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Methemoglobinemia is an acquired or inherited condition resulting from oxidative stress or dysfunction of the NADH-cytochrome b5 reductase or associated pathways. This study describes the clinical, pathophysiological, and molecular genetic features of a cat with hereditary methemoglobinemia. Whole genome sequencing and mRNA transcript analyses were performed in affected and control cats. Co-oximetry, ektacytometry, Ellman’s assay for reduced glutathione concentrations, and CYB5R activity were assessed. A young adult European domestic shorthair cat decompensated at induction of anesthesia and was found to have persistent methemoglobinemia of 39 ± 8% (reference range < 3%) of total hemoglobin which could be reversed upon intravenous methylene blue injection. The erythrocytic CYB5R activity was 20 ± 6% of normal. Genetic analyses revealed a single homozygous base exchange at the beginning of intron 3 of the CYB5R3 gene, c.226+5G>A. Subsequent mRNA studies confirmed a splice defect and demonstrated expression of two mutant CYB5R3 transcripts. Erythrocytic glutathione levels were twice that of controls. Mild microcytosis, echinocytes, and multiple Ca2+-filled vesicles were found in the affected cat. Erythrocytes were unstable at high osmolarities although highly deformable as follows from the changes in elongation index and maximal-tolerated osmolarity. Clinicopathological presentation of this cat was similar to other cats with CYB5R3 deficiency. We found that methemoglobinemia is associated with an increase in red blood cell fragility and deformability, glutathione overload, and morphological alterations typical for stress erythropoiesis.

Polymyxin B (PolyB) is used to treat endotoxemia in horses; neurologic and nephrogenic adverse effects occur in humans.To describe PolyB adverse effects in horses.Five healthy horses (ataxia 0/5), 1 horse with cervical osteoarthritis (ataxia 1/5).Prospective blinded randomized cross-over trial; 3-weeks wash out. Horses received PolyB (PolyB 6000 IU/kg IV, 7 doses q12h, n = 6) and PolyB/gentamicin (PolyB 6000 IU/kg IV, q12h 7 doses; gentamicin 10 mg/kg IV q24h 4 doses n = 4, or q12-24 h 5 doses because of an additional erroneous dose, n = 2). Daily neurological examinations were video recorded, and ataxia graded by 3 observers. Urine status, urinary GGT/creatinine ratio, plasma creatinine, and urea were assessed every other day, EMG daily. Mixed model analysis was used to evaluate factors associated with ataxia grade and [PolyB].Median ataxia score increased from 0/5 (range 0-2/5) to 2/5 (range 1-3/5) during administration and declined to 0.5/5 (range 0-2/5) after cessation. Gentamicin co-administration (P .01, effect size: .8), number of PolyB doses (P .001, effect size: .6), and time since last PolyB dose (P .001, effect size: .5) had a significant effect on ataxia grades, while horse, day, [Genta], [PolyB], and [PolyB]PolyB caused transient ataxia, worsening with cumulative PolyB doses and gentamicin co-administration. Nephrotoxicity of PolyB was only evident when gentamicin was co-administered.

Viscoelastic testing as a bedside test to assess global haemostasis has gained popularity in the past decade, with rotational thromboelastometry (ROTEM) and thromboelastography (TEG) being the two commonly used devices. TEG studies suggest analysis 30 min after blood sampling. However, the reproducibility of results over time for ROTEM analysis using lyophilized samples in dogs has not been established. In this study, we investigated the influence of time on viscoelastic testing, using 33 healthy staff-/client-owned dogs for blood sampling and repeated measurements of ROTEM tracings at three different time points after blood collection. Additionally, a group of 21 hospitalized patients with suspected coagulation disorders were included to investigate whether stability over time was comparable between healthy and ill dogs. We demonstrated a significant difference of ROTEM tracings over time, with a tendency towards hypocoagulability over time. These changes do have a clinical relevance as they exceed reference intervals and could therefore lead to erroneous conclusions about a patient’s coagulation status. Therefore, time-specific reference intervals are proposed and presented in this publication.

[177Lu]Lu-Ibu-DAB-PSMA was previously characterized with moderate albumin-binding properties enabling high tumor accumulation but reasonably low retention in the blood. The aim of this study was to investigate [177Lu]Lu-Ibu-DAB-PSMA in preclinical in vivo experiments and compare its therapeutic efficacy and potential undesired side effects with those of [177Lu]Lu-PSMA-617 and the previously developed [177Lu]Lu-PSMA-ALB-56. BALB/c nude mice without tumors were investigated on Day 10 and 28 after injection of 10 MBq radioligand. It was revealed that most plasma parameters were in the same range for all groups of mice and histopathological examinations of healthy tissue did not show any alternations in treated mice as compared to untreated controls. Based on these results, a therapy study over twelve weeks was conducted with PC-3 PIP tumor-bearing mice for comparison of the radioligands’s therapeutic efficacy up to an activity of 10 MBq (1 nmol) per mouse. In agreement with the increased mean absorbed tumor dose, [177Lu]Lu-Ibu-DAB-PSMA (~ 6.6 Gy/MBq) was more effective to inhibit tumor growth than [177Lu]Lu-PSMA-617 (~ 4.5 Gy/MBq) and only moderately less potent than [177Lu]Lu-PSMA-ALB-56 (~ 8.1 Gy/MBq). As a result, the survival of mice treated with 2 MBq of an albumin-binding radioligand was significantly increased (p, European Journal of Nuclear Medicine and Molecular Imaging, 49 (11), ISSN:1619-7070, ISSN:1619-7089

The extent to which Swiss veterinary practitioners follow the guidelines for quality assurance of the American Society for Veterinary Clinical Pathology (ASVCP) for point-of-care (POC) testing is unknown. Thus, the aim of this study was to assess the availability, application, and quality management of POC analyzers in Swiss veterinary practices/clinics. For this purpose, we created an online questionnaire on laboratory equipment, quality management, and biosafety, which all members of the Society of Swiss Veterinarians (GST) were invited to complete. In total, 192 clinics/practices participated, of which 69% had automated POC analyzers, mainly for clinical chemistry (99%) and/or hematology (86%). Sample analyses and equipment maintenance were mostly performed by veterinary technicians (81% and 68%, respectively). Reference intervals were adopted from manufacturers (80%) or literature (17%). The results showed that most participants perform basic internal quality control (chemistry: 75%; hematology: 86%), and many use at least two levels of quality control material (47%-48%). Controls are mostly run once a month (chemistry: 36%; hematology: 35%) or ≤4 times/year (36% and 25%). Only three clinics/practices reported participation in an external quality assessment program; comparative testing was more common (chemistry: 42%; hematology: 52%). Only one-quarter of the participants stated that they make use of the data generated through internal and external quality control measures. In conclusion, POC analyzers are widely available in Swiss veterinary clinics/practices, and internal quality control is performed to some extent. However, quality assessment and management and biosafety awareness and measures need to be improved, ideally with the support of clinical pathologists.Es ist nicht bekannt inwieweit Schweizer Tierärzte die Richtlinien zur Qualitätssicherung der American ­Society for Veterinary Clinical Pathology (ASVCP) für Point-of-Care-Tests (POC) einhalten. Ziel dieser Studie war es daher, die Verfügbarkeit, Anwendung und das Qualitätsmanagement von POC-Analysegeräten in Schweizer Tierarztpraxen/-kliniken zu untersuchen. Zu diesem Zweck wurde ein Online - Fragebogen zu Laborgeräten, Qualitätsmanagement und biologischen Sicherheit an alle Mitglieder der Gesellschaft Schweizerischer Tierärzte (GST) versandt. Insgesamt nahmen 192 Kliniken/Praxen teil. 69% hatten automatisierte POC Analysegeräte, dies hauptsächlich für die klinische Chemie (99%) und/oder Hämatologie (86%). Probenanalysen und Gerätewartung wurde überwiegend von Veterinärmedizinern durchgeführt (81% bzw. 68%). Referenzintervalle wurden von Herstellern (80%) oder aus der Literatur (17%) übernommen. Die Ergebnisse zeigten, dass die meisten Teilnehmer eine interne Qualitätskontrolle durchführten (Chemie: 75%; Hämatologie: 86%) und mindestens zwei Qualitätskontrollmaterialien (47%–48%) verwendeten. Die Kontrollen wurden meistens einmal im Monat (Chemie: 36%; Hämatologie: 35%) oder ≤ 4-mal pro Jahr (36% und 25%) durchgeführt. Drei Kliniken/Praxen meldeten die Teilnahme an einem externen Qualitätsbewertungsprogramm; Vergleichstests waren häufiger (Chemie: 42%; Hämatologie: 52%). Ein Viertel der Teilnehmer nutzten die durch interne und externe Qualitätskontrollmaßnahmen generierten Daten. Zusammenfassend, POC-Analysegeräte sind in Schweizer Tierkliniken/-praxen weit verbreitet und interne Qualitätskontrolle werden teilweise durchgeführt. Qualitätskontrollen und Management, sowie das Bewusstsein und die Maßnahmen für die biologische Sicherheit müssen verbessert werden, idealerweise mit Unterstützung von klinischen Pathologen.On ignore dans quelle mesure les vétérinaires suisses respectent les directives d’assurance qualité de l’American Society for Veterinary Clinical Pathology (ASVCP) pour les tests au point de service (Point of Care, POC). Ainsi, l’objectif de cette étude était d’évaluer la disponibilité, l’application et la gestion de la qualité des analyseurs POC dans les cabinets/cliniques vétérinaires suisses. À cette fin, nous avons créé un questionnaire en ligne sur les équipements de laboratoire, la gestion de la qualité et la biosécurité que tous les membres de la Société suisse des vétérinaires (GST) ont été invités à remplir. Au total, 192 cliniques/cabinets ont participé, dont 69% avaient des analyseurs POC automatisés, principalement pour la chimie clinique (99%) et/ou l’hématologie (86%). Les analyses des échantillons et la maintenance de l›équipement ont été principalement effectuées par des assistant(e)s en médecine vétérinaires (81% et 68%, respectivement). Les intervalles de référence ont été fixés sur la base des indications des fabricants (80%) ou de la littérature (17%). Les résultats ont montré que la plupart des participants effectuent un contrôle de qualité interne de base (chimie: 75%; hématologie: 86%) et que beaucoup utilisent au moins deux niveaux de matériel de contrôle de la qualité (47% –48%). Les contrôles sont principalement effectués une fois par mois (chimie: 36%; hématologie: 35%) ou ≤4 fois / an (36% et 25%). Seules trois cliniques/cabinets ont déclaré avoir participé à un programme externe d’évaluation de la qualité. Les tests comparatifs étaient plus courants (chimie: 42%; hématologie: 52%). Un quart seulement des participants ont déclaré utiliser les données générées par des mesures de contrôle de qualité internes et externes. En conclusion, les analyseurs POC sont largement disponibles dans les cliniques/cabinets vétérinaires suisses et le contrôle qualité interne est effectué dans une certaine mesure. Cependant, l’évaluation et la gestion de la qualité ainsi que la sensibilisation et les mesures en matière de biosécurité doivent être améliorées, idéalement avec le soutien de pathologistes cliniciens.Non si era a conoscenza fino a che punto i veterinari svizzeri seguivano le direttive per la garanzia della qualità dell’American Society for Veterinary Clinical Pathology (ASVCP) per i test presso le sedi di cura (POC). Lo scopo di questo studio era quindi di valutare la disponibilità, l’applicazione e la gestione della qualità degli indicatori POC negli studi/cliniche veterinarie svizzere. A questo scopo abbiamo creato un questionario online sulle apparecchiature di laboratorio, sulla gestione della qualità e sulla sicurezza biologica, che tutti i membri della Società dei veterinari svizzeri (GST/SVS) sono stati invitati a compilare. In totale hanno partecipato 192 cliniche/studi, di cui il 69% ha automatizzato gli indicatori POC, principalmente per la chimica clinica (99%) e/o l’ematologia (86%). Le analisi dei campioni e la manutenzione delle apparecchiature vengono eseguite per lo più da tecnici veterinari (81% e 68%, rispettivamente). Gli intervalli di riferimento adottati provengono dai produttori (80%) o dalla letteratura (17%). I risultati hanno evidenziato che la maggior parte dei partecipanti effettua un controllo di qualità interno di base (chimica: 75%; ematologia: 86%), e molti usano almeno due livelli di materiale di controllo della qualità (47%-48%). I controlli vengono eseguiti per lo più una volta al mese (chimica: 36%; ematologia: 35%) o ≤ a 4 volte/anno (36% e 25%). Solo tre cliniche/studi hanno riferito di aver partecipato a un programma di valutazione esterna della qualità; i test comparativi sono stati più comuni (chimica: 42%; ematologia: 52%). Solo un quarto dei partecipanti ha dichiarato di utilizzare i dati generati attraverso misure di controllo della qualità interne ed esterne. In conclusione, gli indicatori POC sono ampiamente disponibili nelle cliniche/studi veterinari svizzeri e il controllo della qualità interno viene effettuato in una certa misura. Tuttavia, la valutazione e la gestione della qualità e la consapevolezza e le misure di biosicurezza devono essere migliorate, idealmente con il supporto di patologisti clinici.