Contribution of canine olfaction in the diagnostic strategy of intermediate and high-risk prostate cancer: a double-blind validation study.

PURPOSE: Prostate cancer diagnosis is confirmed with a prostate biopsy, which is invasive and unpleasant. Adding canine olfaction into the diagnostic protocol could help avoid unnecessary biopsies. This study aims to determine whether dogs can identify ISUP (International Society of Urological Pathology) > 2 prostate cancer. MATERIALS AND METHODS: This double-blind, prospective, validation study included men with suspected prostate cancer between November 2022 and April 2023 in France. They were classified into two groups according to their prostate biopsy results; cases (ISUP > 2) and controls (ISUP < 1 or negative). Seven dogs analyzed their urine. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for canine olfactory detection of ISUP ≥ 2 prostate cancer were measured and compared with that of prostate MRI versus prostate biopsy. RESULTS: The seven dogs analyzed 151 urine samples, 78 from the case group and 73 from the control group. The minimal and maximal observed values were 54% and 86% for sensitivity, and 69% and 88% for specificity. Five dogs had a sensitivity above 73% and six dogs had a specificity above 75%. The kappa coefficient quantifying agreement between the biopsy result and the MRI PI-RADS ≥ 3 was 0.17 [- 0.14; 0.17], 0.20 [0.02-0.33] for PI-RADS ≥ 4 and 0.64 [0.5-0.75] for canine olfaction meaning there is a substantial agreement between the biopsy result and canine olfaction. CONCLUSIONS: Based on this study, the non-invasive and safe canine olfaction technique seems reliable for diagnosing ISUP ≥ 2 prostate cancer. Combined with prostate MRI, it may improve the decision-making process when choosing to perform prostate biopsies.

Ultrasonographic findings may be useful for differentiating interdigital abscesses secondary to migrating grass awns and interdigital furunculosis in dogs.

Grass awn migration and furunculosis are common diseases in dogs that can lead to interdigital subcutaneous lesions with a similar clinical presentation, and occasionally similar ultrasonographic images, but different treatments are required. This retrospective, multicentric, analytical study aimed to determine whether epidemiological, clinical, and ultrasonographic features could be used to differentiate interdigital furunculosis and abscesses secondary to migrating grass awns. Fifty-nine dogs that underwent interdigital ultrasonography were included (interdigital furunculosis [IDF], n = 27; interdigital abscess secondary to a migrating grass awn [IAGA], n = 32). Ultrasonographic images were reviewed by two observers blinded to the diagnosis, who graded nine qualitative and four quantitative parameters for each patient. In both groups, pruritus/licking (IDF 74%, IAGA 70%), a discharging interdigital wound (63% for each group), and thoracic limb involvement (IDF 88%, IAGA 75%) were common features. On ultrasound, a subcutaneous multilinear hyperechoic main element was identified in most dogs (IDF 85%, IAGA 100%). The ability to display this element in a single plane (P < 0.01), the absence of additional hyperechoic linear elements in different planes (P < 0.01), and a surrounding hypoechoic halo (P < 0.05) were significantly more common in dogs with interdigital abscesses secondary to migrating grass awns. A cut-off value of 0.83 cm for the length of the main multilinear element provided a sensitivity of 91% and a specificity of 87% in the diagnosis of a migrating grass awn. Findings supported prioritizing a differential diagnosis of interdigital abscesses secondary to grass awns in dogs with these ultrasonographic characteristics.

Prevalence of neurological disorders in French bulldog: a retrospective study of 343 cases (2002-2016).

BACKGROUND: French Bulldog (FB) has significantly gained in popularity over the last few years, and seems to be frequently affected by various neurological conditions. The purpose of this retrospective study was to report the prevalences of neurological diseases in a large population of FB, presented with neurological signs between 2002 and 2016, and for which a definitive diagnosis was established. A secondary objective was to identify epidemiological characteristics regarding specific diseases in this singular breed. RESULTS: During the study period, 533 FBs were presented for neurological signs, representing 18.7% of all admitted FBs (N = 2846). In total, 343 FBs with definitive diagnosis were included in this descriptive epidemiological study. Hansen type I intervertebral disk herniation (IVDH) was by far the most common neurological disorder (45.5% of all cases). The IVDH location was cervical in 39.8%, and thoracolumbar in 60.2% of cases. The median ages for cervical and thoracolumbar IVDH were 4.2 and 4 years, respectively. C3-C4 was the most commonly affected disk (57.8% of cervical IDVH) all locations combined. Spinal arachnoid diverticulum (SAD) was detected in 25 FBs, representing the second most common myelopathy (11.3%). A concurrent spinal abnormality was identified in 64.0% of SAD cases. Brain tumours represented 36.8% of encephalopathies, with glioma (confirmed or suspected) being the most common. Meningoencephalitis of unknown origin (MUO) represented 25.0% of brain disorders, females less than 5.5 years being more likely to be affected. Aside from central nervous system conditions, otitis interna associated with peripheral vestibular signs and bilateral congenital deafness (associated with white coat) were also common. CONCLUSIONS: The findings of this study suggest that FB seems to be prone to several neurological diseases. IVDH is clearly predominant in FB and cervical location seems more represented than in other breeds. FBs affected by IVDH tend to be younger than previously described, either for both cervical and thoracolumbar locations. Thoracic SAD was the second most common myelopathy, with a concurrent spinal anomaly identified in two thirds of the cases. MUO was more likely to affect young to middle-aged females. These findings could be of interest for owners, breeders, practicing veterinarians and insurance companies.

RADIOGRAPHIC APPEARANCE OF PRESUMED NONCARDIOGENIC PULMONARY EDEMA AND CORRELATION WITH THE UNDERLYING CAUSE IN DOGS AND CATS.

Noncardiogenic pulmonary edema is an important cause of respiratory disease in dogs and cats but few reports describe its radiographic appearance. The purpose of this retrospective case series study was to describe radiographic findings in a large cohort of dogs and cats with presumed noncardiogenic pulmonary edema and to test associations among radiographic findings versus cause of edema. Medical records were retrieved for dogs and cats with presumed noncardiogenic edema based on history, radiographic findings, and outcome. Radiographs were reviewed to assess lung pattern and distribution of the edema. Correlation with the cause of noncardiogenic pulmonary edema was evaluated with a Fisher's exact test. A total of 49 dogs and 11 cats were included. Causes for the noncardiogenic edema were airway obstruction (n = 23), direct pulmonary injury (n = 13), severe neurologic stimulation (n = 12), systemic disease (n = 6), near-drowning (n = 3), anaphylaxis (n = 2) and blood transfusion (n = 1). Mixed, symmetric, peripheral, multifocal, bilateral, and dorsal lung patterns were observed in 44 (73.3%), 46 (76.7%), 55 (91.7%), 46 (76.7%), 46 (76.7%), and 34 (57.6%) of 60 animals, respectively. When the distribution was unilateral, pulmonary infiltration involved mainly the right lung lobes (12 of 14, 85.7%). Increased pulmonary opacity was more often asymmetric, unilateral, and dorsal for postobstructive pulmonary edema compared to other types of noncardiogenic pulmonary edema, but no other significant correlations could be identified. In conclusion, noncardiogenic pulmonary edema may present with a quite variable radiographic appearance in dogs and cats.

Canine atopic dermatitis diagnostic criteria: evaluation of four sets of published criteria among veterinary students.

Canine atopic dermatitis (cAD) is a major teaching point as its diagnosis and treatment are difficult. During 11 weeks, 140 dogs and students (third, fourth, and fifth years) were recruited and paired. One of the four lists of diagnostic criteria was randomly attributed to each student. Concordance results, calculated with Cohen's kappa, ranged from slight (κ=0.07) to moderate (κ=0.53). Favrot's diagnostic criteria received the best results. It has been observed that results are improved with clinical experience. We observed that students often forgot that Favrot's criteria apply only to pruritic dogs and that the fulfillment of the criteria allows only a suspicion, not a diagnosis, of cAD. Primary pruritus and corticosteroid-responsive pruritus were often misunderstood.

Volumetric quantification identifies some left atrial dilations undetected by left atrium:aorta ratio measurements: A prospective echocardiographic study in 155 Cavalier King Charles Spaniels with and without degenerative mitral valve disease.

INTRODUCTION: Degenerative mitral valve disease (DMVD) is the most common canine heart disease with a high predisposition in Cavalier King Charles Spaniels (CKCSs). Mitral regurgitation related to DMVD can lead to left atrial (LA) dilation, which is associated with survival time. Left-atrial-to-aortic (LA:Ao) ratio assessed by two-dimensional echocardiography is commonly used to evaluate LA size. The objectives of this prospective observational study were therefore 1) to compare different echocardiographic methods (i.e., monoplane and biplane Simpson's methods of discs (SMOD) and area-length methods (ALM)) in evaluating LA volume (LAvol) in CKCSs, 2) to assess LA volumes according to DMVD severity and, 3) compare the ability of LAvol and LA:Ao ratio to identify LA enlargement in CKCSs with subclinical DMVD (i.e., American College of Veterinary Internal Medicine (ACVIM) stage B). MATERIALS AND METHODS: 155 CKCSs, either healthy or affected by DMVD, were recruited. Variability and concordance between volumetric methods were evaluated. Values were analyzed according to 2019 ACVIM stages. RESULTS: All Lin's concordance correlation coefficients regarding intra- and inter-observer variability were considered as very good to excellent. Monoplane methods and ALM produced higher values of LAvol than biplane methods and SMOD, respectively. The upper limit of normal end-systolic LAvol/body weight (LASvol/BW) was defined as 0.90 mL/kg. Left atrial volumes significantly increased with ACVIM stages. Additionally, 37% of stage B1 CKCSs demonstrated LA enlargement using LASvol/BW assessment, with significantly lower LASvol/BW values in dogs with regurgitation fraction ≤30% than in others (p<0.01). CONCLUSION: In CKCSs, LAvol methods are not interchangeable. In ACVIM stage B CKCSs, LAvol quantification is more effective to detect LA enlargement than LA linear measurements.

Descriptive analysis and prognostic factors in cats with myeloma-related disorders: A multicenter retrospective study of 50 cases.

BACKGROUND: Myeloma-related disorders (MRDs) are rare and poorly documented neoplasms of cats. HYPOTHESIS/OBJECTIVES: To describe clinical, clinicopathologic, and imaging findings, response to treatment, and survival time and to identify factors associated with shorter outcomes in cats with MRD. ANIMALS: Fifty cats with a diagnosis of MRD. METHODS: Cats with paraproteinemia confirmed by serum protein electrophoresis (SPE) and either intramedullary plasmacytosis >10%, marked cytonuclear atypia with intramedullary plasmacytosis that ranged between 5% and 10%, or cytologically or histologically confirmed visceral infiltration were retrospectively included from several veterinary referral centers. RESULTS: Bone marrow plasmacytosis and splenic or hepatic involvement were present in 17/27 cats (63%), 36/42 cats (86%), and 27/38 cats (71%), respectively. Anemia was reported in 33/49 cats (67%) and thrombocytopenia in 16/47 cats (34%). Some of the treatments that the cats received included melphalan and prednisolone (n = 19), cyclophosphamide and prednisolone (n = 10), chlorambucil and prednisolone (n = 4), prednisolone (n = 4), or other (n = 4). The overall response rates to melphalan, cyclophosphamide, and chlorambucil in combination with prednisolone were 87%, 90%, and 100%, respectively. Adverse events to melphalan or cyclophosphamide occurred in 65% and 23% of cats, respectively. Median survival time was 122 days (range, 0-1403) and was not significantly associated with chemotherapy protocol. Anemia (hazard ratio [HR], 3.1; 95% confidence interval [CI], 1.0-9.8) and thrombocytopenia (HR, 2.7; 95% CI, 1.2-6.0) were risk factors for shorter survival. CONCLUSIONS AND CLINICAL IMPORTANCE: Our study confirmed the guarded prognosis of MRD in cats and identified risk factors for shorter survival times.

Tolerability of naso-esophageal feeding tubes in dogs and cats at home: Retrospective review of 119 cases.

BACKGROUND: The use of naso-esophageal feeding tubes (NFT) at home could represent an alternative way to reduce the costs for owners and facilitate enteral feeding until recovery of a spontaneous appetite. OBJECTIVE: To describe the use of NFT at home in dogs and cats and evaluate the satisfaction of owners and their capacity to handle the device. ANIMALS: One hundred nineteen client-owned animals (90 cats and 29 dogs) which remained anorexic during hospitalization and were discharged with NFT for at least 24 hours after placement. METHODS: Medical records were reviewed retrospectively, and owners were contacted by telephone calls. Complications were reported according to their relative severity (minor and major). Owners were asked to report their experience and comfort with NFT management. RESULTS: Naso-esophageal feeding tubes were kept in place at home for a median of 6 days (range, 1-17) and 62.2% (95% confidence interval [CI]: 53.3-70.7) of animals recovered a spontaneous appetite while wearing NFT, 60% (95% CI: 44.4-75.6) of the remaining animals recovered a spontaneous appetite after removal. Overall complication rate was 65.5% (95% CI: 57.0-74.0), but only 18.5% (95% CI: 11.5-25.5) required a consultation and no life-threatening complication occurred. Owners were satisfied in 94.1% (95% CI: 89.9-98.3) of cases. CONCLUSION AND CLINICAL IMPORTANCE: Although most animals discharged with NFT at home presented complications, no major adverse effects were reported and NFT were easily handled by owners. This study provides evidence that NFT can be well tolerated at home.

Canine Model of Human Frailty: Adaptation of a Frailty Phenotype in Older Dogs.

Frailty is a clinical presentation resulting from age-related cumulative declines in several physiological systems. The aim of this study was to adapt the concept of frailty to the domestic dog, as a model for frailty research, by characterizing a 5-criterion frailty phenotype using objective measurement, and to investigate its independent association with death. A prospective cohort including 80 Labrador and Golden Retriever dogs aged 9 years or older was conducted between March 2015 and July 2020. An adapted frailty phenotype was defined according to the presence of 5 criteria (weakness, slowness, poor endurance, low physical activity, and shrinking) evaluated at baseline from physical performance tests and items from questionnaire and physical examination. Survival analysis was used to investigate the association between frailty status and time to all-cause death over 5 years of follow-up. Frailty status was significantly associated with all-cause death, with median survival times of 10.5 months, 35.4 months, and 42.5 months, respectively for dogs with 3 or more criteria (frail dogs), dogs with 1 or 2 criteria (prefrail dogs), and nonfrail dogs. Independently of age, sex, breed, sterilization, and sex-sterilization interaction, frail dogs died significantly faster than nonfrail dogs at baseline (adjusted hazard ratio = 5.86; 95% confidence interval = 2.45-14.0; p < .01). This significant association persisted after controlling for other potential confounders. Frailty, assessed by a 5-criterion phenotype, was predictive of all-cause death, in geriatric Labrador and Golden Retriever dogs. The concept of frailty seems adaptable to the dog.

Acupuncture has potential in managing axial stiffness in steeplechase racehorses: a blinded prospective randomized preliminary study.

OBJECTIVE: Evaluate the short-term effects of acupuncture on the dynamic manifestations of axial stiffness in steeplechase racehorses. ANIMALS: 12 steeplechase racehorses presenting signs of axial stiffness during training. METHODS: Horses were randomly assigned to either an acupuncture treatment by an experienced certified acupuncturist (n = 6) or no treatment as negative controls (6). The horses' locomotion was evaluated during training before treatment (D0) and 7 (D7) and 14 (D14) days after by their rider and trainer through a questionnaire. Additionally, the improvement of their dorsal flexibility 2 days after treatment was evaluated subjectively at the trot, free jumping at the canter was evaluated by expert clinicians, and free jumping at the trot was evaluated objectively via inertial measurement units. RESULTS: Significantly more horses were improved on D7 and D14 in the acupuncture group (6/6) compared with the control group (1/5; P =.01) according to the scores set by the trainer and riders. Subjective evaluation of the dorsal flexibility also revealed a significant improvement (P = .04) for horses receiving the acupuncture treatment (median improvement score, 0.50 [reference range, 0.5 to 0.9]) compared with control horses (-0.25 [reference range, -0.5 to 0]). CLINICAL RELEVANCE: Acupuncture may be an interesting nondoping strategy to improve clinical signs of axial stiffness and performance on steeplechase racehorses.

Systolic third sound associated with systolic anterior motion of the mitral valve in cats with obstructive hypertrophic cardiomyopathy.

BACKGROUND: Third heart sounds in cats frequently are associated with hypertrophic cardiomyopathy (HCM) but their exact characterization and timing within the cardiac cycle remains unknown. OBJECTIVES: Characterize third heart sounds in cats by phonocardiography and test the ability of 3 observers with different levels of experience and training to recognize third systolic heart sounds in cats. ANIMALS: Fifty client-owned cats of different breeds presented for heart screening. METHODS: Cats were prospectively assessed using an electronic stethoscope (with digital recording) and then underwent full conventional echocardiographic examination. Audio recordings were blindly assessed in a random order by 3 observers: the cardiologist who collected clinical data, as well as a trained and an untrained junior veterinarian. Cohen's kappa coefficients were calculated to quantify agreement between the opinion of each observer and the echocardiography results (considered the gold standard). RESULTS: Twenty cats had a third systolic sound on phonocardiography and an obstructive HCM phenotype with systolic anterior motion of the mitral valve (SAM) on echocardiography. Agreement with echocardiography was very good for the experienced cardiologist, substantial for the trained junior veterinarian, and poor for the untrained junior veterinarian (kappa of 0.92, 0,64, and 0.08, respectively). CONCLUSIONS AND CLINICAL IMPORTANCE: We describe here a new auscultatory abnormality in cats with obstructive HCM. It could help a trained non-cardiologist veterinarian in suspecting obstructive HCM in cats based on auscultation only.

Canine olfactory detection of SARS-CoV-2-infected humans-a systematic review.

PURPOSE: To complement conventional testing methods for severe acute respiratory syndrome coronavirus type 2 infections, dogs' olfactory capability for true real-time detection has been investigated worldwide. Diseases produce specific scents in affected individuals via volatile organic compounds. This systematic review evaluates the current evidence for canine olfaction as a reliable coronavirus disease 2019 screening tool. METHODS: Two independent study quality assessment tools were used: the QUADAS-2 tool for the evaluation of laboratory tests' diagnostic accuracy, designed for systematic reviews, and a general evaluation tool for canine detection studies, adapted to medical detection. Various study design, sample, dog, and olfactory training features were considered as potential confounding factors. RESULTS: Twenty-seven studies from 15 countries were evaluated. Respectively, four and six studies had a low risk of bias and high quality: the four QUADAS-2 nonbiased studies resulted in ranges of 81%-97% sensitivity and 91%-100% specificity. The six high-quality studies, according to the general evaluation system, revealed ranges of 82%-97% sensitivity and 83%-100% specificity. The other studies contained high bias risks and applicability and/or quality concerns. CONCLUSIONS: Standardization and certification procedures as used for canine explosives detection are needed for medical detection dogs for the optimal and structured usage of their undoubtful potential.

Alendronate treatment in cats with persistent ionized hypercalcemia: A retrospective cohort study of 20 cases.

BACKGROUND: Limited information is available concerning treatment of ionized hypercalcemia in cats. HYPOTHESIS/OBJECTIVES: Describe clinical findings in a cohort of cats with persistent ionized hypercalcemia and evaluate long-term tolerance and efficacy of alendronate in these patients. ANIMALS: Twenty cats with persistent ionized hypercalcemia of undetermined origin, presented for routine or referral consultation at the teaching hospital of Maisons-Alfort (France). METHODS: Medical records were retrospectively reviewed. Cats were divided into Group 1 (cats that received alendronate as well as other treatments, n = 11) and Group 2 (cats that did not receive alendronate, n = 9). Survival analysis (Kaplan-Meier method, log-rank test, and Cox proportional hazard models) was conducted to compare time to selected outcomes. RESULTS: Azotemia was present in 15 cats (75%). Alendronate treatment was administered and well tolerated during the entire follow-up period (median, 9.5 months; interquartile range [IQR], 6.3; 27) in all cats from Group 1, except in 1 cat that developed severe hypophosphatemia, prompting treatment discontinuation. Univariate analysis determined that alendronate treatment was significantly associated with shorter time to reach a 15% decrease in ionized calcium concentration (iCa) from baseline during follow-up (119 days vs median not reached, P = .02). This association was no longer significant after adjustment for age and initial iCa. CONCLUSIONS AND CLINICAL IMPORTANCE: Alendronate overall was well tolerated with chronic use in this cohort, and can be considered a treatment option for persistent ionized hypercalcemia in cats.

Diagnostic accuracy of non-invasive detection of SARS-CoV-2 infection by canine olfaction.

BACKGROUND: Throughout the COVID-19 pandemic, testing individuals remains a key action. One approach to rapid testing is to consider the olfactory capacities of trained detection dogs. METHODS: Prospective cohort study in two community COVID-19 screening centers. Two nasopharyngeal swabs (NPS), one saliva and one sweat samples were simultaneously collected. The dog handlers (and the dogs…) were blinded with regards to the Covid status. The diagnostic accuracy of non-invasive detection of SARS-CoV-2 infection by canine olfaction was assessed as compared to nasopharyngeal RT-PCR as the reference standard, saliva RT-PCR and nasopharyngeal antigen testing. RESULTS: 335 ambulatory adults (143 symptomatic and 192 asymptomatic) were included. Overall, 109/335 participants tested positive on nasopharyngeal RT-PCR either in symptomatic (78/143) or in asymptomatic participants (31/192). The overall sensitivity of canine detection was 97% (95% CI, 92 to 99) and even reached 100% (95% CI, 89 to 100) in asymptomatic individuals compared to NPS RT-PCR. The specificity was 91% (95% CI, 72 to 91), reaching 94% (95% CI, 90 to 97) for asymptomatic individuals. The sensitivity of canine detection was higher than that of nasopharyngeal antigen testing (97% CI: 91 to 99 versus 84% CI: 74 to 90, p = 0.006), but the specificity was lower (90% CI: 84 to 95 versus 97% CI: 93 to 99, p = 0.016). CONCLUSIONS: Non-invasive detection of SARS-CoV-2 infection by canine olfaction could be one alternative to NPS RT-PCR when it is necessary to obtain a result very quickly according to the same indications as antigenic tests in the context of mass screening.

Scent dogs in detection of COVID-19: triple-blinded randomised trial and operational real-life screening in airport setting.

OBJECTIVE: To estimate scent dogs' diagnostic accuracy in identification of people infected with SARS-CoV-2 in comparison with reverse transcriptase polymerase chain reaction (RT-PCR). We conducted a randomised triple-blinded validation trial, and a real-life study at the Helsinki-Vantaa International Airport, Finland. METHODS: Four dogs were trained to detect COVID-19 using skin swabs from individuals tested for SARS-CoV-2 by RT-PCR. Our controlled triple-blinded validation study comprised four identical sets of 420 parallel samples (from 114 individuals tested positive and 306 negative by RT-PCR), randomly presented to each dog over seven trial sessions. In a real-life setting the dogs screened skin swabs from 303 incoming passengers all concomitantly examined by nasal swab SARS-CoV-2 RT-PCR. Our main outcomes were variables of diagnostic accuracy (sensitivity, specificity, positive predictive value, negative predictive value) for scent dog identification in comparison with RT-PCR. RESULTS: Our validation experiments had an overall accuracy of 92% (95% CI 90% to 93%), a sensitivity of 92% (95% CI 89% to 94%) and a specificity of 91% (95% CI 89% to 93%) compared with RT-PCR. For our dogs, trained using the wild-type virus, performance was less accurate for the alpha variant (89% for confirmed wild-type vs 36% for alpha variant, OR 14.0, 95% CI 4.5 to 43.4). In the real-life setting, scent detection and RT-PCR matched 98.7% of the negative swabs. Scant airport prevalence (0.47%) did not allow sensitivity testing; our only SARS-CoV-2 positive swab was not identified (alpha variant). However, ad hoc analysis including predefined positive spike samples showed a total accuracy of 98% (95% CI 97% to 99%). CONCLUSIONS: This large randomised controlled triple-blinded validation study with a precalculated sample size conducted at an international airport showed that trained scent dogs screen airport passenger samples with high accuracy. One of our findings highlights the importance of continuous retraining as new variants emerge. Using scent dogs may present a valuable approach for high-throughput, rapid screening of large numbers of people.

Identifying SARS-COV-2 infected patients through canine olfactive detection on axillary sweat samples; study of observed sensitivities and specificities within a group of trained dogs.

There is an increasing need for rapid, reliable, non-invasive, and inexpensive mass testing methods as the global COVID-19 pandemic continues. Detection dogs could be a possible solution to identify individuals infected with SARS-CoV-2. Previous studies have shown that dogs can detect SARS-CoV-2 on sweat samples. This study aims to establish the dogs' sensitivity (true positive rate) which measures the proportion of people with COVID-19 that are correctly identified, and specificity (true negative rate) which measures the proportion of people without COVID-19 that are correctly identified. Seven search and rescue dogs were tested using a total of 218 axillary sweat samples (62 positive and 156 negative) in olfaction cones following a randomised and double-blind protocol. Sensitivity ranged from 87% to 94%, and specificity ranged from 78% to 92%, with four dogs over 90%. These results were used to calculate the positive predictive value and negative predictive value for each dog for different infection probabilities (how likely it is for an individual to be SARS-CoV-2 positive), ranging from 10-50%. These results were compared with a reference diagnostic tool which has 95% specificity and sensitivity. Negative predictive values for six dogs ranged from ≥98% at 10% infection probability to ≥88% at 50% infection probability compared with the reference tool which ranged from 99% to 95%. Positive predictive values ranged from ≥40% at 10% infection probability to ≥80% at 50% infection probability compared with the reference tool which ranged from 68% to 95%. This study confirms previous results, suggesting that dogs could play an important role in mass-testing situations. Future challenges include optimal training methods and standardisation for large numbers of detection dogs and infrastructure supporting their deployment.

Disruption of the Bcchs3a chitin synthase gene in Botrytis cinerea is responsible for altered adhesion and overstimulation of host plant immunity.

The fungal cell wall is a dynamic structure that protects the cell from different environmental stresses suggesting that wall synthesizing enzymes are of great importance for fungal virulence. Previously, we reported the isolation and characterization of a mutant in class III chitin synthase, Bcchs3a, in the phytopathogenic fungus Botrytis cinerea. We demonstrated that virulence of this mutant is severely impaired. Here, we describe the virulence phenotype of the cell-wall mutant Bcchs3a on the model plant Arabidopsis thaliana and analyze its virulence properties, using a variety of A. thaliana mutants. We found that mutant Bcchs3a is virulent on pad2 and pad3 mutant leaves defective in camalexin. Mutant Bcchs3a was not more susceptible towards camalexin than the wild-type strain but induced phytoalexin accumulation at the infection site on Col-0 plants. Moreover, this increase in camalexin was correlated with overexpression of the PAD3 gene observed as early as 18 h postinoculation. The infection process of the mutant mycelium was always delayed by 48 h, even on pad3 plants, probably because of lack of mycelium adhesion. No loss in virulence was found when Bcchs3a conidia were used as the inoculum source. Collectively, these data led us to assign a critical role to the BcCHS3a chitin synthase isoform, both in fungal virulence and plant defense response.

Dose-response analyses using restricted cubic spline functions in public health research.

Taking into account a continuous exposure in regression models by using categorization, when non-linear dose-response associations are expected, have been widely criticized. As one alternative, restricted cubic spline (RCS) functions are powerful tools (i) to characterize a dose-response association between a continuous exposure and an outcome, (ii) to visually and/or statistically check the assumption of linearity of the association, and (iii) to minimize residual confounding when adjusting for a continuous exposure. Because their implementation with SAS® software is limited, we developed and present here an SAS macro that (i) creates an RCS function of continuous exposures, (ii) displays graphs showing the dose-response association with 95 per cent confidence interval between one main continuous exposure and an outcome when performing linear, logistic, or Cox models, as well as linear and logistic-generalized estimating equations, and (iii) provides statistical tests for overall and non-linear associations. We illustrate the SAS macro using the third National Health and Nutrition Examination Survey data to investigate adjusted dose-response associations (with different models) between calcium intake and bone mineral density (linear regression), folate intake and hyperhomocysteinemia (logistic regression), and serum high-density lipoprotein cholesterol and cardiovascular mortality (Cox model).

Clinical response to 2 protocols of aerosolized gentamicin in 46 dogs with Bordetella bronchiseptica infection (2012-2018).

BACKGROUND: Bordetella bronchiseptica (Bb) infection commonly causes respiratory disease in dogs. Gentamicin delivered by aerosol maximizes local drug delivery without systemic absorption but clinical response to protocols remains undetermined. OBJECTIVES: To compare the clinical response to 2 protocols of aerosolized delivery of gentamicin in bordetellosis. ANIMALS: Forty-six dogs with Bb infection confirmed by culture or quantitative polymerase chain reaction on bronchoalveolar lavage. METHODS: Retrospective study. Administration of aerosolized gentamicin for ≥10 minutes q12h for ≥3 weeks using 4 mg/kg diluted with saline (group 1) or undiluted 5% solution (group 2). Clinical response firstly assessed after 3-4 weeks and treatment pursued by 3-weeks increments if cure not reached. Cure defined as absence of cough persisting at least a week after treatment interruption. RESULTS: Demographic data were similar between both groups. Clinical cure at 3-4 weeks was more frequently observed with the use of undiluted solution (19/33 vs 3/13 dogs, P = .03) in association with a shorter median duration of treatment (4 vs 6 weeks, P = .01). Dogs from group 2 having less than 1000 cells/µL in lavage were also more likely to be cured at 3-4 weeks than dogs with more than 1000 cells/µL [9/9 vs 10/19, P = .006] and median duration of treatment in that subgroup of animals was reduced (3 vs 5 weeks, P = .02). CONCLUSION AND CLINICAL IMPORTANCE: Aerosolized delivery of gentamicin seems effective for inducing clinical cure in Bb infection. Clinical response appears better using undiluted 5% solution, particularly in the subgroup of dogs having less than 1000 cells/µL in lavage.

Can the detection dog alert on COVID-19 positive persons by sniffing axillary sweat samples? A proof-of-concept study.

The aim of this proof-of-concept study was to evaluate if trained dogs could discriminate between sweat samples from symptomatic COVID-19 positive individuals (SARS-CoV-2 PCR positive) and those from asymptomatic COVID-19 negative individuals. The study was conducted at 2 sites (Paris, France, and Beirut, Lebanon), followed the same training and testing protocols, and involved six detection dogs (three explosive detection dogs, one search and rescue dog, and two colon cancer detection dogs). A total of 177 individuals were recruited for the study (95 symptomatic COVID-19 positive and 82 asymptomatic COVID-19 negative individuals) from five hospitals, and one underarm sweat sample per individual was collected. The dog training sessions lasted between one and three weeks. Once trained, the dog had to mark the COVID-19 positive sample randomly placed behind one of three or four olfactory cones (the other cones contained at least one COVID-19 negative sample and between zero and two mocks). During the testing session, a COVID-19 positive sample could be used up to a maximum of three times for one dog. The dog and its handler were both blinded to the COVID-positive sample location. The success rate per dog (i.e., the number of correct indications divided by the number of trials) ranged from 76% to 100%. The lower bound of the 95% confidence interval of the estimated success rate was most of the time higher than the success rate obtained by chance after removing the number of mocks from calculations. These results provide some evidence that detection dogs may be able to discriminate between sweat samples from symptomatic COVID-19 individuals and those from asymptomatic COVID-19 negative individuals. However, due to the limitations of this proof-of-concept study (including using some COVID-19 samples more than once and potential confounding biases), these results must be confirmed in validation studies.