Unveiling FDA-Approved Drugs and Formulations in the Management of Bladder Cancer: A Review.

Urological cancers are one of the most prevalent malignancies around the globe. Specifically, bladder cancer severely threatens the health of humans because of its heterogeneous and aggressive nature. Extensive studies have been conducted for many years in order to address the limitations associated with the treatment of solid tumors with selective substances. This article aims to provide a summary of the therapeutic drugs that have received FDA approval or are presently in the testing phase for use in the prevention or treatment of bladder cancer. In this review, FDA-approved drugs for bladder cancer treatment have been listed along with their dose protocols, current status, pharmacokinetics, action mechanisms, and marketed products. The article also emphasizes the novel preparations of these drugs that are presently under clinical trials or are in the approval stage. Thus, this review will serve as a single point of reference for scientists involved in the formulation development of these drugs.

Neuronavigation-Guided Transcranial Histotripsy (NaviTH) System.

OBJECTIVE: The goal of the work described here was to develop the first neuronavigation-guided transcranial histotripsy (NaviTH) system and associated workflow for transcranial ablation. METHODS: The NaviTH system consists of a 360-element, 700 kHz transmitter-receiver-capable transcranial histotripsy array, a clinical neuronavigation system and associated equipment for patient-to-array co-registration and therapy planning and targeting software systems. A workflow for NaviTH treatments, including pre-treatment aberration correction, was developed. Targeting errors stemming from target registration errors (TREs) during the patient-to-array co-registration process, as well as focal shifts caused by skull-induced aberrations, were investigated and characterized. The NaviTH system was used in treatments of two <96 h post-mortem human cadavers and in experiments in two excised human skullcaps. RESULTS: The NaviTH was successfully used to create ablations in the cadaver brains as confirmed in post-treatment magnetic resonance imaging A total of three ablations were created in the cadaver brains, and targeting errors of 9, 3.4 and 4.4 mm were observed in corpus callosum, septum and thalamus targets, respectively. Errors were found to be caused primarily by TREs resulting from transducer tracking instrument design flaws and imperfections in the treatment workflow. Transducer tracking instrument design and workflow improvements reduced TREs to <2 mm, and skull-induced focal shifts, following pre-treatment aberration correction, were 0.3 mm. Total targeting errors of the NaviTH system following the noted improvements were 2.5 mm. CONCLUSIONS: The feasibility of using the first NaviTH system in a human cadaver model has been determined. Although accuracy still needs to be improved, the proposed system has the potential to allow for transcranial histotripsy therapies without requiring active magnetic resonance treatment guidance.

MR Imaging-based Biomarker Development in Hemorrhagic Stroke Patients Including Brain Iron Quantification, Diffusion Tensor Imaging, and Phenomenon of Ultra-early Erythrolysis.

This review article discusses the role of MR imaging-based biomarkers in understanding and managing hemorrhagic strokes, focusing on intracerebral hemorrhage (ICH) and aneurysmal subarachnoid hemorrhage. ICH is a severe type of stroke with high mortality and morbidity rates, primarily caused by the rupture of small blood vessels in the brain, resulting in hematoma formation. MR imaging-based biomarkers, including brain iron quantification, ultra-early erythrolysis detection, and diffusion tensor imaging, offer valuable insights for hemorrhagic stroke management. These biomarkers could improve early diagnosis, risk stratification, treatment monitoring, and patient outcomes in the future, revolutionizing our approach to hemorrhagic strokes.

Focused update to guidelines for endovascular therapy for emergent large vessel occlusion: basilar artery occlusion patients.

BACKGROUND: Endovascular therapy (EVT) dramatically improves clinical outcomes for patients with anterior circulation emergent large vessel occlusion (ELVO) strokes. With recent publication of two randomized controlled trials in favor of EVT for basilar artery occlusions, the Society of NeuroInterventional Surgery (SNIS) Standards and Guidelines Committee provides this focused update for the existing SNIS guideline, 'Current endovascular strategies for posterior circulation large vessel occlusion stroke.' METHODS: A structured literature review and analysis of studies related to posterior circulation large vessel occlusion (basilar or vertebral artery) strokes treated by EVT was performed. Based on the strength and quality of the evidence, recommendations were made by consensus of the writing committee, with additional input from the full SNIS Standards and Guidelines Committee and the SNIS Board of Directors. RESULTS: Based on the results of the most recent randomized, controlled trials on EVT for basilar or vertebral artery occlusion, the expert panel agreed on the following recommendations. For patients presenting with an acute ischemic stroke due to an acute basilar or vertebral artery occlusion confirmed on CT angiography, National Institutes of Health Stroke Scale (NIHSS) score of ≥6, posterior circulation Alberta Stroke Program Early CT Score (PC-ASPECTS) ≥6, and age 18-89 years: (1) thrombectomy is indicated within 12 hours since last known well (class I, level B-R); (2) thrombectomy is reasonable within 12-24 hours from the last known well (class IIa, level B-R); (3) thrombectomy may be considered on a case by case basis for patients presenting beyond 24 hours since last known well (class IIb, level C-EO). In addition, thrombectomy may be considered on a case by case basis for patients aged <18 years or >89 years on a case by case basis (class IIb, level C-EO). CONCLUSIONS: The indications for EVT of ELVO strokes continue to expand and now include patients with basilar artery occlusion. Further prospective, randomized controlled trials are warranted to elucidate the efficacy and safety of EVT in populations not included in this set of recommendations, and to confirm long term outcomes.

Characterization of Blood-Brain Barrier Opening Induced by Transcranial Histotripsy in Murine Brains.

OBJECTIVE: Transcranial histotripsy has shown promise as a non-invasive neurosurgical tool, as it has the ability to treat a wide range of locations in the brain without overheating the skull. One important effect of histotripsy in the brain is the blood-brain barrier (BBB) opening (BBBO) at the ablation site, but there is a knowledge gap concerning the extent of histotripsy-induced BBBO. Here we describe induction of BBBO by transcranial histotripsy and use of magnetic resonance imaging (MRI) and histology to quantify changes in BBBO at the periphery of the histotripsy ablation zone over time in the healthy mouse brain. METHODS: An eight-element, 1 MHz histotripsy transducer with a focal distance of 32.5 mm was used to treat the brains of 23 healthy female BL6 mice. T1-gadolinium (T1-Gd) MR images were acquired immediately following histotripsy treatment and during each of the subsequent 4 wk to quantify the size and intensity of BBB leakage. RESULTS: The T1-Gd MRI results revealed that the hyperintense BBBO volume increased over the first week and subsided gradually over the following 3 wk. Histology revealed complete loss of tight junction proteins and blood vessels in the center of the ablation region immediately after histotripsy, partial recovery in the periphery of the ablation zone 1 wk following histotripsy and near-complete recovery of tight junction complex after 4 wk. CONCLUSION: These results provide the first evidence of transcranial histotripsy-induced BBBO and repair at the periphery of the ablation zone.

The interplay among a dental procedure, infective endocarditis, and an acute ischemic stroke.

BACKGROUND: This case report highlights the rare association among a dental procedure, infective endocarditis, and an acute ischemic stroke. CASE DESCRIPTION: A 54-year-old woman who experienced an acute ischemic stroke 5 weeks after a tooth extraction is described. The initial symptoms of this patient included mild to moderate word-finding difficulty and right facial droop. Computed tomographic angiography revealed a left M1 segment middle cerebral artery occlusion (thrombolysis in cerebral infarction scale, 0) with reconstitution of the distal middle cerebral branches through arterial collaterals. After initial administration of tissue plasminogen activator, endovascular thrombectomy was successfully performed with thrombolysis in cerebral infarction scale 3 (complete) recanalization. After the procedure, the patient showed improvement in language and neurologic deficits. Imaging showed multifocal, bilateral, cortical, and deep brain hemorrhages. Blood cultures grew Streptococcus mitis, ultimately leading to the diagnosis of endocarditis. Echocardiographic imaging revealed moderate to severe aortic insufficiency, a mitral valve vegetation, and mild mitral valve regurgitation. After evaluation by the cardiothoracic surgery team, the patient was discharged with intravenous antibiotics and short-term outpatient follow-up with the cardiothoracic surgery team. PRACTICAL IMPLICATIONS: Dental procedures, although generally safe, can introduce oral bacteria into the bloodstream, leading to bacterial seeding of cardiac valves and subsequent infective endocarditis. Recognizing infective endocarditis subsequent to a dental procedure, including a tooth extraction, as a potential cause of an acute ischemic stroke is vital so that prompt treatment can be initiated.

Case of postoperative mitral and tricuspid valve repair with large vessel occlusion ischaemic stroke: successfully treated with mechanical thrombectomy extracting subocclusive thrombus containing foreign material.

A woman in her 60s with a history of prior ischaemic stroke developed acute onset slurring of speech, left-sided facial droop and left-sided weakness and was found on CT angiography to have a subocclusive thrombus multiple days after undergoing mitral and tricuspid valve repair surgery. A stent retriever and aspiration catheter were used to successfully remove the subocclusive material which was identified as 'foreign material' on histology. Ultimately, the patient demonstrated clinical improvement.Foreign material embolism is a rare but serious complication that can occur during or after mitral and tricuspid valve repair surgery. It can cause ischaemic stroke and prompt recognition and immediate intervention are necessary to prevent serious complications.The case report highlights the successful use of stent retriever-mediated suction thrombectomy to remove a foreign material embolism in a patient. It emphasises the importance of timely intervention to prevent serious complications and shows the potential benefits of this technique.

Scleral ectasia stabilization following intra-arterial chemotherapy in an eye with recurrent retinoblastoma.

Purpose: To report a case of recurrent retinoblastoma following transpupillary thermotherapy (TTT) with development of scleral ectasia, as well as their successful treatment with intra-arterial chemotherapy. Observations: A 15-month-old girl with bilateral retinoblastoma presented with recurrent retinoblastoma and associated scleral ectasia with concern for extraocular extension after receiving multiple round of systemic chemotherapy and TTT. Given her negative systemic evaluation, decision was made to pursue intra-arterial chemotherapy. After completion of six rounds of 3-agent intra-arterial chemotherapy, the recurrent retinoblastoma had completely regressed and the scleral ectasia had improved and fibrosed. Conclusions and importance: The sclera is classically viewed as hyperthermy-resistant to TTT. Here, we describe scleral ectasia due to aggressive TTT with recurrence of the retinoblastoma. Our treatment with intra-arterial chemotherapy not only caused complete regression of the recurrent retinoblastoma, but it also contributed to the stabilization and improvement of the weakened scleral.

Genetic Enhancement of Cereals Using Genomic Resources for Nutritional Food Security.

Advances in genomics resources have facilitated the evolution of cereal crops with enhanced yield, improved nutritional values, and heightened resistance to various biotic and abiotic stresses. Genomic approaches present a promising avenue for the development of high-yielding varieties, thereby ensuring food and nutritional security. Significant improvements have been made within the omics domain, specifically in genomics, transcriptomics, and proteomics. The advent of Next-Generation Sequencing (NGS) techniques has yielded an immense volume of data, accompanied by substantial progress in bioinformatic tools for proficient analysis. The synergy between genomics and computational tools has been acknowledged as pivotal for unravelling the intricate mechanisms governing genome-wide gene regulation. Within this review, the essential genomic resources are delineated, and their harmonization in the enhancement of cereal crop varieties is expounded upon, with a paramount focus on fulfilling the nutritional requisites of humankind. Furthermore, an encompassing compendium of the available genomic resources for cereal crops is presented, accompanied by an elucidation of their judicious utilization in the advancement of crop attributes.

The potential of 3D models and augmented reality in teaching cross-sectional radiology.

What was the educational challenge?The complexity and variability of cross-sectional imaging present a significant challenge in imparting knowledge of radiologic anatomy to medical students.What was the solution?Recent advancements in three-dimensional (3D) segmentation and augmented reality (AR) technology provide a promising solution. These advances allow for the creation of interactive, patient-specific 3D/AR models which incorporate multiple imaging modalities including MRI, CT, and 3D rotational angiography can help trainees understand cross-sectional imaging.How was the solution implemented?To create the model, DICOM files of patient scans with slice thicknesses of 1 mm or less are exported to a computer and imported to 3D Slicer for registration. Once registered, the files are segmented with Vitrea software utilizing thresholding, region growing, and edge detection. After the creation of the models, they are then imported to a web-based interactive viewing platform and/or AR application.What lessons were learned that are relevant to a wider global audience?Low-resource 3D/AR models offer an accessible and intuitive tool to teach radiologic anatomy and pathology. Our novel method of creating these models leverages recent advances in 3D/AR technology to create a better experience than traditional high and low-resource 3D/AR modeling techniques. This will allow trainees to better understand cross-sectional imaging.What are the next steps?The interactive and intuitive nature of 3D and AR models has the potential to significantly improve the teaching and presentation of radiologic anatomy and pathology to a medical student audience. We encourage educators to incorporate 3D segmentation models and AR in their teaching strategies.

Transcranial histotripsy parameter study in primary and metastatic murine brain tumor models.

OBJECTIVE: This study investigated the effect of various histotripsy dosages on tumor cell kill and associated bleeding in two murine brain tumor models (glioma [Gl261] and lung metastasis [LL/2-Luc2]). METHODS AND MATERIALS: GL261 or LL/2-Luc2 cells were cultured and implanted into the brains of C57BL/6 mice. Histotripsy (1-cycle pulses, 5 Hz PRF, 30 MPa-P) was performed using a 1 MHz transducer for five different dosages for each cell line: 5, 20 or 200 pulses per location (PPL) at a single treatment point, or 5 or 10-20 PPL at multiple treatment points. MRI, bioluminescence imaging and histology were used to assess tumor ablation and treatment effects within 4-6 h post-treatment. RESULTS: All treatment groups resulted in a reduction of BLI intensity for the LL/2-Luc2 tumors, with significant signal reductions for the multi-point groups. The average pre-/post-treatment BLI flux (photons/s, ×108) for the different treatment groups were: 4.39/2.19 (5 PPL single-point), 5.49/1.80 (20 PPL single-point), 3.86/1.73 (200 PPL single-point), 2.44/1.11 (5 PPL multi-point) and 5.85/0.80 (10 PPL multi-point). MRI and H&E staining showed increased tumor damage and hemorrhagic effects with increasing histotripsy dose for both GL261 and LL/2-Luc2 tumors, but the increase in tumor damage was diminished beyond 10-20 PPL for single-point treatments and outweighed by increased hemorrhage. In general, hemorrhage was confined to be within 1 mm of the treatment boundary for all groups. CONCLUSIONS: Our results suggest that a lower number of histotripsy pulses at fewer focal locations can achieve substantial tumor kill while minimizing hemorrhage.

Histotripsy Treatment of Murine Brain and Glioma: Temporal Profile of Magnetic Resonance Imaging and Histological Characteristics Post-treatment.

OBJECTIVE: Currently, there is a knowledge gap in our understanding of the magnetic resonance imaging (MRI) characteristics of brain tumors treated with histotripsy to evaluate treatment response as well as treatment-related injuries. Our aim was to bridge this gap by investigating and correlating MRI with histological analysis after histotripsy treatment of mouse brain with and without brain tumors and evaluating the evolution of the histotripsy ablation zone on MRI over time. METHODS: An eight-element, 1 MHz histotripsy transducer with a focal distance of 32.5 mm was used to treat orthotopic glioma-bearing mice and normal mice. The tumor burden at the time of treatment was ∼5 mm3. T2, T2*, T1 and T1-gadolinium (Gd) MR images and histology of the brain were acquired on days 0, 2 and 7 for tumor-bearing mice and days 0, 2, 7, 14, 21 and 28 post-histotripsy for normal mice. RESULTS: T2 and T2* sequences most accurately correlated with histotripsy treatment zone. The treatment-induced blood products, T1 along with T2, revealed blood product evolution from oxygenated, de-oxygenated blood and methemoglobin to hemosiderin. And T1-Gd revealed the state of the blood-brain barrier arising from the tumor or histotripsy ablation. Histotripsy leads to minor localized bleeding, which resolves within the first 7 d as evident on hematoxylin and eosin staining. By day 14, the ablation zone could be distinguished only by the macrophage-laden hemosiderin, which resides around the ablation zone, rendering the treated zone hypo-intense on all MR sequences. CONCLUSION: These results provide a library of radiological features on MRI sequences correlated to histology, thus allowing for non-invasive evaluation of histotripsy treatment effects in in vivo experiments.

Successful retrieval of ethylene vinyl alcohol (EVOH) from the left middle cerebral artery during preoperative embolization of a juvenile nasopharyngeal angiofibroma (JNA).

Preoperative embolization of a juvenile nasopharyngeal angiofibroma (JNA) using ethyl vinyl alcohol (EVOH) is an effective adjunctive treatment prior to surgical resection. While liquid embolic agents are safe to use, we present a unique case involving the migration of EVOH into the left middle cerebral artery (MCA) through an external carotid artery-internal carotid artery (ECA-ICA) collateral during preoperative embolization using a dual-lumen balloon catheter. A 16-year-old male presented with left-sided nasal congestion, new nasal intonation in voice, and epistaxis. CT imaging showed a hypervascular mass centered within the left posterior nasal cavity and nasopharynx with expansion of the ipsilateral sphenopalatine foramen. A JNA was diagnosed, and preoperative embolization was performed prior to surgical resection. During the embolization procedure, EVOH migrated into the intracranial circulation through a hypertrophied ECA-ICA collateral. Angiography confirmed embolic material at the left MCA bifurcation. The embolic material was successfully removed using a balloon guide catheter and stentriever. This case is presented to highlight potential complications and rescue techniques used in the setting of non-target embolization occurring during JNA embolization.

Comparing internal versus external carotid artery branch delivery of intraarterial chemotherapy for the treatment of retinoblastoma.

PURPOSE: The goal of this study was to compare the efficacy of intraarterial chemotherapy (IAC) for retinoblastoma delivered via the ophthalmic artery (OA) division of the internal carotid artery (ICA) versus alternative branches of the external carotid artery (ECA). METHODS: We performed a retrospective chart review of patients receiving IAC for retinoblastoma at a single institution. Subjects were divided into three groups: those that received IAC solely through the OA branch of the ICA, those that initially received IAC through the OA branch of the ICA but were later switched to the ECA, and those that only received IAC through the ECA. The main outcomes compared included globe salvage rate and reduction in tumor thickness and size. RESULTS: A total of 30 eyes from 26 patients were included. A total of 91 (58%) sessions of IAC were performed through the OA division of the ICA and 65 (42%) were performed through branches of the ECA. Eleven eyes (37%) solely received IAC through the OA branch of the ICA, 16 eyes (53%) were converted to ECA treatment, and 3 eyes solely received IAC through branches of the ECA. Statistical analysis did not show any significant difference in globe salvage rate or reduction in tumor thickness and size. CONCLUSION: The use of alternative approaches for IAC when the OA branch of the ICA catheterization is not feasible allows for safe continued delivery of highly effective IAC, leading to similar outcomes in terms of globe salvage and reduction in tumor size.

Newer Updates in Pediatric Vascular Diseases.

Pediatric neurovascular pathology directly involves or is in close proximity to the central nervous system (CNS). These vascular pathologies can occur in isolation or in association with broader syndromes. While some vascular pathologies are unique to the pediatric population, the full spectrum of adult neurovascular lesions can also affect children however, may present differently both clinically and on diagnostic imaging. Non-invasive (Ultrasound, CT, MRI) imaging plays a critical role in the diagnosis, treatment planning, and follow-up of vascular lesions involving the CNS. The modality can be chosen based on the age of the child, urgency of diagnosis, and local availability. Each modality has sensitivities and specificities which vary based on the location and imaging findings of a specific neurovascular pathology. In addition to non-invasive options, digital subtraction angiography (DSA) may be used as both a diagnostic and therapeutic imaging method for pediatric vascular lesions of the central nervous system. The diagnosis and management of pediatric cerebrovascular disease requires the close collaboration between pediatricians and pediatric specialists including neuroradiologists, neurologists, neurosurgeons, cardiologists, neurointerventionalists, and anesthesiologists among others. A detailed understanding of imaging findings, natural history, and treatment options is essential to guide and monitor imaging and treatment. The goal of this review is to provide the reader with an overview on pediatric neurovascular pathologies, provide examples of pathognomonic imaging findings, and present a brief review of endovascular treatment options, if applicable.

Neuroendovascular Procedures in Patients with Ehlers-Danlos Type IV: Multicenter Case Series and Systematic Review.

BACKGROUND: Ehlers-Danlos type IV or vascular Ehlers-Danlos syndrome (vEDS) is a rare inherited disorder characterized by profound vascular fragility resulting from defective production of type III procollagen. Cerebrovascular diseases including spontaneous dissections, cerebral aneurysms, and cavernous carotid fistulae are common. Endovascular therapies in this patient population are known to be higher risk, although many studies (before 2000) involved older techniques and equipment. The purpose of this study is to investigate the safety and efficacy of modern neuroendovascular techniques in the treatment of cerebrovascular diseases in patients with vEDS. METHODS: We combined a multi-institutional retrospective case series at 3 quaternary-care centers with a systematic literature review of individual case reports and case series spanning 2000-2021 to evaluate the safety and efficacy of neuroendovascular procedure in patients with vEDS with cerebrovascular diseases. RESULTS: Fifty-nine patients who underwent 66 neuroendovascular procedures were evaluated. Most of the patients had direct cavernous carotid fistulas (DCCF). Neuroendovascular procedures had a 94% success rate, with a complication rate of 30% and a mortality of 7.5%. CONCLUSIONS: Neuroendovascular procedures can be performed with a high rate of success in the treatment of cerebrovascular diseases in patients with vEDS, although special care is required because complication rates and mortality are high. Access site and procedure-related vascular injuries remain a significant hurdle in treating vEDS with cerebrovascular diseases, even with modern techniques.

Iatrogenic pseudoaneurysm of the middle meningeal artery during embolization of bilateral chronic subdural hematomas.

Summary/AbstractMiddle meningeal artery embolization has become an important treatment option for chronic subdural hematomas. While the treatment is safe, we present a unique case of development of an iatrogenic middle meningeal artery pseudoaneurysm during endovascular embolization with use of a dual-lumen balloon catheter used for injection of a liquid embolic agent. A 62-year-old man on Coumadin for portal vein thrombosis presented to the hospital with headache and supratherapeutic INR. Imaging revealed bilateral acute on chronic subdural hematomas. Given his medical comorbidities he underwent endovascular middle meningeal artery embolization. During the embolization, angiography revealed a pseudoaneurysm of the middle meningeal artery related to use of a dual-lumen balloon catheter. This pseudoaneurysm was successfully treated with ethylene vinyl alcohol embolization. Intracranial pseudoaneurysm related to balloon catheter use is a rare cause of iatrogenic pseudoaneurysm and could lead to life-threatening intracranial bleeding. Therefore, recognition and timely treatment are important.