Clinical characterisation of a novel paroxysmal dyskinesia in Welsh terrier dogs.

Breed specific paroxysmal dyskinesias are increasingly recognised in veterinary medicine. We aimed to characterise the phenomenology, clinical course and prevalence of a previously unreported paroxysmal dyskinesia in the Welsh terrier breed. Clinical records of five Welsh terriers with paroxysmal episodes were reviewed. Additionally, owners of Welsh terriers were invited to complete a questionnaire with the aim of characterising paroxysmal episodes in the wider breed population. Clinical examinations (n = 5) and diagnostic investigations (n = 3) of affected Welsh terriers were within normal limits, apart from mild-moderate ventriculomegaly on cranial magnetic resonance imaging (n = 3). The survey of Welsh terrier owners revealed episodes consistent with a paroxysmal dyskinesia in 41 (22.8%) of 177 respondents. Median age of onset was 59 months. Episodes were predominantly characterised by sustained hypertonicity with periods of limb flexion, abnormal head and body posture, with preserved consciousness. Episode duration ranged from 30 s to 30 min (median, 3 min 30 s), with frequency varying widely between dogs. Affected dogs demonstrated a stable to improving clinical course in most cases. This study investigated a previously unreported paroxysmal dyskinesia in Welsh terriers. Similar clinical signs within the breed were potentially consistent with an inherited cause, worthy of further investigation.

Serum anti-GM2 and anti-GalNAc-GD1a IgG antibodies are biomarkers for acute canine polyradiculoneuritis.

OBJECTIVES: A previous single-country pilot study indicated serum anti-GM2 and anti-GA1 anti-glycolipid antibodies as potential biomarkers for acute canine polyradiculoneuritis. This study aims to validate these findings in a large geographically heterogenous cohort. MATERIALS AND METHODS: Sera from 175 dogs clinically diagnosed with acute canine polyradiculoneuritis, 112 dogs with other peripheral nerve, cranial nerve or neuromuscular disorders and 226 neurologically normal dogs were screened for anti-glycolipid antibodies against 11 common glycolipid targets to determine the immunoglobulin G anti-glycolipid antibodies with the highest combined sensitivity and specificity for acute canine polyradiculoneuritis. RESULTS: Anti-GM2 anti-glycolipid antibodies reached the highest combined sensitivity and specificity (sensitivity: 65.1%, 95% confidence interval 57.6 to 72.2%; specificity: 90.2%, 95% confidence interval 83.1 to 95.0%), followed by anti-GalNAc-GD1a anti-glycolipid antibodies (sensitivity: 61.7%, 95% confidence interval 54.1 to 68.9%; specificity: 89.3%, 95% confidence interval 82.0 to 94.3%) and these anti-glycolipid antibodies were frequently present concomitantly. Anti-GA1 anti-glycolipid antibodies were detected in both acute canine polyradiculoneuritis and control animals. Both for anti-GM2 and anti-GalNAc-GD1a anti-glycolipid antibodies, sex was found a significantly associated factor with a female to male odds ratio of 2.55 (1.27 to 5.31) and 3.00 (1.22 to 7.89), respectively. Anti-GalNAc-GD1a anti-glycolipid antibodies were more commonly observed in dogs unable to walk (OR 4.56, 1.56 to 14.87). CLINICAL SIGNIFICANCE: Anti-GM2 and anti-GalNAc-GD1a immunoglobulin G anti-glycolipid antibodies represent serum biomarkers for acute canine polyradiculoneuritis.

Unilateral decrease in inner ear signal in fluid-attenuated inversion recovery sequences in previously suspected canine idiopathic vestibular syndrome.

The aetiology of canine idiopathic vestibular syndrome (IVS) remains unclear. In human medicine, characteristic magnetic resonance imaging (MRI) techniques are used to demonstrate differences in endolymph composition between affected and unaffected inner ears. The purpose of this study was to determine whether similar MRI techniques could help to detect changes in the inner ears of canine IVS patients. Medical records from two veterinary referral clinics were reviewed retrospectively. Dogs were included if they had a diagnosis of IVS, obvious lateralisation of clinical signs, and an MRI of the vestibular system. A region of interest (ROI) was manually outlined by defining the anatomical area of the inner ear in T2-weighted and fluid-attenuated inversion recovery (FLAIR) images. In order to calculate the ratio of FLAIR suppression of each ear, the mean grey value of the ROI was determined in both sequences. If a unilateral decrease in suppression was identified, it was compared with the direction of clinical signs. In total, 80 dogs were included in the study. There was a significantly lower degree of suppression on the affected compared to the unaffected side (0.8886 vs. 0.9348, respectively; P = 0.0021). In 92.5% of cases, there was agreement between the most suppressed side on MRI and the direction of clinical signs. This study provides preliminary evidence about the appearance of endolymph on MRI of dogs with IVS. Further studies are needed to investigate associations between the severity of MRI changes and prognosis.

The use of ondansetron for the treatment of nausea in dogs with vestibular syndrome.

BACKGROUND: Vestibular syndrome is often accompanied by nausea. Drugs currently approved for its treatment have been developed to stop vomiting but not nausea. The efficacy of 5-HT3 receptor antagonists to reduce nausea has been described for chemotherapy, but not for nausea secondary to vestibular disorders. METHODS: Sixteen dogs with vestibular syndrome-associated nausea were included in the open-label, multicentre study. The intensity of nausea-like behaviour was analysed before ondansetron administration (0.5 mg/kg i.v.) and 2 h afterwards, using a validated 5-point-scale. The occurrence and frequency of salivation, lip licking, restlessness, vocalisation, lethargy, and vomiting were assessed. RESULTS: All dogs initially showed signs of nausea, whereas only 31% showed vomitus. The intensity of nausea was significantly reduced in all dogs (p ≤ 0.0001) 2 h after ondansetron administration, including the clinical signs of nausea analysed in 11 dogs (salivation [p = 0.0078], lip licking [p = 0.0078], restlessness [p = 0.0039], and lethargy [p = 0.0078]) except for vocalisation (p > 0.9999). CONCLUSIONS: The results provide preliminary evidence of the potential benefit of ondansetron in the treatment of nausea, which was present in all examined dogs. Vomiting was only observed in 5 dogs indicating that nausea can occur separately and should not be perceived only as a preceding stimulation of the vomiting centre.

Activity and components of the granulocyte colony-stimulating factor pathway in hidradenitis suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory disease, characterized by painful, purulent and destructive skin alterations in intertriginous areas. OBJECTIVES: We investigated the expression and role in HS of granulocyte colony-stimulating factor (G-CSF), the regulator of neutrophil biology, as clinical signs of a neutrophilic granulocyte-driven inflammation are distinctive in the disease. METHODS: Skin and blood samples obtained from different cohorts of patients with HS and control individuals were assessed by RNA sequencing, quantitative polymerase chain reaction on reverse transcribed mRNA, and/or enzyme-linked immunosorbent assay. Mechanistic studies using keratinocytes, dermal fibroblasts, immune cell populations and skin biopsies were performed. RESULTS: G-CSF was abundant in HS skin, particularly in inflamed nodules and abscesses. Its levels even exceeded those found in other inflammatory skin diseases. Interleukin (IL)-1 and IL-17, respectively, induced G-CSF production by fibroblasts and keratinocytes. These effects were enhanced by tumour necrosis factor (TNF)-α and IL-36. Accordingly, fibroblasts separated from HS lesions expressed G-CSF, and IL-1 receptor antagonist reduced G-CSF levels in explanted HS skin. G-CSF blood levels positively correlated with severity of HS. Elevated lesional G-CSF receptor levels were linked to upregulation of molecules that contribute to prolonged activation of neutrophils by components of bacteria and damaged host cells [formyl peptide receptor 1 (FPR1), FPR2 and free fatty acid receptor 2 (FFAR2)], neutrophil survival [TNF receptor superfamily member 10C (TNFRSF10C/TRAIL-R3) and TNF receptor superfamily member 6B], kinases (tyrosine-protein kinase HCK and hexokinase 3), and skin destruction [MMP25 (matrix metalloproteinase 25) and ADAM8 (disintegrin and metalloproteinase domain-containing protein 8)]. G-CSF elevated the expression of FPR1, FFAR2, and TNFRSF10C/TRAIL-R3 in neutrophils and synergized with bacterial components to induce skin-destructive enzymes. CONCLUSIONS: The G-CSF pathway engages both tissue and immune cells, is strongly activated in HS lesions, and offers the opportunity to target the neutrophil-driven inflammation.

Associations between neutering and idiopathic epilepsy in Labrador retrievers and Border collies under primary veterinary care in the UK.

There are sparse published scientific data on associations between neutering and the severity and survival of dogs with idiopathic epilepsy. This study aimed to explore the timing of neutering with respect to onset of seizures in dogs with idiopathic epilepsy. Associations between neutering and both age of onset of seizures and the occurrence of cluster seizures or status epilepticus were examined. Survival analysis investigated the effects of sex-neuter categories. The median survival time of Border collies was compared with data previously reported in literature. The study included veterinary primary-care clinical data on 117 Labrador retrievers and 57 Border collies diagnosed with idiopathic epilepsy from the VetCompass project in the UK. The majority (74.2%; P≤0.001) of neutered cases were neutered before the onset of seizures. Age (years) at onset of seizures did not differ between dogs intact at time of onset and dogs neutered before onset of seizures (males 3.6 vs. 3.7; P=0.468 and females 3.4 vs. 4.1; P=0.154). Neuter status was not associated with the occurrence of cluster seizures (males P=0.947 and females P=0.844). Dogs intact at onset of seizures had longer median survival times than dogs neutered before onset of seizures (males, 1436 days vs. 1234 days; P=0.019; females, 1778.5 days vs. 1261 days; P=0.027). Median survival time of 1393 days for Border collies was longer than previously reported (P≤0.001). These results do not support recommendations to neuter dogs with idiopathic epilepsy within an evidence-based treatment plan.

Pregabalin for the treatment of syringomyelia-associated neuropathic pain in dogs: A randomised, placebo-controlled, double-masked clinical trial.

Pregabalin is the first-line treatment for neuropathic pain (NeP) in humans. Dogs with Chiari-like malformation and syringomyelia (CM/SM) associated with NeP could benefit from pregabalin. The aim of this study was to evaluate the efficacy of pregabalin for NeP in dogs with CM/SM. Eight dogs with symptomatic CM/SM were included in a double-masked, randomised, crossover placebo-controlled clinical trial. All dogs received anti-inflammatory drugs as base-line treatment during placebo or pregabalin phase of 14±4 days each. Analgesic efficacy was assessed with a daily numerical rating scale (NRS) recorded by dog owners (0-10, 10=worst pain) and quantitative sensory testing at baseline, placebo and pregabalin phases. Blood samples were collected to report pregabalin exposure and to assess renal function. Daily NRS scores recorded by dog owners in the pregabalin group were lower than in the placebo group (P=0.006). Mechanical thresholds were higher with pregabalin compared to baseline or placebo (P=0.037, P<0.001). Cold latency at 15°C was prolonged on the neck and humeri with pregabalin compared to baseline (P<0.001 for both) or placebo (P=0.02, P=0.0001). Cold latency at 0°C was longer on pregabalin compared to baseline and placebo (P=0.001, P=0.004). There was no pregabalin accumulation between first and last dose. This study demonstrates the efficacy of pregabalin for the treatment of NeP due to CM/SM on daily pain scores recorded by dog owners. Pregabalin significantly reduced mechanical hyperalgesia, cold hyperalgesia (0°C) and allodynia (15°C) compared to placebo. Pregabalin was non-cumulative and well tolerated with occasional mild sedation.

Cine balanced fast field echo magnetic resonance imaging of canine spinal arachnoid diverticulae pulsation.

Canine spinal arachnoid diverticulae (SAD) are characterised by focal cerebrospinal fluid dilatations within the subarachnoid space, most commonly associated with nonpainful paresis and ataxia secondary to chronic compressive myelopathy. Numerous imaging techniques have been described for diagnosis of this condition, including myelography, computed tomography myelography, and magnetic resonance imaging (MRI). The present retrospective study investigated the utility of cine balanced fast field echo (cine bFFE) MRI sequences in measuring pulsatile flow in 12 dogs with SAD. The secondary aim was to determine the prevalence and location of syringes in relation to SAD, as the co-occurrence of these conditions has not been previously reported. The degree of SAD pulsation was calculated as the change in area per cardiac cycle on sagittal (n = 12/12) and transverse (n = 7/12) cardiac-gated cine bFFE MRI sequences. Pulsation was identified on all sequences, with a median ratio of change in SAD area of 0.14 (range, 0.10-0.27; n = 12) on sagittal cine bFFE and 0.23 (range, 0.05-0.53; n = 7) on transverse cine bFFE sequences. Significant differences between minimum and maximum SAD dimensions were identified on sagittal (P = 0.002) and transverse measurements (P = 0.018). A moderate prevalence of syringomyelia was identified (n = 6/12; 50%) on T2W sequences, occurring both cranial (n = 4/12; 33%) and caudal (n = 2/12; 17%) to the SAD. These results support the ability of cine bFFE sequences to identify dynamic pulsation of canine SAD. This technique is currently limited by banding artifacts and its inability to quantify flow velocity and abnormal flow jets.

Ophthalmic complications following ocular penetration during routine dentistry in 13 cats.

CASE HISTORY Thirteen cats developed ophthalmic complications following dental procedures in Australia and New Zealand between December 2014 and February 2018. All cats had at least one maxillary tooth extracted and some received a transoral maxillary nerve block. CLINICAL FINDINGS Ocular signs were identified at a median of 1.5 (min 0, max 14) days following elective dental procedures and included fibrin in the anterior chamber, aqueous flare, vision loss and miosis. Response to medical management was poor overall, with 7/13 (54%) cats undergoing subsequent enucleation and one cat was subjected to euthanasia shortly after the dental procedure due to ocular disease. The remaining five cats were managed medically. Of these, four exhibited signs of persistent inflammation at the last ophthalmic assessment, and one was subsequently subjected to euthanasia due to reasons unrelated to ocular health. Active inflammation resolved in one cat, however the lesions caused by previous inflammation persisted. PATHOLOGICAL FINDINGS Assessment of six enucleated globes showed a variety of pathological changes, with marked fibrinous exudation and suppurative inflammation as predominant features. A scleral penetration site was identified in three globes. Four globes had lens capsule rupture and phacoclastic uveitis. DIAGNOSIS Endophthalmitis following iatrogenic globe penetration during routine dental procedures. CLINICAL RELEVANCE This case series demonstrates that globe penetration during dental procedures carries a poor prognosis for the eye. Clinicians should be aware of the risks of ocular trauma during dental procedures in cats and great care should be taken to avoid ocular penetration, particularly during tooth extractions. Transoral maxillary nerve blocks should be avoided or used with extreme caution in cats.

A review of treatment options for behavioural manifestations of clinical anxiety as a comorbidity in dogs with idiopathic epilepsy.

Psychiatric comorbidities affect a large percentage of people with epilepsy and have a detrimental impact on their quality of life. Recently, behavioural comorbidities, with similar characteristics to human psychiatric diseases, have been identified in dogs with idiopathic epilepsy. In particular, behaviours motivated by the fear-anxiety emotional system have been found to be associated with the occurrence of idiopathic epilepsy in both dogs receiving anti-epileptic drugs, and drug-naïve dogs. There has been little research into the relationship between epilepsy and behavioural signs, and even less into potential treatment protocols. The following article will review available literature from human medicine to describe the current state of knowledge about the bi-directional relationship between anxiety and epilepsy, draw parallels from reported anxiogenic and anxiolytic properties of anti-epileptic drugs and attempt to provide pharmaceutical and behavioural guidance for veterinary patients with epilepsy and comorbid anxiety.

Personalized risk prediction of postoperative cognitive impairment - rationale for the EU-funded BioCog project.

Postoperative cognitive impairment is among the most common medical complications associated with surgical interventions - particularly in elderly patients. In our aging society, it is an urgent medical need to determine preoperative individual risk prediction to allow more accurate cost-benefit decisions prior to elective surgeries. So far, risk prediction is mainly based on clinical parameters. However, these parameters only give a rough estimate of the individual risk. At present, there are no molecular or neuroimaging biomarkers available to improve risk prediction and little is known about the etiology and pathophysiology of this clinical condition. In this short review, we summarize the current state of knowledge and briefly present the recently started BioCog project (Biomarker Development for Postoperative Cognitive Impairment in the Elderly), which is funded by the European Union. It is the goal of this research and development (R&D) project, which involves academic and industry partners throughout Europe, to deliver a multivariate algorithm based on clinical assessments as well as molecular and neuroimaging biomarkers to overcome the currently unsatisfying situation.

The effect of induction therapy on established CMV specific T cell immunity in living donor kidney transplantation.

Cytomegalovirus (CMV) infection influences both short and long term outcomes in immunosuppressed organ transplant recipients. The aim of this study was to evaluate the effect of different induction immunosuppression regimens on CMV specific T cell response in patients with already established CMV immunity. In 24 seropositive living donor kidney recipients, the frequency of CMV specific T cells was determined by ELISPOT (Enzyme-Linked ImmunoSpot) assay prior and 6 months after transplantation. Recipients' peripheral blood mononuclear cells were stimulated with immediate-early (IE1) and phosphoprotein 65 (pp65) CMV-derived peptide pools and the number of cells producing interferon gamma (IFN-gamma) was assessed. Patients received quadruple immunosuppression based either on depletive rabbit antithymocyte globulin (rATG) or non-depletive basiliximab induction and tacrolimus/mycophenolate mofetil/steroids. Patients with rATG induction received valgancyclovir prophylaxis. No effects of different induction agents on CMV specific T cell immunity were found at sixth month after kidney transplantation. There were no associations among dialysis vintage, pretransplant CMV specific T cell immunity, and later CMV DNAemia. Similarly, no effect of CMV prophylaxis on CMV specific T cell immunity was revealed. This study shows no effect of posttransplant immunosuppression on CMV specific T cell immunity in living donor kidney transplant recipients with CMV immunity already established, regardless of lymphocyte depletion and CMV prophylaxis.

Intranasal Midazolam versus Rectal Diazepam for the Management of Canine Status Epilepticus: A Multicenter Randomized Parallel-Group Clinical Trial.

BACKGROUND: Intranasal administration of benzodiazepines has shown superiority over rectal administration for terminating emergency epileptic seizures in human trials. No such clinical trials have been performed in dogs. OBJECTIVE: To evaluate the clinical efficacy of intranasal midazolam (IN-MDZ), via a mucosal atomization device, as a first-line management option for canine status epilepticus and compare it to rectal administration of diazepam (R-DZP) for controlling status epilepticus before intravenous access is available. ANIMALS: Client-owned dogs with idiopathic or structural epilepsy manifesting status epilepticus within a hospital environment were used. Dogs were randomly allocated to treatment with IN-MDZ (n = 20) or R-DZP (n = 15). METHODS: Randomized parallel-group clinical trial. Seizure cessation time and adverse effects were recorded. For each dog, treatment was considered successful if the seizure ceased within 5 minutes and did not recur within 10 minutes after administration. The 95% confidence interval was used to detect the true population of dogs that were successfully treated. The Fisher's 2-tailed exact test was used to compare the 2 groups, and the results were considered statistically significant if P < .05. RESULTS: IN-MDZ and R-DZP terminated status epilepticus in 70% (14/20) and 20% (3/15) of cases, respectively (P = .0059). All dogs showed sedation and ataxia. CONCLUSIONS AND CLINICAL IMPORTANCE: IN-MDZ is a quick, safe and effective first-line medication for controlling status epilepticus in dogs and appears superior to R-DZP. IN-MDZ might be a valuable treatment option when intravenous access is not available and for treatment of status epilepticus in dogs at home.

Spinal Arachnoid Diverticula: Outcome in 96 Medically or Surgically Treated Dogs.

BACKGROUND: Little is reported about the role of medical management in the treatment of spinal arachnoid diverticula (SAD) in dogs. OBJECTIVES: To describe the outcome of 96 dogs treated medically or surgically for SAD. ANIMALS: Ninety-six dogs with SAD. METHODS: Retrospective case series. Medical records were searched for spinal arachnoid diverticula and all dogs with information on treatment were included. Outcome was assessed with a standardized questionnaire. RESULTS: Fifty dogs were managed medically and 46 dogs were treated surgically. Dogs that underwent surgery were significantly younger than dogs that received medical management. No other variables, related to clinical presentation, were significantly different between both groups of dogs. The median follow-up time was 16 months (1-90 months) in the medically treated and 23 months (1-94 months) in the surgically treated group. Of the 38 dogs treated surgically with available long-term follow-up, 82% (n = 31) improved, 3% (n = 1) remained stable and 16% (n = 6) deteriorated after surgery. Of the 37 dogs treated medically with available long-term follow-up, 30% (n = 11) improved, 30% (n = 11) remained stable, and 40% (n = 15) deteriorated. Surgical treatment was more often associated with clinical improvement compared to medical management (P = .0002). CONCLUSIONS AND CLINICAL IMPORTANCE: The results of this study suggest that surgical treatment might be superior to medical treatment in the management of SAD in dogs. Further studies with standardized patient care are warranted.

Physiological reactivity to spontaneously occurring seizure activity in dogs with epilepsy and their carers.

There is a complex bidirectional relationship between stress and epilepsy. Stressful stimuli and subsequent cortisol release act as a trigger for seizure activity in some individuals with epilepsy, and seizure activity itself may act as a stressor to the affected individual. Epilepsy is the most common chronic neurological condition in domestic dogs and requires chronic management by their human carers, impacting upon the quality of life of both dog and carer. Seizures occur unpredictably and may be stressful for carers to witness and manage. In the present study we investigated the role of seizure activity as a stressor, measuring the effect of spontaneously occurring seizure activity in dogs with epilepsy upon their own cortisol levels and that of their carers. Furthermore, we tested whether individual differences in HPA reactivity were associated with owner personality characteristics and the quality of the dog-carer relationship. Saliva samples were obtained from sixteen dog-carer dyads in the home setting 20 and 40minute post-seizure, and at time-matched points on the following (non-seizure) day. Significant differences in cortisol levels were found in dogs at 40minute post-seizure (265.1% increase), and at 20minute post-seizure in their carers (40.5% increase). No associations were found between cortisol reactivity and the strength of the dog-carer bond. Carers with higher neuroticism scores exhibited higher cortisol levels at both post-seizure sampling points. As there was a gender bias in the carer sample (15/16 were female), and there are known sex differences in cortisol reactivity in response to psychological stress, the conclusions of this study may be limited to female carers. These findings are the first to objectively demonstrate the acutely stressful effects of seizures in dogs with epilepsy and their carers.

Clinical presentation, diagnostic findings and outcome in dogs diagnosed withpresumptive spinal-only meningoen-cephalomyelitis of unknown origin.

OBJECTIVES: To summarise clinical presentation, diagnostic findings and long-term outcome for dogs clinically diagnosed with meningoencephalomyelitis of unknown origin affecting the spinal cord alone. METHODS: Medical records were reviewed for dogs diagnosed with presumptive spinal-only meningoencephalomyelitis of unknown origin between 2006 and 2015. RESULTS: 21 dogs were included; the majority presented with an acute (43%) or chronic (52%) onset of neurological signs. Ambulatory paresis was the most common neurological presentation (67%). Neurological examination most commonly revealed a T3-L3 myelopathy, and spinal hyperaesthesia was a common finding (71%). A spinal cord lesion was visible in 90% of cases on magnetic resonance imaging. Eighteen lesions (86%) showed parenchymal contrast enhancement and 17 lesions (81%) showed contrast enhancement of overlying meninges. All dogs were treated with immunosuppressive doses of glucocorticosteroids, sometimes combined with cytosine arabinoside. At time of data capture, 10/21 dogs (48%) had died or been euthanased because of the condition. Overall median survival time was 669 days. CLINICAL SIGNIFICANCE: Meningoencephalomyelitis of unknown origin should be considered in the differential diagnosis of dogs presenting with a progressive myelopathy. Magnetic resonance imaging features can possibly help to distinguish presumptive meningoencephalomyelitis of unknown origin from other more common spinal diseases. Overall, long-term survival is guarded, approximately 50% of dogs will die or be euthanased despite appropriate therapy.

Lipocalin-2 is expressed by activated granulocytes and keratinocytes in affected skin and reflects disease activity in acne inversa/hidradenitis suppurativa.

BACKGROUND: Acne inversa (AI)/hidradenitis suppurativa is a chronic inflammatory disease characterized by painful axillary, inguinal and perianal skin lesions with deep-seated nodules, abscesses and fistulae. OBJECTIVES: This study aimed to identify and characterize the key players in AI pathogenesis. METHODS: Epidemiological and anamnestic data for patients with AI were collected, and blood and skin samples were also taken. Healthy participants and patients with psoriasis served as controls. Assessment of samples and cultures of primary cells was performed by enzyme-linked immunosorbent assay, quantitative polymerase chain reaction on reverse transcribed mRNA, and immunohistochemistry. RESULTS: Of 35 mediators quantified in the blood of patients with AI, lipocalin-2 (LCN2) appeared as one of the most significantly upregulated parameters compared with healthy participants [85·8 ± 12·2 (n = 18) vs. 41·8 ± 4·2 (n = 15); P < 0·001]. Strongly elevated LCN2 expression was present in AI lesions, with granulocytes and keratinocytes being sources of this expression. In vitro, these cells upregulated LCN2 production in response to tumour necrosis factor (TNF)-α, and a positive relationship between systemic TNF-α and LCN2 levels (rs = 0·55, P = 0·011; n = 20) was evident for AI. LCN2 blood levels correlated with AI disease severity (rs = 0·65, P < 0·001; n = 29), but not with disease duration, age, sex, body mass index or smoking habit. Detailed analyses revealed a link with the number of skin regions containing nodules and fistulae, but not scars. CONCLUSIONS: LCN2 might serve as a blood biomarker for the objective assessment of inflammatory activity in AI. We suggest a self-amplification loop comprising TNF-α, neutrophilic granulocytes and LCN2, which contributes to the recurrent skin neutrophil infiltration in AI, clinically evident as pus.

Associations Between Anesthetic Variables and Functional Outcome in Dogs With Thoracolumbar Intervertebral Disk Extrusion Undergoing Decompressive Hemilaminectomy.

BACKGROUND: Outcome of acute experimental spinal cord injury is strongly associated with tissue perfusion and oxygenation. Cardiopulmonary depression could affect outcome in dogs undergoing general anesthesia for surgical treatment of thoracolumbar intervertebral disk extrusion (IVDE). HYPOTHESIS/OBJECTIVES: To evaluate the effects of general anesthesia on functional outcome in dogs undergoing surgery to treat thoracolumbar IVDE. ANIMALS: Eighty-four client-owned dogs with acute thoracolumbar IVDE treated by decompressive hemilaminectomy. METHODS: Exploratory, retrospective observational study. Medical records were reviewed for clinical presentation and anesthetic monitoring variables, including duration of anesthesia and surgery, hypotension, bradycardia, temperature, and respiratory parameters. Multivariable regression tree analysis was performed to explore associations between anesthetic variables and functional outcome scores after 6 weeks, as well as return to ambulatory status. RESULTS: Episodes of bradycardia (69%) and hypotension (57%) were frequent. Across all outcome measures, regression tree analysis highlighted functional grade at presentation as the primary determining factor, and among pain perception negative dogs, there was a possible association between increased duration of surgery and poorer outcome. In dogs with intact pain perception, duration of bradycardia, mean body temperature, and mean end-tidal carbon dioxide were highlighted. CONCLUSIONS AND CLINICAL IMPORTANCE: Exploratory statistical methods can facilitate hypothesis-generating studies to inform prospective investigations in veterinary medicine. Although the mechanism is uncertain, increased duration of surgery might be associated with poorer outcome in pain perception negative dogs with thoracolumbar IVDE.

[Prevalence and severity of pulmonary embolism are dependent on clinical and paraclinical parameters : Analysis of 1,943 consecutive patients with CT pulmonary angiography]. / Prävalenz und Schwere der Lungenarterienembolie in Abhängigkeit von klinischen und paraklinischen Parametern : Analyse von 1943 konsekutiven Patienten mit CT-Pulmonalisangiographie.

BACKGROUND: Patients with pulmonary embolism (PE) have heterogeneous symptoms. Clinical scores and age-adjusted D­dimer should help clinicians to establish the correct diagnosis. METHODS: A cohort of 1,943 consecutive patients with positive D­dimer levels who were referred for CT pulmonary angiography (CTPA) over a period of 5 years to rule PE in or out were retrospectively analyzed. RESULTS: On CTPA n = 362 (19 %) had PE. The prevalence of PE increased stepwise with increasing D­dimer levels (prevalence of PE with 10 percentiles of D­dimers was: 3 %, 4 %, 7 %, 8 %, 8 %, 21 %, 20 %, 27 %, 37 %, 52 %; p < 0.001). D­dimers > 2.0 were significantly associated with PE (OR 7.17 95 % CI 5.27-9.76, p < 0.001). Chest discomfort and tachypnea showed no association with PE. Dyspnoea, pleuritic pain, and general fatigue showed significant associations with age: pleuritic chest pain was more frequent in patients aged < 76 years than in patients aged > 76 years (15 % vs 3 %; p < 0.001) and was highly significantly associated with PE (OR 4.99 95 % CI 2.83-8.81; p < 0.001). General fatigue was more prevalent in patients aged > 76 years (44 % vs 24 %; p < 0.001). PE patients with D­dimers > 6.0 mg/l were hemodynamically more compromised than patients with D­dimers < 6.0 mg/l: tachycardia 32 % vs 20 %, p = 0.015; right ventricular strain on echocardiography: 38 % vs 23 %, p = 0.003; right ventricular strain on ECG: 27 % vs 13 %; p  = 0.001; resuscitation 4 % vs 0 %, p = 0.003; lytic therapy 6 % vs 1 %, p = 0.014. CONCLUSION: The symptoms of PE patients are often vague. Particularly in older patients, fatigue may be the only symptom. The absolute level of D­dimers, particularly > 2.0 mg/l, is a strong predictor of PE. A D­dimer level > 6.0 mg/l is associated with more severe hemodynamic impairment in patients with PE.