Diagnostic yield of cytologic analysis of pericardial effusion in dogs.

BackgroundPericardial effusion cytology is believed by many to be of limited value, yet few studies have evaluated its diagnostic utility.ObjectivesTo determine the diagnostic utility of cytologic analysis of pericardial effusion in dogs and to determine if consideration of additional data could improve the diagnostic yield.AnimalsTwo hundred and fifty-nine dogs with cytologic analysis of pericardial effusion performed between April 1990 and June 2012.MethodsElectronic medical records from a university teaching hospital were retrospectively reviewed; signalment, complete blood count, serum biochemistry, cytologic analysis of pericardial effusion, and echocardiographic data were recorded. Cytology was classified as diagnostic (infectious or neoplastic) or nondiagnostic (hemorrhagic or other) and groups were compared with multiple Student's t-tests.ResultsCytology was grouped as nondiagnostic (92.3%) or diagnostic (7.7%) and characterized as hemorrhagic (90%), neoplastic (4.6%), infectious (3.1%), or other (2.3%). Overall cytologic analysis of pericardial effusion diagnostic utility was 7.7% and increased to 20.3% if the effusion hematocrit (HCT) <10%; echocardiographic evidence of a mass did not result in a significant increase in the diagnostic utility.Conclusions and clinical importanceThe diagnostic utility of cytologic analysis of canine pericardial effusion is variable depending on the underlying etiology. In this group of dogs, the diagnostic yield of cytologic analysis was greater for pericardial effusion samples in which the HCT was less than 10%

Impact of primary kidney disease on the effects of empagliflozin in patients with chronic kidney disease: secondary analyses of the EMPA-KIDNEY trial

Background: The EMPA KIDNEY trial showed that empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death in patients with chronic kidney disease mainly through slowing progression. We aimed to assess how effects of empagliflozin might differ by primary kidney disease across its broad population. Methods: EMPA-KIDNEY, a randomised, controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA). Patients were eligible if their estimated glomerular filtration rate (eGFR) was 20 to less than 45 mL/min per 1·73 m2, or 45 to less than 90 mL/min per 1·73 m2 with a urinary albumin-to-creatinine ratio (uACR) of 200 mg/g or higher at screening. They were randomly assigned (1:1) to 10 mg oral empagliflozin once daily or matching placebo. Effects on kidney disease progression (defined as a sustained ≥40% eGFR decline from randomisation, end-stage kidney disease, a sustained eGFR below 10 mL/min per 1·73 m2, or death from kidney failure) were assessed using prespecified Cox models, and eGFR slope analyses used shared parameter models. Subgroup comparisons were performed by including relevant interaction terms in models. EMPA-KIDNEY is registered with ClinicalTrials.gov, NCT03594110. Findings: Between May 15, 2019, and April 16, 2021, 6609 participants were randomly assigned and followed up for a median of 2·0 years (IQR 1·5–2·4). Prespecified subgroupings by primary kidney disease included 2057 (31·1%) participants with diabetic kidney disease, 1669 (25·3%) with glomerular disease, 1445 (21·9%) with hypertensive or renovascular disease, and 1438 (21·8%) with other or unknown causes. Kidney disease progression occurred in 384 (11·6%) of 3304 patients in the empagliflozin group and 504 (15·2%) of 3305 patients in the placebo group (hazard ratio 0·71 [95% CI 0·62–0·81]), with no evidence that the relative effect size varied significantly by primary kidney disease (pheterogeneity=0·62). The between-group difference in chronic eGFR slopes (ie, from 2 months to final follow-up) was 1·37 mL/min per 1·73 m2 per year (95% CI 1·16–1·59), representing a 50% (42–58) reduction in the rate of chronic eGFR decline. This relative effect of empagliflozin on chronic eGFR slope was similar in analyses by different primary kidney diseases, including in explorations by type of glomerular disease and diabetes (p values for heterogeneity all >0·1). Interpretation: In a broad range of patients with chronic kidney disease at risk of progression, including a wide range of non-diabetic causes of chronic kidney disease, empagliflozin reduced risk of kidney disease progression. Relative effect sizes were broadly similar irrespective of the cause of primary kidney disease, suggesting that SGLT2 inhibitors should be part of a standard of care to minimise risk of kidney failure in chronic kidney disease. Funding: Boehringer Ingelheim, Eli Lilly, and UK Medical Research Council

Ethical Awareness, Ethical Judgment and Whistleblowing: A Moderated Mediation Analysis

This study aims to examine the ethical decision-making (EDM) model proposed by Schwartz (J Bus Ethics, doi:10.1007/s10551-015-2886-8,2016), where we consider the factors of non-rationality and aspects that affect ethical judgments of auditors to make the decision to blow the whistle. In this paper, we argue that the intention of whistleblowing depends on ethical awareness (EAW) and ethical judgment (EJW) as well as there is a mediation–moderation due to emotion (EMT) and perceived moral intensity (PMI) of auditors. Data were collected using an online surveywith 162 external auditors who worked on audit firms in Indonesia as well as 173 internal auditors working in the manufacturing and financial services. The result of multigroup analysis shows that emotion (EMT) can mediate the relationship between EAW and EJW. The nature of this relationship is more complex and then tested by adding moderating variables using consistent partial least squares approach. We found that EMT and PMI can improve the relationship between ethical judgments and whistleblowing intentions. These findings indicate that internal auditors are more likely to blow the whistle than external auditors; and reporting wrongdoing internally and anonymously are the preferred way of professional accountants to blow the whistle in Indonesia

Early mechanisms of neutrophil activation and transmigration in acute lung injury

Introduction:Neutrophil transmigration is multifactorial and primarily driven by selectins and β2-integrins (CD11b/CD18), whose expression are dependent on the underlying stimulus. Ventilator-induced lung injury (VILI) results in a predominantly CD18-independent mechanism of neutrophil recruitment, while direct endotoxin-induced lung injury results from a CD18-dependent mechanism. We previously observed that lack of NADPH oxidases DUOX1 and DUOX2 resulted in reduced neutrophil influx in a VILI model of lung injury but had no influence on neutrophil influx after LPS exposure. Based on these observations, we hypothesized that DUOX1/DUOX2 are an important component of CD18-independent mechanisms of neutrophil recruitment in the lung. Methods:We exposed Duoxa -/- (KO) mice and Duoxa +/+ (WT) mice to either an intratracheal exposure of lipopolysaccharide (LPS/endotoxin)-or high tidal volume ventilation and compared expression of neutrophil markers between groups. WT mice (129S6/SvEvTac) were obtained from Taconic Biosciences (One Discovery Drive Suite 304; Rensselaer, NY 1244) and were allowed to acclimatize for one week prior to study enrollment. KO mice were generated as previously described [Grasberger 2012] and bred in-house on a 129S6 background. We provided positive-pressure ventilation at a tidal volume of 10 ml/kg with 2 cmH20 positive end-expiratory pressure (PEEP). Mice were assigned to groups consisting of KO (n = 5) and WT (n = 5) in each group and divided into non-ventilated, positive-pressure ventilation, or LPS IT exposure groups. Positive-pressure ventilation was instituted for 4-h using a FlexiVent (Flexiware 8.1, Scireq, Montreal, QC, Canada). Lipopolysaccharide (Salmonella enterica serotype tryphimurium L6143, Millipore Sigma) was administered via an intratracheal (IT) route at a dose of 0.1 mg/kg. Mice were humanely euthanized at 4-h post-injection consistent with the UC Davis IAUCAC-approved protocol. Results:As previously observed, neutrophilic influx into the airways was significantly impaired in the Duoxa -/- (KO) mice after VILI, but not after LPS exposure. LPS-induced lung injury resulted in upregulation of CD11b+ neutrophils and shedding of CD62L and CD162 regardless of DUOX expression, whereas VILI resulted in upregulation of CD49+ neutrophils in the Duoxa +/+ (WT) mice but not the Duoxa -/- (KO) mice. Conclusion:Our data suggest DUOX is required for CD18-independent mechanisms of neutrophil recruitment in the lung induced by acute lung injury, but not for canonical CD18depedent mechanisms after LPS exposure

Arthropathies Associated with Basic Calcium Phosphate Crystals

Basic calcium phosphate (BCP) crystals refer to a family of crystals including partially carbonate substituted hydroxyapatite, octacalcium phosphate, and tricalcium phosphate. These crystals have been found in and around joints and have been associated with several forms of arthritis and periarthritis. Identification of BCP crystals remains problematic because of the lack of a simple, reliable analytic procedure. Methods currently in use include alizarin red S staining, labelled diphosphonate binding, scanning and transmission electron microscopy with energy dispersive X-ray microanalysis, X-ray diffraction, and atomic force microscopy. Periarthropathies associated with BCP crystals include calcific tendinitis and bursitis. Intra-articular BCP crystal deposition is common in osteoarthritis, often found together with calcium pyrophosphate dihydrate crystals. Uncommon conditions in which BCP crystals are found include destructive shoulder arthropathies, acute inflammatory attacks of arthritis, and erosive arthritis. Secondary deposition of BCP crystals has been observed in chronic renal failure, in patients with collagen vascular diseases, following neurologic injury and after local corticosteroid injection