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1.
Hypertens Res ; 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38982290

ABSTRACT

Blood pressure or flow measurements have been associated with vascular health and cognitive function. We proposed that energetic hemodynamic parameters may provide a more nuanced understanding and stronger correlation with cognitive function, in comparisons with conventional aortic and carotid pressure and flow parameters. The study comprised 1858 participants, in whom we assessed cognitive function via MoCA method, and measured central aortic and carotid pressure and flow waveforms. In addition to various pressure and flow parameters, we calculated energetic hemodynamic parameters through integration of pressure multiplying flow with respect to time. Energetic hemodynamic parameters, particularly aortic and carotid mean and pulsatile energy and pulsatility index (PI), were significantly associated with MoCA score more than any aortic and carotid pressure and flow parameters, after adjusting for age, sex, education, depression score, heart rate, BMI, HDL-cholesterol, and glucose levels. MoCA exhibited a strong positive relationship with carotid mean energy (standardized beta = 0.053, P = 0.0253) and a negative relationship with carotid energy PI (standardized beta = -0.093, P = 0.0002), exceeding the association with all traditional pressure- or flow-based parameters. Aortic pressure reflection coefficient at the aorto-carotid junction was positively correlated with mean carotid energy and negatively correlated with PI. Aortic characteristic impedance positively correlated with carotid energy PI but not mean energy. Our research indicates that energetic hemodynamic parameters, particularly carotid mean energy and carotid energy PI, have a stronger association with MoCA scores than traditional pressure- or flow-based metrics. This correlation with cognitive function is notably influenced by the properties of the aorto-carotid interface.

2.
Article in English | MEDLINE | ID: mdl-38984878

ABSTRACT

OBJECTIVE: Pulse-synchronous tinnitus (PST) has been linked to multiple anatomical variants of the central venous outflow tract (CVOT) including sigmoid sinus (SS) dehiscence and diverticulum. This study investigates flow turbulence, pressure, and wall shear stress along the CVOT and proposes a mechanism that results in SS dehiscence and PST. STUDY DESIGN: Case series. SETTING: Tertiary Academic Center. METHODS: Venous models were reconstructed from computed tomography scans of 3 patients with unilateral PST. Two models for each patient are obtained: a symptomatic and contralateral asymptomatic side. A turbulent model-enabled commercial flow solver was used to simulate the pulsatile blood flow over the cardiac cycle through the models. Fluid flow through the transverse and SS junction was analyzed to observe the velocity, pressure, turbulent kinetic energy (TKE), and shear stress over a simulated cardiac cycle. RESULTS: Fluid flow on the symptomatic side showed increased vorticity in the presence of an SS diverticulum. Higher TKE with periodicity following the cardiac cycle was observed on the symptomatic side, and a sharp increase was observed if SS diverticulum was present. Shear stress was highest near the narrowest segments of the vessel. Pressure was observed to be lower on the symptomatic side at the transverse-SS junction for all 3 patients. CONCLUSION: Computational fluid dynamics modeling of blood flow through the CVOT in PST suggests that low pressure may be the cause of dehiscence, and tinnitus may result from periodic increases in TKE.

3.
IEEE Open J Eng Med Biol ; 5: 330-338, 2024.
Article in English | MEDLINE | ID: mdl-38899025

ABSTRACT

Goal: To establish Pulse2AI as a reproducible data preprocessing framework for pulsatile signals that generate high-quality machine-learning-ready datasets from raw wearable recordings. Methods: We proposed an end-to-end data preprocessing framework that adapts multiple pulsatile signal modalities and generates machine-learning-ready datasets agnostic to downstream medical tasks. Results: a dataset preprocessed by Pulse2AI improved systolic blood pressure estimation by 29.58%, from 11.41 to 8.03 mmHg in root-mean-square-error (RMSE) and its diastolic counterpart by 26.01%, from 7.93 to 5.87 mmHg in RMSE. For respiration rate (RR) estimation, Pulse2AI boosted performance by 19.69%, from 1.47 to 1.18 breaths per minute (BrPM) in mean-absolute-error (MAE). Conclusion: Pulse2AI turns pulsatile signals into machine learning (ML) ready datasets for arbitrary remote health monitoring tasks. We tested Pulse2AI on multiple pulsatile modalities and demonstrated its efficacy in two medical applications. This work bridges valuable assets in remote sensing and internet of medical things to ML-ready datasets for medical modeling.

4.
Cureus ; 16(5): e59811, 2024 May.
Article in English | MEDLINE | ID: mdl-38846216

ABSTRACT

BACKGROUND: Neurovascular compression syndromes (NVCS), encompassing conditions such as trigeminal neuralgia, hemifacial spasm, and glossopharyngeal neuralgia, significantly impair patient quality of life through abnormal vascular compression and micro-pulsation of vasculature on cranial nerves at the Obersteiner-Redlich zone. The modulation of pulsatile flow dynamics via endovascular stents presents a novel research frontier for alleviating these syndromes. AIM: The primary aim of this investigation was to delineate the impact of various endovascular stents on pulsatile flow within an in vitro model of a blood vessel, thereby elucidating their potential applicability in the therapeutic management of NVCS. MATERIALS AND METHODS: A simple in vitro analog of a posterior circulation artery was developed, employing an intravenous pump to replicate cardiac-induced blood flow. Within this model, alterations in pulsatile flow were quantitatively assessed following the introduction of three categorically distinct endovascular stents, varying in size. This assessment was facilitated through the employment of both micro-Doppler and Doppler ultrasound methodologies. RESULTS: The Pipeline 5x35 mm stent (Medtronic, Minneapolis, MN) demonstrated the most significant reductions in peak systolic velocity (Vmax) and pulsatility index (PI), PI especially over the stent, suggesting its potential for drastically altering blood flow dynamics. Similarly, Neuroform Atlas 4.5x30 mm and Neuroform Atlas 4x24 mm stents (Stryker, Kalamazoo, MI) also showed notable decreases in hemodynamic parameters, albeit to different extents. Statistical analysis confirmed that these changes were significantly different from the control (P < 0.0001 for PI and Vmax; P < 0.05 for inter-stent comparisons), except for proximal PI means, which did not significantly differ from the control (P = 0.2777). CONCLUSION: These findings affirm the potential of endovascular stents to substantially modulate arterial pulsatility. The observed decrease in pulsatile flow resultant from endovascular stent application has the potential to attenuate ectopic nerve excitation, a hallmark of NVCS. Consequently, this research highlights the prospective utility of endovascular stents in developing minimally invasive therapeutic approaches for NVCS.

5.
Bioengineering (Basel) ; 11(6)2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38927848

ABSTRACT

This study aimed to investigate the effect of the transverse sinus (TS) stenosis (TSS) position caused by arachnoid granulation on patients with venous pulsatile tinnitus (VPT) and to further identify the types of TSS that are of therapeutic significance for patients. Multiphysics interaction models of six patients with moderate TSS caused by arachnoid granulation and virtual stent placement in TSS were reconstructed, including three patients with TSS located in the middle segment of the TS (group 1) and three patients with TTS in the middle and proximal involvement segment of the TS (group 2). The transient multiphysics interaction simulation method was applied to elucidate the differences in biomechanical and acoustic parameters between the two groups. The results revealed that the blood flow pattern at the TS and sigmoid sinus junction was significantly changed depending on the stenosis position. Preoperative patients had increased blood flow in the TSS region and TSS downstream where the blood flow impacted the vessel wall. In group 1, the postoperative blood flow pattern, average wall pressure, vessel wall vibration, and sound pressure level of the three patients were comparable to the preoperative state. However, the postoperative blood flow velocity decreased in group 2. The postoperative average wall pressure, vessel wall vibration, and sound pressure level of the three patients were significantly improved compared with the preoperative state. Intravascular intervention therapy should be considered for patients with moderate TSS caused by arachnoid granulations in the middle and proximal involvement segment of the TS. TSS might not be considered the cause of VPT symptoms in patients with moderate TSS caused by arachnoid granulation in the middle segment of the TS.

6.
Comput Methods Programs Biomed ; 254: 108298, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38936154

ABSTRACT

BACKGROUND: Synchronous acquisition of haemodynamic signals is crucial for their multimodal analysis, such as dynamic cerebral autoregulation (DCA) analysis of arterial blood pressure (ABP) and transcranial Doppler (TCD)-derived cerebral blood velocity (CBv). Several technical problems can, however, lead to (varying) time-shifts between the different signals. These can be difficult to recognise and can strongly influence the multimodal analysis results. METHODS: We have developed a multistep, cross-correlation-based time-shift detection and synchronisation algorithm for multimodal pulsatile haemodynamic signals. We have developed the algorithm using ABP and CBv measurements from a dataset that contained combinations of several time-shifts. We validated the algorithm on an external dataset with time-shifts. We additionally quantitatively validated the algorithm's performance on a dataset with artificially added time-shifts, consisting of sample clock differences ranging from -0.2 to 0.2 s/min and sudden time-shifts between -4 and 4 s. The influence of superimposed noise and variation in waveform morphology on the time-shift estimation was quantified, and their influence on DCA-indices was determined. RESULTS: The instantaneous median absolute error (MedAE) between the artificially added time-shifts and the estimated time-shifts was 12 ms (median, IQR 12-12, range 11-14 ms) for drifts between -0.1 and 0.1 s/min and sudden time-shifts between -4 and 4 s. For drifts above 0.1 s/min, MedAE was higher (median 753, IQR 19 - 766, range 13 - 772 ms). When a certainty threshold was included (peak cross-correlation > 0.9), MedAE for all drifts-shift combinations decreased to 12 ms, with smaller variability (IQR 12 - 13, range 8 - 22 ms, p < 0.001). The time-shift estimation is robust to noise, as the MedAE was similar for superimposed white noise with variance equal to the signal variance. After time-shift correction, DCA-indices were similar to the original, non-time-shifted signals. Phase shift differed by 0.17° (median, IQR 0.13-0.2°, range 0.0038-1.1°) and 0.54° (median, IQR 0.23-1.7°, range 0.0088-5.6°) for the very low frequency and low frequency ranges, respectively. DISCUSSION: This algorithm allows visually interpretable detection and accurate correction of time-shifts between pulsatile haemodynamic signals (ABP and CBv).

7.
J Med Case Rep ; 18(1): 266, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38822435

ABSTRACT

BACKGROUND: Sigmoid sinus wall dehiscence can lead to pulsatile tinnitus with a significant decrease in quality of life, occasionally leading to psychiatric disorders. Several surgical and endovascular procedures have been described for resolving dehiscence. Within endovascular procedures, the sagittal sinus approach could be a technical alternative for tracking and accurate stent positioning within the sigmoid sinus when the jugular bulb anatomy is unfavorable. CASE PRESENTATION: A retrospective case series of three patients with pulsatile tinnitus due to sigmoid sinus wall dehiscence without intracranial hypertension was reviewed from January 2018 to January 2022. From the participants enrolled, the median age was 50.3 years (range 43-63), with 67% self-identifying as female and 33% as male. They self-identified as Hispanic. Sigmoid sinus dehiscence was diagnosed using angiotomography, and contralateral transverse sinus stenosis was observed in all patients. Patients underwent surgery via a navigated endovascular sagittal sinus approach for sigmoid sinus stenting. No neurological complications were associated with the procedure. Pulsatile tinnitus improved after the procedure in all patients. CONCLUSIONS: Superior sagittal sinus resection for sigmoid sinus wall stenting is a safe and effective technique. Pulsatile tinnitus due to sigmoid sinus wall dehiscence could be treated using the endovascular resurfacing stenting technique. However, further research is needed to evaluate the potential benefit of contralateral stenting for removing sinus dehiscence when venous stenosis is detected. However, resurfacing sigmoid sinus wall dehiscence results in symptomatic improvement.


Subject(s)
Endovascular Procedures , Stents , Tinnitus , Humans , Female , Male , Tinnitus/surgery , Tinnitus/etiology , Adult , Middle Aged , Endovascular Procedures/methods , Retrospective Studies , Cranial Sinuses/surgery , Superior Sagittal Sinus/surgery , Treatment Outcome , Constriction, Pathologic/surgery
8.
Article in English | MEDLINE | ID: mdl-38842617

ABSTRACT

PURPOSE OF REVIEW: The purpose of this review is to provide an updated approach to the evaluation and management of pulsatile tinnitus (PT), an uncommon but often treatable subtype of tinnitus. RECENT FINDINGS: Secondary PT can be due to either vascular or non-vascular etiologies, including, but not limited to: neoplasm, arteriovenous malformation or fistula, idiopathic intracranial hypertension, dural venous sinus stenosis, otoacoustic etiologies (e.g., otosclerosis, patulous eustachian tube) and bony defects (e.g., superior semicircular canal dehiscence). Computed tomography (CT) and magnetic resonance imaging (MRI) imaging have comparable diagnostic yield, though each may be more sensitive to specific etiologies. If initial vascular imaging is negative and a vascular etiology is strongly suspected, digital subtraction angiography (DSA) may further aid in the diagnosis. Many vascular etiologies of PT can be managed endovascularly, often leading to PT improvement or resolution. Notably, venous sinus stenting is an emerging therapy for PT secondary to idiopathic intracranial hypertension with venous sinus stenosis. Careful history and physical exam can help establish the differential diagnosis for PT and guide subsequent evaluation and management. Additional studies on the efficacy and long-term outcome of venous sinus stenting for venous stenosis are warranted.

9.
Int J Nephrol Renovasc Dis ; 17: 175-195, 2024.
Article in English | MEDLINE | ID: mdl-38882658

ABSTRACT

Introduction: The causes of chronic kidney disease (CKD) in people living in Sub-Saharan Africa await identification. Also, whether cardiovascular risk and disease extent differ among patients with different CKD etiologies is uncertain. Methods: In this prospective cross-sectional study, we examined the presumed causes of chronic kidney disease (CKD) and their relationships with cardiovascular risk and disease in 743 consecutive patients from a sub-Saharan low-income population. Results: Hypertensive nephropathy (HNP) (60.2%), diabetic nephropathy (DNP) (24.4%), HIV associated CKD (20.0%) and glomerular disease (13.6%) comprised the major CKD etiologies upon enrolment at the hospital nephrology clinic. Pulse pressure was larger in patients with concurrent HNP and DNP than in those with HNP only (p<0.001). Pulse pressure and systolic blood pressure were larger in HNP or/and DNP patients than those with HIV associated CKD and glomerular disease (p=0.04 to <0.001). Cardiovascular disease was more prevalent in patients with HNP and concurrent HNP and DNP than those from other etiologic categories (p<0.05). HNP and DNP were associated with pulsatile pressures (pulse pressure and systolic blood pressure) independent of one another (p<0.01). In adjusted product of coefficient mediation analysis, mean arterial or distending pressure accounted fully for the potential impact of HNP on pulsatile pressures (103.9-115.7%) but not for that of DNP on the respective pressures (-2.0%-(-)7.5%). Conclusion: HNP is by far the most prevalent presumed cause of CKD in this African population. Cardiovascular risk and disease differ markedly across CKD etiological categories.

10.
Interv Neuroradiol ; : 15910199241245451, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38715430

ABSTRACT

Venous sinus stenting for dural venous sinus outflow obstruction due to an intrinsic filling obstruction or extrinsic stenosis is an increasingly popular treatment strategy for idiopathic intracranial hypertension (IIH) and isolated pulsatile tinnitus (PT). The most common site of stenosis is the lateral venous sinus at the transverse-sigmoid junction. Approximately 10% of the population has a persistent occipital venous sinus (OVS), a variant that may be the dominant venous drainage pathway in the setting of a hypoplastic or aplastic transverse sinus. OVS stenosis has been rarely associated with IIH and isolated PT with only a handful published cases. We herein report a retrospective series of OVS stenting in five patients, four of whom presented with non-IIH PT and one with IIH.

11.
Neurosurg Clin N Am ; 35(3): 293-303, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38782522

ABSTRACT

Pulsatile tinnitus (PT) requires detailed workup to evaluate for an underlying structural cause. With advances in neuroimaging, structural venous abnormalities that can cause PT have becoming increasingly recognized. A number of anomalies, including dural arteriovenous fistulas, idiopathic intracranial hypertension, transverse sinus stenosis, sigmoid sinus wall abnormalities, jugular venous anomalies, and hypertrophied emissary veins, have been implicated in flow disruption and turbulence in the vicinity of auditory structures, resulting in PT. Endovascular treatment options, including stenting, coiling, and embolization with liquid agents, have demonstrated high efficacy and safety. These treatments can lead to symptomatic relief in carefully selected cases.


Subject(s)
Tinnitus , Humans , Central Nervous System Vascular Malformations/therapy , Central Nervous System Vascular Malformations/complications , Cranial Sinuses/diagnostic imaging , Cranial Sinuses/surgery , Embolization, Therapeutic/methods , Endovascular Procedures/methods , Tinnitus/therapy , Tinnitus/etiology
12.
Arch Endocrinol Metab ; 68: e230101, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38739523

ABSTRACT

Objective: Both pulsatile gonadotropin-releasing hormone (GnRH) and combined gonadotropin therapy are effective to induce spermatogenesis in men with congenital hypogonadotropic hypogonadism (CHH). This study aimed to evaluate the effect of pulsatile GnRH therapy on spermatogenesis in male patients with CHH who had poor response to combined gonadotropin therapy. Materials and methods: Patients who had poor response to combined gonadotropin therapy ≥ 6 months were recruited and shifted to pulsatile GnRH therapy. The rate of successful spermatogenesis, the median time to achieve spermatogenesis, serum gonadotropins, testosterone, and testicular volume were used for data analysis. Results: A total of 28 CHH patients who had poor response to combined gonadotropin (HCG/HMG) therapy for 12.5 (6.0, 17.75) months were recruited and switched to pulsatile GnRH therapy for 10.0 (7.25, 16.0) months. Sperm was detected in 17/28 patients (60.7%). The mean time for the appearance of sperm in semen was 12.0 (7.5, 17.5) months. Compared to those who could not achieve spermatogenesis during pulsatile GnRH therapy, the successful group had a higher level of LH60min (4.32 vs. 1.10 IU/L, P = 0.043) and FSH60min (4.28 vs. 1.90 IU/L, P = 0.021). Testicular size increased during pulsatile GnRH therapy, compared to previous HCG/ HMG therapy (P < 0.05). Conclusion: For CHH patients with prior poor response to one year of HCG/ HMG therapy, switching to pulsatile GnRH therapy may induce spermatogenesis.


Subject(s)
Gonadotropin-Releasing Hormone , Hypogonadism , Spermatogenesis , Testosterone , Humans , Male , Spermatogenesis/drug effects , Gonadotropin-Releasing Hormone/administration & dosage , Hypogonadism/drug therapy , Adult , Testosterone/administration & dosage , Testosterone/blood , Testosterone/therapeutic use , Young Adult , Treatment Outcome , Chorionic Gonadotropin/administration & dosage , Chorionic Gonadotropin/therapeutic use , Menotropins/administration & dosage , Menotropins/therapeutic use , Testis/drug effects , Drug Therapy, Combination , Pulse Therapy, Drug , Adolescent
13.
Laryngoscope ; 2024 May 28.
Article in English | MEDLINE | ID: mdl-38804647

ABSTRACT

OBJECTIVE: Sigmoid sinus wall anomalies (SSWA) are closely linked to venous pulsatile tinnitus (PT). This study aims to demonstrate that SSWA develops progressively rather than being congenital. METHODS: We retrospectively analyzed 42 PT patients with SSWA who had at least two non-operative CT scans at our clinic. CT images were longitudinally assessed to track SSWA progression, while MRI and Doppler ultrasound evaluated transverse sinus stenosis and venous hemodynamics. Changes in PT perception were tracked using the tinnitus handicap inventory (THI) questionnaire. RESULTS: Among the 42 SSWA patients, 12 (28.6%) exhibited progression. Anastomosis between diploic vein and diverticulum was significantly higher compared to the dehiscence cohort (p < 0.01). Within the diverticulum group, seven individuals (30.4%) experienced enlargement, with a mean diverticular wall expansion of 5.9% ± 11.4%. Progressive erosion was observed in two cases (12.5%) in the dehiscence cohort, with a mean sigmoid plate erosion of 3.8% ± 10.1%. In cases progressing from dehiscence to diverticulum, three subjects transitioned, with a mean sigmoid sinus wall length expansion of 43.8% ± 31.9%. SSWA progression showed a significant negative correlation with QBILATERAL (r = -0.857, p = 0.014), and there was a significant difference between initial and revisit THI scores (p < 0.01). CONCLUSION: SSWA can undergo morphological progression, indicating it is a progressive clinical condition rather than congenital. LEVEL OF EVIDENCE: 4 Laryngoscope, 2024.

14.
Interv Neuroradiol ; : 15910199241250082, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38693768

ABSTRACT

OBJECTIVE: Aspiration with a pump or syringe is a mainstay of mechanical thrombectomy (MT) for acute ischemic stroke (AIS), but this technology has seen minimal evolution. Non-continuous adaptive pulsatile aspiration (APA) has been proposed as a potential alternative to standard continuous aspiration as a means of improving revascularization efficiency. METHODS: Using a pathophysiological flow bench model with a synthetic clot, we performed in vitro thrombectomies using the ALGO® Von Vascular, Inc. (Sunrise, FL) APA pump. A total of 25 FDA-approved aspiration catheters were tested, representing inner diameters (ID) from 0.035 in. to 0.088 in. The pump was used in 30 trials with each catheter to remove a simulated M1 occlusion. Revascularization, clot ingestion, time to clot removal, and distal embolization were measured. RESULTS: Among catheters tested using APA, first-pass TICI 3 revascularization was achieved in 100% of the 750 thrombectomy trials using 25 different catheters. There were no distal emboli detected in any trial run. Complete clot ingestion into the pump collection chamber was achieved in 87% to 100% of trials (overall 95%) with clot in the remaining trials corking within the catheter and removed from the model. Time from clot contact to clot removal ranged from 11 s to 90 s (mean 22.6 s, SD 16.8 s), which was negatively correlated with catheter ID (p = 0.007). CONCLUSION: APA via the Von Vascular, Inc. ALGO® pump achieved a high success rate in an in vitro MT model. All catheters tested with the pump achieved complete reperfusion in all trials, and complete clot ingestion into the pump was seen in a majority of trials. The promising in vitro performance of APA using multiple catheters warrants future in vivo investigation.

15.
Heliyon ; 10(10): e29064, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38813204

ABSTRACT

Almost all biological processes in the human body are regulated by circadian rhythm, which results in drastically different biochemical and physiological conditions throughout a 24 h period. Hence, suitable drug delivery systems should be efficiently monitored to attain the required therapeutic plasma concentration and therapeutic drug responses when needed as per chrono pharmacological concepts. "Chronotherapy" is the fast and transient release of a particular quantity of drug substance post a predetermined off-release period, termed as 'lag time'. Due to rhythmic variations, it is typically unnecessary to administer a medicine drug in an unhealthy condition constantly. Pulsatile drug delivery systems have received a lot of attention in pharmaceutical development because they give a quick or rate-controlled drug release after administration, followed by an anticipated lag period. Patients with various illnesses, such as asthma, hypertension, joint inflammation, and ulcers, can benefit from a pulsatile drug delivery system. Thus, a pulsatile drug delivery system may be a potential system for managing different diseases. This review mainly focuses on pulsatile drug delivery systems. It reviews and discusses the rationale, drug release mechanism, need, and system classification. In addition, it covers mainly externally regulated pulsatile drug delivery systems and recent advances in pulsatile systems like artificial intelligence and 3D printing. It also covers the ethical issues associated with pulsatile drug delivery systems.

16.
Int J Pharm ; 658: 124204, 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38710297

ABSTRACT

Pulsatile drug delivery is hardly achieved by conventional gastro-retentive dosage forms. Artesunate as a typical anti-malaria medicine needs oral pulsatile release. Here, artesunate-loaded pulsatile-release multi-unit gastro-retentive tablets (APGTs) were prepared with a semi-solid extrusion three-dimensional (3D) printing method. An APGT was composed of three units: artesunate-loaded immediate and delayed release units and a block unit. The matrix of the immediate/delayed release units consisted of polyvinylpyrrolidone (PVP) K30 and croscarmellose sodium, which improved the rapid release of artesunate when contacting water. The block unit consisted of octadecanol, hydroxypropyl methyl cellulose K15M, PVP K30, and poloxamer F68. APGTs showed multi-phase release in simulated gastric liquids (SGLs). The first immediate release phase continued for 1 h followed by a long block phase for 7 h. The second rapid release phase was initiated when the eroded holes in the block unit extended to the inner delayed release unit, and this phase continued for about 14 h. Low-density APGTs could ensure their long-term floating in the stomach. Oral APGTs remained in the rabbit stomach for about 20 h. 3D printing provides a new strategy for the preparation of oral pulsatile-release tablets.


Subject(s)
Antimalarials , Artesunate , Delayed-Action Preparations , Drug Liberation , Povidone , Printing, Three-Dimensional , Tablets , Artesunate/administration & dosage , Artesunate/chemistry , Artesunate/pharmacokinetics , Animals , Rabbits , Antimalarials/administration & dosage , Antimalarials/chemistry , Antimalarials/pharmacokinetics , Povidone/chemistry , Hypromellose Derivatives/chemistry , Excipients/chemistry , Drug Delivery Systems , Administration, Oral , Carboxymethylcellulose Sodium/chemistry , Poloxamer/chemistry , Gastric Mucosa/metabolism
17.
World Neurosurg ; 184: 361-371, 2024 04.
Article in English | MEDLINE | ID: mdl-38590070

ABSTRACT

Venous sinus stenosis has garnered increasing academic attention as a potential etiology of idiopathic intracranial hypertension (IIH) and pulsatile tinnitus (PT). The complex anatomy of the cerebral venous sinuses and veins plays a crucial role in the pathophysiology of these conditions. Venous sinus stenosis, often found in the superior sagittal or transverse sinus, can lead to elevated intracranial pressure (ICP) and characteristic IIH symptoms. Stenosis, variations in dural venous anatomy, and flow dominance patterns contribute to aberrant flow and subsequent PT. Accurate imaging plays a vital role in diagnosis, and magnetic resonance (MR) venography is particularly useful for detecting stenosis. Management strategies for IIH and PT focus on treating the underlying disease, weight management, medical interventions, and, in severe cases, surgical or endovascular procedures. Recently, venous sinus stenting has gained interest as a minimally invasive treatment option for IIH and PT. Stenting addresses venous sinus stenosis, breaking the feedback loop between elevated ICP and stenosis, thus reducing ICP and promoting cerebrospinal fluid outflow. The correction and resolution of flow aberrances can also mitigate or resolve PT symptoms. While venous sinus stenting remains an emerging field, initial results are promising. Further research is needed to refine patient selection criteria and evaluate the long-term efficacy of stenting as compared to traditional treatments.


Subject(s)
Intracranial Hypertension , Pseudotumor Cerebri , Tinnitus , Humans , Pseudotumor Cerebri/complications , Pseudotumor Cerebri/diagnosis , Pseudotumor Cerebri/surgery , Tinnitus/diagnosis , Tinnitus/etiology , Tinnitus/therapy , Constriction, Pathologic/complications , Constriction, Pathologic/diagnostic imaging , Constriction, Pathologic/surgery , Intracranial Hypertension/complications , Intracranial Hypertension/diagnosis , Cranial Sinuses/diagnostic imaging , Cranial Sinuses/surgery , Stents/adverse effects
18.
World Neurosurg ; 184: 372-386, 2024 04.
Article in English | MEDLINE | ID: mdl-38590071

ABSTRACT

Although numerous case series and meta-analyses have shown the efficacy of venous sinus stenting (VSS) in the treatment of idiopathic intracranial hypertension and idiopathic intracranial hypertension-associated pulsatile tinnitus, there remain numerous challenges to be resolved. There is no widespread agreement on candidacy; pressure gradient and failed medical treatment are common indications, but not all clinicians require medical refractoriness as a criterion. Venous manometry, venography, and cerebral angiography are essential tools for patient assessment, but again disagreements exist regarding the best, or most appropriate, diagnostic imaging choice. Challenges with the VSS technique also exist, such as stent choice and deployment. There are considerations regarding postprocedural balloon angioplasty and pharmacologic treatment, but there is insufficient evidence to formalize postoperative decision making. Although complications of VSS are relatively rare, they include in-stent stenosis, hemorrhage, and subdural hematoma, and the learning curve for VSS presents specific challenges in navigating venous anatomy, emphasizing the need for wider availability of high-quality training. Recurrence of symptoms, particularly stent-adjacent stenosis, poses challenges, and although restenting and cerebrospinal fluid-diverting procedures are options, there is a need for clearer criteria for retreatment strategies. Despite these challenges, when comparing VSS with traditional cerebrospinal fluid-diverting procedures, VSS emerges as a favorable option, with strong clinical outcomes, lower complication rates, and cost-effectiveness. Further research is necessary to refine techniques and indications and address specific aspects of VSS to overcome these challenges.


Subject(s)
Intracranial Hypertension , Pseudotumor Cerebri , Tinnitus , Humans , Pseudotumor Cerebri/complications , Pseudotumor Cerebri/diagnostic imaging , Pseudotumor Cerebri/surgery , Tinnitus/etiology , Tinnitus/surgery , Constriction, Pathologic/diagnostic imaging , Constriction, Pathologic/surgery , Constriction, Pathologic/complications , Cranial Sinuses/diagnostic imaging , Cranial Sinuses/surgery , Stents/adverse effects , Intracranial Hypertension/surgery , Intracranial Hypertension/complications , Treatment Outcome , Retrospective Studies
19.
World Neurosurg ; 184: 387-394, 2024 04.
Article in English | MEDLINE | ID: mdl-38590072

ABSTRACT

This review explores the future role of venous sinus stenting (VSS) in the management of idiopathic intracranial hypertension and pulsatile tinnitus. Despite its favorable safety profile and clinical outcomes compared with traditional treatments, VSS is not yet the standard of care for these conditions, lacking high-level evidence data and guidelines for patient selection and indications. Current and recently completed clinical trials are expected to provide data to support the adoption of VSS as a primary treatment option. Additionally, VSS shows potential in treating other conditions, such as dural arteriovenous fistula and cerebral venous sinus thrombosis, and it is likely that the procedure will continue to see an expansion of its approved indications. The current lack of dedicated venous stenting technology is being addressed with promising advancements, which may improve procedural ease and patient outcomes. VSS also offers potential for expansion into modulation of brain electrophysiology via endovascular routes, offering exciting possibilities for neurodiagnostics and treatment of neurodegenerative disorders.


Subject(s)
Endovascular Procedures , Intracranial Hypertension , Pseudotumor Cerebri , Humans , Treatment Outcome , Stents , Cranial Sinuses/surgery , Endovascular Procedures/methods , Retrospective Studies
20.
J Biomech Eng ; 146(10)2024 10 01.
Article in English | MEDLINE | ID: mdl-38683061

ABSTRACT

Computational fluid dynamics (CFD) simulations are widely used to develop and analyze blood-contacting medical devices such as left ventricular assist devices (LVADs). This work presents an analysis of the transient behavior of two centrifugal LVADs with different designs: HeartWare VAD and HeartMate3. A scale-resolving methodology is followed through Large Eddy Simulations, which allows for the visualization of turbulent structures. The three-dimensional (3D) LVAD models are coupled to a zero-dimensional (0D) 2-element Windkessel model, which accounts for the vascular resistance and compliance of the arterial system downstream of the device. Furthermore, both continuous- and pulsatile-flow operation modes are analyzed. For the pulsatile conditions, the artificial pulse of HeartMate3 is imposed, leading to a larger variation of performance variables in HeartWare VAD than in HeartMate3. Moreover, CFD results of pulsatile-flow simulations are compared to those obtained by accessing the quasi-steady maps of the pumps. The quasi-steady approach is a predictive tool used to provide a preliminary approximation of the pulsatile evolution of flow rate, pressure head, and power, by only imposing a speed pulse and vascular parameters. This preliminary quasi-steady solution can be useful for deciding the characteristics of the pulsatile speed law before running a transient CFD simulation, as the former entails a significant reduction in computational cost in comparison to the latter.


Subject(s)
Heart-Assist Devices , Hydrodynamics , Pulsatile Flow , Models, Cardiovascular , Computer Simulation , Centrifugation , Humans
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