Stroke in mitral valve prolapse: risk factors and left atrial function in cryptogenic versus non-cryptogenic ischemic subtypes.

Background and purpose: Mitral valve prolapse (MVP) has been associated with an increased risk of ischemic stroke. Older age, thicker mitral leaflets, and significant mitral regurgitation (MR) leading to atrial fibrillation have been traditionally considered risk factors for ischemic stroke in MVP. However, specific risk factors for MVP-stroke subtypes are not well defined. The aim of this study is to evaluate clinical and echocardiographic parameters, including left atrial (LA) function, in MVP with cryptogenic (C) vs. non-cryptogenic (NC) stroke. Methods: In this case-control matched study, MVPs were identified in consecutive echocardiograms obtained after a stroke from January 2013 to December2016 at the University of California, San Francisco. MVP was defined as leaflet displacement ≥2 mm in the parasternal long-axis view at end-systole. Age/gender matched MVPs without stroke and healthy controls without MVP were also identified. We analyzed LA end-systolic/diastolic volume index, emptying fraction (LAEF), function index (LAFI), and global longitudinal strain in all MVPs and controls. We also measured left ventricular (LV) volume indexes, mass index, ejection fraction (EF), degree of MR and leaflet thickness. Results: We identified a total of 30 MVPs (age 70 ± 12, 50% females) with stroke (11 with C- and 19 with NC-stroke), 20 age/gender matched MVPs without a stroke and 16 controls. MVPs without stroke had lower BMI, less hypertension but more MR (≥moderate in 45% vs. 17%), more abnormal LA function (lower LAEF, LAFI) and larger LV volumes/mass (all p < 0.05) when compared to MVPs with stroke. Leaflet thickness was overall mild (<3 mm) and similar in the 2 groups. Within the MVP stroke group, NC-stroke had higher BMI, more hypertension and more atrial fibrillation compared to C-stroke. In the variables tested, patients with C-stroke did not differ from controls. Conclusions: MVP-related MR may be protective against stroke despite abnormal LA function. Risk of NC-stroke in MVP is related to common stroke risk factors rather than mitral valve leaflet thickness. The etiology of C-stroke in MVP warrants further studies.

Clinical evaluation of pulsatile tinnitus: history and physical examination techniques to predict vascular etiology.

BACKGROUND: Pulsatile tinnitus (PT) may be due to a spectrum of cerebrovascular etiologies, ranging from benign venous turbulence to life threatening dural arteriovenous fistulas. A focused clinical history and physical examination provide clues to the ultimate diagnosis; however, the predictive accuracy of these features in determining PT etiology remains uncertain. METHODS: Patients with clinical PT evaluation and DSA were included. The final etiology of PT after DSA was categorized as shunting, venous, arterial, or non-vascular. Clinical variables were compared between etiologies using multivariate logistic regression, and performance at predicting PT etiology was determined by area under the receiver operating curve (AUROC). RESULTS: 164 patients were included. On multivariate analysis, patient reported high pitch PT (relative risk (RR) 33.81; 95% CI 3.81 to 882.80) compared with exclusively low pitch PT and presence of a bruit on physical examination (9.95; 2.04 to 62.08; P=0.007) were associated with shunting PT. Hearing loss was associated with a lower risk of shunting PT (0.16; 0.03 to 0.79; P=0.029). Alleviation of PT with ipsilateral lateral neck pressure was associated with a higher risk of venous PT (5.24; 1.62 to 21.01; P=0.010). An AUROC of 0.882 was achieved for predicting the presence or absence of a shunt and 0.751 for venous PT. CONCLUSION: In patients with PT, clinical history and physical examination can achieve high performance at detecting a shunting lesion. Potentially treatable venous etiologies may also be suggested by relief with neck compression.

The Clinical Impact of Recent Methamphetamine Exposure in Aneurysmal Subarachnoid Patients.

Background: Methamphetamines (MA) are a frequently used drug class with potent sympathomimetic properties that can affect cerebral vasculature. Conflicting reports in literature exist about the effect of exposure to MA on vasospasm risk and clinical outcomes in aneurysmal subarachnoid hemorrhage (aSAH). This study aimed to characterize the impact of recent MA use on the timing, severity and features of vasospasm in aneurysmal subarachnoid as well as neurological outcomes. Methods: We retrospectively screened 441 consecutive patients admitted to a tertiary care hospital with a diagnosis of SAH who underwent at least one cerebral digital subtraction angiogram (DSA). Patients were excluded if no urinary toxicology screen was performed within 24 hours of admission, if there was a diagnosis of non-aneurysmal SAH, or if ictus was greater than 72 hours from hospital admission. Vasospasm characteristics were collected from DSA and transcranial doppler (TCD) studies and demographic as well as clinical outcome data was abstracted from the chart. Results: 129 patients were included and 24 tested positive for MA. Among the 312 excluded patients, 281 did not have a urinary toxicology screen and 31 had a non-aneurysmal pattern of SAH or ictus occurring greater than 72 hours from hospital admission. No significant differences were found in respect to patient age, sex, or admission Hunt and Hess Score or Modified Fisher Scale based on MA use. There was no difference in the severity of vasospasm or time to peak severity using either TCD or DSA criteria on multivariate analysis. Aneurysms were more likely to be in the anterior circulation for both groups, however the MA cohort experienced less vasospasm involving the anterior circulation and more isolated posterior circulation vasospasm. There was no difference in delayed cerebral ischemia (DCI) incidence, length of ICU stay, need for ventriculoperitoneal shunt placement, functional outcome at discharge or hospital mortality. Interpretation: Recent MA use was not associated with worse vasospasm severity, time to vasospasm, or DCI in aSAH patients. Further investigations about localized MA effects in the posterior circulation and impact on long-term functional outcomes are warranted.

More than just noise: Association of pulsatile tinnitus with anxiety, depression, and reduction of quality of life.

BACKGROUND: While many of the causes of pulsatile tinnitus (PT) are treatable with endovascular approaches, the risks of treatment must be balanced with the risks of the underlying cause and the psychological impact of symptoms on patients. While many physicians have anecdotal experience, the comorbid relationship of depression and anxiety with PT is unknown. The objectives of this study are to quantify the prevalence of depression and anxiety, and, to identify the demographic risk factors for impactful depression and anxiety in patients with PT. METHODS: Subjects recruited from online PT groups filled out secure online questionnaires that included demographic questions, validated Tinnitus Functional Index (TFI) as well as PHQ-9 and GAD-7 questionnaires to assess the prevalence of concurrent depression and anxiety, respectively. RESULTS: Sample included 515 surveys (84% female, 65% unemployed, mean(sd) age = 46.4 years (14.2)). Median symptom duration was 1.9 years. Data showed 46% and 37% of patients with moderate to severe depression and anxiety, respectively. Higher TFI scores were associated with moderate to severe depression (OR 1.07; 95% CI 1.06-1.09, p < 0.001) and anxiety (OR 1.05, 95% CI 1.04-1.06, p < 0.001), with TFI subscores also independently being associated in a univariate analysis. CONCLUSIONS: The prevalence of moderate to severe depression and anxiety in the PT population, which was previously unknown, is estimated in our study to be 46% and 37%, respectively. Significant association of TFI score with increased depression and anxiety scales adds further evidence of the impact of PT on the psychological health of these patients.

Cerebrovascular pulsatile tinnitus: causes, treatments, and outcomes in 164 patients with neuroangiographic correlation.

BACKGROUND: Pulsatile tinnitus (PT) can cause significant detriment to quality of life and may herald a life-threatening condition. Endovascular evaluation is the gold standard for the definitive diagnosis of PT and facilitates treatment. However, no large study has determined the distribution of causes and treatment outcomes of PT evaluated endovascularly. METHODS: Consecutive patients evaluated at a multidisciplinary PT clinic from a single academic center were retrospectively reviewed. Patients with a suspected cerebrovascular etiology of PT based on clinical and/or non-invasive imaging, who were evaluated by endovascular techniques (arteriography, venography, manometry, and/or balloon test occlusion), were included in analysis. Baseline clinical features and treatment results by final etiology of PT were compared. RESULTS: Of 552 patients referred for PT evaluation, 164 patients (29.7%) who underwent endovascular evaluation of PT were included. Mean (±SD) age at first clinical evaluation was 54.3±14.1 years (range 25-89 years); 111 patients (67.7%) were female. PT causes were 75.6% vascular and 24.4% non-vascular. Arteriovenous shunting lesions caused 20.7% of cases, venous etiologies 48.2%, and arterial etiologies 6.7%. Of patients with a shunting lesion treated with endovascular embolization, 96.9% had lasting significant improvement or resolution in PT. Endovascular stenting for venous sinus stenosis gave 84.6% of patients lasting improvement or resolution in PT. Arterial and non-vascular PT had fewer patients treated endovascularly and less improvement in PT symptoms. CONCLUSION: PT with a suspected vascular cause is most often attributable to venous etiologies. PT caused by arteriovenous shunting or venous sinus stenosis may be effectively treated endovascularly.

Geometric and Morphologic Features of Ruptured Intracranial Aneurysms Associated with Methamphetamine Use.

BACKGROUND: Methamphetamine (MA) use is associated with poor outcomes after aneurysmal subarachnoid hemorrhage (aSAH). MA exerts both hemodynamic and inflammatory effects, but whether these manifest with altered intracranial aneurysm (IA) remodeling is unknown. The objective of this study was to compare IA geometric and morphologic features in patients with and without MA detected on urine toxicology (Utox) at presentation. METHODS: We retrospectively reviewed 160 consecutive patients with SAH and Utox at time of admission. Geometric-morphologic IA characteristics were assessed by blinded neuroradiologists. Studied features were maximum sac diameter, location, size, ellipsoid volume, aspect ratio, size ratio, volume: neck ratio, dome: neck ratio, bottleneck factor, morphology (saccular, fusiform/dissecting, blister, mycotic), and presence of bleb, vasculopathy, or additional unruptured IA. RESULTS: Of 139/160 patients with aSAH, 23/139 (16.5%) were Utox MA+. There was no difference in aneurysm subtype frequency, presence of bleb, vasculopathy, or presence of an additional (unruptured) aneurysm with a trend toward posterior circulation location and higher Hunt and Hess grade (P = 0.09 for both) in the MA+ group. Maximum IA sac diameter, ellipsoid volume, dome-neck ratio, and size ratio were similar between groups. Only the aspect ratio (AR) differed between groups (MA+ = 2.20 vs. MA- = 1.74, P = 0.02). The AR remained a significant predictor of Utox MA+ in a multiple logistic regression analysis (odds ratio 1.87, 95% confidence interval 1.06-3.39). CONCLUSIONS: Active use of methamphetamine is independently associated with larger AR in patients with ruptured IA. This may indicate hazardous remodeling due to hemodynamic and/or inflammatory changes.

Brain herniation (encephalocele) into arachnoid granulations: prevalence and association with pulsatile tinnitus and idiopathic intracranial hypertension.

PURPOSE: Brain herniation into arachnoid granulations (BHAG) of the dural venous sinuses is a recently described finding of uncertain etiology. The purpose of this study was to investigate the prevalence of BHAG in a cohort of patients with pulsatile tinnitus (PT) and to clarify the physiologic and clinical implications of these lesions. METHODS: The imaging and charts of consecutive PT patients were retrospectively reviewed. All patients were examined with MRI including pre- and post-contrast T1- and T2-weighted sequences. Images were reviewed separately by three blinded neuroradiologists to identify the presence of BHAG. Their location, signal intensity, size, presence of arachnoid granulation, and associated dural venous sinus stenosis were documented. Clinical records were further reviewed for idiopathic intracranial hypertension, history of prior lumbar puncture, and opening pressure. RESULTS: Two hundred sixty-two consecutive PT patients over a 4-year period met inclusion criteria. PT patients with BHAG were significantly more likely to have idiopathic intracranial hypertension than PT patients without BHAG (OR 4.2, CI 1.5-12, p = 0.006). Sixteen out of 262 (6%) patients were found to have 18 BHAG. Eleven out of 16 (69%) patients had unilateral temporal or occipital lobe herniations located in the transverse sinus or the transverse-sigmoid junction. Three out of 16 (19%) patients had unilateral cerebellar herniations and 2/16 (13%) patients had bilateral BHAG. CONCLUSION: In patients with PT, BHAG is a prevalent MRI finding that is strongly associated with the clinical diagnosis of IIH. The pathogenesis of BHAG remains uncertain, but recognition should prompt comprehensive evaluation for IIH.

Management of vascular causes of pulsatile tinnitus.

Pulsatile tinnitus is a debilitating symptom affecting millions of Americans and can be a harbinger of hemorrhagic or ischemic stroke. Careful diagnostic evaluation of pulsatile tinnitus is critical in providing optimal care and guiding the appropriate treatment strategy. When a vascular cause of pulsatile tinnitus has been established, attention must be focused on the patient's risk of hemorrhagic stroke, ischemic stroke, or blindness, as well as the risks of the available treatment options, in order to guide decision-making. Herein we review our approach to management of the vascular causes of pulsatile tinnitus and provide a literature review while highlighting gaps in our current knowledge and evidence basis.

Diagnostic Approach to Pulsatile Tinnitus: A Narrative Review.

Importance: Pulsatile tinnitus is a debilitating symptom affecting millions of Americans and can be a harbinger of hemorrhagic or ischemic stroke. Careful diagnostic evaluation of pulsatile tinnitus is critical in providing optimal care and guiding the appropriate treatment strategy. Observations: An underlying cause of pulsatile tinnitus can be identified in more than 70% of patients with a thorough evaluation. We advocate categorizing the myriad causes of pulsatile tinnitus into structural, metabolic, and vascular groups. Structural causes of pulsatile tinnitus include neoplasms and temporal bone pathologic abnormalities. Metabolic causes of pulsatile tinnitus include ototoxic medications and systemic causes of high cardiac output. Vascular causes of pulsatile tinnitus include idiopathic intracranial hypertension and dural arteriovenous fistulas. This categorization facilitates a practical evaluation, referral, and treatment pattern. Conclusions and Relevance: Categorizing the underlying cause of pulsatile tinnitus ensures that dangerous causes of pulsatile tinnitus are not missed, and that patients receive the appropriate care from the proper specialist when needed.

MRI and MR angiography evaluation of pulsatile tinnitus: A focused, physiology-based protocol.

BACKGROUND AND PURPOSE: Pulsatile tinnitus (PT) is the subjective sensation of a pulse-synchronous sound, most often due to a cerebrovascular etiology. PT can severely impact quality of life and may indicate a life-threatening process, yet a timely and accurate diagnosis can often lead to effective treatment. Clinical assessment with a history and physical examination can often suggest a diagnosis for PT, but is rarely definitive. Therefore, PT should be evaluated with a comprehensive and targeted radiographic imaging protocol. MR imaging provides a safe and effective means to evaluate PT. Specific MR sequences may be used to highlight different elements of cerebrovascular anatomy and physiology. However, routine MR evaluation of PT must comply with economic and practical constraints, while effectively capturing both common and rarer, life-threatening etiologies of PT. METHODS: In this state-of-the-art review, we describe our institutional MR protocol for evaluating PT. RESULTS: This protocol includes the following dedicated sequences: time-of-flight magnetic resonance angiography; arterial spin labeling; spoiled gradient recalled acquisition in the steady state; time-resolved imaging of contrast kinetics; diffusion weighted imaging, and 3-dimensional fluid-attenuated inversion recovery. CONCLUSIONS: We describe the physiologic and clinical rationale for including each MR sequence in a comprehensive PT imaging protocol, and detail the role of MR within the broader evaluation of PT, from clinical presentation to treatment.

Endovascular Biopsy of Vertebrobasilar Aneurysm in Patient With Polyarteritis Nodosa.

Background and Purpose: The management of unruptured intracranial aneurysms remains controversial. The decisions to treat are heavily informed by estimated risk of bleeding. However, these estimates are imprecise, and better methods for stratifying the risk or tailoring treatment strategy are badly needed. Here, we demonstrate an initial proof-of-principle concept for endovascular biopsy to identify the key molecular pathways and gene expression changes associated with aneurysm formation. We couple this technique with single cell RNA sequencing (scRNAseq) to develop a roadmap of the pathogenic changes of a dolichoectatic vertebrobasilar aneurysm in a patient with polyarteritis nodosa. Methods: Endovascular biopsy and fluorescence activated cell sorting was used to isolate the viable endothelial cells (ECs) using the established techniques. A single cell RNA sequencing (scRNAseq) was then performed on 24 aneurysmal ECs and 23 patient-matched non-aneurysmal ECs. An integrated panel of bioinformatic tools was applied to determine the differential gene expression, enriched signaling pathways, and cell subpopulations hypothesized to drive disease pathogenesis. Results: We identify a subset of 7 (29%) aneurysm-specific ECs with a distinct gene expression signature not found in the patient-matched control ECs. A gene set enrichment analysis identified these ECs to have increased the expression of genes regulating the leukocyte-endothelial cell adhesion, major histocompatibility complex (MHC) class I, T cell receptor recycling, tumor necrosis factor alpha (TNFα) response, and interferon gamma signaling. A histopathologic analysis of a different intracranial aneurysm that was later resected yielded a diagnosis of polyarteritis nodosa and positive staining for TNFα. Conclusions: We demonstrate feasibility of applying scRNAseq to the endovascular biopsy samples and identify a subpopulation of ECs associated with cerebral aneurysm in polyarteritis nodosa. Endovascular biopsy may be a safe method for deriving insight into the disease pathogenesis and tailoring the personalized treatment approaches to intracranial aneurysms.

Explainability Metrics of Deep Convolutional Networks for Photoplethysmography Quality Assessment.

Photoplethysmography (PPG) is a noninvasive way to monitor various aspects of the circulatory system, and is becoming more and more widespread in biomedical processing. Recently, deep learning methods for analyzing PPG have also become prevalent, achieving state of the art results on heart rate estimation, atrial fibrillation detection, and motion artifact identification. Consequently, a need for interpretable deep learning has arisen within the field of biomedical signal processing. In this paper, we pioneer novel explanatory metrics which leverage domain-expert knowledge to validate a deep learning model. We visualize model attention over a whole testset using saliency methods and compare it to human expert annotations. Congruence, our first metric, measures the proportion of model attention within expert-annotated regions. Our second metric, Annotation Classification, measures how much of the expert annotations our deep learning model pays attention to. Finally, we apply our metrics to compare between a signal based model and an image based model for PPG signal quality classification. Both models are deep convolutional networks based on the ResNet architectures. We show that our signal-based one dimensional model acts in a more explainable manner than our image based model; on average 50.78% of the one dimensional model's attention are within expert annotations, whereas 36.03% of the two dimensional model's attention are within expert annotations. Similarly, when thresholding the one dimensional model attention, one can more accurately predict if each pixel of the PPG is annotated as artifactual by an expert. Through this testcase, we demonstrate how our metrics can provide a quantitative and dataset-wide analysis of how explainable the model is.

An isolated ruptured spinal aneurysm presents with a thalamic Infarct: case report.

BACKGROUND: Isolated spinal artery aneurysms are extremely rare, and their pathogenesis, clinical presentation, and treatment strategies are poorly established. We report only the second case of a patient with an isolated posterior spinal aneurysm and concurrent left thalamic infarct and review the literature to help clarify treatment strategies of isolated spinal aneurysms. CASE PRESENTATION: A 49-year-old patient presented with acute onset walking difficulty followed by diaphoresis, back and abdominal pain, and paraplegia. Imaging was notable for a hemorrhagic spinal lesion with compression at T12 through L4 and an acute left thalamic infarct. Surgical exploration revealed an isolated posterior spinal artery aneurysm. The aneurysm was surgically resected and the patient had partial recovery six months post-operatively. CONCLUSIONS: Isolated posterior spinal artery aneurysms of the thoracolumbar region are rare lesions that commonly present with abdominal pain, radiating back pain, and lower extremity weakness. Imaging may not provide a definitive diagnosis. The three primary treatment strategies are conservative management, endovascular treatment, or surgical resection. In patients with symptomatic cord compression, immediate surgical intervention is indicated to preserve neurologic function. In all other cases, the artery size, distal flow, morphology, and location may guide management.

Venous sinus stenting as a treatment approach in patients with idiopathic intracranial hypertension and encephaloceles.

BACKGROUND: Stenosis of a dural venous sinus is the most common cause of idiopathic intracranial hypertension (IIH) and can be classified as either intrinsic or extrinsic. Intrinsic stenoses are characterized by a focal filling defect within the sinus secondary to an enlarged arachnoid granulation or fibrous septa while extrinsic stenoses tend to be long and smooth-tapered and are most commonly secondary to external compression from the adjacent brain parenchyma. Brain herniations, or encephaloceles, into arachnoid granulations in dural venous sinuses have rarely been reported in the literature in patients with IIH. We propose that dural venous sinus stenting (VSS) may be a safe and effective treatment approach in patients with an encephalocele and IIH. METHODS: We retrospectively analyze three cases of patients with encephalocele who underwent VSS for treatment of medically refractory IIH at our institution. RESULTS: One patient underwent stenting ipsilateral and two patients underwent stenting contralateral to the side of their encephaloceles. No technical related issues or complications occurred during either of the three stenting procedures. Two out of the three patients had complete resolution in their IIH-related symptoms and normalization of cerebrospinal (CSF) pressures shortly after stenting. We await clinical follow-up in the third patient. CONCLUSIONS: Our results suggest that VSS is a technically feasible and effective approach in treating patients with medically refractory IIH and encephaloceles.

Neurovascular disease, diagnosis, and therapy: Cervical and intracranial atherosclerosis, vasculitis, and vasculopathy.

Stroke is a leading cause of death, disability, and financial burden in the United States. Perhaps more than any other disease process, the rapidity with which the diagnosis and treatment of stroke are successfully achieved is paramount to the reduction of its associated morbidity and mortality. Steno-occlusive intracranial vascular disease, the most notorious culprit of cerebral ischemia and/or hemorrhage, traces its etiology to native and embolic atherosclerosis as well as various forms of vascular inflammation, insult, and dysfunction. Distinguishing between these causes is a critical first step in the diagnosis and treatment of a patient presenting with cerebrovascular compromise. In this chapter, we delineate the clinical and imaging features of cervical and intracranial atherosclerosis, vasculitis, and vasculopathy, along with the evidence behind the treatments which comprise their current-day standard of care. The modern imaging armamentarium is diverse and complex, with contrast-enhanced and non-contrast MR angiography, CT angiography, digital subtraction angiography, and ultrasound; each playing an important role in providing rapid insight into the patient's disease process. Understanding these imaging techniques and their application in the acute setting is critical for the provider caring for stroke patients.

Controversies and Advances in Adult Intracranial Bypass Surgery in 2020.

Cerebral revascularization utilizing a variety of bypass techniques can provide either flow augmentation or flow replacement in the treatment of a range of intracranial pathologies, including moyamoya disease, intracranial atherosclerotic disease, and complex aneurysms that are not amenable to endovascular or simple surgical techniques. Though once routine, the publication of high-quality prospective evidence, along with the development of flow-diverting stents, has limited the indications for extracranial-to-intracranial (EC-IC) bypass. Nevertheless, advances in imaging, assessment of cerebral hemodynamics, and surgical technique have changed the risk-benefit calculus for EC-IC bypass. New variations of revascularization surgery involving multiple anastomoses, flow preserving solutions, IC-IC constructs, and posterior circulation bypasses have been pioneered for otherwise difficult to treat pathology including giant aneurysms, dolichoectasia, and medically refractory intracranial atherosclerosis. This review provides a practical update on recent advances in adult intracranial bypass surgery.

Catastrophic stroke burden in a patient with uncontrolled psoriasis and psoriatic arthritis: a case report.

BACKGROUND: Psoriasis is the most common chronic inflammatory condition involving the T helper cell system. Population studies have demonstrated that patients with psoriasis and/or psoriatic arthritis have an increased risk of developing vascular risk factors, including diabetes, hypertension, and obesity, and increased risk of adverse vascular events, including myocardial infarction and stroke. Population studies have generally investigated the individual contributions of psoriasis and psoriatic arthritis to development of vascular risk factors; fewer studies have investigated the additive contribution of comorbid inflammatory disorders. We present a case of a woman with psoriasis, psoriatic arthritis, and comorbid vascular risk factors. CASE PRESENTATION: A 49 year-old Caucasian woman with a history of severe psoriasis and psoriatic arthritis since adolescence presented with bilateral lower extremity weakness. She was found to have acute bilateral watershed infarcts and multifocal subacute infarcts. Her evaluation revealed vascular risk factors and elevated non-specific systemic inflammatory markers; serum and cerebral spinal fluid did not reveal underlying infection, hypercoagulable state, or vasculitis. Over the course of days, she exhibited precipitous clinical deterioration related to multiple large vessel occlusions, including the bilateral anterior cerebral arteries and the left middle cerebral artery. Autopsy revealed acute thrombi and diffuse, severe atherosclerosis. CONCLUSION: Patients with early onset inflammatory disease activity or comorbid inflammatory disorders may have an even higher risk of developing metabolic syndrome and adverse vascular events compared to patients with late-onset disease activity or with a single inflammatory condition. The described case illustrates the complex relationship between inflammatory disorders and vascular risk factors. The degree of systemic inflammation, as measured by severity of disease activity, has been shown to have a dose-response relationship with comorbid vascular risk factors and vascular events. Dysregulation of the Th1 and Th17 system has been implicated in the development of atherosclerosis and may explain the severe atherosclerosis seen in such chronic inflammatory conditions. Further research will help refine screening and management guidelines to account for comorbid inflammatory disorders and related disease severity.

Photoplethysmography based atrial fibrillation detection: a review.

Atrial fibrillation (AF) is a cardiac rhythm disorder associated with increased morbidity and mortality. It is the leading risk factor for cardioembolic stroke and its early detection is crucial in both primary and secondary stroke prevention. Continuous monitoring of cardiac rhythm is today possible thanks to consumer-grade wearable devices, enabling transformative diagnostic and patient management tools. Such monitoring is possible using low-cost easy-to-implement optical sensors that today equip the majority of wearables. These sensors record blood volume variations-a technology known as photoplethysmography (PPG)-from which the heart rate and other physiological parameters can be extracted to inform about user activity, fitness, sleep, and health. Recently, new wearable devices were introduced as being capable of AF detection, evidenced by large prospective trials in some cases. Such devices would allow for early screening of AF and initiation of therapy to prevent stroke. This review is a summary of a body of work on AF detection using PPG. A thorough account of the signal processing, machine learning, and deep learning approaches used in these studies is presented, followed by a discussion of their limitations and challenges towards clinical applications.

Generalizability of SuperAlarm via Cross-Institutional Performance Evaluation.

Bedside patient monitors are ubiquitous tools in modern critical care units to provide timely patient status. However, current systems suffer from high volume of false alarms leading to alarm fatigue, one of top technical hazards in clinical settings. Many studies are racing to develop improved algorithms towards precision patient monitoring, while little has been done to investigate the aspect of algorithm generalizability across different health institutions. Our group has been developing an evolving framework termed SuperAlarm that extracts multivariate patterns in data streams (monitor alarms, electronic health records and physiologic waveforms) of modern health enterprise to predict patient deterioration and has demonstrated great potential in mitigating alarm fatigue. In this study, we further investigate the generalizability of SuperAlarm by designing a comprehensive approach to achieve performance comparison in predicting in-hospital code blue (CB) events across two health institutions. SuperAlarm model trained with alarm data in one institution is tested on both internal and external test sets. Results show comparable performance with sensitivity up to 80% within one-hour window of events and over 90% in reduction of false alarms in both institutions. Cross-institutional performance agreement can be further improved by predicting a more stringent CB subtype (cardiopulmonary arrest), with internal sensitivity lying within 95% confident interval of external one up to 8-hour before event onset. The cross-institutional performance comparison offers first-hand knowledge on both advantages and challenges in generalizing a prediction algorithm across different institutions, which hold key information to guide the design of model training and deployment strategy.

Sound Measurement in Patient-Specific 3D Printed Bench Models of Venous Pulsatile Tinnitus.

HYPOTHESIS: We hypothesize patient-specific flow models to be an adequate in vitro surrogate to allow for characterization of pulsatile tinnitus (PT) that affects three to five million Americans. BACKGROUND: PT, rhythmic sounds without an extracorporeal source that patients appreciate, can be caused by aberrant blood flow in large cerebral veins near the cochlea. To investigate the sound production mechanism, we created 3D printed flow models based on patient-specific cerebral venous anatomies. METHODS: Magnetic resonance angiography datasets from two patients with PT were used to generate patient-specific 3D printed flow models. A flow circuit connecting the patient-specific models to a pulsatile, continuous flow pump simulating cardiac cycle was created. Sound recordings were made along the surface of the models using an electronic stethoscope. Peak-to-rms amplitude, and area under the power spectral density (PSD) curve values were computed to evaluate the sound measurements. Wilcoxon rank sum test was used to statistically determine the differences in measurements between the patient-specific models. RESULTS: In patient-1, the recordings (peak-to-rms) from the internal jugular vein stenosis of baseline model (4.29 ±â€Š1.26 for 146 samples) were significantly louder (p < 0.001) than that of the altered model (3.29 ±â€Š0.96 for 143 samples). In patient-2, the sound measured at the transverse sinus stenosis in the pre-lumbar puncture model (4.84 ±â€Š1.11 for 148 samples) was significantly louder (p < 0.0001) than that of the post-lumbar puncture model (3.14 ±â€Š0.87 for 135 samples). CONCLUSIONS: The models are able to generate sounds very similar to those appreciated by patients and examiners in the cases of objective PT.