Inflammatory biomarker concentrations in dogs with gastric dilatation volvulus with and without 24-h intravenous lidocaine
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SUBMITTER: Brunner A
PROVIDER: S-EPMC10794732 | biostudies-literature | 2023 Jan
REPOSITORIES: biostudies-literature
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Project description:Gastric dilatation-volvulus (GDV) syndrome is a life-threatening emergency and its physiopathology and treatment have been studied for decades. Despite ongoing research, the mortality rate is still high. The aims of this study are to describe the treatment and outcome of GDV patients treated from 2011 to 2024 at the veterinary teaching hospital of Grugliasco (Turin, Italy); to analyze risk and prognostic factors, comparing the obtained data with current literature; and to evaluate how patients' management has changed over the years. The study included 130 dogs with a confirmed GDV diagnosis that underwent surgery. The data were extracted from the digital and hardcopy clinical record, combined with the imaging diagnostic software and an interview submitted to the dogs' owners. The analysis showed the predominance (25.38%) of German Shepherd dogs, as well as of males (59.25%); among the latter, intact dogs were most represented (53.1%). Age between 5-10 years was most frequent in the examined population (54.69%). The surgical technique went through changes during the examined period: the belt loop has been abandoned in favor of the incisional gastropexy. The survival rate of GDV surgically treated dogs was 86.4%. Lactate blood concentration and splenectomy were not assessed as relevant prognostic factors.
| S-EPMC11851494 | biostudies-literature
Project description:Canine gastric dilatation-volvulus (GDV) is a common life-threatening condition occurring primarily in large and giant breeds with a 3.9% to 36.7% lifetime risk. GDV is a complex disease with risk factors including age, diet, behavior, family history, and genetics. The genetic correlates of GDV have not previously been systematically explored. We undertook multiplatform genome-wide association analysis (GWAS) of 253 dogs including 106 healthy dogs and 147 dogs with at least one GDV episode. The study included ten dog breeds enriched for Borzoi, German Shepherd (GSD), Great Dane, and Standard Poodle. SNP array genotyping was performed on constitutional DNA from all 241 samples to identify GDV-associated SNPs and CNVs. To increase the coverage of our study we performed imputation analysis of the SNP data as well as additional whole genome sequencing (WGS) on a subset of 33 dogs (15 healthy dogs and 18 GDV patients from the three most represented breeds). Twenty-one patients were genotyped by both SNP and WGS platforms. The GWAS was conducted across breeds as well as on specific breeds using a mixed linear model adjusting for relatedness, population structure and sex. After genome-wide Bonferroni correction, we identified a significant protective GDV-associated SNP, rs851737064, occurring in an intergenic region, across all breeds. The signal was most significant in Collies, German Shorthaired Pointers, and Great Danes. Subsequent focused analysis across these three breeds identified 12 additional independent, protective and deleterious SNPs with significant GDV association. Additional GWAS conducted on Borzoi, GSD and Great Dane yielded significant genome-wide GDV associations in 11 independent SNPs, while that in Borzoi alone identified 2 independent GDV-associated SNPs. We then used WGS data to validate the imputation analysis. Notable significant SNPs included genes involved in gastric tone and motility including VHL, NALCN, and PRKCZ. From the WGS data we also detected two independent GDV-associated SNPs in Borzoi, GSD and Great Dane breeds on an intergenic region on chromosome 7 not covered by previous analyses. These data provide important new information regarding canine GDV risk factors and facilitate generation of hypotheses regarding the genetic and molecular underpinnings this syndrome.
2020-12-01 | GSE141128 | GEO
Project description:Canine gastric dilatation-volvulus (GDV) is a common life-threatening condition occurring primarily in large and giant breeds with a 3.9% to 36.7% lifetime risk. The genetic correlates of GDV have not previously been systematically explored. We undertook an inter-breed genome-wide association analysis (GWAS) of 253 dogs from ten breeds including 106 healthy dogs and 147 dogs with at least one GDV episode. SNP array genotyping followed by imputation was conducted on 241 samples to identify GDV-associated single-nucleotide polymorphisms (SNPs) and copy number variations (CNVs). A subset of 33 dogs (15 healthy dogs and 18 GDV patients from the three most represented breeds) was characterized by whole genome sequencing (WGS). After genome-wide Bonferroni correction, we identified a significant putatively protective intergenic SNP (rs851737064) across all breeds. The signal was most significant in Collies, German Shorthaired Pointers, and Great Danes. Subsequent focused analysis across these three breeds identified 12 significant additional putatively protective or deleterious SNPs. Notable significant SNPs included those occurring in genes involved in gastric tone and motility including VHL, NALCN, and PRKCZ. These data provide important new clues to canine GDV risk factors and facilitate generation of hypotheses regarding the genetic and molecular underpinnings this syndrome.
| S-EPMC7694454 | biostudies-literature
Project description:Euthanasia of companion animals in veterinary emergency medicine is a common cause of death. Euthanasia is economic when it is the consequence of the pet owner's inability to afford essential treatment while a viable medical alternative to euthanasia exists. Gastric dilatation-volvulus (GDV) is an acute life-threatening emergency condition of dogs; if left untreated, rapid death is highly likely. Surgical treatment leads to survival of around 80-90% of dogs; however, such treatment is costly. Therefore, pre-surgical euthanasia may be largely economically motivated. Having pet insurance, a financial instrument to reduce the burden of unforeseen veterinary medical costs on pet owners, would be expected to abolish the risk for pre-surgical economic euthanasia. We therefore aimed to determine whether pet insurance attenuates the risk of pre-surgical economic euthanasia in dogs with GDV. Non-referred dogs (n = 260) with GDV and known insurance status seen at 24 emergency clinics over a 2-year period were included. Relevant data (e.g., insurance status, age, comorbidities, outcome) were retrospectively extracted from a pet insurer's claim records (insured animals) or from electronic medical records of participating hospitals (non-insured animals). Forty-one percent of dogs (106 of 260 dogs) did not survive to hospital discharge; 82 (77%) of non-survivors died before surgery, all through euthanasia. The pre-surgical euthanasia rate was 10% in insured and 37% in non-insured dogs (p < 0.001). When adjusted for the effect of age, deposit size, comorbidities, and blood lactate concentration, the absence of insurance increased the odds of pre-surgical euthanasia by a factor of 7.4 (95% CI 2.0 to 37; p = 0.002). Of dogs undergoing surgery, 86% survived to hospital discharge. Overall, 80% of insured animals and 53% of non-insured animals survived to hospital discharge (p < 0.001). Thus, insurance was associated with a marked decrease in risk of pre-surgical euthanasia indicating that the cause of pre-surgical euthanasia of dogs with GDV is predominantly economic in nature. The rate of pre-surgical euthanasia in dogs with GDV may emerge as a suitable marker to quantify economic decision making of pet owners and to measure the impact of financial interventions aimed at mitigating economic duress associated with cost of veterinary emergency care.
| S-EPMC7752994 | biostudies-literature
Project description:Identification of genetic susceptibility factors associated with canine gastric dilatation-volvulus
| PRJNA592193 | ENA
Project description:BackgroundLarge and giant dog breeds have a high risk for gastric dilatation-volvulus (GDV) which is an acute, life-threatening condition. Previous work by our group identified a strong risk of GDV linked to specific alleles in innate and adaptive immune genes. We hypothesize that variation in the genes of the immune system act through modulation of the gut microbiome, or through autoimmune mechanisms, or both, to predispose dogs to this condition. Here, we investigate whether differences in the canine fecal microbiome are associated with GDV and are linked to previously identified risk alleles.Methodology/principle findingsFecal samples from healthy Great Danes (n = 38), and dogs with at least one occurrence of GDV (n = 37) were collected and analyzed by paired-end sequencing of the 16S rRNA gene. Dietary intake and temperament were estimated from a study-specific dietary and temperament questionnaire. Dogs with GDV had significantly more diverse fecal microbiomes than healthy control dogs. Alpha diversity was significantly increased in dogs with GDV, as well as dogs with at least one risk allele for DRB1 and TRL5. We found no significant association of dietary intake and GDV. Dogs with GDV showed a significant expansion of the rare lineage Actinobacteria (p = 0.004), as well as a significantly greater abundance of Firmicutes (p = 0.004) and a significantly lower abundance of Bacteroidetes (p<0.004). There was a significant difference in the abundance of 10 genera but after correction for multiple comparisons, none were significant. Bacterial phyla were significantly different between controls and dogs with GDV and at least one risk allele for DRB1 and TRL5. Actinobacteria were significantly higher in dogs with GDV and with one risk allele for DRB1 and TLR5 but not DLA88 genes. Furthermore, Collinsella was significantly increased in dogs with at least one risk allele for DRB1 and TLR5. Logistic regression showed that a model which included Actinobacteria, at least one risk allele,and temperament, explained 29% of the variation in risk of GDV in Great Danes.ConclusionsThe microbiome in GDV was altered by an expansion of a minor lineage and was associated with specific alleles of both innate and adaptive immunity genes. These associations are consistent with our hypothesis that immune genes may play a role in predisposition to GDV by altering the gut microbiome. Further research will be required to directly test the causal relationships of immune genes, the gut microbiome and GDV.
| S-EPMC5995382 | biostudies-literature
Project description:Endoscopic submucosal dissection (ESD) is an advanced therapy for early gastric neoplasm and requires sedation with adequate analgesia. Lidocaine is a short-acting local anesthetic, and intravenous lidocaine has been shown to have analgesic efficacy in surgical settings. The aim of this study was to assess the effects of intravenous lidocaine on analgesic and sedative requirements for ESD and pain after ESD.Sixty-six patients scheduled for ESD randomly received either intravenous lidocaine as a bolus of 1.5 mg/kg before sedation, followed by continuous infusion at a rate of 2 mg/kg/h during sedation (lidocaine group; n = 33) or the same bolus and infusion volumes of normal saline (control group; n = 33). Sedation was achieved with propofol and fentanyl. The primary outcome was fentanyl requirement during ESD. We recorded hemodynamics and any events during ESD and evaluated post-ESD epigastric and throat pain.Fentanyl requirement during ESD reduced by 24% in the lidocaine group compared with the control group (105 ± 28 vs. 138 ± 37 μg, mean ± SD; P < 0.001). The lidocaine group reached sedation faster [40 (20-100) vs. 55 (30-120) s, median (range); P = 0.001], and incidence of patient movement during ESD decreased in the lidocaine group (3% vs. 26%, P = 0.026). Numerical rating scale for epigastric pain was significantly lower at 6 hours after ESD [2 (0-6) vs. 3 (0-8), median (range); P = 0.023] and incidence of throat pain was significantly lower in the lidocaine group (27% vs. 65%, P = 0.003). No adverse events associated with lidocaine were discovered.Administration of intravenous lidocaine reduced fentanyl requirement and decreased patient movement during ESD. Moreover, it alleviated epigastric and throat pain after ESD. Thus, we conclude that the use of intravenous adjuvant lidocaine is a new and safe sedative method during ESD.
| S-EPMC4863806 | biostudies-literature
Project description:Adrenaline is known to prolong the duration of local anesthesia but its effects on the pharmacokinetic processes of local anesthetic drugs are not fully understood. Our objective was to develop a compartmental model for quantification of adrenaline's impact on the pharmacokinetics of perineurally-injected lidocaine in the dog. Dogs were subjected to paravertebral brachial plexus block using lidocaine alone or adrenalinated lidocaine. Data was collected through a prospective, randomised, blinded crossover protocol performed over three periods. Blood samples were collected during 180 minutes following block execution. Compartmental pharmacokinetic models were developed and their goodness-of-fit were compared. The lowering effects of adrenaline on the absorption of lidocaine were statistically determined with one-sided tests. A one-compartment disposition model with two successive zero-order absorption processes best fitted our experimental data. Adrenaline decreased the peak plasma lidocaine concentration by approximately 60% (P < 0.001), decreased this local anesthetic's fast and slow zero-order absorption rates respectively by 50% and 90% (P = 0.046, and P < 0.001), which respective durations were prolonged by 90% and 1300% (P < 0.020 and P < 0.001). Lidocaine demonstrated a previously unreported atypical absorption profile following its paravertebral injection in dogs. Adrenaline decreased the absorption rate of lidocaine and prolonged the duration of its absorption.
| S-EPMC5221883 | biostudies-literature
Project description:This study aimed to evaluate the effects of epidural anaesthesia with lidocaine in combination with general anaesthesia with propofol on some immunologic indices in dogs undergoing ovariohysterectomy. Twelve adult dogs were anesthetized with propofol (induction: 7 mg/kg; maintenance: 0.4 mg/kg/min) and were then allocated into either groups of epidural saline (control) or epidural lidocaine (4 mg/kg; treatment). All the included animals underwent ovariohysterectomy operation. The immune responses, hematologic parameters and cortisol levels were assessed in the predetermined intervals. Evaluation of the innate immunity revealed higher significant levels in the bactericidal, lysozyme and myeloperoxidase activities at 4 hours after surgery in the treatment. In the humoral immunity, the total immunoglobulin level was significantly higher in the treatment. In the assessment of cellular immunity, higher significant values were detected in the delayed skin sensitivity to phytohemagglutinine injection after 48 and 72 hours in the treatment. Moreover, higher significant levels were observed in the number and percentage of lymphocytes as well as an increase in the percentage of monocytes in the treatment at 4 hours after the operation. Notably, the cortisol hormone in the treatment was lower than control at 4 hours of the surgery. In conclusion, epidural anaesthesia with lidocaine when added to general anaesthesia with propofol attenuated the suppression of the innate and cellular immune responses produced by anaesthesia and surgery in the dogs.
| S-EPMC8238226 | biostudies-literature
Project description:The neglected tropical disease onchocerciasis, or river blindness, is caused by infection with the filarial nematode Onchocerca volvulus. Current estimates indicate that 17 million people are infected worldwide, the majority of them living in Africa. Today there are no non-invasive tests available that can detect ongoing infection, and that can be used for effective monitoring of elimination programs. In addition, to enable pharmacodynamic studies with novel macrofilaricide drug candidates, surrogate endpoints and efficacy biomarkers are needed but are non-existent. We describe the use of a multimodal untargeted mass spectrometry-based approach (metabolomics and lipidomics) to identify onchocerciasis-associated metabolites in urine and plasma, and of specific lipid features in plasma of infected individuals (O. volvulus infected cases: 68 individuals with palpable nodules; lymphatic filariasis cases: 8 individuals; non-endemic controls: 20 individuals). This work resulted in the identification of elevated concentrations of the plasma metabolites inosine and hypoxanthine as biomarkers for filarial infection, and of the urine metabolite cis-cinnamoylglycine (CCG) as biomarker for O. volvulus. During the targeted validation study, metabolite-specific cutoffs were determined (inosine: 34.2 ng/ml; hypoxanthine: 1380 ng/ml; CCG: 29.7 ng/ml) and sensitivity and specificity profiles were established. Subsequent evaluation of these biomarkers in a non-endemic population from a different geographical region invalidated the urine metabolite CCG as biomarker for O. volvulus. The plasma metabolites inosine and hypoxanthine were confirmed as biomarkers for filarial infection. With the availability of targeted LC-MS procedures, the full potential of these 2 biomarkers in macrofilaricide clinical trials, MDA efficacy surveys, and epidemiological transmission studies can be investigated.
| S-EPMC8659328 | biostudies-literature