Point-of-care detection of fibrosis in liver transplant surgery using near-infrared spectroscopy and machine learning.

Introduction: Visual assessment and imaging of the donor liver are inaccurate in predicting fibrosis and remain surrogates for histopathology. We demonstrate that 3-s scans using a handheld near-infrared-spectroscopy (NIRS) instrument can identify and quantify fibrosis in fresh human liver samples. Methods: We undertook NIRS scans on 107 samples from 27 patients, 88 from 23 patients with liver disease, and 19 from four organ donors. Results: Liver disease patients had a median immature fibrosis of 40% (interquartile range [IQR] 20-60) and mature fibrosis of 30% (10%-50%) on histopathology. The organ donor livers had a median fibrosis (both mature and immature) of 10% (IQR 5%-15%). Using machine learning, this study detected presence of cirrhosis and METAVIR grade of fibrosis with a classification accuracy of 96.3% and 97.2%, precision of 96.3% and 97.0%, recall of 96.3% and 97.2%, specificity of 95.4% and 98.0% and area under receiver operator curve of 0.977 and 0.999, respectively. Using partial-least square regression machine learning, this study predicted the percentage of both immature (R 2 = 0.842) and mature (R 2 = 0.837) with a low margin of error (root mean square of error of 9.76% and 7.96%, respectively). Conclusion: This study demonstrates that a point-of-care NIRS instrument can accurately detect, quantify and classify liver fibrosis using machine learning.

Biglycan and reduced glycolysis are associated with breast cancer cell dormancy in the brain.

Exit of quiescent disseminated cancer cells from dormancy is thought to be responsible for metastatic relapse and a better understanding of dormancy could pave the way for novel therapeutic approaches. We used an in vivo model of triple negative breast cancer brain metastasis to identify differences in transcriptional profiles between dormant and proliferating cancer cells in the brain. BGN gene, encoding a small proteoglycan biglycan, was strongly upregulated in dormant cancer cells in vivo. BGN expression was significantly downregulated in patient brain metastases as compared to the matched primary breast tumors and BGN overexpression in cancer cells inhibited their growth in vitro and in vivo. Dormant cancer cells were further characterized by a reduced expression of glycolysis genes in vivo, and inhibition of glycolysis in vitro resulted in a reversible growth arrest reminiscent of dormancy. Our study identified mechanisms that could be targeted to induce/maintain cancer dormancy and thereby prevent metastatic relapse.

Survey of electroencephalography usage and techniques for dogs.

Background: Canine epilepsy is a chronic common neurologic condition where seizures may be underreported. Electroencephalography (EEG) is the patient-side test providing an objective diagnostic criterion for seizures and epilepsy. Despite this, EEG is thought to be rarely used in veterinary neurology. Objectives: This survey study aims to better understand the current canine EEG usage and techniques and barriers in veterinary neurology. Methods: The online Qualtrics link was distributed via listserv to members of the American College of Veterinary Internal Medicine (ACVIM) Neurology Specialty and the European College of Veterinary Neurology (ECVN), reaching at least 517 veterinary neurology specialists and trainees worldwide. Results: The survey received a 35% response rate, for a total of 180 participant responses. Fewer than 50% of veterinary neurologists are currently performing EEG and it is performed infrequently. The most common indication was to determine a discrete event diagnosis. Other reasons included monitoring treatment, determining brain death, identifying the type of seizure or epilepsy, localizing foci, sleep disorders, for research purposes, and post-op brain surgery monitorization. Most respondents interpreted their own EEGs. Clinical barriers to the performance of EEG in dogs were mainly equipment availability, insufficient cases, and financial costs to clients. Conclusion: This survey provides an update on EEG usage and techniques for dogs, identifying commonalities of technique and areas for development as a potential basis for harmonization of canine EEG techniques. A validated and standardized canine EEG protocol is hoped to improve the diagnosis and treatment of canine epilepsy.

Robust SARS-CoV-2 T cell responses with common TCRαß motifs toward COVID-19 vaccines in patients with hematological malignancy impacting B cells.

Immunocompromised hematology patients are vulnerable to severe COVID-19 and respond poorly to vaccination. Relative deficits in immunity are, however, unclear, especially after 3 vaccine doses. We evaluated immune responses in hematology patients across three COVID-19 vaccination doses. Seropositivity was low after a first dose of BNT162b2 and ChAdOx1 (∼26%), increased to 59%-75% after a second dose, and increased to 85% after a third dose. While prototypical antibody-secreting cells (ASCs) and T follicular helper (Tfh) cell responses were elicited in healthy participants, hematology patients showed prolonged ASCs and skewed Tfh2/17 responses. Importantly, vaccine-induced expansions of spike-specific and peptide-HLA tetramer-specific CD4+/CD8+ T cells, together with their T cell receptor (TCR) repertoires, were robust in hematology patients, irrespective of B cell numbers, and comparable to healthy participants. Vaccinated patients with breakthrough infections developed higher antibody responses, while T cell responses were comparable to healthy groups. COVID-19 vaccination induces robust T cell immunity in hematology patients of varying diseases and treatments irrespective of B cell numbers and antibody response.

Study protocol for PREPARE: a phase II feasibility/safety randomised controlled trial on PeRiopErative Penicillin AlleRgy TEsting.

INTRODUCTION: Patient-reported antibiotic allergy labels (AALs) are common. These labels have been demonstrated to have a negative impact on use of appropriate antibiotics and patient-related health outcomes. These patients are more likely to receive suboptimal antibiotics, have increased rates of surgical site infections and are more likely to be colonised with multidrug-resistant organisms. Increasing recognition that antibiotic allergy forms a key part of good antimicrobial stewardship has led to calls for greater access to antibiotic allergy assessment.PREPARE is a pilot randomised controlled trial of beta-lactam allergy assessment and point of care delabelling in perioperative patients utilising a validated antibiotic allergy assessment tool that has been repurposed into a smartphone application. The aim of the study is to assess the feasibility and safety of this approach in the perioperative outpatient setting. METHODS AND ANALYSIS: Adult participants requiring elective surgery and are likely to require prophylactic intravenous antibiotics will be recruited. During the intervention phase, participants will be randomised to the intervention or control arm, with control patients receiving usual standard of care. Those randomised to intervention undertake a risk assessment via the smartphone application, with those deemed low risk proceeding to direct oral provocation with either a penicillin or cephalosporin. Study outcomes will be evaluated in the postintervention phase, 30 and 90 days after surgery.Feasibility of intervention delivery and recruitment will be reported as proportions with respective 95% CIs. Participants who experience an antibiotic adverse event will be reported by group with respective 95% CIs and compared using modified Poisson regression model with robust SE estimation. ETHICS AND DISSEMINATION: This protocol has received approval from the Austin Health human research and ethics committee, Heidelberg, Victoria, Australia (HREC/17/Austin/575). Results will be disseminated via publication in peer-reviewed journals as well as presentation at international conferences. TRIAL REGISTRATION NUMBER: ACTRN12620001295932.

Australian Donation and Transplantation Biobank: A Research Biobank Integrated Within a Deceased Organ and Tissue Donation Program.

We aimed to facilitate the donation of tissue samples for research by establishing a centralized system integrated in the organ donation program for collection, storage, and distribution of samples (the Australian Donation and Transplantation Biobank [ADTB]). Methods: Feasibility of a research biobank integrated within the deceased organ and tissue donation program was assessed. DonateLife Victoria sought consent for ADTB donation after consent was received for organ donation for transplantation from the donor's senior available next of kin. ADTB samples were collected during donation surgery and distributed fresh to researchers or stored for future research. The main outcome measures were ADTB donation rates, ADTB sample collection, ADTB sample use, and to identify ethical considerations. Results: Over 2 y, samples were collected for the ADTB from 69 donors (28% of 249 donors). Samples were obtained from the spleen (n = 59, 86%), colon (n = 57, 83%), ileum (n = 56, 82%), duodenum (n = 55, 80%), blood (n = 55, 80%), bone marrow (n = 55, 80%), skin (n = 54, 78%), mesenteric lymph nodes (n = 56, 81%), liver (n = 21, 30%), lung (n = 29, 42%), and lung-draining lymph node (n = 29, 42%). Heart (n = 20), breast (n = 1), and lower urinary tract (n = 1) samples were obtained in the second year. Five hundred fifty-six samples were used in 19 ethics-approved research projects spanning the fields of immunology, microbiology, oncology, anatomy, physiology, and surgery. Conclusions: The integration of routine deceased donation and transplantation activities with a coordinated system for retrieval and allocation of donor samples for use in a range of research projects is feasible and valuable.

Immunotherapy in the context of immune-specialized environment of brain metastases.

Brain metastases (BrM) develop in 20-40% of patients with advanced cancer. They mainly originate from lung cancer, melanoma, breast cancer, and renal cell carcinoma, and are associated with a poor prognosis. While patients with BrM traditionally lack effective treatment options, immunotherapy is increasingly gaining in importance in this group of patients, with clinical trials in the past decade demonstrating the efficacy and safety of immune checkpoint blockade in BrM originating from specific tumor types, foremost melanoma. The brain is an immune-specialized environment with several unique molecular, cellular, and anatomical features that affect immune responses, including those against tumors. In this review we discuss the potential role that some of these unique characteristics may play in the efficacy of immunotherapy, mainly focusing on the lymphatic drainage in the brain and the role of systemic anti-tumor immunity that develops due to the presence of concurrent extracranial disease in addition to BrM.

Outcomes After Liver Transplantation With Incidental Cholangiocarcinoma.

Cholangiocarcinoma (CCA) is currently a contraindication to liver transplantation (LT) in the United Kingdom (UK). Incidental CCA occurs rarely in some patients undergoing LT. We report on retrospective outcomes of patients with incidental CCA from six UK LT centres. Cases were identified from pathology records. Data regarding tumour characteristics and post-transplant survival were collected. CCA was classified by TNM staging and anatomical location. 95 patients who underwent LT between 1988-2020 were identified. Median follow-up after LT was 2.1 years (14 days-18.6 years). Most patients were male (68.4%), median age at LT was 53 (IQR 46-62), and the majority had underlying PSC (61%). Overall median survival after LT was 4.4 years. Survival differed by tumour site: 1-, 3-, and 5-year estimated survival was 82.1%, 68.7%, and 57.1%, respectively, in intrahepatic CCA (n = 40) and 58.5%, 42.6%, and 30.2% in perihilar CCA (n = 42; p = 0.06). 1-, 3-, and 5-year estimated survival was 95.8%, 86.5%, and 80.6%, respectively, in pT1 tumours (28.2% of cohort), and 65.8%, 44.7%, and 31.1%, respectively, in pT2-4 (p = 0.018). Survival after LT for recipients with incidental CCA is inferior compared to usual outcomes for LT in the United Kingdom. LT for earlier stage CCA has similar survival to LT for hepatocellular cancer, and intrahepatic CCAs have better survival compared to perihilar CCAs. These observations may support LT for CCA in selected cases.

Study protocol: Australasian Registry of Severe Cutaneous Adverse Reactions (AUS-SCAR).

INTRODUCTION: Severe cutaneous adverse reactions (SCAR) are a group of T cell-mediated hypersensitivities associated with significant morbidity, mortality and hospital costs. Clinical phenotypes include Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS) and acute generalised exanthematous pustulosis (AGEP). In this Australasian, multicentre, prospective registry, we plan to examine the clinical presentation, drug causality, genomic predictors, potential diagnostic approaches, treatments and long-term outcomes of SCAR in Australia and New Zealand. METHODS AND ANALYSIS: Adult and adolescent patients with SCAR including SJS, TEN, DRESS, AGEP and another T cell-mediated hypersensitivity, generalised bullous fixed drug eruption, will be prospectively recruited. A waiver of consent has been granted for some sites to retrospectively include cases which result in early mortality. DNA will be collected for all prospective cases. Blood, blister fluid and skin biopsy sampling is optional and subject to patient consent and site capacity. To develop culprit drug identification and prevention, genomic testing will be performed to confirm human leukocyte antigen (HLA) type and ex vivo testing will be performed via interferon-γ release enzyme linked immunospot assay using collected peripheral blood mononuclear cells. The long-term outcomes of SCAR will be investigated with a 12-month quality of life survey and examination of prescribing and mortality data. ETHICS AND DISSEMINATION: This study was reviewed and approved by the Austin Health Human Research Ethics Committee (HREC/50791/Austin-19). Results will be published in peer-reviewed journals and presented at relevant conferences. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry (ACTRN12619000241134).

Defective Severe Acute Respiratory Syndrome Coronavirus 2 Immune Responses in an Immunocompromised Individual With Prolonged Viral Replication.

We describe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific immune responses in a patient with lymphoma and recent programmed death 1 (PD-1) inhibitor therapy with late onset of severe coronavirus disease 2019 disease and prolonged SARS-CoV-2 replication, in comparison to age-matched and immunocompromised controls. High levels of HLA-DR+/CD38+ activation, interleukin 6, and interleukin 18 in the absence of B cells and PD-1 expression was observed. SARS-CoV-2-specific antibody responses were absent and SARS-CoV-2-specific T cells were minimally detected. This case highlights challenges in managing immunocompromised hosts who may fail to mount effective virus-specific immune responses.

The Role of Immunological and Clinical Biomarkers to Predict Clinical COVID-19 Severity and Response to Therapy-A Prospective Longitudinal Study.

Background: The association of pro-inflammatory markers such as interleukin-6 (IL-6) and other biomarkers with severe coronavirus disease 2019 (COVID-19) is of increasing interest, however their kinetics, response to current COVID-related treatments, association with disease severity and comparison with other disease states associated with potential cytokine storm (CS) such as Staphylococcus aureus bacteraemia (SAB) are ill-defined. Methods: A cohort of 55 hospitalized SARS-CoV-2 positive patients was prospectively recruited - blood sampling was performed at baseline, post-treatment and hospital discharge. Serum IL-6, C-reactive protein (CRP) and other laboratory investigations were compared between treatment groups and across timepoints. Acute serum IL-6 and CRP levels were then compared to those with suspected COVID-19 (SCOVID) and age and sex matched patients with SAB and patients hospitalized for any non-infectious condition (NIC). Results: IL-6 was elevated at admission in the SARS-CoV-2 cohort but at lower levels compared to matched SAB patients. Median (IQR) IL-6 at admission was 73.89 pg/mL (30.9, 126.39) in SARS-CoV-2 compared to 92.76 pg/mL (21.75, 246.55) in SAB (p=0.017); 12.50 pg/mL (3.06, 35.77) in patients with NIC; and 95.51 pg/mL (52.17, 756.67) in SCOVID. Median IL-6 and CRP levels decreased between admission and discharge timepoints. This reduction was amplified in patients treated with remdesivir and/or dexamethasone. CRP and bedside vital signs were the strongest predictors of COVID-19 severity. Conclusions: Knowledge of the kinetics of IL-6 did not offer enhanced predictive value for disease severity in COVID-19 over common investigations such as CRP and vital signs.

Immune Checkpoint Blockade - How Does It Work in Brain Metastases?

Immune checkpoints restrain the immune system following its activation and their inhibition unleashes anti-tumor immune responses. Immune checkpoint inhibitors revolutionized the treatment of several cancer types, including melanoma, and immune checkpoint blockade with anti-PD-1 and anti-CTLA-4 antibodies is becoming a frontline therapy in metastatic melanoma. Notably, up to 60% of metastatic melanoma patients develop metastases in the brain. Brain metastases (BrM) are also very common in patients with lung and breast cancer, and occur in ∼20-40% of patients across different cancer types. Metastases in the brain are associated with poor prognosis due to the lack of efficient therapies. In the past, patients with BrM used to be excluded from immune-based clinical trials due to the assumption that such therapies may not work in the context of "immune-specialized" environment in the brain, or may cause harm. However, recent trials in patients with BrM demonstrated safety and intracranial activity of anti-PD-1 and anti-CTLA-4 therapy. We here discuss how immune checkpoint therapy works in BrM, with focus on T cells and the cross-talk between BrM, the immune system, and tumors growing outside the brain. We discuss major open questions in our understanding of what is required for an effective immune checkpoint inhibitor therapy in BrM.

Magnetic resonance imaging muscle lesions in presumptive canine fibrocartilaginous embolic myelopathy.

This retrospective cohort study reports the observation of magnetic resonance imaging (MRI) epaxial muscle hyperintensity in dogs diagnosed with presumptive fibrocartilaginous embolic myelopathy (FCEM) (n = 61). It further reports the observation of vertebral column hyperesthesia lasting > 12 hours. The hypothesis tested was that the finding of MRI epaxial muscle hyperintensity correlated with dogs presenting with hyperesthesia. Client-owned dogs diagnosed with presumptive FCEM by specific MRI criteria were included. Statistical analysis was performed using Fisher's exact test. Twenty-three percent (14/61) of MRIs displayed abnormal muscle hyperintensity and 43% (26/61) exhibited vertebral column hyperesthesia. No relationship was found between muscle hyperintensity and pain persisting beyond 12 hours. The muscle hyperintensity remains of unknown significance. That 43% of presumptive FCEM cases have prolonged signs of pain is a higher prevalence than previously reported, and may affect clinical differential diagnoses. This is especially significant in cases in which MRI is not possible and a presumptive diagnosis must be based on the clinical signs.

Imagerie par résonance magnétique des lésions des muscles dans la myélopathie embolique fibrocartilagineuse canine présumée. Cette étude rétrospective de cohorte signale les observations de l'imagerie par résonance magnétique (IRM) pour l'hyperintensité du muscle épaxial chez les chiens diagnostiqués avec une myélopathie embolique fibrocartilagineuse (MEFC) présumée (n = 61). Elle signale aussi l'observation de l'hyperesthésie de la colonne vertébrale durant > 12 heures. L'hypothèse qui a été testée était qu'il y avait une corrélation entre l'observation de l'hyperintensité du muscle épaxial par IRM et les chiens présentés avec de l'hyperesthésie. Les chiens appartenant à des clients pour lesquels un diagnostic présomptif de MEFC avait été posé à l'aide du critère spécifique de l'IRM ont été inclus. L'analyse statistique a été réalisée en utilisant le test exact de Fisher. Vingt-trois pour cent (14/61) des IRM affichaient une hyperintensité anormale du muscle et 43 % (26/61) présentaient de l'hypersthésie de la colonne vertébrale. Aucun lien n'a été trouvé entre l'hyperintensité musculaire et la douleur persistant au-delà de 12 heures. La signification de l'hyperintensité musculaire est toujours inconnue. Le taux de 43 % de cas présomptifs de MEFC affichant des signes de douleur prolongée représente une prévalence supérieure aux données déjà signalées et pourrait affecter les diagnostics cliniques différentiels. Ce fait revêt une importance particulière lorsque l'IRM n'est pas possible et qu'un diagnostic présomptif doit se baser sur les signes cliniques.(Traduit par Isabelle Vallières).

Computed Tomography and Biomechanical Comparison between Trans-Articular Screw Fixation and 2 Polymethylmethacrylate Cemented Constructs for Ventral Atlantoaxial Stabilization.

OBJECTIVES: Canine ventral atlantoaxial stabilization methods have been constantly evolving over the past few decades. Yet, proper experimental data comparing the feasibility and biomechanical properties of currently available surgical options are lacking. The aims of this study were (1) to describe and compare the safety profiles and biomechanical properties of three ventral atlantoaxial stabilization methods; and (2) to test whether recently reported optimal implant definitions constitute reasonable guidelines. METHODS: Three types of atlantoaxial stabilization including trans-articular screw fixation (TSF) and two cemented constructs (MI5 and MI6) were performed in 21 Beagle cadavers. Post-surgical computed tomography (CT) images of the constructs and biomechanical data were then generated and statistically analysed. RESULTS: The CT data revealed that TSF achieved significantly better apposition than cemented constructs. Out of 91 screws positioned, 4.4% were graded as dangerous and 86.8% as optimal. Optimal positioning was most challenging to obtain for mono-cortical screws. Analysis of biomechanical data suggested that all three techniques could likely achieve similar rates of atlantoaxial fusion when submitted to physiological loads but also that cemented constructs were less prone to failure compared with TSF. CLINICAL SIGNIFICANCE: This study provides evidence that all three techniques are technically feasible and biomechanically viable but also that the evaluated surgical guidelines could be improved.

Association between tumour infiltrating lymphocytes, histotype and clinical outcome in epithelial ovarian cancer.

BACKGROUND: There is evidence that some ovarian tumours evoke an immune response, which can be assessed by tumour infiltrating lymphocytes (TILs). To facilitate adoption of TILs as a clinical biomarker, a standardised method for their H&E visual evaluation has been validated in breast cancer. METHODS: We sought to investigate the prognostic significance of TILs in a study of 953 invasive epithelial ovarian cancer tumour samples, both primary and metastatic, from 707 patients from the prospective population-based SEARCH study. TILs were analysed using a standardised method based on H&E staining producing a percentage score for stromal and intratumoral compartments. We used Cox regression to estimate hazard ratios of the association between TILs and survival. RESULTS: The extent of stromal and intra-tumoral TILs were correlated in the primary tumours (n = 679, Spearman's rank correlation = 0.60, P < 0.001) with a similar correlation in secondary tumours (n = 224, Spearman's rank correlation = 0.62, P < 0.001). There was a weak correlation between stromal TIL levels in primary and secondary tumour samples (Spearman's rank correlation = 0.29, P < 0.001) and intra-tumoral TIL levels in primary and secondary tumour samples (Spearman's rank correlation = 0.19, P = 0.0094). The extent of stromal TILs differed between histotypes (Pearson chi2 (12d.f.) 54.1, P < 0.0001) with higher levels of stromal infiltration in the high-grade serous and endometriod cases. A significant association was observed for higher intratumoral TIL levels and a favourable prognosis (HR 0.74 95% CI 0.55-1.00 p = 0.047). CONCLUSION: This study is the largest collection of epithelial ovarian tumour samples evaluated for TILs. We have shown that stromal and intratumoral TIL levels are correlated and that their levels correlate with clinical variables such as tumour histological subtype. We have also shown that increased levels of both intratumoral and stromal TILs are associated with a better prognosis; however, this is only statistically significant for intratumoral TILs. This study suggests that a clinically useful immune prognostic indicator in epithelial ovarian cancer could be developed using this technique.

Generalized myoclonic epilepsy with photosensitivity in juvenile dogs caused by a defective DIRAS family GTPase 1.

The clinical and electroencephalographic features of a canine generalized myoclonic epilepsy with photosensitivity and onset in young Rhodesian Ridgeback dogs (6 wk to 18 mo) are described. A fully penetrant recessive 4-bp deletion was identified in the DIRAS family GTPase 1 (DIRAS1) gene with an altered expression pattern of DIRAS1 protein in the affected brain. This neuronal DIRAS1 gene with a proposed role in cholinergic transmission provides not only a candidate for human myoclonic epilepsy but also insights into the disease etiology, while establishing a spontaneous model for future intervention studies and functional characterization.

Canine atlantoaxial optimal safe implantation corridors - description and validation of a novel 3D presurgical planning method using OsiriX™.

BACKGROUND: Canine ventral atlantoaxial (AA) stabilization is most commonly performed in very small dogs and is technically challenging due to extremely narrow bone corridors. Multiple implantation sites have been suggested but detailed anatomical studies investigating these sites are lacking and therefore current surgical guidelines are based upon approximate anatomical landmarks. In order to study AA optimal safe implantation corridors (OSICs), we developed a method based on computed tomography (CT) and semi-automated three-dimensional (3D) mathematical modelling using OsiriX™ and Microsoft®Excel software. The objectives of this study were 1- to provide a detailed description of the bone corridor analysis method and 2- to assess the reproducibility of the method. CT images of the craniocervical junction were prospectively obtained in 27 dogs and our method of OSIC analysis was applied in all dogs. For each dog, 13 optimal implant sites were simulated via geometrical simplification of the bone corridors. Each implant 3D position was then defined with respect to anatomical axes using 2 projected angles (ProjA). The safety margins around each implant were also estimated with angles (SafA) measured in 4 orthogonal directions. A sample of 12 simulated implants was randomly selected and each mathematically calculated angle was compared to direct measurements obtained within OsiriX™ from 2 observers repeated twice. The landmarks simulating anatomical axes were also positioned 4 times to determine their effect on ProjA reproducibility. RESULTS: OsiriX could be used successfully to simulate optimal implant positions in all cases. There was excellent agreement between the calculated and measured values for both ProjA (ρc = 0.9986) and SafA (ρc = 0.9996). Absolute differences between calculated and measured values were respectively [ProjA = 0.44 ± 0.53°; SafA = 0.27 ± 0.25°] and [ProjA = 0.26 ± 0.21°; SafA = 0.18 ± 0.18°] for each observer. The 95 % tolerance interval comparing ProjA obtained with 4 different sets of anatomical axis landmarks was [-1.62°, 1.61°] which was considered appropriate for clinical use. CONCLUSIONS: A new method for determination of optimal implant placement is provided. Semi-automated calculation of optimal implant 3D positions could be further developed to facilitate preoperative planning and to generate large descriptive anatomical datasets.

Clinical and MRI findings in three dogs with polycystic meningiomas.

One spayed female Labrador retriever and two castrated male golden retrievers were evaluated for chronic (i.e., ranging from 3 wk to 24 wk) neurologic signs localizable to the prosencephalon. Signs included seizures, circling, and behavior changes. MRI demonstrated extra-axial, contrast-enhancing, multiloculated, fluid-filled, cyst-like lesions with a mass effect, causing compression and displacement of brain parenchyma. Differential diagnoses included cystic neoplasm, abscess or other infectious cyst (e.g., alveolar hydatid cyst), or fluid-filled anomaly (e.g., arachnoid cyst). The cyst-like lesions were attached to the rostral falx cerebri in all cases. In addition, case 2 had a second polycystic mass at the caudal diencephalon. Surgical biopsy (case 3 with a single, rostral tumor via transfrontal craniectomy) and postmortem histology (in cases 1 and 2) confirmed polycystic meningiomas. Tumor types were transitional (cases 1 and 3) and fibrous (case 2), with positive immunohistochemical staining for vimentin. Case 3 was also positive for E-cadherin, s100, and CD34. In all cases, staining was predominantly negative for glial fibrillary acid protein and pancytokeratins, supporting a diagnosis of meningioma. This report describes the first cases of polycystic meningiomas in dogs. Polycystic meningiomas are a rare, but important, addition to the differential diagnoses for intracranial cyst-like lesions, significantly affecting planning for surgical resection and other therapeutic interventions.