated peptides that showed significant relationships with IMT. Conclusions: The peptides with m/z 2081, 2091, and 2378 are possible biomarkers of leg ischemia but are not associated with carotid atherosclerosis in LEAD patients.

Carotid Intima-Media Thickness in Indian Patients With Non-alcoholic Fatty Liver Disease: A Systematic Review and a Meta-Analysis.

There is a significant association of non-alcoholic fatty liver disease (NAFLD) with cardiovascular disease (CVD). Most CVDs begin with atherosclerosis in the arteries, which can be reliably measured as the carotid intima-media thickness (CIMT) by ultrasound. Given that ethnic and regional differences have an impact on NAFLD, we aimed to evaluate the association of NAFLD patients from India with subclinical atherosclerosis, measured as CIMT. A thorough literature search was performed on four electronic databases using combinations of several keywords. The relevant data were pooled in a random or fixed-effect model, based on heterogeneity, to calculate the pooled standardised mean difference (SMD), or odds ratio (OR) with 95% confidence interval (CI). The final analysis included a total of 15 studies with 1196 NAFLD and 1482 control subjects. NAFLD patients had a 21.3% higher mean CIMT than the controls. The pooled SMD was 1.001 (95% CI: 0.627-1.375, p < 0.001). Three studies that balanced cardiometabolic risk factors found a similar association (p = 0.037). Furthermore, NAFLD was significantly associated with the presence of high (>0.8 mm) CIMT (pooled OR = 5.4, 95% CI: 2.0-14 .9) and carotid plaques (pooled OR = 10.24, 95% CI: 5.74-18.26). The mean CIMT was also higher in diabetic NAFLD than in the diabetic control (pooled SMD = 1.07, 95% CI = 0.818-1.324, p < 0.001). There is a significant positive association between the marker of subclinical atherosclerosis and NAFLD in India. This might give more light on screening and follow-up plans for such patients.

Vascular Anomaly Presenting as Neurological Crisis: A Case Report of Dolichoectasia-Induced Seizures.

A rare brain vasculature illness called dolichoectasia (DE) causes the blood vessels to enlarge and elongate. DE describes an irregular enlargement and dilatation of arteries; this condition primarily affects big blood vessels such as the internal carotid and vertebrobasilar arteries. A range of neurological symptoms may result from this illness because of the compression of nearby structures or changed hemodynamics. Although it is documented more commonly in the vertebrobasilar circulation, rarely it can be seen in the anterior circulation, as in our case. The brainstem structures and cranial nerves are compressed in DE, resulting in turbulent blood flow that causes vertigo and tinnitus and frequently damages the brain's small blood vessels. One risk factor for ischemic stroke is DE. The occurrence of seizures in DE is not so common. Here, we report a case of a 20-year-old female, bioengineering UG with generalized tonic-clonic seizure diagnosed to have DE on MRI.

Successful Percutaneous Rescue Treatment of Acute Carotid Stent Thrombosis Utilizing a Modified Embolic Protection Device.

Acute Carotid Stent Thrombosis (ACST) is a rare complication of Carotid Artery Stenting (CAS) with a potentially fatal outcome. We report a case of ACST occurring five minutes after the end of a successful CAS procedure that was promptly treated by carotid stent-in-stent implantation using a new percutaneous strategy based on the creation of a modified embolic protection device. Following the procedure, we did not observe brain lesions suggestive of acute cerebral ischemic events at the CT scan performed at 48 hours, as well as no neurological deficits in the following days.

Malignant peripheral nerve sheath tumor mimicking carotid body tumor, a rare case report and review of literature.

INTRODUCTION AND IMPORTANCE: Malignant Peripheral Nerve Sheath Tumor (MPNST) is a rare type of soft tissue sarcoma. It is an aggressive tumor with high rates of local recurrence and distant metastasis. MPNST rarely occurs in the neck. We present a case of cervical MPNST manifesting as Carotid Body Tumor (CBT). CASE PRESENTATION: A 67-year-old man presented with a neck mass. The mass was rapidly enlarging and imaging studies favored CBT. A previous attempt at surgical resection failed, and the compressive symptoms were progressive during recent weeks. After multidisciplinary discussion, the tumor was resected and pathological evaluation confirmed the diagnosis of MPNST. Post-operative metastatic work-up showed lung metastasis, and the patient died approximately one year after surgery. CLINICAL DISCUSSION: Cervical MPNST is rare, and surgery is the mainstay of its treatment. Pre-operative tissue diagnosis is recommended when possible, and immunohistochemical staining is necessary for prompt diagnosis. Adjuvant therapy may be helpful in metastatic cases or incomplete resection. Nevertheless, local recurrence and distant metastasis especially to the lungs are common, as in our case. CONCLUSION: MPNST is one of the potential causes of cervical masses and considering its invasive behavior, surgical resection is recommended as soon as the diagnosis is made.

Racial differences in adoption and outcomes of transcarotid artery revascularization among high-risk adults with carotid artery stenosis.

INTRODUCTION: Differential access to new technologies may contribute to racial disparities in surgical outcomes but has not been well-studied in the treatment of carotid artery stenosis. We examined race-based differences in adoption and outcomes of transcarotid artery revascularization (TCAR) among high-risk non-Hispanic (NH) NH Black and NH white adults undergoing carotid revascularization. METHODS: We conducted a retrospective analysis of TCAR, transfemoral carotid artery stenting (TF-CAS), and carotid endarterectomy (CEA) procedures performed for carotid artery stenosis from 1/2015 to 7/2023 in the Vascular Quality Initiative. NH Black and NH white adults were included if they met Centers for Medicare & Medicaid Services high-risk criteria. Hospitals and physicians were categorized as TCAR-capable if they had previously performed at least one TCAR prior to the time of a given procedure. We fit logistic and linear regressions, adjusted a priori for common demographic, clinical, and disease characteristics, to estimate associations of race with receipt of TCAR (versus CEA or TF-CAS), and to explore associations between race, hospital and physician characteristics, and perioperative composite stroke/death/myocardial infarction. RESULTS: Of 159,471 high-risk patients undergoing revascularization for carotid artery stenosis (mean age 72 years, 38.5% female, 5.3% NH Black), 28,722 (18.0%) received TCAR, including 16.9% of NH Black adults and 18.1% of NH white adults (P<0.001). After controlling for patient and disease characteristics, NH Black patients were less likely than NH white patients to receive TCAR (aOR 0.92, 95% CI 0.87 to 0.99). The use of TCAR did not vary by race among patients treated at TCAR-capable hospitals (aOR 0.98, 95% CI 0.91 to 1.05) or by TCAR-capable physicians (aOR 1.01, 95% CI 0.93 to 1.10); however, NH Black race was associated with lower odds of receiving treatment in these settings (TCAR-capable hospital: aOR 0.93 [0.88 to 0.98]; TCAR-capable physician: aOR 0.92 [0.87 to 0.98]). NH Black race was associated with higher odds of stroke/death/MI in the full cohort (aOR 1.18, 95% CI 1.03 to 1.36), but not in the subgroup of patients who received TCAR (aOR 0.87, 95% CI 0.56 to 1.34). CONCLUSIONS: TCAR attenuated racial disparities in perioperative morbidity and mortality associated with carotid revascularization, but NH Black adults were less likely than NH white adults to receive TCAR. Relatively worse access for NH Black adults to technologically-advanced treatment settings may partially explain the broader persistence of race-based differences in carotid revascularization treatment patterns and outcomes.

Use of the Win Ratio for Analysis of Stroke Trials: Description, Illustration, and Planned Use in the Second European Carotid Surgery Trial (ECST-2).

Randomized trials in stroke often focus on outcomes beyond a single clinical event. Trials of stroke prevention commonly use composite outcomes that include multiple components (eg, death, stroke, or myocardial infarction). A major limitation is that all events count equally but may differ markedly in terms of clinical severity. Trials in acute stroke often use ordinal outcomes or scale scores. Limitations include the requirement for statistical assumptions and the difficulty of handling the competing risk of death. We introduce the win ratio as an alternative method. It works by placing components of a composite into a hierarchy, whereby clinically more important outcomes take priority over less important ones. We illustrate how it works using data from 2 major stroke trials: the ICSS (International Carotid Stenting Study, a trial in stroke prevention) and the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands). Potential benefits of the win ratio approach include the possibility to (1) emphasize the clinically most important outcomes, (2) combine components of different outcome types into a composite (eg, a mixture of time-to-event, continuous, and categorical), and (3) naturally handle the competing risk of death in analyses of quantitative outcomes. The win ratio will be used in the upcoming analysis of the ECST-2 (Second European Carotid Surgery Trial), which has a hierarchical primary outcome of (1) time to perioperative death, fatal stroke, or fatal myocardial infarction (most important); (2) time to nonfatal stroke; (3) time to nonfatal myocardial infarction (excluding silent infarcts); and (4) new silent cerebral infarct on brain imaging (least important). The win ratio provides a useful clinically relevant method for analyzing trial outcomes. It has some advantages over conventional methods, and we recommend its wider application in future stroke trials.

Subacute in-stent thrombosis after carotid artery stenting in a patient with gene polymorphisms associated with aspirin and clopidogrel resistance: a case report.

BACKGROUND: Carotid artery stenting (CAS) is a key treatment option for moderate to severe carotid artery stenosis. Carotid stent thrombosis (CST), a rare complication of CAS, has gained significant attention because of its catastrophic nature. More evidences are needed to guide the diagnosis and treatment of CST. CASE PRESENTATION: This study reports a rare case of sub-acute CST following CAS in a 50-year-old male patient who had experienced repeated cerebrovascular events on the premise of taking antiplatelet drugs. He also suffered an occlusion of the left middle cerebral artery (MCA) in the M2 segment, likely caused by an embolus detached from the stent thrombus. The cause of CST in this patient was presumed to be dual antiplatelet resistance (AR), as indicated by genetic testing. After treated with guide catheter-directed thrombolysis, thrombus aspiration, and a second round of thrombolysis, his in-stent thrombus was basically cleared. His M2 occlusion was resolved by mechanical thrombectomy using the Solitaire FR/Stent with Intermediate Catheter Assisting technique. The patient recovered well after replacement of antiplatelet drugs, and no new thromboembolic event occurred during the 13-month follow-up period. CONCLUSIONS: The occurrence rate of AR-related CST may be underestimated as the cause of majority CST cases remains unclear. Implementation of genetic test for aspirin and clopidogrel resistance may be helpful to find the possible cause of CST and to avoid future repeated cerebrovascular events by replacement of antiplatelet drugs.

Free-Cell Area Impact on Stroke Prevention in Asymptomatic Patients Undergoing Carotid Artery Stenting: The "Carotid Artery sTenting And CeLl-area Impact on Stroke and Major Adverse events" (CATACLISMA) Multicenter Registry.

PURPOSE: The study investigated the association between cell-stent area and cerebrovascular events incidence in asymptomatic patients undergoing carotid artery stenting (CAS). MATERIALS AND METHODS: This is an observational, retrospective, multicenter, cohort study. Between 2012 and 2022, all patients undergoing primary CAS for severe asymptomatic carotid artery stenosis were evaluated. Three groups were defined on the basis of the cell area (open cell, OC; closed cell, CC; double layer, DL). Periprocedural primary outcomes were 30-day stroke, mortality, myocardial infarction (MI), and major adverse event (MAE, stroke/mortality composite outcome) rates. Follow-up primary outcomes included overall survival, stroke-free survival (SFS), freedom from ipsilateral stroke (FFiS), and freedom from stroke-related mortality (FF-SRM). Data were analyzed at short-term (1 year) and mid-term (2.5 years) period. RESULTS: A total of 1096 CAS were considered (787 men, 71.8%, median age = 74 years). Technical success was achieved in 99.5% procedures. Periprocedural 30-day stroke rate was 1.5% (OC: 1.1%, CC: 2.3%, DL: 1%, p=0.27), mortality was 0.7% (OC: 1.1%, CC: 0.3%, DL: 0.5%, p=0.35), and no MI was recorded. The MAE rate was 2.1% (OC: 2%, CC: 2.6%, DL: 1.5%, p=0.66). Median follow-up was 46 months. At 1 and 2.5 years, estimated overall survival was 96.1% and 91% (p=0.41), SFS was 99.1% and 98.2% (p=0.007, CC stroke rates 2.9% and 4.2% at timepoints), FFiS was 99.4% and 99% (p=0.014, CC FFiS rates 1.7% and 2.6% at timepoints) and FF-SRM was 99.5% and 99% (p=0.28). During follow-up, no stroke events occurred in DL group. CC design showed higher rates of any (4.2%) and ipsilateral stroke (2.6%) within 2.5 years. CONCLUSION: In asymptomatic patients undergoing CAS, the contemporary overall stroke incidence is 1.5%. No statistical differences were observed in terms of 30-day stroke incidence among groups. The closed free-cell area showed higher rates of any and ipsilateral stroke within 2.5 years. The DL stents may offer the best available performances in terms of mid-term stroke prevention. CLINICAL IMPACT: The study analyzed the contemporary results of carotid artery stenting (CAS) focusing on the impact of cell-stent area on peri- and post-operative cerebrovascular events in a multicenter real-world experience. In asymptomatic patients undergoing CAS the contemporary overall stroke incidence is 1.5%. No statistical differences were observed in terms of 30-day stroke incidence among groups. The closed free-cell area showed higher rates of any and ipsilateral stroke within 2.5 years. DL stents may offer the best available performances in terms of mid-term stroke prevention.

ALTERED CONTROL OF BREATHING IN A RAT MODEL OF ALLERGIC LOWER AIRWAY INFLAMMATION.

Obstructive sleep apnea (OSA) is highly prevalent in patients with asthma. Asthma, dose-dependently to its duration, promotes incident OSA, suggesting that asthma plays a role in OSA pathogenesis. We hypothesized that asthma-related inflammation alters breathing control mechanisms, specifically the carotid chemoreflex. Accordingly, we measured hypoxic ventilatory responses (HRV) in awake, unrestrained, ovalbumin (OVA)-sensitized Brown Norway rats and compared them with responses in sham-sensitized (SALINE) controls. To differentiate the role of allergic inflammation from bronchoconstriction, we repeated HVR after administration of formoterol, a long-acting bronchodilator. Blood and bronchoalveolar lavage (BAL) fluid were collected for quantification of inflammatory cytokines. The rise in ventilatory equivalent for O2 evoked by acute exposure to hypoxia was augmented following sensitization by OVA, whereas it remained stable after SALINE. This augmentation was driven by increased breathing frequency with no change in tidal volume. Tachypneic hyperventilation in normoxia was also observed with OVA. Neither the increased HVR nor excessive normoxic ventilation was affected by formoterol, suggesting that they were not secondary to lung mechanical constraints. Higher levels of inflammatory cytokines were observed in BAL fluid and serum of OVA vs. SALINE. In OVA, serum interleukin-5 correlated with change (baseline to post-sensitization) in ventilatory response to severe hypoxia (FIO2, 0.09). These observations are consistent with inflammation-induced enhancement of carotid chemoreflex function, i.e. increased controller gain, and they suggest a possible role for asthma-related allergic inflammation in the ventilatory instability known to promote upper airway collapse and sleep apnea in humans.

Symptomatic Nonstenotic Carotids: A Topical Review.

Historically, the management of carotid artery disease has primarily focused on the degree of stenosis as the main indicator for assessing stroke etiology, risk, and need for intervention. However, accumulating evidence suggests that structural and biological features within the arterial wall, such as intraplaque hemorrhage, may have superior diagnostic, prognostic, and therapeutic values. Under current guidelines, unless an atheroma results in ≥50% stenosis, it is not considered the cause of a cerebrovascular event. This results in extensive and often unproductive diagnostic workup, prescription of ineffective medical therapy, and preclusion of patients from receiving revascularization procedures that have been shown to prevent recurrent cerebrovascular events in cases of ≥50% stenosis. A subset of embolic strokes of undetermined source, which account for up to 25% of all ischemic cerebrovascular events, are thought to be due to thromboembolic phenomena from undiagnosed plaque disruptions in nonstenotic arteries (<50% stenosis). Recently, it has been proposed to reclassify this subgroup of patients as symptomatic nonstenotic carotid if the carotid plaque ipsilateral to the cerebrovascular event presents with high-risk features including intraplaque hemorrhage, lipid-rich necrotic core, thinning/rupture of the fibrous cap, and ulceration. In this review, we first provide a historical overview of the chain of events and circumstances that resulted in the present management of carotid artery disease. Second, we embed the contemporary biomarkers of plaque vulnerability in a modern mechanistic paradigm of carotid plaque disruption and thromboembolization. Third, we review the clinically available imaging tools to detect these biomarkers, and how their use has started to shed light on the prevalence and natural history of this underdiagnosed condition. Fourth, we review recent clinical studies employing a contemporary definition of symptomatic nonstenotic carotid and discuss targeted treatments for this condition. Finally, we make a case to generate the much-needed high-level evidence to align the clinical management of patients with symptomatic nonstenotic carotid with a contemporary understanding of plaque disruption and thromboembolization.

Indirect Carotid Cavernous Fistula with Ocular Manifestations: A Case Report.

ABSTRACT: Carotid-cavernous fistulas are rare entity with incidence of less than 1%, refers to abnormal connections between the carotid artery and cavernous sinus. Indirect types usually occur in elderly female patients and can resolve spontaneously with conservative management like external manual compression of the carotid artery. We report a case of 65-year-old female who presented with complaints of redness, proptosis, chemosis, headache and ophthalmoplegia in her right eye. Digital subtraction angiography revealed Barrow type B indirect carotid-cavernous fistulas. External manual carotid compression was done after which her symptoms improved significantly. Thus, indirect type carotid-cavernous fistulas can occur spontaneously and could be a sight threatening condition especially in elderly females but can resolve with conservative management.

Unstable Plaque is a Treatable Cause of Cognitive Decline.

While many risk factors are modifiable, there remains a compelling need for novel approaches to prevent cognitive impairment. We propose that unstable carotid plaque causes microemboli that, in turn, cause microinfarcts and other adverse pathophysiological cerebral processes, which individually do not manifest clinically but cumulatively manifest as cognitive decline and ultimately cognitive impairment. Animal models support multiple cerebral microemboli having adverse effects on cognition. By addressing the source for microembolization by endarterectomy or stenting, patients with high-grade atherosclerotic stenosis may have better cognitive outcomes. If our hypothesis is verified, then treatment of carotid plaque at elevated risk of generating cerebral microemboli would be effective in preserving cognition, regardless of whether the stenosis is high-grade or causing cerebral hemispheric hypoperfusion.

The External Carotid Artery and the Styloid Process.

BACKGROUND: The external carotid artery (ECA) is typically regarded as coursing between the styloid muscles to continue into the parotid space. The anatomical possibility of an ECA with an ascending parapharyngeal trajectory continuing posteriorly to an elongated styloid process (ESP), thus retrostyloid, to the parotid space is overlooked. It was, therefore, aimed to document the prevalence of this retrostyloid variant of the ECA's course. METHODS: We investigated a retrospective random cohort of 160 archived CT angiograms of 97 males and 63 females aged between 47 and 76. The presence of an ESP and the retrostyloid course of the ECA were bilaterally documented. RESULTS: An ESP was identified in 99/320 sides (30.94%), regardless of the ECA course. In the overall group, we obtained 35% null cases for the two variables on the right and 34.06% for the left. ESPs were identified in 8.75% on the right side and 10.31% on the left. The ECAs had retrostyloid courses in 6.25% on the right side and 5.63% on the left. Thus, of the 320 ECAs documented on both sides, 221 (69.06%) had no retrostyloid courses, and we did not identify any ESP in those cases. ESPs were detected in 19.06% of the sides but without retrostyloid ECAs, and retrostyloid courses of the ECAs were detected in 11.88%. CONCLUSIONS: The possibility of a retrostyloid course of the ECA should not be ignored. An ESP may misinform the surgeon about the main carotid artery located immediately deep to it.

Cerebrovascular pulsatility indicates preoperative subcortical cognitive impairment and an increased risk for postoperative delirium in elderly patients undergoing elective spine surgery.

Introduction: Advances in spine surgery enable safe interventions in elderly patients, but perioperative neurocognitive disorders (pNCD), such as post-operative delirium (POD) and cognitive dysfunction (POCD), remain a serious concern. Pre-operative cognitive impairment is a major risk factor for pNCD. Comprehensive pre-operative cognitive assessments are not feasible in clinical practice, making effective screening methods desirable. This study investigates whether pre-operative cerebrovascular duplex sonography can assess subcortical (vascular) cognitive impairment and the risk for POD. Methods: This prospective single-center study recruited patients aged ≥60 years scheduled for elective spine surgery at a German university hospital. Patients underwent pre-operative assessments including cognitive abilities (CERAD test battery), structural MRI, and cerebrovascular duplex sonography. POD screening was conducted three times daily for at least 3 days. The primary hypothesis, that the mean pulsatility index (PI) of both internal carotid arteries (ICA) predicts POD risk, was tested using logistic regression. Secondary analyses examined the association between POD risk and ICA flow (time-averaged peak velocities, TAPV) and correlations with cognitive profiles and MRI characteristics. Results: POD occurred in 22% of patients (n = 22/99) within three postoperative days. Patients with POD were significantly older (75.9 ± 5.4 vs. 70.0 ± 6.9 years, p < 0.01) but did not differ by gender (p = 0.51). ICA PI significantly predicted POD risk (OR = 5.46 [95%CI: 1.81-16.49], p = 0.003), which remained significant after adjustment for age and duration of surgery (ORadj = 6.38 [95% CI: 1.77-23.03], p = 0.005). TAPV did not inform the POD risk (p = 0.68). ICA PI Pre-operative cognitive scores were significantly associated with ICA PI (mean CERAD score: r = -0.32, p < 0.001). ICA PI was also significantly associated with total white matter lesion volume (τ = 0.19, p = 0.012) and periventricular white matter lesion volume (τ = 0.21, p = 0.007). Discussion: This is the first study to demonstrate that cerebrovascular duplex sonography can assess the risk for POD in elderly spine surgery patients. Increased ICA PI may indicate subcortical impairment, larger white matter lesion load, and lower white matter volume, predisposing factors for POD. Pre-operative cerebrovascular duplex sonography of the ICA is widely available, easy-to-use, and efficient, offering a promising screening method for POD risk. Increased ICA PI could supplement established predictors like age to adjust surgical and peri-operative procedures to individual risk profiles.