Prognose und Risikofaktoren der röntgenologischen Lungenveränderungen neonataler Fohlen

Deckblatt Content 5 Abbreviations 10 1\. Introduction 13 2. Literature review 15 3. Study design 41 4. Results 61 5. Discussion 81 6. Summary 99 7. Zusammenfassung 101 8. Literatur references 103 Acknowledgements 114A retrospective study was conducted to explore the association between selected clinical variables, the manifestation of neonatal thoracic radiographic abnormalities and the prognosis of foals with respiratory disease admitted to a referral center. The study was performed in two sections, including 128 and 163 foals, respectively. Section one: The clinical and prognostic significance of radiographic pattern, distribution and severity of thoracic radiographic changes in neonatal foals 207 thoracic radiographs were evaluated to assess the impact of radiographic pattern recognition, distribution, and severity of pulmonary changes on short-term survival of neonatal foals. The study further investigated the association between selected clinical parameters and the radiographic manifestation of neonatal respiratory disease. The evaluation of interstitial and alveolar-interstitial radiographic patterns within the caudodorsal, caudoventral and cranioventral lung regions proved to be highly reliable between viewers in the study. SIRS was related to increased pulmonary infiltrates within the caudodorsal lung region. Dyspneic foals displayed more extensive pulmonary infiltrates within the cranioventral lung, which was associated with advanced respiratory disease and lower survival rates. A fibrinogen concentration > 400 mg/dL was also related to increased cranioventral radiographic abnormalities. In addition, tachypnea most consistently related to diffuse (caudodorsal, caudoventral and cranioventral) pulmonary changes. Neutropenia, milk reflux from the nares, upper airway pathology, abnormal respiratory sounds, failure of passive transfer (IgG concentration <400 mg/dL), immaturity or fever, however, were not related to radiographic pattern, distribution or severity of radiographic changes. Sixty-five percent of foals with radiographic pulmonary disease were discharged alive from our referral hospital. Concurrent caudodorsal and caudoventral radiographic disease was most frequently observed in this foal population. Increased caudodorsal radiographic scores retained statistical significance as a prognostic indicator for non-survival in a multiple stepwise logistic regression analysis. Section two: Risk factors and prognostic variables for survival of foals with radiographic evidence of pulmonary disease The medical records of 163 neonatal foals, which had thoracic radiographs taken within 48 hours of admission to a referral hospital, were reviewed. The objective of this study was twofold: First to identify risk factors for the development of thoracic radiographic changes, and second to identify prognostic indicators for survival in foals with radiographic evidence of pulmonary disease. Failure of passive transfer (IgG concentration ≤ 400 mg/dL) was the only multivariate risk factor for radiographic evidence of respiratory disease in 163 foals. Additionally, hypoxemic patients (PaO2 ≤ 60 mmHg) were 4.9 times more likely to show radiographic abnormalities in a subset of foals with arterial blood gas results. Foals with a creatinine concentration > 1.7 mg/dL upon presentation, dyspnea and a history of dystocia were significantly more likely to die based on the multivariate statistical outcome analysis. An anion gap 20 mEq/dL was strongly correlated with non- survival in a subset of foals with arterial blood gas results. These variables represent clinical and hematological parameters that can be readily obtained during the initial patient evaluation. The presence of a high anion gap appeared to have the greatest clinical impact and may be a useful prognostic parameter in patients with radiographic evidence of respiratory disease. In contrast, the majority of physical examination parameters, which are usually obtained during the general respiratory evaluation of foals (e.g. evaluation of tachypnea, abnormal respiratory sounds, fever, weakness and milk reflux from the nares), were unrelated to outcome.Eine retrospektive Studie wurde durchgeführt um den Zusammenhang zwischen selektierten klinischen Daten, der Manifestierung röntgenologischer Thoraxveränderungen und der Prognose neonataler Fohlen mit Erkrankungen des Respirationstrakts zu erforschen. Die Studie erfolgte in zwei Teilen und basierte auf 128 (Sektion 1), bzw. 163 (Sektion 2) neonataler Fohlen. Sektion 1: Der klinische und prognostische Wert von Art, Verteilung und Grad röntgenologischer Veränderungen im Thorax neonataler Fohlen 207 thorakale Röntgenaufnahmen wurden bewertet um die Auswirkung von Art, Verteilung und Grad der röntgenologischen Veränderungen auf die Überlebenschance neonataler Fohlen zu erforschen. Die Studie untersuchte weiterhin den Zusammenhang zwischen selektierten klinischen Daten und der röntgenologischen Manifestierung respiratorischer Erkrankungen. Die Beurteilung der interstitiellen und alveolar-interstitiellen Veränderungen im kaudodorsalen, kaudoventralen und kranioventralen Lungenfeld zeigte einen hohen Übereinstimmungsgrad zwischen Gutachtern. Fohlen mit systemisch entzündlichen Veränderungen zeigten einen höheren Grad pathologischer Infiltrate im kaudodorsalen Lungenbereich. Dyspnoe dagegen, war mit kranioventralen Lungenveränderungen verbunden. Eine Fibrinkonzentration > 400 mg/dL war ebenfalls ein Indiz für kranioventrale Lungenpathologie. Zusätzlich wurde eine hohe Atemfrequenz (> 55 Atemzüge pro Minute) mit weitverteilten (kranioventalen, kaudodorsalen, kaudoventralen) Lungenveränderungen verbunden. Unreife Fohlen, Milchausfluss aus den Nüstern, Veränderung der oberen Atemwege, pathologische Lungengeräusche, Immunoglobulinkonzentrationen < 400 mg/dL, Neutropenie oder Fieber hatten keinen Einfluss auf den Grad, die Art und das Ausmaß röntgenologischer Befunde. Fünfundsechzig Prozent aller Fohlen mit röntgenologischen Veränderungen des Thorax überlebten ihre Erkrankung. Übergreifende Veränderungen im kaudodorsalen und kaudoventralen Lungenbereich wurden am häufigsten beobachtet. Eine Assoziation zwischen kaudodorsalen Lungenfeldschäden und geringeren Überlebenschancen blieb in der multivarianten Regressionsanalyse erhalten. Sektion 2: Risikofaktoren und prognostische Indizien in Fohlen mit röntgenologischen Veränderungen des Thorax Die Krankendateien von 163 Fohlen, welche thorakale Röntgenbilder innerhalb von 48 Stunden nach der Hospitalaufnahme erhielten, wurden in die Studie einbezogen. Das Ziel dieser Untersuchung war die Identifizierung von Risikofaktoren und prognostischen Indizien in Fohlen mit röntgenologischen Veränderungen des Thorax. Eine Immunoglobulin-konzentation < 400 mg/dL war der einzige multivariante Risikofaktor für die Feststellung röntgenologischer Veränderungen. Zusätzlich waren Thoraxveränderungen 4.9 mal häufiger in Fohlen mit einer PaO2 Konzentration < 60 mmHg. Fohlen einer Schwergeburt, mit Dyspnoe oder einer Kreatin Konzentration > 1.7 mg/dL zeigten signifikant höhere Sterberaten in der multivarianten statistischen Analyse. Eine Anionendifferenz ≥ 20 mEq/dL in Fohlen welche einer arteriellen Blutgasanalyse unterzogen wurden, hatten ebenfalls eine signifikant niedrigere Überlebenschance. Diese Variablen und hämatologischen Parameter können mit geringem Aufwand während der Aufnahme eines Patienten erhalten werden. Eine hohe Anionendifferenz zeigte die stärkste statistische und klinische Signifikanz in dieser Studie, und kann als prognostischer Parameter in Patienten mit röntgenologischen Erkrankungen des Respirationstrakts dienen. Die meisten allgemeinen Untersuchungsvariablen, jedoch, (Atemzugfrequenz, Auskultationsbefunde, Fieber, Schwäche und Milchausfluss aus den Nüstern) erwiesen sich als nicht- diagnostische Prognoseparameter

A Novel Strategy for Development of Recombinant Antitoxin Therapeutics Tested in a Mouse Botulism Model

Antitoxins are needed that can be produced economically with improved safety and shelf life compared to conventional antisera-based therapeutics. Here we report a practical strategy for development of simple antitoxin therapeutics with substantial advantages over currently available treatments. The therapeutic strategy employs a single recombinant ‘targeting agent’ that binds a toxin at two unique sites and a ‘clearing Ab’ that binds two epitopes present on each targeting agent. Co-administration of the targeting agent and the clearing Ab results in decoration of the toxin with up to four Abs to promote accelerated clearance. The therapeutic strategy was applied to two Botulinum neurotoxin (BoNT) serotypes and protected mice from lethality in two different intoxication models with an efficacy equivalent to conventional antitoxin serum. Targeting agents were a single recombinant protein consisting of a heterodimer of two camelid anti-BoNT heavy-chain-only Ab VH (VHH) binding domains and two E-tag epitopes. The clearing mAb was an anti-E-tag mAb. By comparing the in vivo efficacy of treatments that employed neutralizing vs. non-neutralizing agents or the presence vs. absence of clearing Ab permitted unprecedented insight into the roles of toxin neutralization and clearance in antitoxin efficacy. Surprisingly, when a post-intoxication treatment model was used, a toxin-neutralizing heterodimer agent fully protected mice from intoxication even in the absence of clearing Ab. Thus a single, easy-to-produce recombinant protein was as efficacious as polyclonal antiserum in a clinically-relevant mouse model of botulism. This strategy should have widespread application in antitoxin development and other therapies in which neutralization and/or accelerated clearance of a serum biomolecule can offer therapeutic benefit

The effect of inhaled heliox on peak flow rates in normal and brachycephalic dogs

Background Heliox, a mixture of helium and oxygen, alleviates airway obstruction in people and improves air flow, and its use has been proposed in dogs. Brachycephalic dogs have naturally occurring airway obstruction where heliox might be a useful therapeutic option. Objective The purposes of this study were to (1) determine the impact of breathing heliox on peak inspiratory and expiratory flows (PIF/PEF) in healthy dogs and (2) determine if brachycephalic dogs and mesocephalic dogs have similar responses to inhaled heliox. Animals Eleven healthy dogs: 5 mesocephalic and 6 brachycephalic dogs. Methods A prospective study. Tidal breathing flow‐volume loops were recorded when dogs were breathing room air (nitrogen‐oxygen) and heliox. Peak inspiratory and expiratory flow rates were recorded and the subjective shape of loops assessed. Peak inspiratory and expiratory flows pre‐ and post‐heliox were compared using a Mann‐Whitney Rank sum test with a P‐value of <.05 considered significant. Results In inhaled heliox, PIF and PEF were evaluated by tidal breathing flow‐volume loops. In mesocephalic dogs, PIF increased from a median of 820 mL/s (range, 494‐1010 mL/s) to 1386 mL/s; P = .02; and for PEF from 688 mL/s to 1793 mL/s (P = .04), whereas in brachycephalic dogs, the median PIF increased from 282 mL/s to 694 mL/s; P = .01 and the median PEF increased from 212 mL/s to 517 mL/sec; P = .03. Brachycephalic dogs showed normalization of loop shapes. Conclusions and clinical importance Heliox improves flow rate and appears to improve flow patterns in brachycephalic dogs

Humoral response to an equine encephalitis vaccine in healthy alpacas

Objective—To determine humoral responses to an equine encephalitis vaccine in healthy alpacas. Design—Clinical trial. Animals—39 healthy alpacas on 1 farm and 86 healthy alpacas on a second farm. Procedures—All alpacas were given 3 doses IM of a bivalent, killed-virus equine encephalitis vaccine, with 4 weeks between doses. Eastern equine encephalitis (EEE) virus neutralizing antibody responses were determined with a plaque reduction neutralization assay every 14 days in alpacas on the first farm and 70 days after the first dose of vaccine on the second farm. Results—For alpacas on the first farm, geometric mean virus neutralizing antibody titer peaked 2 weeks after the third vaccine dose was given (ie, day 70). At this time, 29 of 38 (76%) animals were seropositive for antibodies against EEE virus, and percentage of animals ≤ 2 years old that were seropositive (16/17) was significantly higher than percentage of animals \u3e 6 years old that were seropositive (1/5). For alpacas on the second farm, 76 (88%) were seropositive on day 70, and percentage of animals ≤ 2 years old that were seropositive (24/24) was significantly higher than percentage of animals \u3e 6 years old that were seropositive (27/33). For both farms, geometric mean titer on day 70 was significantly higher in animals \u3c 2 years old than in animals \u3e 6 years old. Conclusions and Clinical Relevance—Results suggested that inoculation of alpacas with 3 doses of a bivalent, killed-virus equine encephalitis vaccine induced a humoral antibody response against EEE virus

Metagenomic Next-Generation Sequencing Reveal Presence of a Novel Ungulate Bocaparvovirus in Alpacas

Viruses belonging to the genus Bocaparvovirus (BoV) are a genetically diverse group of DNA viruses known to cause respiratory, enteric, and neurological diseases in animals, including humans. An intestinal sample from an alpaca (Vicugna pacos) herd with reoccurring diarrhea and respiratory disease was submitted for next-generation sequencing, revealing the presence of a BoV strain. The alpaca BoV strain (AlBoV) had a 58.58% whole genome nucleotide percent identity to a camel BoV from Dubai, belonging to a tentative ungulate BoV 8 species (UBoV8). Recombination events were lacking with other UBoV strains. The AlBoV genome was comprised of the NS1, NP1, and VP1 proteins. The NS1 protein had the highest amino acid percent identity range (57.89&ndash;67.85%) to the members of UBoV8, which was below the 85% cut-off set by the International Committee on Taxonomy of Viruses. The low NS1 amino acid identity suggests that AlBoV is a tentative new species. The whole genome, NS1, NP1, and VP1 phylogenetic trees illustrated distinct branching of AlBoV, sharing a common ancestor with UBoV8. Walker loop and Phospholipase A2 (PLA2) motifs that are vital for virus infectivity were identified in NS1 and VP1 proteins, respectively. Our study reports a novel BoV strain in an alpaca intestinal sample and highlights the need for additional BoV research

The fecal microbiota of healthy donor horses and geriatric recipients undergoing fecal microbial transplantation for the treatment of diarrhea.

Background and aimsFecal microbial transplantation (FMT), a treatment for certain gastrointestinal conditions associated with dysbiosis in people, is also empirically employed in horses with colitis. This study used microbiota high-throughput sequencing to compare the fecal microbial profile of healthy horses to that of geriatric microbial transplant recipients experiencing diarrhea and tested whether FMT restores microbiota diversity.MethodsTo evaluate the effect of environment and donor characteristics on the intestinal microbiota, fecal samples were collected per rectum from 15 healthy young-adult (2-12 years) and 15 geriatric (≥20 years) horses. Additionally, FMT was performed for 3 consecutive days in 5 geriatric horses with diarrhea using feces from the same healthy donor. Fecal samples were collected from both donor and recipient prior to each FMT and from recipients 24 hours following the last FMT. The profile of the fecal bacterial microbiota was compared using 16S amplicon sequencing.Results and conclusionsIn contrast to diet and farm location, age did not significantly affect the healthy equine fecal microbiota, indicating that both healthy geriatric and young-adult horses may serve as FMT donors. The fecal microbiota of horses with diarrhea was significantly more variable in terms of β-diversity than that of healthy horses. An inverse correlation between diarrhea score and relative abundance of Verrucomicrobia was identified in surviving FMT recipients. At study completion, the fecal microbiota of horses which responded to FMT had a higher α-diversity than prior to treatment and was phylogenetically more similar to that of the donor