Programmed Death Ligand 1 (PD-L1) Expression and CD8 + Tumor-infiltrating Lymphocyte-based Tumor Immune Microenvironment Classification in Gynecologic Carcinosarcoma: Prognostic Impact and Implications for Therapy.

To investigate the prevalence and prognostic significance of programmed death ligand-1 (PD-L1) expression and CD8 + tumor-infiltrating lymphocytes (TILs) in gynecologic carcinosarcoma, 81 cases (68 uterine, 12 ovarian, and 1 fallopian tube) were immunostained with PD-L1 and CD8 using tissue microarrays (3 mm core diameter) from intratumoral areas with the highest TILs. Tumor proportion score (TPS) ≥1% and combined positive score (CPS) ≥1 were considered positive for PD-L1. CD8 + TILs were counted in each core, and CD8 + TIL density (CD8TILD) was calculated. Cases were classified as CD8 Neg (<1.4/mm 2 CD8TILD), CD8 Pos (≥1.4/mm 2 CD8TILD) and CD8 HIGH (≥14/mm 2 CD8TILD) and grouped into 4 tumor immune microenvironment (TIME) groups: (1) PD-L-1 Pos /CD8 Pos , (2) PD-L1 Neg /CD8 Neg , (3) PD-L1 Pos /CD8 Neg , and (4) PD-L1 Neg /CD8 Pos . PD-L1 expression by TPS and CPS was detected in 19.8% and 39.6% cases, respectively. Kaplan-Meier curves with log-rank analysis showed that higher density of CD8 + TILs were associated with longer overall survival (OS) ( P =0.05 for CD8 Pos and P =0.014 for CD8 HIGH ), and CD8 HIGH status was associated with longer OS irrespective of tumor stage ( P =0.045, hazard ratio: 0.11, 95% confidence interval: 0.014-0.951). Thirty-three percent of patients belonged to TIME group 1. PD-L1 expression and TIME groups were not associated with OS or progression-free survival. We found that high density of CD8 + TILs is an independent indicator of better OS. In 33% cases PD-L1 expression is associated with increased CD8 + TILs ("acquired immune evasion" pattern of PD-L1 expression), hence they may benefit from anti PD-1/PD-L1 therapy. PD-L1 expression alone and TIME groups do not affect survival in gynecologic carcinosarcoma.

Sensitivity and specificity of fine needle aspiration for the diagnosis of mediastinal lesions.

Fine needle aspiration cytology (FNAC) of mediastinal masses allows for rapid on-site evaluation and the triaging of material for ancillary studies. However, surgical pathology is often considered to be the gold standard for diagnosis. This study examines the sensitivity and specificity of FNAC compared to a concurrent or subsequent surgical pathology specimen in 77 mediastinal lesions. The overall sensitivity for mediastinal mass FNAC was 78% and the overall specificity was 98%. For individual categories the sensitivity and specificity of FNAC was respectively as follows: inflammatory/infectious (33%, 99%), metastatic carcinoma (93%, 100%), lymphoma (84%, 97%), cysts (25%, 100%), soft tissue tumors (100%, 100%), paraganglioma (50%, 100%), germ cell tumor (100%, 99%), thymoma (87%, 94%), thymic carcinoma (60%, 100%), benign thymus (0%, 100%), and indeterminate (100%, 90%). For different locations within the mediastinum the sensitivity and specificity of FNAC was respectively as follows: anterosuperior mediastinum (80%, 98%), posterior mediastinum (33%, 95%), middle mediastinum (100%, 100%), and mediastinum, NOS (79%, 99%). Thus, mediastinal FNAC is fairly sensitive, very specific, and is a valuable technique in the diagnosis of mediastinal masses.

Metastatic Breast Carcinoma in Cerebrospinal Fluid: A Cytopathological Review of 15 Cases.

The incidence of metastatic carcinoma to the meninges ("meningeal carcinomatosis" [MC]) is increasing due to longer survival of patients and improved imaging techniques. Currently, MC is best diagnosed by cytopathological evaluation of cerebrospinal fluid (CSF). Breast primaries are the commonest cause of MC; although cytopathological features thereof have not been, as yet, fully characterized. In this study of meningeal mammary carcinomatosis, relevant clinicopathological data and archived cytopathological preparations of all "suspicious" and "positive" CSF specimens (1992-2015), from patients with a history of breast carcinoma, were retrieved and reviewed. Twenty-three "positive" CSF specimens, derived from 15 patients formed the basis of this study. All specimens were processed as Cytospin preparations, and stained by Papanicolaou and Diff-Quik techniques. All patients were female, with a mean age of 57 (range: 32-85) years. Mean interval between initial diagnosis of breast carcinoma and "positive" CSF was 32 (range 6-84) months. All 23 specimens (100%) were "cellular" (>10 carcinoma cells). Eighteen (78%) specimens showed only isolated nonclustered cells, and 5 (22%) specimens showed both cell clusters and isolated cells. In most "positive" cases, metastatic breast carcinoma cells showed variation in cell size, with hyperchromatic nuclei, irregular nuclear membranes, prominent nucleoli and cytoplasmic vacuolization. The background in some CSF samples showed red blood cells and fibrin admixed with rare lymphocytes and histiocytes. One specimen showed necrotic debris. Papanicolaou and Diff-Quik-stained Cytospin preparations were equally diagnostic, as the aforementioned findings were present in both types of preparation.

A Souvenir From France: Acrodermatitis Chronica Atrophicans Presenting in the United States.

A 70-year-old man was referred by his rheumatologist to our dermatology clinic for evaluation of dermatitis on his right arm that appeared 3 months earlier. The skin lesion was asymptomatic and the patient denied current systemic symptoms, including fever, chills, and joint pain; however, 10 months prior to this presentation he experienced arthritis in the left knee. At that time, Borrelia serology revealed positive IgG (6.07; <0.8 negative, 0.8 to 0.99 borderline, ≥1 positive) and negative IgM titers. The patient had not received treatment for Lyme disease in the past. He was referred to rheumatology for evaluation of possible Lyme disease but did not follow up until 10 months later. The arthritis has since resolved. He travels frequently to France and recalls multiple tick bites during these trips.

Health assessment of free-ranging endangered Australian sea lion (Neophoca cinerea) pups: effect of haematophagous parasites on haematological parameters.

Evaluation of the health status of free-ranging populations is important for understanding the impact of disease on individuals and on population demography and viability. In this study, haematological reference intervals were developed for free-ranging endangered Australian sea lion (Neophoca cinerea) pups within the context of endemic hookworm (Uncinaria sanguinis) infection and the effects of pathogen, host, and environment factors on the variability of haematological parameters were investigated. Uncinaria sanguinis was identified as an important agent of disease, with infection causing regenerative anaemia, hypoproteinaemia, and a predominantly lymphocytic-eosinophilic systemic inflammatory response. Conversely, the effects of sucking lice (Antarctophthirus microchir) were less apparent and infestation in pups appears unlikely to cause clinical impact. Overall, the effects of U. sanguinis, A. microchir, host factors (standard length, body condition, pup sex, moult status, and presence of lesions), and environment factors (capture-type and year of sampling) accounted for 26-65% of the total variance observed in haematological parameters. Importantly, this study demonstrated that anaemia in neonatal Australian sea lion pups is not solely a benign physiological response to host-environment changes, but largely reflects a significant pathological process. This impact of hookworm infection on pup health has potential implications for the development of foraging and diving behaviour, which would subsequently influence the independent survival of juveniles following weaning. The haematological reference intervals developed in this study can facilitate long-term health surveillance, which is critical for the early recognition of changes in disease impact and to inform conservation management.

Ivermectin treatment of free-ranging endangered Australian sea lion (Neophoca cinerea) pups: effect on hookworm and lice infection status, haematological parameters, growth, and survival.

A placebo-controlled study was used to investigate the effectiveness of ivermectin to treat hookworm (Uncinaria sanguinis) and lice (Antarctophthirus microchir) infections in free-ranging Australian sea lion (Neophoca cinerea) pups and to test the hypotheses that these parasitic infections cause anaemia, systemic inflammatory responses, and reduced growth, and contribute towards decreased pup survival. Ivermectin was identified as an effective and safe anthelmintic in this species. Pups administered ivermectin had significantly higher erythrocyte counts and significantly lower eosinophil counts compared to controls at 1-2 months post-treatment, confirming that U. sanguinis and/or A. microchir are causatively associated with disease and demonstrating the positive effect of ivermectin treatment on clinical health parameters. Higher growth rates were not seen in ivermectin-treated pups and, unexpectedly, relatively older pups treated with ivermectin demonstrated significantly reduced growth rates when compared to matched saline-control pups. Differences in survival were not identified between treatment groups; however, this was attributed to the unexpectedly low mortality rate of recruited pups, likely due to the unintended recruitment bias towards pups >1-2 months of age for which mortality due to hookworm infection is less likely. This finding highlights the logistical and practical challenges associated with treating pups of this species shortly after birth at a remote colony. This study informs the assessment of the use of anthelmintics as a tool for the conservation management of free-ranging wildlife and outlines essential steps to further the development of strategies to ensure the effective conservation of the Australian sea lion and its parasitic fauna.

Epidemiology of hookworm (Uncinaria sanguinis) infection in free-ranging Australian sea lion (Neophoca cinerea) pups.

Understanding the fundamental factors influencing the epidemiology of wildlife disease is essential to determining the impact of disease on individual health and population dynamics. The host-pathogen-environment relationship of the endangered Australian sea lion (Neophoca cinerea) and the parasitic hookworm, Uncinaria sanguinis, was investigated in neonatal pups during summer and winter breeding seasons at two biogeographically disparate colonies in South Australia. The endemic occurrence of hookworm infection in Australian sea lion pups at these sites was 100% and post-parturient transmammary transmission is likely the predominant route of hookworm infection for pups. The prepatent period for U. sanguinis in Australian sea lion pups was determined to be 11-14 days and the duration of infection approximately 2-3 months. The mean hookworm infection intensity in pups found dead was 2138 ± 552 (n = 86), but a significant relationship between infection intensity and faecal egg count was not identified; infection intensity in live pups could not be estimated from faecal samples. Fluctuations in infection intensity corresponded to oscillations in the magnitude of colony pup mortality, that is, higher infection intensity was significantly associated with higher colony pup mortality and reduced pup body condition. The dynamic interaction between colony, season, and host behaviour is hypothesised to modulate hookworm infection intensity in this species. This study provides a new perspective to understanding the dynamics of otariid hookworm infection and provides evidence that U. sanguinis is a significant agent of disease in Australian sea lion pups and could play a role in population regulation in this species.

Uncinaria sanguinis sp. n. (Nematoda: Ancylostomatidae) from the endangered Australian sea lion, Neophoca cinerea (Carnivora: Otariidae).

This study investigates the identity of hookworms parasitising the Australian sea lion, Neophoca cinerea (Péron), from three colonies in South Australia, Australia. The Australian sea lion is at risk of extinction because its population is small and genetically fragmented. Using morphological and molecular techniques, we describe a single novel species, Uncinaria sanguinis sp. n. (Nematoda: Ancylostomatidae). The new species is most similar to hookworms also parasitic in otariid hosts, Uncinaria lucasi Stiles, 1901 and Uncinaria hamiltoni Baylis, 1933. Comparative morphometrics offered limited utility for distinguishing between species within this genus whilst morphological features and differences in nuclear ribosomal DNA sequences delineated U. sanguinis sp. n. from named congeners. Male specimens of U. sanguinis sp. n. differ from U. lucasi and U. hamiltoni by relatively shorter anterolateral and externodorsal rays, respectively, and from other congeners by the relative lengths and angulations of bursal rays, and in the shape of the spicules. Female specimens of U. sanguinis sp. n. are differentiated from Uncinaria spp. parasitic in terrestrial mammals by differences in vulval anatomy and the larger size of their eggs, although are morphologically indistinguishable from U. lucasi and U. hamiltoni. Molecular techniques clearly delimited U. sanguinis sp. n. as a distinct novel species. Obtaining baseline data on the parasites of wildlife hosts is important for the investigation of disease and the effective implementation and monitoring of conservation management.

Cellular heterogeneity of pluripotent stem cell-derived cardiomyocyte grafts is mechanistically linked to treatable arrhythmias.

Preclinical data have confirmed that human pluripotent stem cell-derived cardiomyocytes (PSC-CMs) can remuscularize the injured or diseased heart, with several clinical trials now in planning or recruitment stages. However, because ventricular arrhythmias represent a complication following engraftment of intramyocardially injected PSC-CMs, it is necessary to provide treatment strategies to control or prevent engraftment arrhythmias (EAs). Here, we show in a porcine model of myocardial infarction and PSC-CM transplantation that EAs are mechanistically linked to cellular heterogeneity in the input PSC-CM and resultant graft. Specifically, we identify atrial and pacemaker-like cardiomyocytes as culprit arrhythmogenic subpopulations. Two unique surface marker signatures, signal regulatory protein α (SIRPA)+CD90-CD200+ and SIRPA+CD90-CD200-, identify arrhythmogenic and non-arrhythmogenic cardiomyocytes, respectively. Our data suggest that modifications to current PSC-CM-production and/or PSC-CM-selection protocols could potentially prevent EAs. We further show that pharmacologic and interventional anti-arrhythmic strategies can control and potentially abolish these arrhythmias.

Mifepristone induced liver injury in a patient with Cushing syndrome: a case report and review of the literature.

BACKGROUND: Mifepristone, also known as RU-486, is an anti-progestational steroid with similar chemical structure to anabolic steroids. Given as a single dose in conjunction with misoprostol, mifepristone is used to induce medical abortion. Mifepristone administered chronically at a higher dose is also approved for the management of hypercortisolism. There have been only 2 reported cases of mifepristone associated liver injury, in both cases, in the setting of Cushing syndrome. We report a third patient with Cushing syndrome with mifepristone induced liver injury with unique histological findings that provide insight to the pathophysiology of liver injury in mifepristone and anabolic steroids. CASE PRESENTATION: Patient is a 63-year-old Caucasian female Cushing disease with no prior history of liver disease. She was started on mifepristone and semaglutide. Ninety days after initiating mifepristone, she developed deep jaundice, severe pruritus, fatigue, and nausea. Liver tests revealed a mixed hepatocellular/cholestatic pattern. Viral and autoimmune serologies were negative and there was no biliary dilatation on imaging. Liver biopsy showed severe cholestasis but no bile duct injury. Focal endothelialitis was present within a central venule. Cholestatic symptoms persisted for one month after presentation before slowly subsiding. Four months after stopping mifepristone, the patient's symptoms completely resolved, and liver tests became normal. Compilation of Roussell Uclaf Causality Assessment Method score indicated probable causality. CONCLUSIONS: Mifepristone shares a similar chemical structure as synthetic anabolic/androgenic steroids and there are many similarities in the clinical presentation of liver injury. This case and the 2 other reported cases share similar clinical characteristics. The observation of endothelialitis in our patient may provide a mechanistic link between mifepristone, or anabolic steroids in general, and the development of vascular complications such as peliosis.

Protocol for non-invasive assessment of spontaneous movements of group-housed animals using remote video monitoring.

Frequent monitoring of laboratory animals is critical for ensuring animal welfare and experimental data collection. To minimize the adverse and confounding effects caused by current monitoring protocols and human presence, we developed a low-cost, non-invasive, remotely accessible, extensible infrared video monitoring system. This protocol describes the construction and operation of the system, followed by applying deep-learning neural networks to track group-housed, unmarked mice for objective behavioral quantification. This system can be adapted to a variety of home-cage environments and species.

Histologic Findings in Gynecologic Tissue From Transmasculine Individuals Undergoing Gender-Affirming Surgery.

CONTEXT.­: Gender-affirming surgery is part of a multidisciplinary approach in gender transitioning. Deeper histologic examination may strengthen care for transmasculine individuals and increase the understanding of the influence of hormonal therapy in specific organs. OBJECTIVE.­: To evaluate and catalogue histologic findings of tissue obtained from gender-affirming gynecologic surgery and cervical cytology specimens. DESIGN.­: This is an institutional review board-approved retrospective study that included transmasculine individuals who underwent gender-affirming gynecologic surgery from January 2015 to June 2020. All surgical gynecologic pathology and cervical cytology slides were reviewed by 2 pathologists. RESULTS.­: Fifty-five patients were included, which represented 40 uteri, 35 bilateral ovaries, 15 vaginectomy specimens, and 24 cervical cytology results. The median age was 27 years (range, 18-56), and 94% (50 of 53) of patients were receiving testosterone for at least 1 year. Seventy-five percent (30 of 40) of endometria were inactive, while 25% (10 of 40) showed evidence of cycling. Transitional cell metaplasia was the most common finding in the cervix (17 of 40) and vagina (15 of 15), reflecting a high percentage (4 of 24) of unsatisfactory or ASC-US (atypical squamous cells of undetermined significance) cervical cytologies. Prostatic-type glands were identified in 20% (8 of 40) of cervices and 67% (10 of 15) of vaginectomy specimens. Multiple bilateral cystic follicles and evidence of follicular maturation were present in 57% (20 of 35) of cases. Four cases showed paratubal epididymis-like mesonephric remnant hypertrophy. CONCLUSIONS.­: A comprehensive evaluation of tissue from gender-affirming surgery increases knowledge of the changes following androgen therapy in transmasculine individuals and may contribute to optimal patient care by raising awareness of normal histologic variations in this population.

Cervicovaginal cytology, HPV testing and vaginal flora in transmasculine persons receiving testosterone.

BACKGROUND: Testosterone is one of the strategies that transmasculine persons can elect in order to align physical traits to their gender identity. Previous studies have shown morphologic changes in the genital tract associated with testosterone. Here, we aim to evaluate cervicovaginal cytology specimens (Pap tests) and high-risk HPV (HR-HPV) testing from transmasculine individuals receiving testosterone. METHODS: This is a retrospective cohort of 61 transmasculine individuals receiving testosterone from 2013 to 2021. Cytologic diagnoses from 65 Pap tests were correlated with HPV status and histologic follow-up and compared with the institutional data and a cohort of cisgender women with atrophic changes. RESULTS: The median age was 28 years and median time of testosterone use was 3 years. Transmasculine persons showed significantly higher rates of HSIL (2%) and unsatisfactory (16%) when compared with the institutional data and atrophic cohort of cisgender women. After reviewing slides of 46 cases, additional findings were noted: atrophy was present in 87%, glycogenated cells were seen in 30%, and Lactobacilli were substantially decreased in 89%. Among 32 available HPV tests, 19% were positive for HR-HPV and 81% were negative. On histologic follow-up, all HR-HPV-positive cases with abnormal cytology showed HSIL, while none of the HPV-negative cases revealed HSIL. CONCLUSION: Our study cohort demonstrated a high percentage of abnormal Pap tests in transmasculine persons receiving testosterone. Testosterone seems to induce changes in squamous cells and shifts in vaginal flora. HR-HPV testing can be a useful adjunct in the workup of abnormal Pap tests from transmasculine individuals.

Developing Immune Profiles of Endangered Australian Sea Lion (Neophoca cinerea) Pups Within the Context of Endemic Hookworm (Uncinaria sanguinis) Infection.

As a top predator, the endangered Australian sea lion (Neophoca cinerea) is a sentinel of ecosystem change, where population trends can reflect broader shifts in the marine environment. The population of this endemic pinniped was historically diminished by commercial sealing, and recovery has been slowed by fishery interactions, disease and, potentially, pollutants. Hookworm infects 100% of neonatal pups and has been identified as a contributor to population decline. Here, a multivariable approach using traditional serological and novel molecular tools such as qPCR and ddPCR was used to examine immune phenotypes of developing Australian sea lion pups infected with the endemic hookworm (Uncinaria sanguinis) from two South Australian colonies. Results show changing immunophenotypes throughout the patent period of infection represented by pro-inflammatory cytokines (IL-6), IgG and acute-phase proteins. Although cytokines may prove useful as markers of resistance, in this study, IL-6 is determined to be an early biomarker of inflammation in Australian sea lion pups, excluding the alternative hypothesis. Additionally, immunological differences between animals from high- and low-intensity hookworm seasons, as well as ivermectin-treated animals, indicate hookworm infection modulation of the host immune response, as evidenced by a lower IL-6 mRNA expression in the non-treated groups. This study of the Australian sea lion is an example of an ecoimmunological approach to disease investigation, which can be applied to evaluate the impact of environmental and anthropogenic factors on susceptibility to infectious diseases in free-ranging species.

TAMFT-3A and TAMFT-3B2 homeologs are associated with wheat preharvest sprouting.

The phenomenon of preharvest sprouting (PHS), caused by rain after physiological maturity and prior to harvest, negatively affects wheat (Triticum aestivum L.) production and end use. Investigating the genetics that control PHS resistance may result in increased control of seed dormancy. Multiple genes involved in the development of seed dormancy are associated with PHS. In this study, the TaMFT (3A, 3B1, 3B2, 3D), TaMKK3-4A, and TaVP1-3B genes were assessed for association with PHS in a double-haploid line (DHL) hard red winter wheat population derived from a BC1 cross between the cultivars Loma and Warhorse, where Loma was the recurrent and PHS susceptible parent. The 162 BC1 DHL lines were grown over two field seasons and PHS susceptibility was assessed by measuring PHS resistance in physiologically mature heads. The PHS variation was associated with the TaMFT-A and the B2 homeolog with Loma carrying mutant forms of each gene. No sequence variation between Loma and Warhorse was detected in the exons of the TaMFT-B1 and D homeologs. No association between PHS resistance and TaMKK3-4A or TaVp1-3B variation was observed, though Loma and Warhorse vary for TaMKK3-4A and TaVp1-3B mutations reported to be PHS associated. Previous research has shown TaMFT-3A as having a large impact on PHS resistance. In the current study, the TaMFT-3A and TaMFT-3B2 alleles each explained 14% of observed PHS variation. Markers for both TaMFT-3A and TaMFT-3B2 should be used in selecting for increased wheat dormancy and PHS resistance.

Recanalization-Like Neovascularization of Placental Intervillous Hematoma: First Two Reports.

Placental intervillous hematomas have not previously been reported to undergo any sort of change, maturation, or healing. In this article, we present the first 2 case reports of recanalization-like neovascularization within placental hematomas: a 0.15 cm focus in an intervillous fibrin thrombus and a 0.2 cm focus in a subchorionic hematoma. Increased recognition and further studies are needed to gain a better understanding of this seemingly rare phenomenon and the factors that govern the lack of typical organization in placental hematomas. This might lead to a deeper knowledge of the repair process in general and shed light on how to control it in diseases caused by excessive repair.

Case study documenting the diagnosis of idiopathic CD4+ Lymphocytopenia in a patient with atypical fungal infection (disseminated blastomycosis) by FNA of adrenal mass.

Idiopathic CD4+ lymphocytopenia, described in 1992 by the Centers for Disease Control, is characterized by persistent CD4+ lymphocytopenia (less than 300 cells per micro-liter) in nonimmunosuppressed, HIV negative individuals, who present with atypical infections. This rare though likely undiagnosed entity is associated with chronic disseminated forms of either fungal or bacterial infections in otherwise healthy adults. We report a case of a 59-year-old male with ring-enhancing brain lesions, bilateral adrenal masses, lung and vocal cord nodules, where the diagnosis of exclusion was metastatic malignancy. Fine needle aspiration (FNA) of the adrenal mass and a subsequent vocal cord biopsy confirmed chronic widely disseminated blastomycosis. Flow cytometric evaluation of peripheral blood documented persistent selective CD4+ lymphocytopenia with T8 (suppressor) T-Lymphocyte count within normal range. We believe that idiopathic CD4+ lymphocytopenia is an important etiologic factor to be considered for patients who present with mass lesions and are diagnosed by FNA with atypical fungal infections. We relate the diagnostic criteria for idiopathic CD4+ lymphocytopenia and the importance of providing on-site triage for FNA samples for fungal studies and correlation for flow cytometry.

Adrenal Hypercortisolism: A Closer Look at Screening, Diagnosis, and Important Considerations of Different Testing Modalities.

Although prolonged hypercortisolism is associated with increased mortality and substantial morbidity, the clinical signs and symptoms are wide ranging and often nonspecific, contributing to challenges in diagnosis, as well as treatment delays. Greater awareness is needed among clinicians to help identify which patients should undergo biochemical screening for excess cortisol. Several biochemical tests are available, each with important caveats that should be considered in the context of the individual patient. Cortisol secretion varies widely, further complicating the biochemical diagnosis of hypercortisolism, which relies on the use of definitive cutoff values. Patients with hypercortisolism resulting from adrenal adenomas, including those discovered incidentally, often do not present with overt Cushingoid features (plethora, striae, muscle weakness, moon facies, etc.). However, the consequences of prolonged exposure to even slight elevations in cortisol levels are profound, including increased risk of diabetes, hypertension, fractures, cardiovascular events, and mortality. Because most cases of hypercortisolism resulting from an adrenal adenoma can be managed, it is imperative to identify patients at risk and initiate testing early for the best outcomes. The aim of this report is to increase awareness of the indications for screening for hypercortisolism and to review the biochemical screening tests and diagnosis for hypercortisolism associated with adrenal adenomas.

The Diagnosis of Feline Leukaemia Virus (FeLV) Infection in Owned and Group-Housed Rescue Cats in Australia.

A field study was undertaken to (i) measure the prevalence of feline leukaemia virus (FeLV) exposure and FeLV infection in a cross-section of healthy Australian pet cats; and (ii) investigate the outcomes following natural FeLV exposure in two Australian rescue facilities. Group 1 (n = 440) consisted of healthy client-owned cats with outdoor access, predominantly from eastern Australia. Groups 2 (n = 38) and 3 (n = 51) consisted of a mixture of healthy and sick cats, group-housed in two separate rescue facilities in Sydney, Australia, tested following identification of index cases of FeLV infection in cats sourced from these facilities. Diagnostic testing for FeLV exposure/infection included p27 antigen testing using three different point-of-care FeLV kits and a laboratory-based ELISA, real-time polymerase chain reaction (qPCR) testing to detect FeLV proviral DNA in leukocytes, real-time reverse-transcription PCR (qRT-PCR) testing to detect FeLV RNA in plasma, and neutralising antibody (NAb) testing. Cats were classified as FeLV-uninfected (FeLV-unexposed and presumptively FeLV-abortive infections) or FeLV-infected (presumptively regressive and presumptively progressive infections). In Group 1, 370 FeLV-unexposed cats (370/440, 84%), 47 abortive infections (47/440, 11%), nine regressive infections (9/440, 2%), and two progressive infections (2/440, 0.5%) were identified, and 12 FeLV-uninfected cats (12/440, 3%) were unclassifiable as FeLV-unexposed or abortive infections due to insufficient samples available for NAb testing. In Groups 2 and 3, 31 FeLV-unexposed cats (31/89, 35%), eight abortive infections (8/89, 9%), 22 regressive infections (22/89; 25%), and 19 progressive infections (19/89; 21%) were discovered, and nine FeLV-uninfected cats (9/89; 10%) were unclassifiable due to insufficient samples available for NAb testing. One of the presumptively progressively-infected cats in Group 3 was likely a focal FeLV infection. Two other presumptively progressively-infected cats in Group 3 may have been classified as regressive infections with repeated testing, highlighting the difficulties associated with FeLV diagnosis when sampling cats at a single time point, even with results from a panel of FeLV tests. These results serve as a reminder to Australian veterinarians that the threat of FeLV to the general pet cat population remains high, thus vigilant FeLV testing, separate housing for FeLV-infected cats, and FeLV vaccination of at-risk cats is important, particularly in group-housed cats in shelters and rescue facilities, where outbreaks of FeLV infection can occur.

The accuracy and efficacy of real-time continuous glucose monitoring sensor in patients with type 1 diabetes.

BACKGROUND: The accuracy and efficacy of the Medtronic Diabetes (Northridge, CA) Real-Time (RT)-Continuous Glucose Monitoring (CGM) sensor were analyzed in 72 subjects with type 1 diabetes. METHODS: This was a retrospective analysis of 60,050 temporally paired data points (sensor and glucose meter values) obtained during the course of an outpatient ambulatory study evaluating the efficacy of a sensor-augmented pump system in adults and adolescents. Subjects uploaded sensor values and self-monitoring blood glucose data to the CareLink Clinical Application (Medtronic Diabetes) via the Internet, every 2 weeks during the course of the study. RESULTS: The overall percentage of sensor readings within +/-20% or +/-30% agreement of reference glucose readings was 75.6% and 86.8%, respectively. The highest rate of agreement occurred in the 240-400 mg/dL range, where 79.9% of sensor readings were within +/-20% of meter values and 91.5% of sensor readings were within 30% of meter values. The mean absolute relative difference for all subjects was 15.8%, and the median absolute relative difference was 10.9%. The bias was -2.13 mg/dL. Paired glucose measurements from the RT-CGM and meter demonstrated that 95.9% of paired points in the overall subject population fell in zones A and B of the Clarke Error Grid. Consensus Error Grid Analysis established that 99.2% of paired data points were in zones A and B. CONCLUSIONS: This study reports the accuracy of a continuous glucose sensor with a large number of paired data points (60,050). RT-CGM is safe and well tolerated and provides readings that are in close agreement with glucose meter values.