CT measurements of tracheal diameter and length in normocephalic cats.

OBJECTIVES The aim of this study was to measure the tracheal dimensions of normocephalic cats using CT. METHODS CT images of 15 client-owned normocephalic cats were retrospectively evaluated to measure the length of the feline trachea. Transverse and vertical inner diameters were measured in five different tracheal regions, and the cross-sectional area of the tracheal lumen was calculated for each point of measurement. Descriptive statistics were applied using a two-tailed t-test. RESULTS The mean ± SD length of the trachea was 125.13 ± 14.41 mm. Male cats had significantly larger tracheas than female cats. The transverse diameter first increased by 0.94 mm between the most cranial point of measurement and the middle of the trachea. It then decreased by 1.38 mm between the middle of the trachea and the most caudal point of measurement. The vertical diameter decreased by 1.16 mm between the first point of measurement and the penultimate point, and then increased by 0.06 mm between the penultimate point of measurement and the end of the trachea. The two different diameters resulted in an elliptical trachea shape. CONCLUSIONS AND RELEVANCE The feline trachea was circular only at its cranial and caudal ends, and elliptical with a dorsoventral flattening along the rest of its length. Vertical and transverse diameters varied along the entire length. Tracheal shape differences should be considered when performing permanent tracheostomy, tracheal anastomosis or stenting in cats

Comparison of the Trachea in Normocephalic versus Brachycephalic Cats on the Basis of CT-Derived Measurements.

Tracheal hypoplasia is a major concern in brachycephalic dogs, but there is no consensus for the trachea in brachycephalic cats. We aimed to compare tracheal length and diameter between normo- and brachycephalic cats using computed tomography (CT) image measurements and evaluate their usefulness in tracheostomy planning. A total of 15 normocephalic and 14 brachycephalic cats were included in the study. Tracheas of normocephalic cats were significantly longer compared with brachycephalic cats. No difference was detected in tracheal diameter between normocephalic and brachycephalic cats. Both groups had a lateral diameter significantly larger than the dorsoventral diameter at the level of the cranial end of the manubrium sterni and at the level of the second rib. Normocephalic and brachycephalic cats' tracheas have the same dorsoventral flattening at the level of the cranial end of the manubrium sterni and at the level of the second rib. The location between the 4th and 5th cervical vertebrae seems the best place to perform a tracheostomy in cats due to its round shape and easily accessible anatomical location. No sign of tracheal hypoplasia in brachycephalic cats was detected. Finally, 7 mm appears to be an adequate diameter for the tracheal tubes used to perform feline tracheostomies

Feline gastrointestinal eosinophilic sclerosing fibroplasia presenting as a rectal mass.

Case summary A 9-year-old neutered male cat was referred owing to dyschezia and weight loss. Abdominal CT revealed a heterogeneous mass in the rectum and thickening of one caudal mesenteric lymph node. The mass induced a focal rectal obstruction. Cytological evaluation of fine-needle aspirates showed signs of mixed inflammation for the rectal mass and a reactive lymph node. Because a definite diagnosis was not achieved, complete resection of the mass via a dorsal approach to the rectum was attempted. Histopathology confirmed complete removal and diagnosed feline gastrointestinal eosinophilic sclerosing fibroplasia (FGESF). The cat was treated with psyllium husks and lactulose after surgery. In the postoperative year, the owner reported normal behaviour, food intake and defecation of the patient. Dyschezia reoccurred 14 months after surgery. Imaging revealed recurrence of a rectal mass. Owing to clinical deterioration, the owner elected for euthanasia. Relevance and novel information This is the first report of rectal FGESF with dyschezia and weight loss as the main clinical signs. The case demonstrates an acceptable outcome for more than 1 year without additional immunosuppressive therapy, and emphasises that FGESF must be considered as a differential diagnosis for rectal masses in cats

Anaesthetic Management of a Labrador Retriever Undergoing Adrenalectomy for Phaeochromocytoma Excision, a Case Report.

Perioperative management of cases undergoing phaeochromocytoma removal should aim at normalising blood pressure and heart rate, restoring volume depletion, and preventing catecholamine release induced by surgical manipulation. In this case report, a novel pharmacological approach in a dog undergoing surgical tumour excision is described. A 7-year-old 25-kg spayed female Labrador Retriever presented for repeated episodes of generalised weakness, pale mucous membranes, tachycardia, tremor, panting, vomiting, and hypertension over the last month was referred for surgical treatment of a left-sided adrenal tumour with invasion of the caudal vena cava. Severe hypertensive episodes occurred repeatedly, starting early during the anaesthetic period, while clipping and cleaning the abdominal area, and continued intraoperatively when the tumour was handled. Moderate hypotension occurred once the tumour was isolated and worsened during temporary caudal vena cava flow interruption and cavotomy. The patient was treated preoperatively with phenoxybenzamine to prevent hypertensive crises. Intraoperatively, magnesium sulphate and urapidil were used to control blood pressure. This treatment was effective in reducing the magnitude of blood pressure spikes but not sufficient to prevent hypertensive peaks, especially during tumour manipulation. Hypotension was treated with synthetic colloid and crystalloid boli, and noradrenaline continuous infusion. Blood transfusion was performed in response to acute bleeding during cavotomy. The dog recovered successfully from anaesthesia and its quality of life was deemed excellent by the owner at the last follow up, 22 months after surgery. The histopathology confirmed the diagnosis of phaeochromocytoma with an invasion of the phrenicoabdominal vein. In the present case, we obtained a successful outcome but failed to provide haemodynamic stability throughout the procedure

Preliminary Studies on the Intrahepatic Anatomy of the Venous Vasculature in Cats.

Hepatic surgeries are often performed in cats to obtain a disease diagnosis, for the removal of masses, or for the treatment of shunts. Whereas the vascular anatomy of the liver has been studied in dogs, such evidence is lacking in cats. The current study used corrosion casts of portal and hepatic veins and computed tomography (CT) analysis of the casts to identify and describe the intrahepatic anatomy in healthy cat livers (n = 7). The results showed that feline livers had a consistent intrahepatic portal and venous anatomy, with only minor disparities in the numbers of secondary and tertiary branches. The feline portal vein consistently divided into two major branches and not three, as previously described in the literature for cats. The finding of a portal vein originating from the right medial lobe branch leading to the quadrate lobe in 4/7 specimens is a novelty of the feline anatomy that was not previously described in dogs. Partial to complete fusion of the caudate process of the caudate and the right lateral lobe, with a lack of clear venous separation between the lobes, was present in two specimens. These findings allowed a detailed description of the most common intrahepatic venous patterns in cats. Further anatomical studies should be encouraged to confirm the present findings and to investigate the utility of this information in surgical settings

Increased Sensitivity of Computed Tomography Scan for Neoplastic Tissues Using the Extracellular Vesicle Formulation of the Contrast Agent Iohexol.

Computed tomography (CT) is a diagnostic medical imaging modality commonly used to detect disease and injury. Contrast agents containing iodine, such as iohexol, are frequently used in CT examinations to more clearly differentiate anatomic structures and to detect and characterize abnormalities, including tumors. However, these contrast agents do not have a specific tropism for cancer cells, so the ability to detect tumors is severely limited by the degree of vascularization of the tumor itself. Identifying delivery systems allowing enrichment of contrast agents at the tumor site would increase the sensitivity of detection of tumors and metastases, potentially in organs that are normally inaccessible to contrast agents, such as the CNS. Recent work from our laboratory has identified cancer patient-derived extracellular vesicles (PDEVs) as effective delivery vehicles for targeting diagnostic drugs to patients' tumors. Based on this premise, we explored the possibility of introducing iohexol into PDEVs for targeted delivery to neoplastic tissue. Here, we provide preclinical proof-of-principle for the tumor-targeting ability of iohexol-loaded PDEVs, which resulted in an impressive accumulation of the contrast agent selectively into the neoplastic tissue, significantly improving the ability of the contrast agent to delineate tumor boundaries

A machine-learning based bio-psycho-social model for the prediction of non-obstructive and obstructive coronary artery disease

Background: Mechanisms of myocardial ischemia in obstructive and non-obstructive coronary artery disease (CAD), and the interplay between clinical, functional, biological and psycho-social features, are still far to be fully elucidated. Objectives: To develop a machine-learning (ML) model for the supervised prediction of obstructive versus non-obstructive CAD. Methods: From the EVA study, we analysed adults hospitalized for IHD undergoing conventional coronary angiography (CCA). Non-obstructive CAD was defined by a stenosis < 50% in one or more vessels. Baseline clinical and psycho-socio-cultural characteristics were used for computing a Rockwood and Mitnitski frailty index, and a gender score according to GENESIS-PRAXY methodology. Serum concentration of inflammatory cytokines was measured with a multiplex flow cytometry assay. Through an XGBoost classifier combined with an explainable artificial intelligence tool (SHAP), we identified the most influential features in discriminating obstructive versus non-obstructive CAD. Results: Among the overall EVA cohort (n = 509), 311 individuals (mean age 67 ± 11 years, 38% females; 67% obstructive CAD) with complete data were analysed. The ML-based model (83% accuracy and 87% precision) showed that while obstructive CAD was associated with higher frailty index, older age and a cytokine signature characterized by IL-1β, IL-12p70 and IL-33, non-obstructive CAD was associated with a higher gender score (i.e., social characteristics traditionally ascribed to women) and with a cytokine signature characterized by IL-18, IL-8, IL-23. Conclusions: Integrating clinical, biological, and psycho-social features, we have optimized a sex- and gender-unbiased model that discriminates obstructive and non-obstructive CAD. Further mechanistic studies will shed light on the biological plausibility of these associations. Clinical trial registration: NCT02737982

An explainable model of host genetic interactions linked to COVID-19 severity

We employed a multifaceted computational strategy to identify the genetic factors contributing to increased risk of severe COVID-19 infection from a Whole Exome Sequencing (WES) dataset of a cohort of 2000 Italian patients. We coupled a stratified k-fold screening, to rank variants more associated with severity, with the training of multiple supervised classifiers, to predict severity based on screened features. Feature importance analysis from tree-based models allowed us to identify 16 variants with the highest support which, together with age and gender covariates, were found to be most predictive of COVID-19 severity. When tested on a follow-up cohort, our ensemble of models predicted severity with high accuracy (ACC = 81.88%; AUCROC = 96%; MCC = 61.55%). Our model recapitulated a vast literature of emerging molecular mechanisms and genetic factors linked to COVID-19 response and extends previous landmark Genome-Wide Association Studies (GWAS). It revealed a network of interplaying genetic signatures converging on established immune system and inflammatory processes linked to viral infection response. It also identified additional processes cross-talking with immune pathways, such as GPCR signaling, which might offer additional opportunities for therapeutic intervention and patient stratification. Publicly available PheWAS datasets revealed that several variants were significantly associated with phenotypic traits such as "Respiratory or thoracic disease", supporting their link with COVID-19 severity outcome.A multifaceted computational strategy identifies 16 genetic variants contributing to increased risk of severe COVID-19 infection from a Whole Exome Sequencing dataset of a cohort of Italian patients

A genome-wide association study for survival from a multi-centre European study identified variants associated with COVID-19 risk of death

: The clinical manifestations of SARS-CoV-2 infection vary widely among patients, from asymptomatic to life-threatening. Host genetics is one of the factors that contributes to this variability as previously reported by the COVID-19 Host Genetics Initiative (HGI), which identified sixteen loci associated with COVID-19 severity. Herein, we investigated the genetic determinants of COVID-19 mortality, by performing a case-only genome-wide survival analysis, 60 days after infection, of 3904 COVID-19 patients from the GEN-COVID and other European series (EGAS00001005304 study of the COVID-19 HGI). Using imputed genotype data, we carried out a survival analysis using the Cox model adjusted for age, age2, sex, series, time of infection, and the first ten principal components. We observed a genome-wide significant (P-value < 5.0 × 10-8) association of the rs117011822 variant, on chromosome 11, of rs7208524 on chromosome 17, approaching the genome-wide threshold (P-value = 5.19 × 10-8). A total of 113 variants were associated with survival at P-value < 1.0 × 10-5 and most of them regulated the expression of genes involved in immune response (e.g., CD300 and KLR genes), or in lung repair and function (e.g., FGF19 and CDH13). Overall, our results suggest that germline variants may modulate COVID-19 risk of death, possibly through the regulation of gene expression in immune response and lung function pathways

The polymorphism L412F in TLR3 inhibits autophagy and is a marker of severe COVID-19 in males

The polymorphism L412F in TLR3 has been associated with several infectious diseases. However, the mechanism underlying this association is still unexplored. Here, we show that the L412F polymorphism in TLR3 is a marker of severity in COVID-19. This association increases in the sub-cohort of males. Impaired macroautophagy/autophagy and reduced TNF/TNFα production was demonstrated in HEK293 cells transfected with TLR3L412F-encoding plasmid and stimulated with specific agonist poly(I:C). A statistically significant reduced survival at 28 days was shown in L412F COVID-19 patients treated with the autophagy-inhibitor hydroxychloroquine (p = 0.038). An increased frequency of autoimmune disorders such as co-morbidity was found in L412F COVID-19 males with specific class II HLA haplotypes prone to autoantigen presentation. Our analyses indicate that L412F polymorphism makes males at risk of severe COVID-19 and provides a rationale for reinterpreting clinical trials considering autophagy pathways. Abbreviations: AP: autophagosome; AUC: area under the curve; BafA1: bafilomycin A1; COVID-19: coronavirus disease-2019; HCQ: hydroxychloroquine; RAP: rapamycin; ROC: receiver operating characteristic; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; TLR: toll like receptor; TNF/TNF-α: tumor necrosis factor