Clinical Signs in 166 Beagles with Different Genotypes of Lafora.

Lafora disease (LD) is a genetic disease affecting beagles, resulting in seizures in combination with other signs. The aim of this study was to describe the clinical signs of LD in beagles with different NHLRC1 genotypes. One hundred and sixty-six beagles were tested for an NHLRC1 gene defect: L/L (n = 67), N/L (n = 32), N/N (n = 67). Owners were asked to participate in a survey about the clinical signs of LD in their dogs. These were recorded for the three possible genotypes in the two age groups, <6 years and ≥6 years. In all genotypes, nearly all the signs of LD were described. In the age group ≥ 6 years, however, they were significantly more frequent in beagles with the L/L genotype. If the following three clinical signs occur together in a beagle ≥ 6 years-jerking of the head, photosensitivity and forgetting things he/she used to be able to do-98.2% of these dogs are correctly assigned to the L/L genotype. If one or two of these signs are missing, the correct classification decreases to 92.1% and 13.2%, respectively. Only the combination of certain signs truly indicates the L/L genotype. Yet, for many dogs, only genetic testing will provide confirmation of the disease.

Molecular detection of Babesia spp. in dogs in Germany (2007-2020) and identification of potential risk factors for infection.

BACKGROUND: In Europe, canine babesiosis is most frequently caused by Babesia canis and Babesia vogeli, and occasionally by Babesia gibsoni.. In Germany, B. canis is recognized as endemic. The aims of this study were to assess how often Babesia spp. infections were diagnosed in a commercial laboratory in samples from dogs from Germany, and to evaluate potential risk factors for infection. METHODS: The database of the LABOKLIN laboratory was screened for Babesia spp.-positive polymerase chain reaction (PCR) tests for dogs for the period January 2007-December 2020. Sequencing was performed for positive tests from 2018 and 2019. Binary logistic regression analysis was performed to determine the effects of sex, season, and year of testing. Questionnaires were sent to the submitting veterinarians to obtain information on travel abroad, tick infestation, and ectoparasite prophylaxis of the respective dogs. Fisher's exact test was used to calculate statistical significance and P < 0.05 was considered statistically significant. RESULTS: In total, 659 out of 20,914 dogs (3.2%) tested positive for Babesia spp. by PCR. Of 172 sequenced samples, B. canis was identified in 156, B. vogeli in nine, B. gibsoni in five, and B. vulpes in two. Season had a statistically significant impact on test results when summer/winter (1.6% tested positive) was compared to spring/autumn (4.7%), with peaks in April (5.2%) and October (7.4%) [P < 0.001, odds ratio (OR) = 3.16]. Sex (male 3.5%, female 2.8%; P = 0.012, OR = 1.49) and age (< 7 years old 4.0%, ≥ 7 years old 2.3%; P < 0.001, OR = 1.76) of the tested dogs also had a statistically significant effect. A statistically significant impact was demonstrated for observed tick attachment (P < 0.001, OR = 7.62) and lack of ectoparasite prophylaxis (P = 0.001, OR = 3.03). The frequency of positive Babesia spp. tests did not significantly differ between the 659 dogs that had never left Germany and the 1506 dogs with known stays abroad (P = 0.088). CONCLUSIONS: The possibility of canine infection with B. canis needs to be especially taken into consideration in spring and autumn in Germany as the activity of the tick Dermacentor reticulatus, a potential vector for canine babesiosis, is highest in these seasons. Travel and importation of dogs are considered major factors associated with canine babesiosis in Germany. However, autochthonous Babesia spp. infections also occur in a considerable number of dogs in Germany.

Comparison of Three Different Diagnostic Assays for Fibroblast Growth Factor-23 (FGF-23) Measurements in Cats: A Pilot Study.

Fibroblast growth factor-23 (FGF-23) is a phosphaturic hormone used to monitor chronic kidney disease (CKD) in humans. The aim of this pilot study was to compare three diagnostic assays and to assess how the results correlate with parameters of renal dysfunction in cats. Four groups of 10 cats each were formed retrospectively according to creatinine, based on IRIS staging. FGF-23 was measured using two different ELISAs (MyBioSource and Kainos ELISA FGF-23 Kit) and an automated assay on the DiaSorin Liaison platform. Measurements were performed in 40 cats. Spearman's rank correlation coefficient showed a strong correlation between the Kainos and DiaSorin assays (ρ = 0.742/p < 0.001) and a low correlation (ρ = 0.443/p = 0.005) between the Kainos and MyBioSource assays. The measurements with the Kainos assay strongly correlated with urea (ρ = 0.835/p < 0.001) and creatinine (ρ = 0.764/p < 0.001), and moderately correlated with SDMA (ρ = 0.580/p < 0.001) and phosphorus (ρ = 0.532/p < 0.001). The results of the MyBioSource and DiaSorin assays only showed a moderate correlation with urea (ρ = 0.624/0.572) and creatinine (ρ = 0.622/0.510) concentrations (p = 0.001 each). The Kainos assay showed the strongest correlation (ρ = 0.806) with the various creatinine concentrations according to the IRIS, followed by the MyBioSource (ρ = 0.663/p < 0.001) and DiaSorin assays (ρ = 0.580/p < 0.001). Overall, the Kainos assay demonstrated the best correlations with both biomarkers and various creatinine concentrations according to the IRIS. Individual assay-based reference values should be established to make a reliable interpretation of FGF-23 levels possible to diagnose or monitor feline CKD.

Fibroblast Growth Factor-23 (FGF-23) in Dogs-Reference Interval and Correlation with Hematological and Biochemical Parameters.

Fibroblast growth factor-23 (FGF-23) is a phosphaturic hormone used to monitor chronic kidney disease (CKD) in humans. The aims of this study were (1) to determine the intra- and interassay precision of the FGF-23 concentrations in dogs as measured via the Kainos ELISA FGF-23 kit, (2) to calculate a reference interval, and (3) to assess the correlation of the FGF-23 concentration with the hematological and biochemical parameters. The coefficient of variation was below 15% for both the intra- and interassay precision, indicating good reproducibility. The reference interval ranged between 95.8 (90% confidence interval: 44.6; 139.2) and 695.1 pg/mL (598.7; 799.1) based on 136 clinically healthy dogs, classified as such according to the information of treating veterinarians as well as the unremarkable results of hematology and biochemistry. The FGF-23 concentration differed significantly between dogs aged <9 and ≥9 years (p = 0.045). Four groups of 10 dogs each were retrospectively formed based on the creatinine concentration classification according to the IRIS staging. Correlation was the strongest for the renal parameters. Statistically significant differences in the FGF-23 concentration were demonstrated between the study groups I and III (p < 0.001), I and IV (p < 0.001), and II and IV (p = 0.005). There was a trend for a rising FGF-23 concentration in older dogs. Due to the wide reference interval, diagnostic cut-offs and/or subject-based FGF-23 reference values in each dog are needed for monitoring and clinical interpretation.

Response to Biologics and Clinical Remission in the Adult German Asthma Net Severe Asthma Registry Cohort.

BACKGROUND: Recently, criteria for evaluation of response to biologics have been proposed and the concept of clinical remission has gained attention as a possible goal even in severe asthma. OBJECTIVE: To analyze the response and remission in the German Asthma Net severe asthma registry cohort. METHODS: We included adults not using a biologic at baseline (V0) and compared patients treated between V0 and 1-year visit (V1) without using a biologic (group A) to patients starting with a biologic after V0 and continuing it up to V1 (group B). We applied the Biologics Asthma Response Score to quantify composite response in good, intermediate, or insufficient. We defined clinical remission (R) as absence of significant symptoms (Asthma Control Test score ≥ 20 at V1) in the absence of exacerbations and oral corticosteroid therapy. RESULTS: Group A included 233 and group B 210 patients, the latter receiving omalizumab (n = 33), mepolizumab (n = 40), benralizumab (n = 81), reslizumab (n = 1), or dupilumab (n = 56). At baseline, group B had less often an allergic phenotype (35.2% vs 41.6%), lower Asthma Control Test score (median, 12 vs 14), more exacerbations in the past year (median, 3 vs 2), and more often high-dose inhaled corticosteroid treatment (71.4% vs 51.5%) than group A. After 1 year of treatment, rates of response (good: 61.4% vs 34.8%; intermediate: 26.7% vs 42.9%; insufficient: 11.9% vs. 22.3%) and/or clinical remission (37.6% vs 17.2%) were higher in group B than in group A. CONCLUSIONS: Despite more severe asthma at baseline, patients treated with biologics had a markedly higher probability of achieving good clinical response and/or remission than patients treated without biologics.

Diagnostic cut-off values for the urinary corticoid:creatinine ratio for the diagnosis of canine Cushing's syndrome using an automated chemiluminescent assay.

BACKGROUND: Cushing's syndrome is one of the most common endocrinopathies in dogs. The preferred screening test for spontaneous Cushing's syndrome is the low-dose dexamethasone suppression test (LDDST). The diagnostic value of urinary cortisol:creatinine ratios (UCCR) is questionable. OBJECTIVES: The aim of this study was to determine diagnostic cut-off values for UCCR testing in comparison with LDDST as a clinical reference standard and to calculate the sensitivity and specificity. METHODS: Data from 2018 to 2020 were obtained retrospectively from a commercial laboratory. Both LDDST and UCCR were measured by automated chemiluminescent immunoassay (CLIA). The maximum interval between both tests was 14 days. The optimal cut-off value for UCCR testing was calculated by the Youden index. The sensitivity and specificity of these cut-off values for the UCCR test and LDDST were assessed by Bayesian latent class models (BLCMs). RESULTS: This study included 324 dogs with both UCCR test and LDDST results. The optimal UCCR cut-off value, calculated by the Youden index, was 47.4 × 10-6 . Any UCCR <40 × 10-6 was interpreted as a negative result, 40-60 × 10-6 as values in a gray zone, and >60 × 10-6 as positive. Using the cut-off of 60 × 10-6 , BLCM showed 91% (LDDST) and 86% (UCCR test) sensitivity and a specificity of 54% (LDDST) and 63% (UCCR test). CONCLUSIONS: Considering an 86% sensitivity and a 63% specificity, UCCR testing may be considered a first-line investigation to rule out Cushing's syndrome using CLIA analysis. Urine samples can be collected noninvasively at home by the owner, reducing the potential impact of stress.

The prevalence of redundant nerve roots in standing positional MRI decreases by half in supine and almost to zero in flexed seated position: a retrospective cross-sectional cohort study.

PURPOSE: This retrospective cross-sectional cohort study investigated the influence of posture on lordosis (LL), length of the spinal canal (LSC), anteroposterior diameter (APD L1-L5), dural cross-sectional area (DCSA) of the lumbar spinal canal, and the prevalence of redundant nerve roots (RNR) using positional magnetic resonance imaging (MRI) (0.6 T). METHODS: Sixty-eight patients with single-level degenerative central lumbar spinal stenosis (cLSS) presenting with RNR in the standing position (STA) were also investigated in supine (SUP) or neutral seated (SIT) and flexed seated (FLEX) positions. Additionally, 45 patients complaining of back pain and without MRI evidence of LSS were evaluated. Statistical significance was set at p < 0.05. RESULTS: Controls (A) and patients with cLSS (B) were comparable in terms of mean age (p = 0.88) and sex (p = 0.22). The progressive transition from STA to FLEX led to a comparable decrease in LL (p = 0.97), an increase in LSC (p = 0.80), and an increase in APD L1-L5 (p = 0.78). The APD of the stenotic level increased disproportionally between the different postures, up to 67% in FLEX compared to 29% in adjacent non-stenotic levels (p < 0.001). Therefore, the prevalence of RNR decreased to 49, 26, and 4% in SUP, SIT, and FLEX, respectively. CONCLUSION: The prevalence of RNR in standing position was underestimated by half in supine position. Body postures modified LL, LSC, and APD similarly in patients and controls. Stenotic levels compensated for insufficient intraspinal volume with a disproportionate enlargement when switching from the STA to FLEX.

The German severe asthma patient: Baseline characteristics of patients in the German Severe Asthma Registry, and relationship with exacerbations and control.

INTRODUCTION: The German Asthma Net Severe Asthma Registry is collecting long-term data from a large cohort of patients aged ≥6 years with severe asthma. This manuscript presents their baseline characteristics, and identifies relationships with exacerbations and/or poor asthma control. METHODS: The registry is collecting routine clinical parameters including: demographics and medical history; disease characteristics (Asthma Control Questionnaire [ACQ]-5, forced expiratory volume in 1 s [FEV1]); exacerbations; and biomarkers (eosinophils, immunoglobulin E [IgE], fractional exhaled nitric oxide [FeNO]). RESULTS: These analyses include data from 2011 patients at 72 sites (91.9% adult). Children (6-17 years) were more likely to be male, whereas more adults were female (males: children/adults 62%/41%). Most were receiving inhaled corticosteroid/long-acting ß2-agonist combinations (78%/81%); 38.0% of adults were receiving systemic steroids. Asthma control was suboptimal in both groups: 21.5%/13.3% were controlled; 10.4%/49.1% were symptomatic; 33.1%/37.2% received emergency asthma treatment in the previous year. Median blood eosinophil (400/238 cells/µL) and IgE levels (494/186 IU/mL) were higher in children; FeNO was lower (19/35 ppb). Patients with ≥2 exacerbations in the previous year had lower FEV1 (absolute and % predicted) and IgE, and higher ACQ-5, FeNO and blood eosinophil levels (all p < 0.05). There was a weak, negative correlation between ACQ-5 and FEV1% predicted in adults (p < 0.001). CONCLUSIONS: These analyses characterise the typical German patient with severe asthma, and provide information on their overall care. Their planned long-term follow-up will assess whether asthma control can be optimised, how best to do so, and most importantly how such optimisation can benefit patients.

Intake of Acetylsalicylic Acid and High Age Are Risk Factors for Iron Deficiency Anemia in Patients with Large Diaphragmatic Hernias.

INTRODUCTION: In 15% of patients with iron deficiency anemia, large diaphragmatic hernias are found as the cause of chronic iron loss. Conversely, iron deficiency anemia is present in 10-40% of diaphragmatic hernia patients. However, it is unclear why some patients with large diaphragmatic hernias develop anemia and others do not. METHODS: We retrospectively analyzed 116 patients with diaphragmatic hernias larger than 5 cm for the presence of anemia and the effect of surgery on this anemia, dividing these patients into 4 groups (group A: 21 patients with anemia/surgery, group B: 27 patients without anemia but with surgery, group C: 34 patients with anemia but without surgery, and group D: 34 patients without anemia/surgery). RESULTS: Women significantly predominated in the patient population (76%). Patients with iron deficiency anemia tended to be significantly older than patients without iron deficiency anemia (74.7 ± 12.2 vs. 69.6 ± 14.8 years, p = 0.08). The proportion of patients taking ASA was significantly higher in the anemia collective (41.8% vs. 9.8%, p < 0.001). Regression analysis further confirmed that higher age and ASA intake correlated significantly with lower hemoglobin in anemic patients. Performing hernia repair significantly decreased anemia rates and PPI use in the anemia patients, while both remained almost the same in the non-operated anemia patients. CONCLUSION: ASA use and advanced age are risk factors for the presence of iron deficiency anemia in patients with large diaphragmatic hernias. Surgical hernia repair is suitable to reduce anemia.

Non-interventional observational study broadens positive benefit-risk assessment of an immunomodulating herbal remedy in the common cold.

Background: The unique extract of a mixture of Baptisiae tinctoriae radix, Echinaceae pallidae/purpureae radix and Thujae occidentalis herba alleviates the typical symptoms of the common cold and shortens the duration of the disease. Purpose: The risk-benefit ratio of a concentrated formulation of this herbal extract was investigated under everyday conditions. Study design: Pharmacy-based, non-interventional, multicenter, open, uncontrolled study registered at DRKS00011068. Methods: For 10 days, patients completed a diary questionnaire rating the severity of each common cold symptom on a 10-point scale. For evaluation, symptoms were combined into the scores "overall severity", "rhinitis", "bronchitis" and "general symptoms". Cox models were used to evaluate the influence of covariates on the time of stable improvement. Results: In total 955 patients (12 to 90 years) were analyzed; 85% assessed the efficacy as good or very good. Response (improvement of the overall severity by at least 50%) was reached at median day 5 (95% CImedian 5-5). General symptoms abated faster than the other complaints. The percentage of predominantly moderate or severe symptoms to predominantly mild or absent symptoms reversed on day 3.9 (interpolation). Results of adolescents and adults did not differ (p = .6013; HR = 0.918). Concomitant medication did not boost the effect of the herbal remedy. Early start of treatment of the cold accelerated the recovery (p = .0486; HR = 0.814). Thirty-four cases of adverse events were self-recorded in the diaries; none of them were serious. The tolerability was assessed as "good or very good" by 98% of the patients. Conclusion: The benefit-risk assessment of this herbal extract clearly remains positive. This non-interventional study accords with and shows transferability of the results of previous placebo-controlled studies with this extract in a real-life setting.