Clinical and genomic differences in supratentorial versus infratentorial NF2 mutant meningiomas.

OBJECTIVE: Mutations in NF2 are the most common somatic driver mutation in sporadic meningiomas. NF2 mutant meningiomas preferentially arise along the cerebral convexities-however, they can also be found in the posterior fossa. The authors investigated whether NF2 mutant meningiomas differ in clinical and genomic features based on their location relative to the tentorium. METHODS: Clinical and whole exome sequencing (WES) data for patients who underwent resection of sporadic NF2 mutant meningiomas were reviewed and analyzed. RESULTS: A total of 191 NF2 mutant meningiomas were included (165 supratentorial, 26 infratentorial). Supratentorial NF2 mutant meningiomas were significantly associated with edema (64.0% vs 28.0%, p < 0.001); higher grade-i.e., WHO grade II or III (41.8% vs 3.9%, p < 0.001); elevated Ki-67 (55.0% vs 13.6%, p < 0.001); and larger volume (mean 45.5 cm3 vs 14.9 cm3, p < 0.001). Furthermore, supratentorial tumors were more likely to harbor the higher-risk feature of chromosome 1p deletion (p = 0.038) and had a larger fraction of the genome altered with loss of heterozygosity (p < 0.001). Infratentorial meningiomas were more likely to undergo subtotal resection than supratentorial tumors (37.5% vs 15.8%, p = 0.021); however, there was no significant difference in overall (p = 0.2) or progression-free (p = 0.4) survival. CONCLUSIONS: Supratentorial NF2 mutant meningiomas are associated with more aggressive clinical and genomic features as compared with their infratentorial counterparts. Although infratentorial tumors have higher rates of subtotal resection, there is no associated difference in survival or recurrence. These findings help to better inform surgical decision-making in the management of NF2 mutant meningiomas based on location, and may guide postoperative management of these tumors.

Systemic calcinosis in a Quarter Horse gelding homozygous for a myosin heavy chain 1 mutation.

CASE DESCRIPTION: A 9-year-old Quarter Horse gelding was presented for lethargy, decreased appetite, polyuria and polydipsia (PU/PD), and severe muscle wasting suggestive of immune-mediated myositis. CLINICAL FINDINGS: The horse displayed lethargy, fever, tachyarrhythmia, inappetence, PU/PD, and severe epaxial and gluteal muscle wasting. Clinicopathologic findings were consistent with previously reported cases of systemic calcinosis in horses, including increased muscle enzyme activity, hyperphosphatemia, increased calcium-phosphorus product, hypoproteinemia, and an inflammatory leukogram. A diagnosis of systemic calcinosis was established by histopathologic evaluation of biopsy specimens from skeletal muscle, lung, and kidney. TREATMENT AND OUTCOME: Symptomatic treatment was complemented by IV treatment with sodium thiosulfate to reverse calcium-phosphate precipitation in soft tissue and PO aluminum hydroxide to decrease intestinal phosphorus absorption and serum phosphorus concentration. CLINICAL RELEVANCE: This is the first report in the veterinary literature of an antemortem diagnosis of systemic calcinosis in the horse that was successfully treated and had favorable long-term outcome.

Superficial Temporal Artery to Middle Cerebral Artery Cranial Bypass for Nonmoyamoya Steno-Occlusive Disease in Patients Who Failed Optimal Medical Treatment: A Case Series.

BACKGROUND: In the post-Carotid Occlusion Surgery Study (COSS) era, multiple reviews suggested subset groups of patients as potential candidates for superficial temporal artery to middle cerebral artery (STA-MCA) bypass. Among them are patients with recurrent strokes despite optimal medical therapy. There is a paucity of data on the outcome of bypass in these specific patients. OBJECTIVE: To examine the safety and efficacy of direct STA-MCA bypass in patients with nonmoyamoya, symptomatic steno-occlusive disease with impaired distal perfusion, who failed optimal medical management or endovascular treatment. METHODS: A retrospective review was performed to identify patients with cerebrovascular steno-occlusive disease who underwent bypass after symptomatic recurrent or rapidly progressive strokes, despite optimal conservative or endovascular treatment. RESULTS: A total of 8 patients (mean age 60 ± 6 yr) underwent direct or combined direct/indirect STA-MCA bypass between 2016 and 2019. All anastomoses were patent. One bypass carried slow flow. There were no procedure-related permanent deficits. One patient developed seizures which were controlled by medications. A total of 7 out of 8 patients were stable or improved clinically at last follow-up (mean 27.3 ± 13.8 mo) without recurrent strokes. One patient did not recover from their presenting stroke, experienced severe bilateral strokes 4 mo postoperatively, and subsequently expired. Modified Rankin Scale (mRS) improved in 6 patients (75%), remained stable in 1 patient (12.5%), and deteriorated in 1 (12.5%). Good long-term functional outcome was achieved in 5 patients (63%, mRS ≤ 2). CONCLUSION: Patients with symptomatic, hypoperfused steno-occlusive disease who fail optimal medical or endovascular treatment may benefit from cerebral revascularization. Direct or combined STA-MCA bypass was safe and provided favorable outcomes in this small series.

Nasopharyngeal Vascular Hamartoma in a Dog.

An 8-year-old spayed female 32 kg Labrador retriever was presented for further investigation into the underlying cause of dyspnea, stertor, and sleep apnea present for three months and worsening over 30 days. There were significant reduction in airflow through the nares and loud inspiratory stridor. Thoracic and cervical radiographs made were normal. A skull CT and retrograde rhinoscopy showed a mass occluding the majority of the nasopharynx above the caudal third of the hard palate. The main differential diagnoses included a neoplastic mass vs. inflammatory mass vs. cyst vs. mucous obstruction. There was no destruction of nasal turbinates, making a benign etiology more likely. Biopsy of the mass showed an inflammatory process. En bloc excision of the mass was performed via ventral rhinotomy without complication. Histopathology of the excised mass revealed it to be a mucosal vascular hamartoma. The dog recovered uneventfully and had no further respiratory issues, short or long term. Although vascular hamartomas are a rare finding in veterinary medicine, they can be found in a wide variety of species and anatomic locations. They should be considered when naming differentials for benign mass lesions throughout the body, including the nasopharynx. Although they are benign masses in nature, they can be clinically significant and should be addressed. Prognosis after removal in this location is excellent.

Radial Arterial Access for Thoracic Intraoperative Spinal Angiography in the Prone Position.

BACKGROUND: Verification of complete occlusion or resection of neurovascular lesions is often performed using intraoperative angiography. Surgery for spinal vascular lesions such as arteriovenous malformations (AVMs) and arteriovenous fistulas (AVFs) is typically performed with the patient in the prone position, making intraoperative angiography difficult. No standardized protocol is available for intraoperative angiography during spinal surgery with the patient in the prone position. We have described our experience using radial artery access for intraoperative angiography in thoracic spinal neurovascular procedures performed with the patient in the prone position. METHODS: We reviewed the data from all patients who had undergone surgical resection of spinal vascular lesions in the prone position with radial artery vascular access for intraoperative angiography. The patients were treated in a hybrid endovascular operating room. RESULTS: A total of 4 patients were treated in the prone position using transradial artery access intraoperative angiography for confirmation of complete resection of the vascular lesions. Of the 4 patients, 2 had undergone surgery for a dural AVF, 1 for a pial AVF, and 1 for an AVM of the filum terminale. None of the patients had experienced any procedural complications. CONCLUSION: Radial artery access for intraoperative angiography during spinal neurovascular procedures in which selective catheterization of a thoracic branch is necessary is feasible, safe, and practical.

Microsurgical Resection of a Spinal Cord Pial Arteriovenous Fistula: 2-Dimensional Operative Video.

We present a patient who was diagnosed 20 yr prior to current presentation with a spinal arteriovenous malformation. This patient had a 10-yr history of worsening back pain (and underwent lumbar fusion), urinary dysfunction leading to 3-yr dependence on intermittent catheterization, lower extremity paresthesias and pain, and progressive weakness with multiple falls, leading to walker then wheelchair dependence for mobility. Magnetic resonance studies showed extensive thoracic cord expansion and edema with enlarged spinal cord surface veins and flow voids extending from spinal levels T6 to the conus medullaris. Partial embolization at an outside institution elicited transient symptom improvement. Repeated spinal angiogram demonstrated persistent T10 pial arteriovenous fistula (AVF) supplied by the posterior spinal artery arising from the right T11 segmental artery as well as by the anterior spinal artery from the left T10 segmental artery. Because additional embolization carried significant risk, we planned open surgery with fistula resection. Informed consent for the surgery and video recording was obtained. The patient was placed in the prone position, and a radial artery access was obtained for intraoperative angiogram. Following a posterior T9-T11 laminectomy and dural opening, a pial dissection was performed to expose the AVF. Intraoperative indocyanine green angiography was used to assist in identifying the feeders and major drainage of the AVF. Post-AVF resection, a formal intraoperative radial access spinal angiogram demonstrated complete resection of the lesion with no residual shunt or early venous drainage. The patient improved significantly and, on last follow-up, is ambulating without any assistive devices.

Novel siadenovirus infection in a cockatiel with chronic liver disease.

A 15-year-old female cockatiel (Nymphicus hollandicus) undergoing long term management for hepatopathy died and underwent necropsy. Microscopic findings were consistent with chronic liver disease characterized by distorted hepatic architecture, fibrosis and biliary proliferation. The additional finding of large intranuclear inclusion bodies within hepatocytes and renal tubular epithelium prompted diagnostic next generation sequencing. The assembled sequences isolated from pooled kidney and liver were related to siadenoviruses. The genus Siadenovirus, within the family Adenoviridae, includes several species of viruses that pathogenically infect avian species including hemorrhagic enteritis virus of turkeys and marble spleen virus of pheasants. Siadenoviruses have previously been reported in seven psittacine species: a plum-headed parakeet (Psittacula cyanocephala), an umbrella cockatoo (Cacatua alba) budgerigars (Melopsittacus undulates), an eastern rosella (Platycercus eximius), a scarlet chested parrot (Neophema splendida), a cockatiel (Nymphicus hollandicus), and a red-crowned parakeet (Cyanoramphus novaezelandiae). This report describes a novel siadenovirus in a cockatiel that is highly identical to budgerigar adenovirus 1 and distinct from PsAdV-2 in cockatiels. We report the clinical pathologic, gross, and histopathologic findings in a cockatiel with chronic hepatitis and a novel siadenovirus, PsAdV-5. The sequencing data is presented with a phylogenetic analysis.

Corneal fibrosarcoma in a cat.

PURPOSE: To present the clinicopathologic features of a Domestic Short-haired cat with spontaneous, intermediate-grade corneal fibrosarcoma, possibly secondary to chronic corneal irritation associated with a corneal sequestrum. METHODS: A 12-year-old, spayed female Domestic Short-haired cat was evaluated for a slowly growing, pink, exophytic mass affecting the left cornea. The cat had presented 6 years previously for bilateral brown corneal sequestra, as well as 3 years previously for a small pale growth on the left cornea hypothesized to be an epithelial inclusion cyst and a corneal ulcer affecting the right eye. Incisional biopsy of the corneal mass indicated intermediate-grade corneal fibrosarcoma within the corneal stroma. Owing to the potential for malignant behavior, the left globe was enucleated. Routine systemic staging was performed prior to surgery with no evidence of metastasis. RESULTS: Definitive diagnosis of corneal fibrosarcoma was made through histopathologic examination of the incisional biopsy. There was an elevated mitotic index, indicating an intermediate-grade phenotype. Histopathology of the enucleated globe substantiated the initial findings, and complete tumor resection was confirmed. Subjacent to the corneal fibrosarcoma, there was a region of necrotic tissue suggestive of a corneal sequestrum. Six months after diagnosis and enucleation, the patient remained healthy with no signs of local spread or distant metastasis. CONCLUSIONS: To the authors' knowledge, this is the first documented case of a corneal fibrosarcoma in a cat.

Extraskeletal Osteosarcoma Induced by a Foreign Body Granuloma.

An 8 yr old spayed female Italian greyhound was presented with a mass in the cranial abdomen. Preliminary evaluation of the dog revealed a large, cavitary, irregularly shaped mass with no definitive association with any abdominal organs. During an exploratory celiotomy, a 16 cm × 12 cm × 6 cm mass was removed. On subsequent histopathology, extraskeletal osteosarcoma induced by a foreign body granuloma was diagnosed. The foreign body granuloma, based on histopathological findings, was suspected to be secondary to a retained surgical sponge from her routine ovariohysterectomy performed 7 yr prior to presentation. Animals with granulomas induced by foreign bodies can remain asymptomatic for years; however, those granulomas can progress to extraskeletal osteosarcomas, which carry a poor prognosis.

Disseminated T-cell lymphoma in a bonobo (Pan paniscus).

Disseminated lymphoma was diagnosed in an 8-year-old male bonobo (Pan paniscus). The male bonobo presented with a 4-6 week history of dyspnea and facial swelling around the eyes; thoracic radiographs and computed tomography scan indicated a craniodorsal mediastinal soft tissue mass. Upon gross examination, there was a large, cream to white mass expanding the mediastinum and pericardial sac. The mass extended along the thoracic aorta and cranial vena cava, through the thoracic inlet, along and encircling the trachea, and bilaterally into the thyroid glands. Microscopically, neoplastic lymphocytes were present in the thymus, trachea, lungs, kidney, heart, and numerous other tissues. Immunohistochemical staining of neoplastic lymphocytes revealed diffuse immunoreactivity for cluster of differentiation (CD)3 indicating T-cell lymphoma. Routine viral screening was negative via polymerase chain reaction.

A vascular hamartoma arising from the cervical spine of a cat.

A 15-month-old cat presented for evaluation of worsening generalized proprioceptive ataxia. Computed tomography of the cervical spine revealed the presence of a compressive extradural bony mass involving the dorsal aspect of C1. Surgical exploration and debulking of the mass was performed. Histological evaluation of the mass revealed fibrovascular tissue consistent with a vascular hamartoma. This mass was deemed to be originating from the soft tissue associated with the C1 vertebra with subsequent bony proliferation. Surgical debulking of the mass resulted in complete resolution of clinical signs with no evidence of recurrence 2 years after surgery.

HBCUs inform students and the community about cervical cancer.

In summary, HBCUs can no longer remain reactive, but must spearhead efforts to increase both the health of the student body, as well as the community at large. HBCUs should collaboratively initiate a "Call to Action", whereby policies and programs could be created to aid in the prevention of HPV and other STIs. To support this action, HBCUs could more actively pursue funding sources that support both universities and the communities in which they exist. Student orientation could be redefined to include short courses in STI awareness and prevention, and be communicated in a manner that is professional, yet engaging to students. Moreover, university departments which have an interest in the health of communities should supervise these efforts. The knowledge of university faculty members within departments of Nursing, Social Work, Public Health, Rehabilitation Counseling and Physical Education should extend beyond the classroom and into the community. Clark commented, "Perhaps course content across departments could be revised to encompass an increased focus on practice skills which support awareness and prevention efforts". Through employment, volunteerism and student internships, each of these disciplines have established relationships with the surrounding community and understand the associated critical needs. Such relationships provide the best environment for both the creation and implementation of services, and provide students with a model of how to "give back" to the community by utilizing their education. Campus health centers should be more prevention-driven beyond the distribution of condoms and pamphlets, to collaborate with local area high schools and community-based organizations to create an information network accessible to students and community residents. Additionally, health centers should promote the availability of HPV vaccination, which depending on state of residence and age, may be free or available at a discounted cost. According to Bynum, some HBCUs have already begun to promote and provide the vaccination, "South Carolina State University is one of the HBCUs which provides the HPV vaccination and promotes HPV prevention. There has been a great initiative by their health center to focus prevention efforts on incoming freshman". HBCU administrations must bear in mind that beyond the campus, students will undoubtedly carry the information learned during college into the communities in which they live after graduation and moreover, utilize this information as a basis for educating their children and families. Community activist and Columbia resident Linda "T'Zima" Brown, whose 16 year-old son is considering application to Delaware State University, believes that HBCUs bear a great responsibility to the well-being of the community, "We as residents should be able to take part in the events that our black colleges have. Black colleges used to operate from a more inclusive, family approach, and we need to get back to that; plus, many HBCUs are supported with our state dollars, so the community should be able to look to them for information aside from what our children relay to us".

Unilateral uveitis in a dog with uveodermatologic syndrome.

CASE DESCRIPTION: A 7-year-old Siberian Husky-type dog with heterochromia irides was evaluated because of signs of pain associated with the right eye. CLINICAL FINDINGS: Unilateral panuveitis, iris bombé, and secondary glaucoma were detected in the right eye. Tear production was low bilaterally. Facial and truncal poliosis and vitiligo were also evident; skin biopsy specimens were obtained from the nasal planum. Uveodermatologic syndrome was diagnosed on the basis of histopathologic findings of a lichenoid interface dermatitis and pigmentary incontinence within the dermis. Immunohistochemical analysis was performed on skin samples retrospectively, and findings were inconclusive. TREATMENT AND OUTCOME: Treatment involved topical (ocular) and oral administration of corticosteroids, oral administration of azathioprine, and topical (ocular) administration of a carbonic anhydrase inhibitor and a lacrimostimulant. The secondary glaucoma was refractory to treatment, and the right eye was enucleated. Uveodermatologic syndrome was confirmed via histologic examination of ocular tissues. The left eye remained free of inflammation 16 months after the initial diagnosis. The periocular skin and skin of the nose partially regained pigment, but the hair did not. CLINICAL RELEVANCE: Some breeds in which uveodermatologic syndrome has been reported (eg, Siberian Huskies, Old English Sheepdogs, Australian Shepherds, and Shetland Sheepdogs) often have heterochromia irides. This case highlights the fact that dogs with asymmetric uveal pigmentation may have unilateral ocular changes; therefore, uveodermatologic syndrome should not be excluded as a differential diagnosis on the basis of unilateral clinical signs.

Lymphoid hyperplasia resulting in immune dysregulation is caused by porcine reproductive and respiratory syndrome virus infection in neonatal pigs.

Amid growing evidence that numerous viral infections can produce immunopathology, including nonspecific polyclonal lymphocyte activation, the need to test the direct impact of an infecting virus on the immune system of the host is crucial. This can best be tested in the isolator piglet model in which maternal and other extrinsic influences can be excluded. Therefore, neonatal isolator piglets were colonized with a benign Escherichia coli, or kept germfree, and then inoculated with wild-type porcine reproductive and respiratory syndrome virus (PRRSV) or sham medium. Two weeks after inoculation, serum IgM, IgG, and IgA levels were 30- to 50-, 20- to 80-, and 10- to 20-fold higher, respectively, in animals receiving virus vs sham controls, although <1% was virus specific. PRRSV-infected piglets also had bronchial tree-associated lymph nodes and submandibular lymph nodes that were 5-10 times larger than colonized, sham-inoculated animals. Size-exclusion fast performance liquid chromatography revealed that PRRSV-infected sera contained high-molecular-mass fractions that contained IgG, suggesting the presence of immune complexes. Lesions, inflammatory cell infiltration, glomerular deposits of IgG, IgM, and IgA, and Abs of all three isotypes to basement membrane and vascular endothelium were observed in the kidneys of PRRSV-infected piglets. Furthermore, autoantibodies specific for Golgi Ags and dsDNA could be detected 3-4 wk after viral inoculation. These data demonstrate that PRRSV induces B cell hyperplasia in isolator piglets that leads to immunologic injury and suggests that the isolator piglet model could serve as a useful model to determine the mechanisms of virus-induced immunopathology in this species.

Cytokine effects on maturation of the phagosomes containing Mycobacteria avium subspecies paratuberculosis in J774 cells.

Mycobacterium avium subspecies paratuberculosis (M. a. ptb) is an intracellular pathogen of macrophages. Intracellular survival of several species of pathogenic mycobacteria is dependent on inhibition of maturation of the phagosomes containing these pathogens into functional phagolysosomes. In activated macrophages, however, this capacity is reduced, leading to increased bacterial killing. It is the hypothesis of this study that there is increased acidification and maturation of the phagosome containing M. a. ptb in interferon gamma and lipopolysaccharide (IFN-gamma/LPS) activated macrophages. In activated macrophages colocalization of M. a. ptb with either a marker of acidic compartments (Lysotracker Red) or compartments containing a late phagosome maturation marker lysosome-associated membrane protein-1 (Lamp-1) were evaluated by laser confocal microscopy. Intracellular survival of M. a. ptb in activated macrophages was evaluated directly using differential fluorescent live/dead staining. The results of this study demonstrated increased colocalization of both Lysotracker Red and Lamp-1 with FITC labeled M. a. ptb, which correlated with decreased survival of M. a. ptb within activated macrophages.