Orally Ingested Self-Powered Stimulators for Targeted Gut-Brain Axis Electrostimulation to Treat Obesity and Metabolic Disorders.

Obesity is a significant health concern that often leads to metabolic dysfunction and chronic diseases. This study introduces a novel approach to combat obesity using orally ingested self-powered electrostimulators. These electrostimulators consist of piezoelectric BaTiO3 (BTO) particles conjugated with capsaicin (Cap) and aim to activate the vagus nerve. Upon ingestion by diet-induced obese (DIO) mice, the BTO@Cap particles specifically target and bind to Cap-sensitive sensory nerve endings in the gastric mucosa. In response to stomach peristalsis, these particles generate electrical signals. The signals travel via the gut-brain axis, ultimately influencing the hypothalamus. By enhancing satiety signals in the brain, this neuromodulatory intervention reduces food intake, promotes energy metabolism, and demonstrates minimal toxicity. Over a 3-week period of daily treatments, DIO mice treated with BTO@Cap particles show a significant reduction in body weight compared to control mice, while maintaining their general locomotor activity. Furthermore, this BTO@Cap particle-based treatment mitigates various metabolic alterations associated with obesity. Importantly, this noninvasive and easy-to-administer intervention holds potential for addressing other intracerebral neurological diseases.

The learning curve for cavernous sinus surgery illustrated by symptomatic intracavernous aneurysm clipping through a pretemporal transcavernous approach.

OBJECTIVE: The anatomy of the cavernous sinus (CS) has been well studied in the laboratory for decades; however, performing surgery in and around the CS is still a challenge. To reveal the learning curve for CS surgery via the pretemporal transcavernous approach (PTTC), surgical procedures were examined. The authors proposed 4 levels of surgical difficulty in opening the walls of the CS through this approach. Details of the approach were illustrated by surgical videos of symptomatic intracavernous aneurysm clipping. METHODS: Four levels of surgical difficulty were proposed. The higher the level, the more the CS walls were opened. Pathologies corresponding to each level of difficulty in and around the CS were categorized in each level together with explanations. From 2015 to 2021, 5 patients with symptomatic intracavernous aneurysms (diplopia due to compressive cranial neuropathy) underwent the PTTC at the authors' institute and served as representative cases in opening the walls of the CS. All CS cases from 2009 to 2021 were reviewed and categorized to demonstrate the learning curve. RESULTS: Four levels of surgical difficulty are as follows: level 1, a basic Dolenc extradural approach, which involves opening the anterior third of the superior and lateral walls of the CS; level 2, mobilizing the internal carotid artery (ICA) and opening the proximal dural ring to enter the roof of the CS and treat lesions around the clinoid and upper cavernous ICA; level 3, opening the entire aspect of the superior and lateral walls of the CS, which involves opening the oculomotor triangle and peeling the lateral wall of the CS to the tentorial incisura; and level 4, mobilizing cranial nerves III, IV, and V1 to gain access to the supra-/infratrochlear triangles to have proximal ICA control and opening the posterior wall as the last step to enter the posterior fossa. Surgical steps were described and illustrated with surgical videos of symptomatic intracavernous aneurysm clipping. CONCLUSIONS: The learning curve for CS surgery is long. The authors use 4 levels of surgical difficulty to describe applications of the PTTC in CS surgery. This approach serves as an effective workhorse in treating CS pathologies with low morbidity and high success rates when performed by experienced neurosurgeons.

Macrophage-Hitchhiked Orally Administered ß-Glucans-Functionalized Nanoparticles as "Precision-Guided Stealth Missiles" for Targeted Pancreatic Cancer Therapy.

The prognosis in cases of pancreatic ductal adenocarcinoma (PDAC) with current treatment modalities is poor owing to the highly desmoplastic tumor microenvironment (TME). Herein, a ß-glucans-functionalized zinc-doxorubicin nanoparticle system (ßGlus-ZnD NPs) that can be orally administered, is developed for targeted PDAC therapy. Following oral administration in PDAC-bearing mice, ßGlus-ZnD NPs actively target/transpass microfold cells, overcome the intestinal epithelial barrier, and then undergo subsequent phagocytosis by endogenous macrophages (ßGlus-ZnD@Mϕ). As hitchhiking cellular vehicles, ßGlus-ZnD@Mϕ transits through the intestinal lymphatic system and enters systemic circulation, ultimately accumulating in the tumor tissue as a result of the tumor-homing and "stealth" properties that are conferred by endogenous Mϕ. Meanwhile, the Mϕ that hitchhikes ßGlus-ZnD NPs is activated to produce matrix metalloproteinases, destroying the desmoplastic stromal barrier, and differentiates toward the M1 -like phenotype, modulating the TME and recruiting effector T cells, ultimately inducing apoptosis of the tumor cells. The combination of ßGlus-ZnD@Mϕ and immune checkpoint blockade effectively inhibits the growth of the primary tumor and suppresses the development of metastasis. It thus represents an appealing approach to targeted PDAC therapy.

A Noninvasive Gut-to-Brain Oral Drug Delivery System for Treating Brain Tumors.

Most orally administered drugs fail to reach the intracerebral regions because of the intestinal epithelial barrier (IEB) and the blood-brain barrier (BBB), which are located between the gut and the brain. Herein, an oral prodrug delivery system that can overcome both the IEB and the BBB noninvasively is developed for treating gliomas. The prodrug is prepared by conjugating an anticancer drug on ß-glucans using a disulfide-containing linker. Following oral administration in glioma-bearing mice, the as-prepared prodrug can specifically target intestinal M cells, transpass the IEB, and be phagocytosed/hitchhiked by local macrophages (Mϕ). The Mϕ-hitchhiked prodrug is transported to the circulatory system via the lymphatic system, crossing the BBB. The tumor-overexpressed glutathione then cleaves the disulfide bond within the prodrug, releasing the active drug, improving its therapeutic efficacy. These findings reveal that the developed prodrug may serve as a gut-to-brain oral drug delivery platform for the well-targeted treatment of gliomas.

The pretemporal trans-cavernous trans-Meckel's trans-tentorial trans-petrosal approach: a combo skill in treating skull base meningiomas.

PURPOSE: Surgical treatments for skull base meningiomas are challenging. We found that most of these lesions (75%), despite locating at the anterior, middle or posterior fossa, could be dealt with a combo skill-the pretemporal trans-cavernous trans-Meckel's trans-tentorial trans-petrosal approach (PCMTP), which adopted the same curvilinear skin incision as for the classic pterional approach. Our aim of this study is to validate the application of this technique in treating skull base meningiomas. METHODS: Patients underwent surgical intervention at our institute during 2010-2018 were retrospectively reviewed. We statistically analyzed the clinical, radiological, and pathological outcomes. RESULTS: In total, 109 patients operated with at least part of the PCMTP combo technique were included. The median follow-up time was 26.6 months. Tumor locations were categorized into: Zone I-sphenoid ridge, olfactory groove, and juxtasellar meningiomas which could be dealt with pterional approach. Zone II-clinoidal and cavernous sinus meningiomas which could be dealt with pretemporal trans-cavernous approach. Zone III-Meckel's and Incisura meningiomas which could be dealt with trans-Meckel's trans tentorial approach. Zone IV-petroclival menigiomas which could be dealt with trans-petrosal approach. When an extensive tumor occupied the anterior, middle, and posterior fossa, the whole combination of the PCMTP technique was applied. The mortality rate is 3.7% (4 patients). Three patients (2.8%) suffered from postoperative deterioration and required occasional assistance. The location of tumor was associated with different Simpson grade removal (p = 0.0015) and resection rate (p < 0.001). CONCLUSION: The PCMTP is effective in treating skull base meningiomas.

Pretemporal transcavernous transtentorial approach for left pontine glioma.

A 39-year-old man, who had a history of spinal myxopapillary ependymoma with cerebrospinal seeding status post twice operations and radiation therapy, presented with aggravating headaches, diplopia, dysphagia, and unsteady gait for 2 weeks. The brain MRI revealed a parenchymal lesion at the left aspect of the pons, about 2.8 × 2.3 × 3.2 cm3. The patient underwent a pretemporal transcavernous transtentorial approach for tumor removal. The pathological report showed an anaplastic astrocytoma. In this approach, a wider surgical corridor was obtained by opening the Meckel's cave and cutting the tentorium, via which a safe entry point into the pons could be determined with neuromonitoring. In the authors' opinion, this approach is safe and effective in selected ventrolateral pontine gliomas. The video can be found here: https://youtu.be/sUt-9QFGgCI.

Pretemporal trans-Meckel's cave transtentorial approach for large petroclival meningiomas.

OBJECTIVE Despite the advances in skull base techniques, large petroclival meningiomas (PCMs) still pose a challenge to neurosurgeons. The authors' objective of this study was to describe a pretemporal trans-Meckel's cave transtentorial approach for large PCMs and to report the surgical outcomes. METHODS From 2014 to 2017, patients harboring large PCMs (> 3 cm) and undergoing their first resection via this procedure at the authors' institute were included. In combination with pretemporal transcavernous and anterior transpetrosal approaches, the trans-Meckel's cave transtentorial route was created. Surgical details are described and a video demonstrating the procedure is included. Retrospective review of the medical records and imaging studies was performed. RESULTS A total of 18 patients (6 men and 12 women) were included in this study, with mean age of 53 years. The mean sizes of the preoperative and postoperative PCMs were 4.36 cm × 4.09 cm × 4.13 cm (length × width × height) and 0.83 cm × 1.08 cm × 0.75 cm, respectively. Gross-total removal was performed in 7 patients, near-total removal (> 95%) in 7 patients, and subtotal removal in 4 patients (> 90% in 3 patients and > 85% in 1 patient). There were no surgical deaths or patients with postoperative hemiplegia. Surgical complications included transient cranial nerve (CN) III palsy (all patients, resolved in 3 months), transient CN VI palsy (2 patients), CN IV palsy (3 patients, partial recovery), hydrocephalus (3 patients), and CSF otorrhea (1 patient). Temporal lobe retraction-related neurological deficits were not observed. CONCLUSIONS A pretemporal trans-Meckel's cave transtentorial approach offers large surgical exposure and multiple trajectories to the suprasellar, interpeduncular, prepontine, and upper-half clival regions without overt traction, which is mandatory to remove large PCMs. To unlock Meckel's cave where a large PCM lies abutting the cave, pretemporal transcavernous and anterior transpetrosal approaches are prerequisites to create adequate exposure for the final trans-Meckel's cave step.

Fluorescence-assisted visualization of facial nerve during mastoidectomy: A novel technique for preventing iatrogenic facial paralysis.

OBJECTIVE: Mastoidectomy can be risky due to the chance of iatrogenic facial nerve dysfunction. Avoiding injuries to the mastoid segment of the facial nerve is mandatory when drilling the bone. With advancements in intraoperative near-infrared indocyanine green (ICG) video angiography, we describe the application of a novel fluorescent guidance technique during mastoidectomies to identify the facial canal with safety. METHODS: Mastoidectomies were performed as the key step in the presigmoid, petrosal or translabyrinthine approaches in 16 patients with different pathologies located at the cerebellopontine angle or petroclival region. After the facial canal was drilled to paper thin, ICG was injected via the central venous catheter. Compared with the dark bony portion, the vessels inside the vasa nervorum were highlighted as a result. The fluorescence guides the operator through the course of the facial nerve and facilitates opening of the internal auditory canal and the dissection of tumors. RESULTS: All 16 facial nerves were recognized during mastoidectomies under fluorescence guidance for varied periods of enhancing time (range, 23-50s). In all, one to four attempts after repeated drilling works to enhance the facial nerve were required before these nerves could be clearly seen. The tumor resection procedure yielded the following results: grossly total removal in seven patients, near total removal in five, and subtotal removal in three. Complete obliteration of a giant vertebral artery aneurysm in one patient was seen in the follow-up angiogram. The post-mastoidectomy facial nerve function, examined by triggered EMG, was preserved in all 16 patients, and no patients had postoperative facial palsy worse than House-Brackmann grade IV after 6 months of follow-up. CONCLUSION: With this novel technique, the course of the facial nerve can be confirmed during mastoidectomy, which reduces the possibility of iatrogenic facial nerve dysfunction. This fluorescence technique is especially helpful in establishing confidence and shortening the learning curve for beginners at mastoidectomies.

Bilobulated paraclinoid aneurysm mimics double aneurysms: a comparison of endovascular coiling and surgical clipping treatments.

This report presents two cases of subarachnoid hemorrhage caused by rupture of paraclinoid aneurysms. Both aneurysms presented a bilobulated appearance upon image study. Both cases were treated successfully, the first with surgical clipping and the second with endovascular coiling. The special bilobulated feature of paraclinoid aneurysm in this particular anatomic location suggests its close relationship with the carotid dural ring. This relationship caused varying degrees of difficulty in both coiling and clipping the aneurysm. We compared the limitations and advantages of both treatments, and suggest that surgical clipping may be the treatment of choice in this region.