The 2023 iteration of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) estimated prevalence, incidence, and health burden for 375 diseases and injuries, including 12 mental disorders. We assess past, current, and emerging trends in the prevalence and burden of mental disorders across sexes and age groups, for 21 regions, 204 countries and territories, and by Socio-demographic Index (SDI) quintile, from 1990 to 2023. Mental disorders included in GBD 2023 were anxiety disorders, major depressive disorder, dysthymia, bipolar disorder, schizophrenia, autism spectrum disorders, conduct disorder, attention-deficit hyperactivity disorder, anorexia nervosa, bulimia nervosa, idiopathic developmental intellectual disability, and a residual category of other mental disorders. A literature review identified epidemiological data for each disorder. These were analysed via a Bayesian meta-regression to estimate prevalence by disorder, sex, age, location, and year. Disorder-specific prevalence was multiplied by disability weights representing the severity of health loss associated with each disorder to estimate years lived with disability (YLDs). Deaths due to anorexia nervosa were assessed with a Cause of Death Ensemble modelling strategy to estimate deaths by sex, age, location, and year, and then multiplied by the standard life expectancy at age of death to estimate years of life lost (YLLs). YLDs equalled disability-adjusted life-years (DALYs) for all mental disorders except anorexia nervosa (the only mental disorder considered as an underlying cause of death in GBD), for which DALYs represented the sum of YLDs and YLLs. We presented prevalence, deaths, YLDs, YLLs, and DALYs as counts, age-specific rates per 100 000 population, and age-standardised rates per 100 000 population. We estimated 1·17 billion (95% uncertainty interval 1·06-1·31) prevalent cases of mental disorders globally in 2023, equivalent to an age-standardised prevalence rate of 14 210·7 cases (12 849·5-15 940·1) per 100 000 population. These estimates represented a 95·5% (75·0-121·2) increase in prevalent cases and 24·2% (11·4-41·4) increase in age-standardised prevalence rate between 1990 and 2023. All mental disorders showed increases in prevalent cases between 1990 and 2023, while notable increases were seen in age-standardised prevalence rates for anxiety disorders, major depressive disorder, dysthymia, anorexia nervosa, bulimia nervosa, schizophrenia, and conduct disorder. There were an estimated 171 million (127-228) DALYs due to mental disorders globally across sex and age in 2023, equivalent to an age-standardised DALY rate of 2070·5 DALYs (1519·1-2750·5) per 100 000 population. Mental disorders contributed to 6·1% (4·8-7·6) of all-cause DALYs in 2023, making them the fifth leading cause of global DALYs (up from 12th in 1990). DALYs were almost entirely composed of YLDs. Mental disorders were the leading cause of YLDs in 2023 (up from second in 1990), explaining 17·3% (14·8-20·6) of all-cause global YLDs. Leading causes of mental disorder DALYs were anxiety disorders (ranked 11th among the 304 diseases and injuries at Level 4 of the GBD cause hierarchy), major depressive disorder (15th), and schizophrenia (41st). Globally in 2023, mental disorder age-standardised DALY rates were higher among females (2239·6 [1643·7-3014·1] per 100 000) than among males (1900·2 [1399·8-2510·8] per 100 000), and peaked in the 15-19 years age group (2617·3 [1850·6-3696·8] per 100 000). All locations showed increased mental disorder DALY rates in 2023 compared with 1990, ranging across countries and territories from 1302·4 (952·7-1683·7) per 100 000 in Viet Nam to 3555·8 (2661·9-4715·0) per 100 000 in the Netherlands. Across SDI quintiles, DALY rates ranged from 1853·0 (1352·1-2469·3) per 100 000 for middle SDI to 2184·1 (1606·1-2890·3) per 100 000 for high SDI. A significant health burden was imposed by mental disorders in all countries and territories in 2023, irrespective of the health resources available. In some instances, this burden has increased over time and is unevenly distributed across populations. Stronger surveillance systems, particularly in low-income and middle-income countries, are required. Additionally, we need more coordinated and inclusive policies to reduce the burden through early treatment and prevention, tailored to sex and age differences across locations. Responding to the mental health needs of our global population, especially those most vulnerable, is an obligation, not a choice. Gates Foundation, Queensland Health, and University of Queensland.
The prevalence of tracheal collapse syndrome (CTCS) and congenital portosystemic shunts (CPSS) in Yorkshire Terriers is poorly characterized. It is conceivable that CPSS could affect the likelihood of CTCS development if the observed prevalence rate of both conditions is lower than the expected prevalence rate based on multiplication of the individual prevalence rates of each condition. Yorkshire Terriers diagnosed with CTCS, CPSS, or both at the Animal Medical Center (AMC). In this cross-sectional, single-institution study, medical records of Yorkshire Terriers were reviewed for patient date of birth, sex, weight, date of last visit, and reported diagnoses of CTCS, CPSS, or both. Medical records were reviewed to confirm the diagnosis of CTCS or CPSS. Observed and expected age-specific prevalence rates were compared within defined age groups. A total of 11 061 Yorkshire Terriers were identified, with 7263 having data for age at last visit available. The observed prevalence of CPSS was 0.8% (93 dogs), severe CTCS was 6.7% (739 dogs), and both conditions were 0.05% (6 dogs). The median age at diagnosis was 2.7 years (interquartile range [IQR], 1.0-5.7) for CPSS and 10.0 years (IQR, 8.0-13.0) for CTCS. The observed age-specific prevalence rate of both conditions (joint) in each age group was similar to the expected joint prevalence rates in each age group. Further investigation is needed to confirm whether there is a link between CPSS and the development of CTCS in Yorkshire Terriers. Investigation into genetic and physiologic interactions is warranted.
To assess interobserver agreement and predictive value of the Combined Horse Anaesthetic Risk Identification and Optimisation Tool (CHARIOT) compared with the American Society of Anesthesiologists Physical Status (ASA-PS) classification system among five groups of evaluators with different levels of expertise, and to explore the association between risk scores and 7-day postoperative mortality. Prospective, observational, single-centre pilot study. A group of 50 client-owned horses. Each horse was assessed (ASA-PS and CHARIOT) before general anaesthesia by one evaluator from each of five groups: equine rotating intern, resident of the European College of Veterinary Anaesthesia and Analgesia (ECVAA), anaesthetist expert (ECVAA Diplomate/residency-trained), equine resident [European College of Veterinary Surgeons (ECVS) or European College of Equine Internal Medicine (ECEIM)] and European Board of Veterinary Specialisation (EBVS) Specialist (ECVS or ECEIM Diplomate). Mixed-effects Poisson regression analysed adjusted mean scores by evaluator type and scoring system, with pairwise comparisons to identify significant differences. Logistic regression and receiver operating characteristic curve analysis assessed associations between scores and 7-day postoperative mortality. Adjusted mean scores (95% confidence interval) for ASA-PS and CHARIOT: anaesthesia experts 2 (1.8-2.2), 13.9 (13.4-14.3); anaesthesia residents 1.9 (1.7-2.2), 13.6 (13.1-14.1); interns 1.9 (1.7-2.1), 13.2 (12.8-13.7); equine residents 1.9 (1.7-2.1), 13.2 (12.8-13.6) and EBVS Specialists 1.8 (1.6-2), 12.7 (12.3-13.1). Pairwise differences existed between ECVAA evaluators (resident and experts) and every other group (p < 0.05). Higher scores for CHARIOT and ASA-PS were associated with increased odds of 7-day postoperative mortality (p < 0.001). Anaesthesia experts assigned higher risk scores with both scales. Higher scores on both scales were associated with increased mortality risk. Multicentre studies are warranted to confirm CHARIOT's predictive performance and to refine its clinical application.
The efficacy of serum urea and creatinine concentrations in the diagnosis of kidney disease in cattle is limited because of their low sensitivity and specificity. Serum symmetric dimethylarginine (SDMA) concentration is correlated with glomerular filtration rate and has been reported to be useful for the diagnosis of kidney disease in other species. Test the hypothesis that SDMA may be an effective biomarker for diagnosing kidney disease in cattle. The objectives were to assess the analytical performance of SDMA measurement using a benchtop analyzer to establish an SDMA reference interval in cattle, and to evaluate the efficacy of plasma SDMA concentration for the diagnosis of kidney disease in cattle. A total of 199 healthy animals (53 male and 96 female beef cattle and 50 female dairy cows) and 27 azotemic cows with confirmed kidney disease. A partial analytical validation of SDMA measurement using bovine plasma was performed including assessments of short- and long-term imprecision, linearity, and stability. The reference interval was established following American Society for Veterinary Clinical Pathology (ASVCP) recommendations. Finally, the diagnostic efficacy of SDMA was assessed by determination of specificity, sensitivity, and the area under the receiver operating characteristic curve. The SDMA measurements showed acceptable analytical performance. The reference interval was 60-160 μg/L. No significant differences were found according to sex, breed, or food supply. Using the upper limit of the reference interval (160 μg/L) as the cut-off, sensitivity and specificity were 0.85 and 0.98, respectively. An SDMA cut-off of 160 μg/L shows promise for diagnosing kidney disease in cattle, but requires confirmation in future studies.
Sustained ventricular arrhythmias (VAs) in horses can require medical intervention. Prompt pharmacological treatment is indicated when the arrhythmia leads to hemodynamic or electrical instability. Established antiarrhythmic treatment of VA in horses includes lidocaine and magnesium, administered parenterally. Other antiarrhythmic agents are used; however, concerns regarding adverse effects, financial restrictions, logistics of administration, and lack of access often limit their use. While anecdotal reports of oral administration of sotalol for treatment of VA in horses exist, sotalol has primarily been described for prevention of recurrent atrial fibrillation or suppression of supraventricular and ventricular ectopy. This case series describes 4 horses with sustained VA treated orally with sotalol. Successful conversion to a predominantly normal sinus rhythm or pre-existing atrial fibrillation was achieved without any adverse effects. Sotalol could be considered as a treatment option in selected, hemodynamically stable cases of VA, especially where other established treatment options are unavailable, ineffective, or unaffordable.
Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease for which novel therapeutic approaches are urgently needed. Transforming Growth Factor-β (TGF-β) plays a central role in IPF pathogenesis by activating lung fibroblasts. Inhibitor of DNA binding (ID) proteins are regulated by TGF-β; however, their role in IPF remains poorly understood. We aimed to evaluate the regulation of ID proteins in IPF and to determine their functional role in human lung fibroblasts (HLF) in vitro and pulmonary fibrosis in vivo. ID protein expression was assessed in lungs and lung fibroblasts from mice and patients with pulmonary fibrosis. In vitro, the effects of ID1/ID3 inhibition and overexpression on HLF proliferation, migration and differentiation into myofibroblasts were evaluated. Genetic and pharmacological approaches were used in vivo to determine the role of ID1/ID3 in pulmonary fibrosis. ID1/ID3 levels were elevated in lungs and lung fibroblasts from mice and patients with pulmonary fibrosis, as well as in HLFs treated with TGF-β. ID1/ID3 knockdown reduced proliferation, migration and differentiation of healthy and IPF-derived HLFs. Bleomycin-exposed ID1/ID3 double KO mice exhibited improved lung function and reduced fibrosis compared with WT mice. Pharmacological inhibition of ID1/ID3 decreased HLF proliferation, migration and differentiation in vitro and attenuated pulmonary fibrosis in vivo. Lung-specific inhibition of ID1/ID3 using adeno-associated viruses expressing short hairpins targeting ID1 and ID3 also reversed pulmonary fibrosis in mice. Mechanistically, ID1/ID3 inhibition reduced fibroblast proliferation through regulation of cell cycle genes and attenuated fibroblast differentiation via the MEK/ERK pathway. Simultaneous inhibition of ID1 and ID3 attenuates pulmonary fibrosis. Targeting ID1/ID3 represents a potential novel therapeutic strategy for IPF.
Myocarditis and myocardial injury associated with feline infectious peritonitis (FIP) recently are being recognized. Prospectively document the frequency of cardiac changes in cats with FIP using echocardiography and cardiac troponin I (cTnI) concentrations. Twenty cats with naturally occurring FIP without previous history of heart disease. Cats diagnosed with FIP were tested for common concurrent infections associated with myocarditis by testing serum for feline immunodeficiency virus (FIV) antibodies, feline leukemia virus antigen (FeLV), Dirofilaria immitis antigen, Bartonella spp. immunoglobulin G (IgG), and Toxoplasma gondii IgG and immunoglobulin M (IgM) as well as by testing blood for nucleic acids of Bartonella spp. and coronavirus (SARS-COV-2). Each cat also was tested for serum cTn1 concentration and underwent an echocardiographic examination. After 12 weeks of treatment with antiviral drugs, serum cTnI concentrations were reassessed. All echocardiographic measurements were normalized to patient body weight. The left ventricular posterior wall from right parasternal long axis and short axis was thickened in 55% (11/20) and 25% (5/20) of cats, respectively. Pleural effusion was present in 40% (8/20) of cats and pericardial effusion in 25% (5/20) of cats, but a cardiac cause was not identified for these effusions. Median cTnI at initial evaluation was 0.37 ng/ml (interquartile range [IQR], 0.20-0.83; upper reference interval, 0.20 ng/ml). Repeat cTnI was performed after 12 weeks of antiviral treatment in 6 cats that initially had increased cTnI (median initial cTnI, 0.75 ng/mL) and, in all 6 cats, cTnI normalized to < 0.20 ng/mL. Cats with FIP can present with increases in cTnI and ventricular wall thickening, findings suggestive of myocarditis or myocardial injury.
The tissue renin-angiotensin system (RAS) has not been characterized in cats. To quantify RAS enzyme activity and angiotensin peptide (AP) concentrations in myocardial and renal tissue obtained at necropsy from healthy cats and cats with hypertrophic cardiomyopathy (HCM). A convenience sample of 17 adult purpose-bred cats, euthanized under other study protocols, with echocardiographically normal hearts (n = 8) or American College of Veterinary Internal Medicine stage B1 (n = 6) or C (n = 3) HCM. Prospective study. Tissues were incubated with spiked angiotensin I (AngI) or II (AngII) under control and inhibitor conditions to assess relative enzyme contributions to AngII or angiotensin 1-7 (Ang1-7) formation. Freezing was delayed for 3 h in paired samples from 7 cats. Angiotensin peptides were also directly quantified in homogenized tissues. Renin-angiotensin system enzyme activity was present in necropsy tissues, which formed AngII and Ang1-7 when incubated with AP precursors. The median contribution of angiotensin-converting enzyme to AngII formation exceeded 85% in all tissues. The 90% confidence limits of the geometric mean of the ratio of the angiotensin production of paired samples met the equivalence requirement in 1/13 experiments. The AP concentrations were quantifiable and did not differ between cats with echocardiographically normal hearts and cats with HCM (myocardial AngI P = .11 and AngII P = .37; kidney AngI P = .84, AngII P = .73, and Ang 1-7 P = .84). Necropsy tissue RAS enzyme activity and some AP concentrations were quantifiable in this cohort. Renin-angiotensin system enzyme activity changed during a short (3 h) postmortem period.
Insulin resistance (IR) is a common complication in diabetic dogs, impairing glycemic control and causing metabolic dysfunction. To assess the utility and determine cutoff values of C-peptide, homeostasis model assessment of IR by C-peptide (HOMA-IR by C-peptide), HOMA-IR by C-Peptide version 2 (HOMA-IRCP2), and homeostasis model assessment 2 of IR (HOMA2-IR) as diagnostic tools for detecting IR and identifying factors related to IR in dogs with diabetes. Seventy-six dogs were enrolled from a referral center and classified into 4 groups: healthy dogs (Healthy group, n = 17), pre-diabetes mellitus (PreDM, n = 11), insulin-dependent diabetes mellitus (IDDM, n = 20), and insulin-resistant diabetes mellitus (DMIR, n = 28). A cross-sectional prospective study. Blood samples were collected from dogs from which food was withheld and analyzed for glucose, C-peptide, and other metabolic indicators. HOMA-IR by C-peptide, HOMA-IRCP2, and HOMA2-IR were determined and compared across groups. The DMIR group exhibited the highest C-peptide and HOMA-IR by C-peptide, HOMA-IRCP2, and HOMA2-IR. Receiver Operating Characteristic curve analysis demonstrated that C-peptide, HOMA-IR by C-peptide, HOMA-IRCP2, and HOMA2-IR identified IR, with area under curve of 0.843 (95% CI, 0.756-0.930), 0.897 (95% CI, 0.819-0.975), 0.893 (95% CI, 0.812-0.973), and 0.789 (95% CI, 0.686-0.893), respectively (P < 0.001). A cutoff level of ≥0.7 ng/mL for C-peptide and ≥120 for HOMA-IR by C-peptide demonstrated the highest sensitivity (92.9%), whereas ≥1.65 for HOMA-IRCP2 showed the highest specificity (97.9%). C-peptide, HOMA-IR by C-peptide, HOMA-IRCP2, and HOMA2-IR are promising, non-invasive indicators of IR. Early identification of IR using these markers might improve clinical outcomes.
In 2020, a permanent change in the antibody used in the Siemens Immulite 2000 cortisol assay resulted in a negative bias of approximately 23%. In response, the manufacturer introduced a veterinary-specific cortisol assay. To compare the analytical and diagnostic agreement between the Siemens Immulite 2000 standard cortisol (SC) and veterinary cortisol (VC) assays. Residual canine serum samples submitted to a veterinary diagnostic laboratory. Cortisol concentrations were measured using both SC and VC kits on the Siemens Immulite 2000 chemiluminescent immunoassay analyzer. A total of 105 dogs contributed 154 cortisol measurements. Median (minimum, maximum) cortisol concentrations for VC and SC assays were 4.19 and 4.67 (<1.00, > 50.00) μg/dL, respectively. Further analysis included only 1 measurement per dog. Cortisol concentrations measured by the 2 assays were highly correlated (Spearman's rho = 0.981, P < .001). Passing-Bablok regression demonstrated no significant constant bias (intercept -0.035; 95% CI, -0.184 to 0.061) or proportional bias (slope 1.036; 95% CI, 0.997-1.098). Bland-Altman analysis showed no significant mean bias between assays (-0.494 μg/dL; 95% CI, -3.524 μg/dL to 4.513 μg/dL), with limits of agreement of -4.353 μg/dL to 5.342 μg/dL. Diagnostic agreement was excellent (Cohen's κ = 0.961); 3/105 cases were classified differently, with discordant results occurring near diagnostic decision thresholds. The SC and VC assays demonstrate strong analytical and diagnostic agreement in canine serum. Use of either assay is unlikely to alter clinical interpretation in most cases, and both assays appear to share similar analytical characteristics.
Uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) is closely associated with the management of HIV and tuberculosis (TB) coinfection because it modulates the metabolism of antiretroviral (ARV) drugs. The frequency of UGT1A1 polymorphisms varies widely among sub-Saharan Africans. However, studies examining the frequency of UGT1A1 polymorphisms and their impact on drug response profiles, accounting for environmental factors, drug-drug and gene-drug interactions and non-compliance remain sparse. Given that HIV and TB treatments often involve complex drug regimens with a high risk of interactions, understanding the role of UGT1A1 polymorphisms in these contexts is crucial. Therefore, this scoping review aims to map existing evidence, synthesise findings on how genetic polymorphisms in the UGT1A1 gene affect the metabolism of ARVs and antituberculosis drugs, and identify gaps in literature regarding their impacts on drug efficacy, toxicity and treatment outcomes in sub-Saharan Africa (SSA). The methodology for this scoping review will follow the guidelines outlined in the Joanna Briggs Institute Methodology Manual. Using the keywords, UGT1A1 polymorphism, HIV and TB coinfection, treatment outcomes and SSA, we will search for articles on PubMed/Medline, Cochrane Library, Embase, Web of Science and Scopus to obtain relevant articles published from January 2010 to April 2026. Two independent reviewers will screen and assess quality of titles and abstracts against the predefined inclusion and exclusion criteria and manage the data using Microsoft Excel. Conflicts will be resolved through discussion and where necessary a third reviewer will be consulted. Findings will be narratively synthesised across polymorphisms and treatment outcomes. The reviewers will meet and discuss the themes that will arise as well as the interpretation of the themes to minimise bias in the findings. The scoping review relies on publicly available published resources, exempting it from ethical review board oversight. The review findings will be shared in a peer-reviewed journal.
Human CD4+ T cells utilize nutrients, including lipids, to support their activation and polarization. Considering the pivotal role of lipoproteins in lipid transport, we reasoned that lipoprotein uptake and processing could effect CD4+ T cell function. Here, we demonstrate that activation of human CD4+ T cells induced expression of LDL receptor (LDLR) to facilitate LDLR-mediated endocytosis of LDL. Degradation of surface LDLR on CD4+ T cells with PCSK9 hampered activation and proliferation of the cells. Lipoprotein deprivation or blocking of lysosomal cholesterol egress impaired activation of mechanistic target of rapamycin complex 1 (mTORC1), affecting CD4+ T cell activation and proliferation. Furthermore, lipoprotein deprivation of cultured primary CD4+ T cells lead to reduced expression of c-MAF and FOXP3, key transcription factors for IL-10, accompanied by reduced IL-10 secretion. The pivotal role of LDLR-mediated lipoprotein uptake for mTORC1 activity, c-MAF and FOXP3 expression, and IL-10 secretion was confirmed using LDLR-dysfunctional CD4+ T cells from patients with homozygous familial hypercholesterolemia. Our study offers valuable insights into the lipoprotein metabolism of human CD4+ T cells and their reliance on the LDLR pathway for activation and polarization, a feature that may be leveraged to modulate CD4+ T cell function.
Identifying causative bacterial species in neonatal foal bacteremia and their antimicrobial susceptibility profiles is essential for guiding appropriate antibiotic therapy. To describe bacterial isolates from blood culture and their antimicrobial susceptibility patterns in neonatal foals from two French institutes, and to assess associations between pretreatment and blood culture positivity, and between in-hospital death (euthanasia or natural death) and the presence of multidrug-resistant (MDR) bacteria. Two hundred forty-three foals (<7 days old) admitted to two equine intensive care units in Normandy with blood cultures. Retrospective cohort study. Associations were assessed using chi-square test. Blood cultures were positive in 43% of foals. Pretreatment was not significantly associated with blood culture positivity (P = .62). Gram-positive isolates predominated (65%). The most common isolates were Staphylococcus spp. (25%), Escherichia coli (11%), and Streptococcus spp. (11%). MDR bacteria represented 26% of isolates, predominantly Gram-positive. Low resistance to aminoglycosides, particularly amikacin (17%) and gentamicin (19%), was observed, whereas resistance to penicillin (53%) and ceftiofur (33%) was more common. Moderate resistance to tetracyclines (between 22% and 31%) was measured within overall bacteria. Similar resistance rates to trimethoprim-sulfamethoxazole and ceftiofur were observed among Gram-positive (≈ 35%) and Gram-negative isolates (26%). Presence (vs absence) of MDR isolates was not significantly associated with in-hospital death (P = .52). Consistent with recent reports, Gram-positive bacteria predominated among neonatal foal blood isolates in our sample. Despite its designation as a critically important human antibiotic, resistance to ceftiofur in our study necessitates utmost restraint in its use.
The adrenocorticotropic hormone (ACTH) stimulation test is used to assess adrenal function. The effects of extended freezing of tetracosactide acetate (TCA), an ACTH analogue, on test performance, remain unexplored. To determine whether TCA retains its biological activity to induce adrenal steroid production when stored in plastic syringes and frozen at -20 °C for prolonged period. Eight adult experimental Beagles divided into 2 groups of 2 males and 2 females each. Prospective case-crossover study. Each dog received 5 μg/kg IV of TCA on 2 occasions, 4 weeks apart (period P1-washout-period P2). Group 1 received frozen then fresh TCA; group 2 received fresh then frozen TCA. Pre- and post-administration blood samples were analyzed at both study periods for cortisol and other steroid metabolites using liquid chromatography-tandem mass spectrometry. A general linear mixed model was used with TCA (fresh vs frozen), period, sequence and timing as fixed factors, and dog as random factor. Frozen TCA stored for a median time of 1.8 years (IQ range 1.5-1.9) induced similar steroid metabolite responses compared with fresh TCA. Median T1 cortisol concentrations were 248 nmol/L (IQ range 231-272) with frozen TCA and 254 nmol/L (IQ range 249-262) with fresh TCA (P = .037). Median T1 17-OHP concentrations were 0.73 μg/L (IQ range 0.67-0.85) with frozen TCA 0.79 μg/L (IQ range 0.71-1.17) with fresh TCA (P = .09). Long-term freezing of TCA in plastic syringes offers a cost-effective strategy and practical alternative during supply shortages.
Bordetella bronchiseptica (Bb) is a common respiratory infection in dogs with potentially serious clinical consequences. A subset of Bb cases require referral to tertiary care institutions, yet these dogs lack characterization. Describe the clinical features, diagnostic findings, management, and outcomes of dogs diagnosed with Bb infections at a tertiary care institution, and evaluate risk factors associated with severe, refractory, or recurrent Bb infections. Fifty-nine client-owned dogs diagnosed with Bb infections at a tertiary care hospital. Retrospective, observational study (1995-2024). Univariable and multivariable logistic regression models were used to identify risk factors associated with negative disease outcomes. Cavalier King Charles Spaniels (CKCS) and Yorkshire Terriers were overrepresented (17.0% and 10.2%, respectively) when compared with hospital admissions from the same period (P <.0001 for both). Nearly 80% of infections were classified as chronic in this population, with a median duration of clinical signs of 30 days. Approximately 40% of cases were classified as severe infections (ie, pneumonia), whereas 54% were classified as refractory. Recurrent Bb infections were uncommon (7%). Mycoplasma spp. coinfections were reported in 37% of cases but were not associated with outcomes. Although no variables were identified as predictors of severe disease, respiratory tract comorbidities (eg, brachycephaly) were associated with refractory infections (P = .04). Yorkshire Terriers and CKCS were overrepresented for Bb infections in a referral population, which could indicate underlying risk factors within these breeds. Structural respiratory tract abnormalities may predispose dogs to refractory Bb infections.
Cardiac arrhythmias are common in horses, but their clinical and prognostic relevance remains poorly defined. Despite the importance of localization for diagnosis and treatment, noninvasive methods to identify arrhythmogenic foci are limited. Evaluate the ability of delta (Δ) 3- and 12-lead ECGs and 2-dimensional (2D) and 3-dimensional (3D) vectorcardiography (VCG) to identify the site of origin of focally induced atrial and ventricular premature depolarizations in horses. Eight healthy horses underwent 2 electrophysiological studies, 1 standing, and 1 under general anesthesia. Premature atrial and ventricular complexes were induced by intracardiac pacing at 29 anatomical sites. Simultaneous Δ 12-lead ECG and VCG recordings were obtained. Mean vector directions were analyzed, and classification accuracy was assessed at the chamber, regional, and site-specific levels. Distinct pacing sites produced reproducible and location-specific activation patterns. For differentiating left- from right-sided origins, 3D-VCG had 99% and 82% accuracies for ventricular and atrial origins, respectively. The simplified Δ-based 2D-VCG also showed strong performance on the chamber level, with accuracies of 94% and 78%, respectively. Accuracy was lower for fine-grained intra-chamber localization, especially in the atria. Although 3D-VCG offers superior spatial resolution, 2D-VCG provides a good balance between diagnostic accuracy and practical applicability, especially for left- vs right-sided localization. Combined Δ 12-lead ECG and VCG enables accurate, noninvasive chamber-level localization of arrhythmia origins in horses. Standardized application in larger cohorts with naturally occurring arrhythmias may support targeted ablation strategies and improve arrhythmia management and sudden cardiac death risk stratification.
Vulvovaginal squamous cell carcinoma (SCC) is an uncommon neoplasm in dogs. An 11-year-old female spayed German Shepherd dog presented with a history of excessive peri-vulvar grooming and a 3 cm × 3 cm irregular mass involving the vagina and vulva. Incisional biopsy confirmed a diagnosis of primary vulvovaginal SCC. Abdominal ultrasonography and thoracic radiographs indicated no evidence of systemic or regional metastasis. Surgical excision and adjuvant radiation therapy were declined, and the patient was treated with lapatinib, an orally administered dual tyrosine kinase inhibitor. Treatment resulted in a partial response within 1 month and complete resolution of the primary lesion within 3 months. No recurrence of the initial lesion was observed after 1 year of treatment despite development of perivulvar cutaneous lesions that were not associated with clinical signs. Lapatinib was well tolerated but did result in acute hepatic injury that was resolved using hepatoprotective antioxidant medication and intermittent treatment cessation.
The translation of nucleic acid amplification into practical point-of-care and biosensor-integrated diagnostics is still significantly impeded by the necessity for rapid sample preparation. For this reason, a broad comparison of seven commercially available kits for DNA/RNA extraction containing their temperature-related adjustments was performed. Extracts isolated from SARS-CoV-2-positive nasopharyngeal swabs, viral stocks, as well as laboratory-prepared suspensions of clinically relevant Gram-positive and Gram-negative bacteria were evaluated by recombinase polymerase amplification (RPA) and real-time PCR. In addition, the impact of transport media for SARS-CoV-2 samples was investigated. Extraction performance varied markedly according to the kit, pathogen, sample background. For SARS-CoV-2, rapid extraction was more effective for samples collected in viral transport medium than in inactivation buffer. Across bacterial targets, performance was species dependent, highlighting substantial differences in compatibility between simplified extraction workflows and downstream amplification. Among the rapid methods tested, a simplified QuickExtract protocol (95 °C, 5 min) provided the most consistent overall results, although it did not uniformly match the reference silica-based method for all targets. In conclusion, these results demonstrate that rapid nucleic acid extraction must be thoroughly evaluated as an essential element of the entire sample-to-answer workflow, rather than being chosen as a standalone preprocessing step for point-of-care molecular diagnostics.
Genome-wide association studies (GWASs) have identified common genetic risk loci for ischemic stroke (IS), primarily in European populations older than 55 years. We aimed to identify common and rare risk variants associated with early-onset IS (ages 18-54) in Taiwan. We conducted GWASs of early-onset and all IS cases, compared with stroke-free controls of Han ethnicity, using the Taiwan Precision Medicine Initiative database, which includes individuals from general outpatient clinics across 16 medical centers. To explore the functional relevance of stroke-associated variants, we investigated fine-mapping and linkage disequilibrium patterns, phenotype correlations using the TOAST etiologic classification in an independent IS cohort, phenome-wide association studies (PheWASs), and pathway enrichment analysis. Furthermore, we examined rare pathogenic variants using whole-exome sequencing in consecutive, unrelated early-onset sporadic and/or familial stroke probands. We identified a robust association between a novel risk locus and early-onset IS (5,546 cases vs 143,017 controls; mean age: 52.7 vs 40.6 years; female: 45.6% vs 58.7%), including the lead single-nucleotide polymorphism (SNP) rs541118668 (CYP4F3) (OR 1.69, 95% CI 1.44-1.98; p = 6.86 × 10-11). In patients with all IS (21,544 cases vs 267,198 controls; mean age: 69.5 vs 53.7 years; female: 43.2% vs 55.5%), this locus and 6 other loci, including the reported rs12509595 (near FGF5) (OR 1.06, 95% CI 1.04-1.08; p = 2.74 × 10-8) in East Asians, were significantly associated. The novel SNPs clustered on chromosome 19p13.12 and were associated with the small vessel occlusion (SVO) subtype in the independent IS cohort (n = 716, p < 0.05). The PheWASs of the risk variants revealed explicit associations with cerebrovascular diseases and no associations with other diseases. The enrichment pathway implicated CYP4F3 in lipid metabolism and inflammatory responses. Moreover, we discovered that 28 of 180 unrelated probands with early-onset IS (15.6%; 16/85 sporadic and 12/87 familial stroke) carried likely pathogenic variants, particularly those with SVO (NOTCH3, HTRA1, HBB, GJA1, and GP1BA) and cerebral venous infarction (PROS1 and F2). Our study identifies a novel age-specific genetic hotspot for IS at chromosome 19p13.12 in Han Chinese. Together with enrichment of subtype-specific rare pathogenic variants, these findings reveal a distinct genetic architecture underlying early-onset stroke in East Asians.
Immune checkpoint inhibitors (ICIs) have transformed oncology in human medicine, providing clinical benefit in a broad spectrum of cancers. Widely available ICIs for dogs are lacking. Evaluate efficacy and safety of gilvetmab, a caninized anti-PD-1 monoclonal antibody. Fifty-one client-owned dogs were evaluated, 25 with stages II-III melanoma and 26 with stages I-III mast cell tumor (MCT). Fifteen dogs with stages III-V lymphoma were also evaluated. Multi-institutional, open-label study. Enrolled dogs were treated with gilvetmab IV at 6 mg/kg q28d or 10 mg/kg q14d; 8 dogs receiving the lower dosage underwent dose escalation with their owners' consent. Safety was evaluated by physical examinations, laboratory testing, and clinical observations made by veterinarians or the dogs' owners. Efficacy was assessed by objective response rate (ORR) and time to progression (TTP) using cRECIST v1.0 and lymphoma response criteria. For melanoma, the ORR was 20% (95% confidence interval [CI], 7%-41%) and median TTP was 56 days. For MCT, the ORR was 46% (95% CI, 27%-67%) and median TTP was not reached. No objective responses were observed in dogs with lymphoma. Serious adverse events of anaphylaxis, hypotension, or tumor hemorrhage occurred in 3 dogs (3/51, 5.9%). Tumor enlargement before regression, consistent with possible pseudoprogression, was observed in 2 dogs with melanoma. Gilvetmab has a reasonable expectation of efficacy and an acceptable preliminary safety profile in dogs with MCT stages I-III and melanoma stages II and III.