A First-in-Human Randomized Study to Assess the Safety, Tolerability, Pharmacokinetics, and Neutralization Profile of Two Investigational Long-Acting Anti-SARS-CoV-2 Monoclonal Antibodies.

INTRODUCTION: COVID-19 remains a significant risk for the immunocompromised given their lower responsiveness to vaccination or infection. Therefore, passive immunity through long-acting monoclonal antibodies (mAbs) offers a needed approach for pre-exposure prophylaxis (PrEP). Our study evaluated safety, anti-SARS-CoV-2 neutralizing activity, nasal penetration, and pharmacokinetics (PK) of two half-life-extended investigational mAbs, AER001 and AER002, providing the first demonstration of upper airway penetration of mAbs with the LS-modification. METHODS: This randomized, double-blind, placebo-controlled phase I study enrolled healthy adults (n = 80) who received two long-acting COVID mAbs (AER001 and AER002), AER002 alone, or placebo. The dose ranged from 100 mg (mg) to 1200 mg per mAb component. The primary objective was to describe the safety and tolerability following intravenous (IV) administration. Secondary objectives were to describe PK, anti-drug antibodies (ADA), neutralization activity levels, and safety evaluation through 6 months of follow-up. RESULTS: The majority (97.6%) of the reported adverse events (AE) post administration were of grade 1 severity. There were no serious adverse events (SAE) or ADAs. AER001 and AER002 successfully achieved an extended half-life of 105 days and 97.5 days, respectively. Participants receiving AER001 and AER002 (300 mg each) or AER002 (300 mg) alone showed 15- and 26-fold higher neutralization levels against D614G and omicron BA.1 than the placebo group 24 h post-administration. Single 300 or 1200 mg IV dose of AER001 and AER002 resulted in nasal mucosa transudation of approximately 2.5% and 2.7%, respectively. CONCLUSION: AER001 and AER002 showed an acceptable safety profile and extended half-life. High serum neutralization activity was observed against D614G and Omicron BA.1 compared to the placebo group. These data support that LS-modified mAbs can achieve durability, safety, potency, and upper airway tissue penetration and will guide the development of the next generation of mAbs for COVID-19 prevention and treatment. TRIAL REGISTRATION: EudraCT Number 2022-001709-35 (COV-2022-001).

Lesions Mimicking Small Vestibular Schwannomas.

Objective Most tumors of the internal auditory canal and cerebellopontine angle (CPA) are vestibular schwannomas (VSs). Preoperative diagnosis is based on typical clinical symptoms and radiological findings. In rare cases, histopathology can, however, show different results. Design This is a retrospective chart and database review. Setting The study was conducted at a tertiary skull base referral center at a university hospital. Participants A total of 207 consecutive cases of VS surgery via the middle cranial fossa approach performed between December 2005 and January 2015 were reviewed. Main Outcome Measures The main outcome measures were definitive histologic findings in 198 specimens, analysis of preoperative magnetic resonance imaging (MRI) and computed tomography. Results Histopathology revealed three meningiomas and two cases of lipochoristomas. Clinical presentation was typical for VS in all five cases. In preoperative MRI, all tumors were suspected to be VSs. Retrospective analysis of the preoperative imaging did not lead to a modification of the diagnosis. Intraoperative findings showed increased adherence of the tumor to the adjacent tissue in two of the five cases. Conclusion CPA lesions other than VSs are unusual but have to be taken into account. In very small tumors, imaging still remains difficult.

Fourth Ventricular AVM with Transdural Drainage.

Arteriovenous malformations (AVMs) of the fourth ventricle are exceptionally rare subtypes of brainstem AVMs. This report illustrates the case of a young man who suffered intraventricular and subarachnoid hemorrhage. Angiography depicted a fourth ventricular AVM that was supplied by branches of the right posterior inferior cerebellar artery and drained via a posterior medullary midline vein into the marginal sinus and cervical radicular and nuchal veins. The drainage pattern is highly uncommon and constitutes a particular challenge for the operative approach.

An endolymphatic sac tumor with imaging features of aneurysmal bone cysts: differential diagnostic considerations.

BACKGROUND: Endolymphatic sac tumors (ELSTs) are rare, slow-growing tumors of the petrous bone. Despite the typical localisation, their radiological diagnosis can be challenging due to the variety of other tumors potentially showing similar features. CASE REPORT: We present a 16-year-old child with progressive hearing loss, vertigo, and tinnitus who had a large petrous bone lesion showing imaging features of both ELSTs and aneurysmal bone cysts (ABCs). The patient underwent preoperative embolization of the tumor-supplying vessels and subsequently a subtotal resection. Histological examination revealed an ELST. CONCLUSION: Despite the rarity of petrous bone ABCs, they should be considered as a differential diagnostic alternative of ELSTs due to their similar imaging appearance.

Leiomyolipoma of the orbit.

Orbital leiomyolipoma is a rare benign tumor characterized by a mixture of mature smooth muscle cells and adipocytes. The authors present a case which, to the best of their knowledge, is the second case of leiomyolipoma of the orbit reported in the ophthalmic literature. A 65-year-old patient presented with a painful and swollen left eye, the symptoms having been present for 1 week. Imaging (CT, MRI follow up) confirmed the presence of a nearly 2-cm lesion medial to the lacrimal gland. A biopsy was planned, and 3 specimens were taken for histologic examination. Histology showed diffusely intermingling smooth muscle cells and mature adipocytes; immunohistochemistry demonstrated positive staining for smooth muscle actin and negativity for HMB45, MART-1, and Cytokeratin AE1/3. Although it is very rare, ophthalmologists should consider leiomyolipoma in the differential diagnosis of orbital tumors. The long-term prognosis for patients affected by this benign tumor is good.

Clinical features, treatment, and prognosis of patients with acute subdural hematomas presenting in critical condition.

OBJECTIVE: Spontaneous acute subdural hematoma (aSDH) may be caused by aneurysm rupture. Patients can present in very poor clinical condition with anisocoria or even bilaterally dilated pupils, absent brainstem reflexes, and cardiac insufficiency. For the clinician, the question is how should these patients be treated? Large series on this subject do not exist because aSDH is a rare event. This report focuses on the prognosis and adverse prognostic factors of these patients. CLINICAL PRESENTATION: We present eight cases of aSDH and subarachnoid hemorrhage attributable to aneurysm rupture. All patients were World Federation of Neurosurgical Societies Grade 5. Four presented with anisocoria, three presented with bilaterally fixed and dilated pupils, and one developed anisocoria in the course of treatment. TREATMENT: As a result of prolonged hypoxia before admission, one patient was not treated and died. In one patient, surgical decompression could not be performed in the acute phase as a result of significant comorbidity. All other patients received decompressive surgery, obliteration of the aneurysm, and medical therapy as well as extensive rehabilitation measures. After 6 months, four had no or only minor neurological deficits; one patient was independent despite hemiparesis. Two patients whose surgical decompression had to be delayed as a result of severe cardiac instability recovered poorly, showed severe neurological deficits, and required permanent care. However, none of the patients survived in a persistent vegetative state. CONCLUSION: Within the spectrum of aneurysmatic hemorrhage, patients with aSDH represent a distinct subgroup. Despite a very poor clinical condition on admission, recovery with only minor deficits or even without neurological deficit is possible. Mass effect and herniation induce a poor clinical condition, which is not directly related to the underlying subarachnoid hemorrhage. Hence, clinical grading systems such as the Hunt and Hess scale or World Federation of Neurosurgical Societies grading are not applicable. We suggest that whenever the medical condition allows, rapid surgical decompression should be performed even in patients who present in very poor neurological condition.

Pseudoaneurysm of the lingual artery after temperature-controlled radiofrequency tongue base reduction: a severe complication.

Temperature-controlled radiofrequency reduction (TCRF) of the tongue base has been developed as an alternative option for the treatment of patients with obstructive sleep apnea syndrome. The technique is propagated as an easy and safe surgical method. The case of a 34-year-old male patient with obstructive sleep apnea syndrome who underwent TCRF is reported. Fourteen days after surgery was performed, heavy bleeding at the base of the tongue occurred. Computed tomography and digital subtraction angiography imaging revealed a pseudoaneurysm of the lingual artery, which was treated endovascularly by detachable and free platinum coils during the same session. The article reports the first case of pseudoaneurysm under TCRF of the tongue base and discusses the diagnostic and therapeutic procedure to handle and avoid life-threatening complications under this method of treatment.

Heparin and air filters reduce embolic events caused by intra-arterial cerebral angiography: a prospective, randomized trial.

BACKGROUND: Intra-arterial cerebral angiography is associated with a low risk for neurological complications, but clinically silent ischemic events after angiography have been seen in a substantial number of patients. METHODS AND RESULTS: In a prospective study, diffusion-weighted magnetic resonance imaging (DW-MRI) before and after intra-arterial cerebral angiography and transcranial Doppler sonography during angiography were used to evaluate the frequency of cerebral embolism. One hundred fifty diagnostic cerebral angiographies were randomized into 50 procedures, each using conventional angiographic technique, or systemic heparin treatment throughout the procedure, or air filters between the catheter and both the contrast medium syringe and the catheter flushing. There was no neurological complication during or after angiography. Overall, DW-MRI revealed 26 new ischemic lesions in 17 patients (11%). In the control group, 11 patients showed a total of 18 lesions. In the heparin group, 3 patients showed a total of 4 lesions. In the air filter group, 3 patients exhibited a total of 4 lesions. The reduced incidence of ischemic events in the heparin and air filter groups compared with the control group was significantly different (P=0.002). Transcranial Doppler sonography demonstrated a large number of microembolic signals that was significantly lower in the air filter group compared with the heparin and control groups (P<0.01), which did not differ from each other. CONCLUSIONS: Air filters and heparin both reduce the incidence of silent ischemic events detected by DW-MRI after intra-arterial cerebral angiography and can potentially lower clinically overt ischemic complications. This may apply to any intra-arterial angiographic procedure.

Camptocormia in Parkinson's disease mimicked by focal myositis of the paraspinal muscles.

We report on a 63-year-old man with idiopathic Parkinson's disease who developed kyphosis and a severe forward flexion of the thoracolumbar spine. A typical feature was an increase during walking or standing and it completely disappeared in the supine position, mimicking the clinical phenomenon of camptocormia (bent spine). In addition to the abnormal posture, a weakness of the erector spinal muscles, local pain, reddening, and elevated temperature of the paraspinal muscles were evident. Creatine kinase was initially elevated, electromyography showed spontaneous activity and a myopathic pattern. Magnetic resonance imaging and bioptic examinations revealed a focal myositis of the paraspinal muscles. This case indicates that camptocormia can be mimicked by focal myositis of paraspinal muscles and must be included in the differential diagnosis, especially when additional symptoms as inflammatory signs or weakness are present.