A longitudinal study of the blood and urine metabolome of Vipera berus envenomated dogs.

Envenomation of dogs by the common European adder (Vipera berus) is associated with high morbidity. The cytotoxic venom of Vipera berus contains enzymes with the potential to cause acute kidney injury, among other insults, however robust biomarkers for such effects are lacking. A prospective observational follow-up study of naturally envenomated dogs and controls was conducted to fill knowledge gaps regarding canine Vipera berus envenomation, attempt to identify novel biomarkers of envenomation and related kidney injury, and elucidate potential long-term effects. Blood and urine samples were analyzed with a global metabolomics approach using liquid chromatography-mass spectrometry, uncovering numerous features significantly different between cases and controls. After data processing and feature annotation, eight features in blood and 24 features in urine were investigated in order to elucidate their biological relevance. Several of these are associated with AKI, while some may also originate from disturbed fatty acid ß-oxidation and soft tissue damage. A metabolite found in both blood and a venom reference sample may represent identification of a venom component in case dogs. Our findings suggest that envenomated dogs treated according to current best practice are unlikely to suffer permanent injury.

Case report: Haemophagocytic histiocytic sarcoma in an english setter.

A 4-year-old English setter presented with a 1-week history of anorexia, lethargy and occasional vomiting. Blood analysis revealed moderate regenerative anaemia, mild monocytosis, thrombocytopaenia, hypoproteinaemia, hypoglobulinaemia, hypocholesterolaemia and increased C-reactive protein. On ultrasonography, the spleen had multifocal hypoechoic lesions. Fine needle aspirates from the spleen and liver showed marked extramedullary haematopoiesis, an increased number of histiocytes, haemosiderin deposits and erythrophagocytosis. A tentative diagnosis of haemophagocytic histiocytic sarcoma (HHS) was made, and the owners elected euthanasia. On autopsy, the liver and spleen were enlarged. The spleen had an uneven surface and a yellow-tan spotted appearance. Histologically, the red pulp was highly cellular and dominated by erythroid cells, as well as a population of larger polygonal cells and aggregates of histiocytes. HHS was confirmed by CD11d immunolabelling. This represents the first documented case of HHS in an English setter.

Retrospective interview-based long-term follow-up study of cats diagnosed with idiopathic cystitis in 2003-2009.

OBJECTIVES: The aim of this study was to register long-term recurrence rates and mortality rates in cats diagnosed with feline idiopathic cystitis (FIC), with an observation period until death or a minimum of 10 years. METHODS: Data regarding recurrence of signs of feline lower urinary tract disease (FLUTD) and FLUTD-related mortality in cats diagnosed with FIC between 2003 and 2009 were obtained through structured telephone interviews with the cat owners from December 2018 until February 2019. The interviews were based on a standardised questionnaire covering whether the cat was still alive or not, whether death/euthanasia were due to FLUTD and whether the cat had experienced recurrent episodes of clinical signs of FLUTD. If recurrences had occurred, exact numbers or estimates of 1-3, 4-6 or >6 recurrences were recorded. RESULTS: The owners of 50/105 FIC cats included in a previous study (48%) were available for inclusion in the present study. At the time of the interview, only 6/50 cats (12%) were still alive. The FLUTD-related mortality rate was 20% (n = 10/50). Twenty-three cats (46%) had no recurrences, three cats (6%) were euthanased shortly after diagnosis, nine cats (18%) had 1-3 recurrences, three cats (6%) had 4-6 recurrences and six cats (12%) had >6 recurrences. For the remaining six cats, the number of recurrences was uncertain. CONCLUSIONS AND RELEVANCE: The long-term prognosis for cats diagnosed with FIC may, based on the results from the present study, be regarded as fairly good, as approximately 70% of the cats either recovered without additional episodes, experienced only a few recurrences, are still alive after a minimum of 10 years since inclusion in the study, or were euthanased for reasons unrelated to FLUTD.

Prevalence of chronic musculoskeletal pain among active and retired military personnel: a systematic review protocol.

OBJECTIVE: The objective of this review is to assess the prevalence of musculoskeletal chronic pain among active and retired members of military forces and to characterize potential factors that could influence the frequency of musculoskeletal chronic pain. INTRODUCTION: Inherent to military occupations is a diverse source of occupational hazards that affect the well-being of individuals at any stage of their military career (active and retired). Chronic pain may result from the continuous exposure to physically demanding tasks and other risks. Moreover, chronic pain has been associated with other comorbidities, including mental health conditions. INCLUSION CRITERIA: Scientific papers in French or English reporting on chronic pain derived from a musculoskeletal cause in active and retired military personnel will be considered. There will be no restriction on participants' country, age, or length of service. METHODS: The published literature will be identified by exploring biomedical, pharmacological, and physiology bibliographic databases. The unpublished literature will be located through the search of thesis and gray literature repositories. This review will follow the condition-context-population approach and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The extracted data will include any detail about the anatomic location, diagnosis, types of studies, and risk factors. The review will follow JBI methods of critical appraisal, data extraction, and data synthesis for reviews containing prevalence data. If enough evidence is found, meta-regression analysis will performed, otherwise a narrative review will be completed. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42020153704.

A neutralizing antibody against DKK1 does not reduce plaque formation in classical murine models of atherosclerosis: Is the therapeutic potential lost in translation?

BACKGROUND AND AIMS: Clinical interventions targeting nonlipid risk factors are needed given the high residual risk of atherothrombotic events despite effective control of dyslipidemia. Dickkopf-1 (DKK1) plays a lipid-independent role in vascular pathophysiology but its involvement in atherosclerosis development and its therapeutic attractiveness remain to be established. METHODS: Patient data, in vitro studies and pharmacological intervention in murine models of atherosclerosis were utilized. RESULTS: In patients' material (n = 127 late stage plaque specimens and n = 10 control vessels), DKK1 mRNA was found to be higher in atherosclerotic plaques versus control arteries. DKK1 protein was detected in the luminal intimal area and in the necrotic core of plaques. DKK1 was released from isolated primary human platelets (~12 - 21-fold) and endothelial cells (~1.4-2.5-fold) upon stimulation with different pathophysiological stimuli. In ApoE-/- and Ldlr-/- mice, plasma DKK1 concentrations were similar to those observed in humans, whereas DKK1 expression in different atheroprone arterial segments was very low/absent. Chronic treatment with a neutralizing DKK1 antibody effectively reduced plasma concentrations, however, plaque lesion area was not reduced in ApoE-/- and Ldlr-/- mice fed a western diet for 14 and 16 weeks. Anti-DKK1 treatment increased bone volume and bone mineral content. CONCLUSIONS: Functional inhibition of DKK1 with an antibody does not alter atherosclerosis progression in classical murine models. This may reflect the absence of DKK1 expression in plaques and more advanced animal disease models could be needed to evaluate the role and therapeutic attractiveness of DKK1 in late stage complications such as plaque destabilization, calcification, rupture and thrombosis.

Urinary tract infection and subclinical bacteriuria in cats: A clinical update.

PRACTICAL RELEVANCE: Urinary tract infection (UTI) is an important cause of feline lower urinary tract disease (FLUTD), particularly in female cats older than 10 years of age. In addition to cats with typical clinical signs of FLUTD or upper UTI, many cats have subclinical bacteriuria, but the clinical relevance of this is currently uncertain. UTIs are one of the most important indications for antimicrobial use in veterinary medicine and contribute to the development of antimicrobial resistance. Adherence to treatment guidelines and confinement to a few first-line antimicrobial agents is imperative to avoid further deterioration of the antimicrobial resistance situation. The decision to treat with antimicrobials should be based on the presence of clinical signs, and/or concurrent diseases, and the results of urine culture and susceptibility testing. CLINICAL CHALLENGES: Distinguishing between cats with bacterial cystitis, and those with idiopathic cystitis and concurrent clinical or subclinical bacteriuria, is challenging, as clinical signs and urinalysis results may be identical. Optimal treatment of subclinical bacteriuria requires clarification as there is currently no evidence that demonstrates a beneficial effect of routine treatment. Management of recurrent UTIs remains a challenge as evidence for most alternatives used for prevention in cats is mainly anecdotal, and no preventive treatment modality is currently recommended. EVIDENCE BASE: This review draws on an extensive literature base in veterinary and human medicine, including the recently updated guidelines of the International Society for Companion Animal Infectious Diseases for the diagnosis and management of bacterial urinary tract infections in dogs and cats. Where published evidence is lacking, the authors describe their own approach; notably, for the bacteriuric cat with chronic kidney disease.

Recurrent episodes of feline lower urinary tract disease with different causes: possible clinical implications.

CASE SERIES SUMMARY: While descriptions of cats with recurrent episodes of feline idiopathic cystitis (FIC) exist, little is published on cats with recurrent episodes of feline lower urinary tract disease (FLUTD) where the cat is diagnosed with different causes of FLUTD at separate episodes. In the present paper, six cats, originally part of larger studies of FLUTD among Norwegian cats, are described. In the project period (2003-2009), these cats had several episodes of FLUTD. At each episode, the cats had a complete physical examination, abdominal imaging, blood work, urinalysis and urine culture performed. Two of the cats initially presented with urolithiasis and subsequently with episodes of non-obstructed FIC. Four of the cats presented with non-obstructed FIC at one or more episodes, but were later diagnosed with urolithiasis or bacterial cystitis without prior catheterisation or other known predisposing factors. RELEVANCE AND NOVEL INFORMATION: Cats with recurrent episodes of FLUTD may present with different causes at different times. The need to thoroughly work-up cats with recurrent episodes of FLUTD at each presentation is emphasised. FIC may be considered as a predisposing factor in cats developing urolithiasis or bacterial cystitis; alternatively, interrelated FLUTD disease mechanisms exists. Thus, applying multimodal environmental enrichment and modification (MEMO) to cats with signs of FLUTD independent of diagnosis should be considered.

Risk factors for idiopathic cystitis in Norwegian cats: a matched case-control study.

OBJECTIVES: The aim of the study was to compare a group of cats with feline idiopathic cystitis (FIC) with a group of control cats without present or previous signs of lower urinary tract disease in order to identify factors in characteristics, personality, behaviour, environment and daily life that would make them more susceptible to the disease. METHODS: The study was a matched case-control study comparing results from telephone interviews based on a standardised questionnaire. The questions were organised into six subject groups: the characteristics of the cat; the cat's environment; the presence of other pets in the household; the cat's feeding and drinking regime; management of the cat's litter box; and the cat's opportunity to perform natural behaviour. RESULTS: The results from the present study showed that a cat diagnosed with FIC was more likely to be overweight and to be of a nervous disposition than the control cats. In addition, several differences between cases and controls were detected at a univariable level of analysis, related to outdoor access and the cats' perceived safety and comfort in their home environments. While not significant after multivariable analysis, these variables may still be of importance owing to potential interrelations. CONCLUSIONS AND RELEVANCE: Several significant differences between cats with FIC and control cats were revealed, and the results support the hypothesis of environmental stress as being a potential factor in the development of FIC.

Antimicrobial susceptibility in bacterial isolates from Norwegian cats with lower urinary tract disease.

Studies of feline lower urinary tract disease (FLUTD) among Norwegian cats have shown higher prevalences of bacterial cystitis than most previously published reports. The aims of the present study were to identify bacterial isolates obtained from the urine of Norwegian cats with FLUTD and their susceptibility to antimicrobial agents. Eighty-two bacterial isolates from 72 urine cultures obtained from 71 different cats were included. Escherichia coli, Staphylococcus species, Enterococcus species and Streptococcus species were the most frequently detected. The percentages of isolates susceptible to the included antimicrobial agents were as follows: enrofloxacin - 92%; trimethoprim/sulfonamide - 91%; nitrofurantoin - 89%; tetracycline - 78%; ampicillin - 73%; amoxicillin/clavulanic acid - 72%; trimethoprim - 68%; amoxicillin - 58%; cephalexin - 51%; spiramycin - 39%; penicillin - 34%; fucidic acid - 34%; lincomycin - 27%. Although several tendencies towards increasing antimicrobial resistance were detected among the isolates included, the species of bacteria isolated and their patterns of antimicrobial resistance were, in general, in concurrence with the existing literature. Thus, the results do not fully explain the higher prevalence of bacterial cystitis found in Norwegian cats. Moreover, additional explanatory factors beside the inclusion of primary accession cases rather than referred cases were not found.

Absence of bacterial DNA in culture-negative urine from cats with and without lower urinary tract disease.

A diagnosis of bacterial cystitis commonly relies on a positive microbiological culture demonstrating the presence of a significant number of colony-forming units/ml urine, as urine within the upper urinary tract, bladder and proximal urethra generally is considered sterile. Recent studies from human and veterinary medicine indicate the presence of non-culturable bacteria in culture-negative urine samples. The aim of the present study was to determine the occurrence of bacterial DNA in culture-negative urine samples from cats with signs of feline lower urinary tract disease (FLUTD) and healthy control cats by 16S ribosomal DNA PCR and subsequent sequencing. The study sample included 38 culture-negative urine samples from cats with FLUTD and 43 culture-negative samples from control cats. Eight culture-positive urine samples from cats with FLUTD were included as external positive controls in addition to negative reaction controls. Of possible methodological limitations, degradation of DNA due to storage, the use of non-sedimented urine for DNA isolation and lack of internal positive reaction controls should be mentioned. The positive controls were recognised, but occurrence of bacterial DNA in culture-negative urine from cats with or without signs of lower urinary tract disease was not demonstrated. However, considering the possible methodological limitations, the presence of bacterial DNA in the urine of culture-negative FLUTD cats cannot be excluded based on the present results alone. Therefore, a prospective study reducing the possibility of degradation of DNA due to storage, in combination with modifications enhancing the chance of detecting even lower levels of bacterial DNA in culture-negative samples, seems warranted.

Adverse reactions to equine-derived F(ab')2 -antivenin in 54 dogs envenomated by Vipera berus berus.

OBJECTIVE: To describe the occurrence of acute and delayed adverse reactions following the administration of an equine-derived F(ab')2 -antivenin in dogs with Vipera berus berus envenomation. DESIGN: Prospective study (2006-2009). SETTING: Private small animal clinics and university small animal teaching hospital in Norway. ANIMALS: Fifty-four dogs with Vipera berus berus envenomation treated with F(ab')2 -antivenin. INTERVENTIONS: Administration of equine-derived antivenin for treatment of Vipera berus berus envenomation in dogs. MEASUREMENTS AND MAIN RESULTS: Acute adverse reactions to antivenin administration occurred in 4/54 dogs (7%), and facial swelling occurred in 2/54 dogs (4%), sudden respiratory distress in 1 dog, and vomiting occurred in 1 dog. The adverse reactions were self-limiting in 3 of the dogs, while 1 dog was treated with corticosteroids to reduce the facial swelling that occurred during administration of antivenin. No delayed adverse reactions believed to be associated with the antivenin administration were noted. CONCLUSIONS: An occurrence of adverse effects comparable to the numbers reported in human medicine (10%) should be expected when administering F(ab')2 -antivenin to dogs with Vipera berus berus envenomation. The results are also comparable with rates of adverse effects reported with antivenin administration for crotalid-envenomated dogs. Further research is required to determine whether there is a relationship between adverse and the number of vials administered or repeated use in the same patient.

Evaluation of urinalyses from untreated adult cats with lower urinary tract disease and healthy control cats: predictive abilities and clinical relevance.

This case-controlled study evaluated urinalyses from 111 primary cases diagnosed with feline lower urinary tract disease (FLUTD) and 101 healthy control cats. Urine samples were analysed by standardised procedures, and differences between the two groups were compared by multivariable logistic regression analysis, while controlling for age, body weight, gender and reproductive status. Further, the ability of using urine sediment findings to predict bacteriuria was evaluated. In addition, urinalyses from cats with bacterial cystitis, idiopathic cystitis, urolithiasis and urethral plugs were compared. The main findings were that increasing body weight was significantly associated with increased odds of FLUTD, while the influence of age and reproductive status was of less importance. Increasing amounts of red blood cells and epithelial cells were significantly associated with increased odds of FLUTD. The predictive ability of using bacterial sediment findings to predict bacterial growth was dependent on subjective grading of the amount of bacteria in the sediment and was, at best, only moderate. The few significant differences found between the different FLUTD diagnoses were of limited diagnostic value.

Prevalence of viral infections in Norwegian cats with and without feline lower urinary tract disease.

The prevalence of various viral infections was examined in primary accession cases of feline lower urinary tract disease (FLUTD) and healthy control cats in Norway. Urine samples from 102 cats with clinical signs of FLUTD and 73 healthy control cats were tested for the presence of feline calicivirus (FCV), feline coronavirus (FCoV) and feline herpesvirus-1 (FHV-1) by polymerase chain reaction. All urinary samples were negative for FCV and FCoV. One (1%) of the FLUTD cats was found to be positive for FHV-1. The results did not indicate an association between the viral infections examined and signs of FLUTD in the study sample.

Bacteriuria in cats with feline lower urinary tract disease: a clinical study of 134 cases in Norway.

Feline lower urinary tract disease (FLUTD) is considered to be one of the most common diagnoses in feline patients. Several authors have concluded that feline idiopathic cystitis is the most common cause of FLUTD, whereas infectious cystitis is diagnosed in only 2% of the cases. In the period from January 2003 to February 2005, 134 cats that presented with signs of lower urinary tract disorders were included in a study at the Norwegian School of Veterinary Science. Ninety-seven percent were first opinion cases. All the cats went through a physical examination, and blood samples were collected for haematology and clinical chemistry. The urine analysis included urine stix, specific gravity, microscopic examination of the sediment and microbiological culturing. The urine samples were collected as voided mid-stream urine samples, by catheter or by cystocentesis and the method used was registered. Of the 134 cats included in the study, 37% were diagnosed as having obstructive and 63% as having non-obstructive FLUTD. In total 44 cats (33%) were diagnosed with bacteriuria, exceeding 10(3) colony forming units per millilitre (cfu/ml) and 33 (25%) of these cats had bacterial growth exceeding 10(4) cfu/ml, either alone or in combination with crystals and/or uroliths. Six cats (18%) with bacterial growth exceeding 10(4) cfu/ml were older than 8 years. No significant difference was found between the sampling methods performed with regard to bacteriuria. This study indicates that bacteriuria may have been underdiagnosed in Norwegian cats with clinical signs of FLUTD. It also confirms the importance of microbiological culturing in first opinion cases with FLUTD and that a skilled operator can get representative samples regardless the choice of method.