Anatomical classification of feline congenital extrahepatic portosystemic shunts based on CT angiography: A SVSTS and VIRIES multi-institutional study in 231 cats.

The prevalence of anatomical-based subtypes of feline congenital extrahepatic portosystemic shunts (EHPSS) has not been completely elucidated. The goal of this study was to use CT angiography to create an anatomical-based nomenclature system for feline congenital EHPSS. Additionally, subjective portal perfusion scores were generated to determine if intrinsic portal vein development was associated with different shunt conformations or patient age at the time of CT. The SVSTS and VIRIES list services were used to recruit cases. Data collected included patient DOB, gender, breed, weight, CT date, and reported diagnosis. Shunts were classified based upon (1) the shunt portal vessel(s) of origin, (2) the shunt systemic vessel(s) of insertion, and (3) any substantial portal vessels contributing to the shunt. Additionally, hepatic portal perfusion was subjectively scored between 1 (poor/none) and 5 (good/normal) based on the caliber of the intrahepatic PVs. A total of 264 CT scans were submitted from 29 institutions. Due to exclusion criteria, 33 (13%) were removed, leaving 231 CT scans to be included. Twenty-five different EHPSS anatomies were identified with five classifications accounting for 78% of all shunts (LGP [53%], LGC-post [11%], LCG [7%], LGC-pre [4%], and PC [4%]). Shunt origin involved the left gastric vein in 75% of the described classifications. Significant differences were identified among the five most common shunt types with respect to age at the time of CT scan (P = .002), breed (P < .001), and subjective portal perfusion score (P < .001). This refined anatomical classification system for feline EHPSS may enable improved understanding, treatment comparisons, and outcome prediction for cats with these anomalies.

Computed tomographic features of an axillary liposarcoma with hepatic metastasis.

A geriatric dog presented for lethargy, dyspnea, and urinary incontinence. Thoracic radiographs demonstrated a large, mixed fat, and soft tissue opaque axillary mass and a pulmonary mass. Computed tomography (CT) further characterized these masses and revealed innumerable fat-attenuating hepatic masses and cranial mediastinal lymphadenopathy. Histopathology of the axillary and hepatic masses confirmed grade two primary axillary liposarcoma with hepatic metastasis. Cytology of the pulmonary mass was consistent with a pulmonary carcinoma. This is the first published CT description of fat-attenuating metastatic hepatic liposarcoma in a dog.

Myositis-specific Antibodies Identify A Distinct Interstitial Pneumonia with Autoimmune Features Phenotype.

Interstitial pneumonia with autoimmune features (IPAF) characterises individuals with interstitial lung disease (ILD) and features of connective tissue disease (CTD) who fail to satisfy CTD criteria. Inclusion of myositis-specific antibodies (MSAs) in the IPAF criteria has generated controversy, as these patients also meet proposed criteria for an anti-synthetase syndrome. Whether MSAs and myositis associated antibodies (MAA) identify phenotypically distinct IPAF subgroups remains unclear.A multi-center, retrospective investigation was conducted to assess clinical features and outcomes in patients meeting IPAF criteria stratified by the presence of MSAs and MAAs. IPAF subgroups were compared to cohorts of patients with idiopathic inflammatory myopathy-ILD (IIM-ILD), idiopathic pulmonary fibrosis (IPF) and non-IIM CTD-ILDs. The primary endpoint assessed was three-year transplant-free survival. Two hundred sixty-nine patients met IPAF criteria, including 35 (13%) with MSAs and 65 (24.2%) with MAAs. Survival was highest among patients with IPAF-MSA and closely approximated those with IIM-ILD. Survival did not differ between IPAF-MAA and IPAF without MSA/MAA cohorts. Usual interstitial pneumonia (UIP) morphology was associated with differential outcome risk, with IPAF patients with non-UIP morphology approximating survival observed in non-IIM CTD-ILDs. MSAs, but not MAAs identified a unique IPAF phenotype characterised by clinical features and outcomes similar to IIM-ILD. UIP morphology was a strong predictor of outcome in others meeting IPAF criteria. Because IPAF is a research classification without clear treatment approach, these findings suggest MSAs should be removed from the IPAF criteria and such patients should be managed as an IIM-ILD.

John's story - living with hereditary haemochromatosis.

Iron can accumulate in the body due to several causes, resulting in iron overload syndrome. The most common cause is hereditary haemochromatosis (HH), a genetic disorder triggered by inactivation of the iron hormone hepcidin, which results in hyperferraemia and excessive tissue iron deposition. Other causes include repeated blood transfusion, iron-loading anaemias and some chronic liver diseases. Left undiagnosed, HH can cause significant damage to the liver, heart, pancreas and joints, because excess iron is toxic. This also increases the risk of hepatocellular carcinoma, especially in those with cirrhosis of the liver, with an estimate of 1 in 10 HH patients affected. The risk of developing type 2 diabetes is increased by 2.5-7.1 times compared with non-diabetic patients. Haemochromatosis is usually considered when elevated serum ferritin and transferrin saturation levels are found. Ferritin in excess of 300 ng/mL usually indicates iron overload. Genetic testing can identify the two most common mutations in the HFE gene - a positive result confirms the diagnosis of haemochromatosis - but there are also rare forms of the disease unrelated to HFE mutations. Liver biopsy can be used to ascertain iron accumulation and histological presence of fibrosis (cirrhosis). Assessment of the hepatic iron index is considered the gold standard for diagnosis of haemochromatosis. Magnetic resonance imaging has been used as a non-invasive alternative to accurately estimate iron deposition levels in the liver, heart, joints and pituitary gland. Population screening is not recommended; however, family members of identified people should be screened to determine their phenotypic or carrier potential. Early diagnosis enables preventative measures to be commenced. Routine treatment is by regular venesection of 500 mL of whole blood per session. An initiation phase of weekly or twice-weekly venesection is common until serum ferritin (SF) is reduced to normal. When SF and other markers are within normal range, regular venesections are usually scheduled 1-3 months apart, depending on the underlying cause and SF response. Dietary iron including red meat and fortified foods such as cereals should be avoided. Vitamin C promotes iron absorption, and supplementation should be avoided, as should alcohol, which can increase the risk of concomitant liver disease. John's story outlines a typical journey through diagnosis, treatment and care during HH while living on Arran, an island off the coast of Scotland. Subsequently, John developed hepatocellular carcinoma, and his treatment and palliative care are described. We wrote this article to give the reader an insight to this silent disorder and the value of recognising the signs and symptoms for early diagnosis and subsequent treatment.

Social Networks as a Key Health Determinant in Acute Illness Recovery: A Lesson from the COVID-19 Pandemic.

BACKGROUND: The COVID-19 pandemic highlighted the importance of considering social determinants of health in health outcomes. Within this spectrum of determinants, social networks garnered attention as the pandemic highlighted the negative effects of social isolation in the context of social distancing measures. Postpandemic, examining the role social networks play in COVID-19 recovery can help guide patient care and shape future health policies. This study aimed to investigate the relationship between social networks and self-rated health change, as well as physical function, in patients recovering from COVID-19 pneumonia. METHODS: This was a retrospective cohort study utilizing clinical data from 2 New York City hospitals and a 9-month follow-up survey of COVID-19 pneumonia survivors. We evaluated a composite Social Network Score from the 6-item Lubben Social Network Scale and its association with 2 outcomes: 1) self-rated health change and 2) physical function. RESULTS: A total of 208 patients were included in this study. A 1-point increase in the Social Network Score was associated with greater odds of both same or improved self-rated health change (odds ratio [OR] 1.07, 95% CI 1.02-1.12, P = .01), as well as unimpaired physical function (OR 1.08, 95% CI 1.03-1.14, P < .01). CONCLUSION: This study emphasized the importance of social networks as a social determinant of health among patients recovering from COVID-19 hospitalization. Targeted interventions to enhance social networks may benefit not only COVID-19 patients but also individuals recovering from other acute illnesses.

Magnetic resonance imaging of a randomized controlled trial investigating predictors of recovery following psychological treatment in adolescents with moderate to severe unipolar depression: study protocol for Magnetic Resonance-Improving Mood with Psychoanalytic and Cognitive Therapies (MR-IMPACT).

BACKGROUND: Major depressive disorders (MDD) are a debilitating and pervasive group of mental illnesses afflicting many millions of people resulting in the loss of 110 million working days and more than 2,500 suicides per annum. Adolescent MDD patients attending NHS clinics show high rates of recurrence into adult life. A meta-analysis of recent research shows that psychological treatments are not as efficacious as previously thought. Modest treatment outcomes of approximately 65% of cases responding suggest that aetiological and clinical heterogeneity may hamper the better use of existing therapies and discovery of more effective treatments. Information with respect to optimal treatment choice for individuals is lacking, with no validated biomarkers to aid therapeutic decision-making. METHODS/DESIGN: Magnetic resonance-Improving Mood with Psychoanalytic and Cognitive Therapies, the MR-IMPACT study, plans to identify brain regions implicated in the pathophysiology of depressions and examine whether there are specific behavioural or neural markers predicting remission and/or subsequent relapse in a subsample of depressed adolescents recruited to the IMPACT randomised controlled trial (Registration # ISRCTN83033550). DISCUSSION: MR-IMPACT is an investigative biomarker component of the IMPACT pragmatic effectiveness trial. The aim of this investigation is to identify neural markers and regional indicators of the pathophysiology of and treatment response for MDD in adolescents. We anticipate that these data may enable more targeted treatment delivery by identifying those patients who may be optimal candidates for therapeutic response. TRIAL REGISTRATION: Adjunctive study to IMPACT trial (Current Controlled Trials: ISRCTN83033550).

Revascularization Strategies in Patients with Coronary Artery Disease and Chronic Obstructive Lung Disease.

Purpose of review: This paper assesses recent literature on the impact of chronic obstructive pulmonary disease (COPD) in patients with coronary artery disease (CAD) undergoing revascularization. Specifically, to determine if there is an optimal revascularization strategy for this patient population, and if there are other modalities to assess the risks. Recent findings: There are limited new data in the last year addressing this clinical question. Recently there have been a series of studies which reinforced that COPD is a key independent risk factor for adverse outcomes after revascularization. There is no optimal revascularization strategy; however, there was a nonsignificant signal of potential benefit with percutaneous coronary intervention (PCI) with short-term outcomes in the SYNTAXES trial. Currently, pulmonary function tests (PFT) are limited in clarifying risk assessments prior to revascularization, and there are investigations into the use of biomarkers to provide further insight into this increased risk of adverse outcomes in patients with COPD. Summary: COPD is a key risk factor for poor outcomes in patients requiring revascularization. More investigations are needed to determine the optimum revascularization strategy.

Diagnosis and management of a laryngeal cyst in a domestic shorthair cat.

Case summary: A 7-year-old male neutered domestic shorthair cat was presented with a 3-month history of dyspnea when exercising and increased respiratory noise when purring. Initial radiographs identified a suspected laryngeal mass. Point-of-care ultrasound found a fluid-filled structure on the larynx, which was drained percutaneously. The cat initially recovered well but, due to recurrence of clinical signs, a CT scan was performed, which confirmed the presence of a laryngeal cyst that was subsequently surgically resected. Histopathological analysis was consistent with a suspected thyroglossal cyst. Relevance and novel information: This is only the second report of a laryngeal cyst in the cat. While malignant laryngeal disease may be more prevalent in the cat, benign differentials should be considered as treatment could be curative, as was observed in this case.

Human Stem Cell-Derived Neurons Repair Circuits and Restore Neural Function.

Although cell transplantation can rescue motor defects in Parkinson's disease (PD) models, whether and how grafts functionally repair damaged neural circuitry in the adult brain is not known. We transplanted hESC-derived midbrain dopamine (mDA) or cortical glutamate neurons into the substantia nigra or striatum of a mouse PD model and found extensive graft integration with host circuitry. Axonal pathfinding toward the dorsal striatum was determined by the identity of the grafted neurons, and anatomical presynaptic inputs were largely dependent on graft location, whereas inhibitory versus excitatory input was dictated by the identity of grafted neurons. hESC-derived mDA neurons display A9 characteristics and restore functionality of the reconstructed nigrostriatal circuit to mediate improvements in motor function. These results indicate similarity in cell-type-specific pre- and post-synaptic integration between transplant-reconstructed circuit and endogenous neural networks, highlighting the capacity of hPSC-derived neuron subtypes for specific circuit repair and functional restoration in the adult brain.

Human leucocyte antigen class II genotype in susceptibility and resistance to co-amoxiclav-induced liver injury.

BACKGROUND & AIMS: Co-amoxiclav is one of the most common causes of drug-induced liver injury (DILI). Although there are previous reports of genetic associations between HLA class II and co-amoxiclav-related DILI, studies to date have been based on very small numbers from single centres only. In order to address this problem we have investigated the role of HLA class II DRB1 and DQB1 in 61 cases of co-amoxiclav DILI as part of a UK-wide multicentre study. METHODS: HLA alleles and genotypes were compared with those of 40 individuals exposed to co-amoxiclav without toxicity (treated controls) and 191 population controls. RESULTS: There were two significant findings from the study. First, HLA-DRB1*15 was increased in patients (53%) versus both treated (33%: OR=2.29: 95% CI: 1.00-5.26) and population controls (30%: OR=2.59:95% CI: 1.44-4.68: p=0.002). Second, DRB1*07 was found to be reduced in patients (9.8%) compared to both treated (35%: OR=0.18: 95% CI: 0.06-0.52: p=0.0011, pc=0.0154) and population controls (29%: OR=0.266: 95% CI: 0.11-0.65: p=0.0019, pc=0.0266). CONCLUSIONS: These results confirm the previously reported significant genetic risk for HLA-DRB1*15 and also provide evidence of a protective effect of the HLA-DRB1*07 family of alleles. HLA alleles and haplotypes may be particularly important in susceptibility and resistance to co-amoxiclav-DILI, but it remains to be seen whether this effect is due to the identified alleles or others in close linkage disequilibrium elsewhere on the MHC.

Using an acuity-adaptable unit for urological services.

The University of Pittsburgh Medical Center--Shadyside Campus uses an acuity-adaptable unit model that has streamlined patient care. Pre-operative preparation and post-operative recovery nursing care on one designated nursing unit provide a less stressful experience for the surgical patient.

Derivation and Validation of a Diagnostic Prediction Tool for Interstitial Lung Disease.

BACKGROUND: Interstitial lung disease (ILD) results in high morbidity and health-care utilization. Diagnostic delays remain common and often occur in nonpulmonology settings. Screening for ILD in these settings has the potential to reduce diagnostic delays and improve patient outcomes. RESEARCH QUESTION: This study sought to determine whether a pulmonary function test (PFT)-derived diagnostic prediction tool (ILD-Screen) could accurately identify incident ILD cases in patients undergoing PFT in nonpulmonology settings. STUDY DESIGN AND METHODS: Clinical and physiologic PFT variables predictive of ILD were identified by using iterative multivariable logistic regression models. ILD status was determined by using a multi-reader approach. An ILD-Screen score was generated by using final regression model coefficients, with a score ≥ 8 considered positive. ILD-Screen test performance was validated in an independent external cohort and applied prospectively to PFTs over 1 year to identify incident ILD cases at our institution. RESULTS: Variables comprising the ILD-Screen were age, height, total lung capacity, FEV1, diffusion capacity, and PFT indication. The ILD-Screen showed consistent test performance across cohorts, with a sensitivity of 0.79 and a specificity of 0.83 when applied prospectively. A positive ILD-Screen strongly predicted ILD (OR, 18.6; 95% CI, 9.4-36.9) and outperformed common ILD clinical features, including cough, dyspnea, lung crackles, and restrictive lung physiology. Prospective ILD-Screen application resulted in a higher proportion of patients undergoing chest CT imaging compared with a historical control cohort (74% vs 56%, respectively; P = .003), with a significantly shorter median time to chest CT imaging (5.6 vs 21.1 months; P < .001). INTERPRETATION: The ILD-Screen showed good test performance in predicting ILD across diverse geographic settings and when applied prospectively. Systematic ILD-Screen application has the potential to reduce diagnostic delays and facilitate earlier intervention in patients with ILD.

Outline and surface disruption in animal camouflage.

Camouflage is an important strategy in animals to prevent predation. This includes disruptive coloration, where high-contrast markings placed at an animal's edge break up the true body shape. Successful disruption may also involve non-marginal markings found away from the body outline that create 'false edges' more salient than the true body form ('surface disruption'). However, previous work has focused on breaking up the true body outline, not on surface disruption. Furthermore, while high contrast may enhance disruption, it is untested where on the body different contrasts should be placed for maximum effect. We used artificial prey presented to wild avian predators in the field, to determine the effectiveness of surface disruption, and of different luminance contrast placed in different prey locations. Disruptive coloration was no more effective when comprising high luminance contrast per se, but its effectiveness was dramatically increased with high-contrast markings placed away from the body outline, creating effective surface disruption. A model of avian visual edge processing showed that surface disruption does not make object detection more difficult simply by creating false edges away from the true body outline, but its effect may also be based on a different visual mechanism. Our study has implications for whether animals can combine disruptive coloration with other 'conspicuous' signalling strategies.

Assessing the survival of transgenic plant DNA in the human gastrointestinal tract.

The inclusion of genetically modified (GM) plants in the human diet has raised concerns about the possible transfer of transgenes from GM plants to intestinal microflora and enterocytes. The persistence in the human gut of DNA from dietary GM plants is unknown. Here we study the survival of the transgene epsps from GM soya in the small intestine of human ileostomists (i.e., individuals in which the terminal ileum is resected and digesta are diverted from the body via a stoma to a colostomy bag). The amount of transgene that survived passage through the small bowel varied among individuals, with a maximum of 3.7% recovered at the stoma of one individual. The transgene did not survive passage through the intact gastrointestinal tract of human subjects fed GM soya. Three of seven ileostomists showed evidence of low-frequency gene transfer from GM soya to the microflora of the small bowel before their involvement in these experiments. As this low level of epsps in the intestinal microflora did not increase after consumption of the meal containing GM soya, we conclude that gene transfer did not occur during the feeding experiment.

Cognitive Behavioral Therapy Lowers Elevated Functional Connectivity in Depressed Adolescents.

Imaging studies have implicated altered functional connectivity in adults with major depressive disorder (MDD). Whether similar dysfunction is present in adolescent patients is unclear. The degree of resting-state functional connectivity (rsFC) may reflect abnormalities within emotional ('hot') and cognitive control ('cold') neural systems. Here, we investigate rsFC of these systems in adolescent patients and changes following cognitive behavioral therapy (CBT). Functional Magnetic Resonance Imaging (fMRI) was acquired from adolescent patients before CBT, and 24-weeks later following completed therapy. Similar data were obtained from control participants. Cross-sectional Cohort: From 82 patients and 34 controls at baseline, rsFC of the amygdala, anterior cingulate cortex (ACC), and pre-frontal cortex (PFC) was calculated for comparison. Longitudinal Cohort: From 17 patients and 30 controls with longitudinal data, treatment effects were tested on rsFC. Patients demonstrated significantly greater rsFC to left amygdala, bilateral supragenual ACC, but not with PFC. Treatment effects were observed in right insula connected to left supragenual ACC, with baseline case-control differences reduced. rsFC changes were significantly correlated with changes in depression severity. Depressed adolescents exhibited heightened connectivity in regions of 'hot' emotional processing, known to be associated with depression, where treatment exposure exerted positive effects, without concomitant differences in areas of 'cold' cognition.

Adolescent Major Depressive Disorder: Neuroimaging Evidence of Sex Difference during an Affective Go/No-Go Task.

Compared to female major depressive disorder (MDD), male MDD often receives less attention. However, research is warranted since there are significant sex differences in the clinical presentation of MDD and a higher rate of suicide in depressed men. To the best of our knowledge, this is the first functional magnetic resonance imaging (fMRI) study with a large sample addressing putative sex differences in MDD during adolescence, a period when one of the most robust findings in psychiatric epidemiology emerges; that females are twice as likely to suffer from MDD than males. Twenty-four depressed and 10 healthy male adolescents, together with 82 depressed and 24 healthy female adolescents, aged 11-18 years, undertook an affective go/no-go task during fMRI acquisition. In response to sad relative to neutral distractors, significant sex differences (in the supramarginal gyrus) and group-by-sex interactions (in the supramarginal gyrus and the posterior cingulate cortex) were found. Furthermore, in contrast to the healthy male adolescents, depressed male adolescents showed decreased activation in the cerebellum with a significant group-by-age interaction in connectivity. Future research may consider altered developmental trajectories and the possible implications of sex-specific treatment and prevention strategies for MDD.

Epigenetic inactivation of the human sprouty2 (hSPRY2) homologue in prostate cancer.

Abnormal signalling events mediated by receptor tyrosine kinases (RTKs) contribute to human carcinogenesis. Sprouty2 (Spry2) is a key antagonistic regulator of RTK signalling and suppression of its expression or function may facilitate proliferation and angiogenesis. Using prostate cancer (CaP) as a model, we investigated the significance of Spry2 in human malignancy. We observed downregulated Spry2 expression in invasive CaP cell lines and high-grade clinical CaP (compared to benign prostatic hyperplasia (BPH) and well-differentiated tumours, P=0.041). A large CpG island is associated with hSPRY2, and extensive hypermethylation of this CpG island was observed in 76-82% of high-grade CaP, while control BPH tissues were predominantly unmethylated (P=0.0005). Furthermore, suppressed Spry2 expression correlated with methylation of the CpG region in clinical samples (P=0.004) and treatment with 5-aza-2'-deoxycytidine reactivated Spry2 expression in LNCaP and PC-3M cells. hSPRY2 maps to the long arm of chromosome 13 (13q31.1), where loss of heterozygosity (LOH) has been reported. We found no evidence of mutation; however, we demonstrated 27-40% LOH using flanking markers to hSPRY2. Hence, while biallelic epigenetic inactivation of hSPRY2 represents the main genetic event in prostate carcinogenesis, the observed 27-40% LOH presents evidence of hemizygous deletion with the remaining allele hypermethylated. We therefore propose hSPRY2 as a potential tumour suppressor locus in CaP.

Functional MRI of emotional memory in adolescent depression.

INTRODUCTION: Major Depressive Disorder (MDD) is a leading cause of disease burden worldwide. Mood-congruent biases in memory tasks are frequently reported in MDD patients, with facilitated memory for negative stimuli. Most functional MRI studies to date have examined the neural correlates of these biases in depressed adults, with fewer studies in adolescents with MDD. Investigation of MDD in adolescence may aid greater understanding of the aetiology and development of the disorder. METHODS: Cognitive biases were investigated in 56 MDD patients aged 11-17 years and a matched group of 30 healthy control participants with a self-referential memory task. Behavioural performance and BOLD fMRI data were collected during both encoding and retrieval stages. RESULTS: The neural response to encoding in adolescents with MDD was found to differ significantly from controls. Additionally, neural responses during encoding and retrieval showed differential relationships with age between patient and control groups, specifically in medial, temporal, and prefrontal regions. CONCLUSIONS: These findings suggest that during adolescence neurophysiological activity associated with emotional memory differs in those with depression compared to controls and may be age sensitive.