Serum C-reactive protein and haptoglobin decrease in the first three months of treatment and relative change in haptoglobin predict remission in dogs with pulmonary coccidioidomycosis.

OBJECTIVE: To evaluate temporal changes in serum C-reactive protein (CRP) and haptoglobin (Hp) concentrations in dogs with pulmonary coccidioidomycosis and assess their utility to detect remission. METHODS: 31 client-owned dogs with newly diagnosed pulmonary coccidioidomycosis from October 2020 to February 2021 were included in a retrospective cohort study that utilized archived serum. Serum was originally obtained at diagnosis and once every 3 months after antifungal administration until either remission or 12 months. Time points were designated as baseline (T0), 3 months (T1), 6 months (T2), 9 months (T3), and 12 months (T4). Serum CRP and Hp were measured at a reference laboratory with ELISA assays. RESULTS: Median serum CRP and Hp concentrations decreased from T0 (CRP, 56 mg/L; Hp, 716.1 mg/dL) to T1 (CRP, 3.3 mg/L; Hp, 240.5 mg/dL); subsequent decreases were not significant. Eighteen (60%) and 16 (53%) of 30 dogs had normal serum CRP and Hp concentrations at T1, respectively. Absolute serum CRP (AUC, 0.58; 95% CI, 0.45 to 0.72) and Hp (AUC, 0.65; 95% CI, 0.52 to 0.78) were poor detectors of remission. However, the percentage change in Hp from T0 to T1 (AUC, 0.90; 95% CI, 0.74 to 1.0) was an excellent predictor of remission within 12 months. CONCLUSIONS: Serum CRP and Hp concentrations decrease in the first 3 months of antifungal treatment in dogs with pulmonary coccidioidomycosis, and the percentage change of Hp may help predict dogs that will achieve remission within 12 months of treatment. CLINICAL RELEVANCE: Serum CRP and Hp may be useful adjunctive biomarkers to monitor treatment response in dogs with pulmonary coccidioidomycosis.

Serum vitamin D metabolite and acute-phase protein concentrations are frequently abnormal in a cohort of hospitalized dogs and cats.

OBJECTIVE: To determine whether serum 25-hydroxyvitamin D (25[OH]D) and 1,25-dihydroxyvitamin D (1,25[OH]2D) concentrations are associated with survival and negatively correlate with acute-phase protein (APP) concentrations in ill dogs and cats admitted to nursing care units. ANIMALS: Client-owned dogs (n = 79) and cats (16) admitted to 2 academic veterinary hospital nursing care units. METHODS: A prospective cohort study was conducted between August 12, 2019, and October 26, 2021. A diagnostic laboratory measured 25(OH)D, 1,25(OH)2D, and haptoglobin (HPT) in dogs and cats; C-reactive protein (CRP) in dogs; and serum amyloid A (SAA) in cats. Serum was collected within 12 hours of admission. Illness severity (acute patient physiologic and laboratory evaluation [APPLEfast]) scores and survival data were recorded. RESULTS: Serum 25(OH)D concentrations were in the deficient range for 22 of 79 dogs and 2 of 16 cats. There were no associations between serum analyte concentrations (25[OH]D, 1,25[OH]2D, and APP) or APPLEfast score and survival in dogs or cats. In dogs, HPT was negatively correlated with 25(OH)D (P = .002; r = -0.34) and 1,25(OH)2D (P = .012; r = -0.28), while CRP was positively correlated with HPT (P = .001; r = 0.32) and APPLEfast score (P = .014; r = 0.16). In cats, 1,25(OH)2D was negatively correlated with APPLEfast scores (P = .055; r = -0.49) and SAA was positively correlated with HPT (P = .002; r = 0.73). CLINICAL RELEVANCE: Serum 25(OH)D or 1,25(OH)2D was not associated with survival in our hospitalized patient population. Relationships between APP and serum vitamin D metabolites with APPLEfast scores in cats warrant further investigation as illness severity biomarkers.

Evaluation of serum 25-hydroxyvitamin D, C-reactive protein, and haptoglobin as biomarkers in dogs newly diagnosed with histoplasmosis.

BACKGROUND: Serum 25-hydroxyvitamin (OH)D, C-reactive protein (CRP), and haptoglobin are useful biomarkers in various infectious diseases and inflammatory disorders in dogs, but their utility in histoplasmosis is unknown. OBJECTIVE: Determine if serum 25(OH)D, CRP, and haptoglobin concentrations are different in dogs with histoplasmosis compared to healthy controls and whether serum globulin, albumin, CRP, or haptoglobin are associated with 25(OH)D concentration. ANIMALS: Twenty-two client-owned dogs (histoplasmosis, n = 12; controls, n = 10). METHODS: Prospective case-control study. Dogs with histoplasmosis were categorized as pulmonary, disseminated, or gastrointestinal (GI) tract. Serum 25(OH)D was measured using modified high-performance liquid chromatography (HPLC). Serum CRP and haptoglobin were measured with ELISA assays. RESULTS: Dogs with histoplasmosis were grouped as disseminated (n = 8) and GI tract (n = 4). No dogs had pulmonary tract involvement alone. Dogs with histoplasmosis (median, interquartile range [IQR]; 11.6 ng/mL, 16.8) had lower serum 25(OH)D concentrations than controls (35.7 ng/mL, 17.6; P < .001). Serum CRP and haptoglobin concentrations were higher in dogs with histoplasmosis (CRP: median, IQR; 63.5 mg/L, 37.1 and haptoglobin: 459.7 mg/dL, 419.6) than controls (CRP: 1.9 mg/L, 2; P < .001 and haptoglobin: 85.5 mg/dL, 106.7; P = .003). Serum 25(OH)D concentration was positively associated with fold change in serum albumin concentration (ρ = 0.77; P < .001), and negatively associated with fold change in serum globulin (ρ = -0.61; P = .003) and CRP concentrations (ρ = -0.56; P = .01). CONCLUSION AND CLINICAL IMPORTANCE: Assay of serum 25(OH)D, CRP, and haptoglobin could have clinical value in dogs with histoplasmosis.

Increasing age and severe intraoperative hypotension associated with nonsurvival in dogs with gallbladder mucocele undergoing cholecystectomy.

OBJECTIVE: To identify prognostic indicators and inflammatory markers associated with nonsurvival in dogs with gallbladder mucoceles (GBMs) following cholecystectomy and to evaluate C-reactive protein (CRP) and haptoglobin concentrations in dogs with GBMs compared to healthy controls. ANIMALS: 25 dogs that underwent cholecystectomy for removal of GBM and 20 healthy control dogs. METHODS: A prospective, multicenter cohort study. Survival outcomes to hospital discharge and 2 weeks postdischarge were recorded from medical records. Laboratory variables, inflammatory markers (CRP and haptoglobin), and 25-hydroxyvitamin(OH) D (25[OH]D) concentrations were measured preoperatively. Associations between signalment, clinicopathologic variables, acute patient physiologic and laboratory evaluation (APPLEFAST) scores, inflammatory markers, 25(OH)D concentration, and survival were analyzed using logistic regression. RESULTS: 76% (19/25) and 68% (17/25) of dogs survived to hospital discharge and 2 weeks postdischarge, respectively. For each additional year of age, the odds of nonsurvival in hospital and 2 weeks postdischarge increased by 2.2 (P = .01; 95% CI, 1.2 to 5.0) and 1.7 (P = .04; 95% CI, 1.0 to 3.2), respectively. Intraoperative systolic blood pressure ≤ 65 mm Hg increased the probability of nonsurvival in hospital (P < .04). Gallbladder perforation, APPLEFAST scores, and preoperative serum concentrations of CRP, haptoglobin, and 25(OH)D were not associated with survival. Serum CRP and haptoglobin concentrations were greater in dogs with GBM compared to controls (P < .001). CLINICAL RELEVANCE: Increasing age and intraoperative systolic blood pressure ≤ 65 mm Hg were associated with nonsurvival in dogs with GBM undergoing cholecystectomy. Serum CRP, haptoglobin, and 25(OH)D were not associated with nonsurvival postcholecystectomy in this sample population.

Serum haptoglobin concentrations in feline inflammatory bowel disease and small-cell alimentary lymphoma: a potential biomarker for feline chronic enteropathies.

OBJECTIVES: The aim of this study was to evaluate serum haptoglobin as a biomarker to differentiate between small-cell alimentary lymphoma and inflammatory bowel disease in cats. METHODS: Client-owned domestic cats with and without chronic gastrointestinal signs were enrolled in the study. Serum was collected from each patient and serum haptoglobin levels were measured using ELISA. In cats with gastrointestinal signs, histopathologic evaluation of endoscopic biopsies harvested from the intestinal tract was used to separate them into inflammatory bowel disease and small-cell lymphoma cohorts. Serum haptoglobin levels were statistically analyzed and compared among the three groups: healthy cats; cats with inflammatory bowel disease; and cats with small-cell alimentary lymphoma. RESULTS: Sixty-two cats were enrolled in the study, including 20 clinically normal cats, 14 cats with small-cell alimentary lymphoma and 28 cats with inflammatory bowel disease. The mean ± SD serum haptoglobin was 73.2 ± 39.1 mg/dl in normal cats, 115.3 ± 72.8 mg/dl in cats with inflammatory bowel disease and 133.1 ± 86.1 mg/dl in cats with small-cell alimentary lymphoma. Cats with inflammatory bowel disease and lymphoma had significantly higher serum haptoglobin than controls, with P values of 0.0382 and 0.0138, respectively. There was no statistical difference between the inflammatory bowel disease and lymphoma cohorts (P = 0.4235). For every one unit increase in serum haptoglobin, the odds of gastrointestinal inflammatory disease (inflammatory bowel disease or small-cell alimentary lymphoma) increased by 1.41% (P = 0.0165). CONCLUSIONS AND RELEVANCE: Serum haptoglobin is a useful biomarker for distinguishing between normal cats and those with gastrointestinal inflammatory disease, but it could not significantly differentiate between inflammatory bowel disease and lymphoma. Additional studies may be beneficial in determining the prognostic significance of serum haptoglobin as it may relate to the severity of gastrointestinal inflammation.

Serum 25-hydroxyvitamin D concentration and infectious respiratory disease complex in shelter dogs.

BACKGROUND: Hypovitaminosis D is a risk factor for the development of respiratory infections in humans and repletion can be protective. OBJECTIVES: Determine if serum 25-hydroxyvitamin (OH)D concentrations are lower in shelter dogs and if 25(OH)D concentrations are associated with clinical signs of canine infectious respiratory disease complex (CIRDC) or with time in the shelter. ANIMALS: One hundred forty-six shelter dogs (clinically ill n = 36, apparently healthy n = 110) and 23 nonshelter control dogs. METHODS: Prospective cohort study. Shelter dogs were grouped as clinically ill or apparently healthy based on the presence or absence, respectively, of clinical signs associated with CIRDC. Serum 25(OH)D concentrations were measured with a competitive chemiluminesence immunoassay. Nucleic acids of agents associated with the CIRDC were amplified by polymerase chain reaction assays. RESULTS: The concentration of 25(OH)D was 7.3 ng/mL (4.5-9.9, 95% confidence interval [CI]) lower in dogs with signs of CIRDC than apparently healthy shelter dogs (t(142) = 2.0, P = .04). Dogs positive for DNA of canine herpesvirus (CHV)-1 had serum 25(OH)D concentrations 14.9 ng/mL (-3.7 to 29.6, 95% CI) lower than dogs that were negative (t(137) = 2.0, P = .04). Serum 25(OH)D concentrations in shelter dogs were not different from control dogs (t(45) = -1.4, P = .17). Serum 25(OH)D concentration was not associated with duration of time in the shelter (F(1, 140) = 1.7, P = .2, R2 = 0.01). CONCLUSION AND CLINICAL IMPORTANCE: Vitamin D could have a role in acute respiratory tract infections in shelter dogs.

Correction: Serum 25-hydroxyvitamin D concentrations in dogs with gallbladder mucocele.

[This corrects the article DOI: 10.1371/journal.pone.0244102.].

The Ulcerative Colitis Response Index for Detection of Mucosal Healing in Patients Treated With Anti-tumour Necrosis Factor.

BACKGROUND: Surrogate markers that accurately detect mucosal healing [MH] in patients with ulcerative colitis [UC] are urgently needed. Several stool neutrophil-related proteins are currently used as biomarkers for MH. However, the sensitivity and specificity are not sufficient to avoid unnecessary endoscopic evaluations. METHODS: Novel serum neutrophil-related markers (neutrophil gelatinase B-associated lipocalin and matrix metalloproteinase-9 [NGAL-MMP-9 complex], cathelicidin LL-37 and chitinase 3-like 1 [CHI3L1]), together with C-reactive protein [CRP] and neutrophil counts were studied. Serum samples were obtained from 176 anti-tumour necrosis factor [anti-TNF]-treated UC patients (145 infliximab [IFX] and 31 adalimumab [ADM]) at baseline and after a median of 9.5 weeks. All patients had active disease prior to treatment (Mayo endoscopic subscore [MES] ≥ 2), and MH was defined as MES ≤ 1. Serum was also obtained from 75 healthy controls. Binary logistic regression analysis was used to generate the Ulcerative Colitis Response Index [UCRI]. The performance of individual markers and UCRI was tested with receiver operating characteristic analysis. RESULTS: All neutrophil-related markers were significantly higher in active UC patients compared to healthy controls. In the IFX cohort, CRP, NGAL-MMP-9, CHI3L1 and neutrophil count decreased significantly after treatment and all marker levels were significantly lower in healers compared to non-healers following IFX. In the ADM cohort, CRP, NGAL-MMP-9, CHI3L1 and neutrophil count decreased significantly only in healers. UCRI [including CRP, CHI3L1, neutrophil count and LL-37] accurately detected MH in both IFX-treated (area under the curve [AUC] = 0.83) and ADM-treated [AUC = 0.79] patients. CONCLUSIONS: The new UCRI index accurately detects MH after treatment with IFX and ADM. This panel is useful for monitoring MH in UC patients under anti-TNF treatment. PODCAST: This article has an associated podcast which can be accessed at https://academic.oup.com/ecco-jcc/pages/podcast.

Serum 25-hydroxyvitamin D concentrations in dogs with gallbladder mucocele.

Gallbladder mucocele (GBM) is a common biliary disorder in dogs. Gallbladder hypokinesia has been proposed to contribute to its formation and progression. The specific cause of gallbladder stasis in dogs with GBM as well as viable treatment options to resolve dysmotility remains unknown. Vitamin D deficiency is one of the many potential causes of gallbladder hypokinesia in humans and repletion results in complete resolution of stasis. Improving our understanding of the relationship between serum vitamin D and GBM could help identify dogs as a model for humans with gallbladder hypokinesia. Furthermore, this relationship could provide insight into the pathogenesis of GBM and support the need for future studies to investigate vitamin D as a novel treatment target. Therefore, goals of this study were i) to determine if serum 25-hydroxyvitamin(OH)D concentrations were decreased in dogs with GBM, ii) if serum 25(OH)D concentrations were different in clinical versus dogs subclinical for GBM, and iii) to determine if serum 25(OH)D concentrations could predict the ultrasonographic type of GBM. Sixty-two dogs (clinical, n = 26; subclinical, n = 36) with GBM and 20 healthy control dogs were included in this prospective observational study. Serum 25(OH)D concentrations were measured with a competitive chemiluminescence immunoassay. Overall, dogs with GBM had lower serum 25(OH)D concentrations than control dogs (P = 0.004). Subsequent subgroup analysis indicated that this difference was only significant in the subclinical group compared to the control dogs (P = 0.008), and serum 25(OH)D concentrations did not significantly differ between dogs clinical for GBM versus subclinical or control dogs, indicating that inflammatory state in clinical dogs was not the major constituent of the observed findings. Decreasing serum 25(OH)D concentrations, but not clinical status, was associated with a more advanced developmental stage of GBM type determined by ultrasonography. Our results indicate that vitamin D has a role in dogs with GBM. Additional studies are needed to assess if reduced vitamin D in dogs with GBM is a cause or effect of their biliary disease and to investigate if vitamin D supplementation could be beneficial for dogs with GBM.

The effect of diet on serum 25-hydroxyvitamin D concentrations in dogs.

BACKGROUND: Vitamin D (vitD) deficiency is linked to many disease states including rickets and cancer, and vitD supplementation to improve response to cancer therapy has been explored. Supplementation may be most appropriate for dogs with suboptimal vitD concentrations. In dogs, the primary source of vitD is diet (predominantly via commercial dog food). Our goal was to determine how food source and supplements affect 25(OH)D concentrations, the storage form of vitD. Serum was collected from clinically healthy dogs, and pet owners were surveyed about food source and supplements. Serum 25(OH)D concentration was measured using a quantitative chemiluminescent assay (LIASON, DiaSorin, Stillwater, MN). RESULTS: Dogs (n = 320) were tested for serum 25(OH)D concentrations (range 9.5-249.2 ng/mL). Dogs were fed commercial diets from forty different manufactures (n = 292); additionally some dogs were fed homemade diets (n = 18) or a combination of commercial and homemade diets (n = 10). Median serum 25(OH)D concentrations in dogs fed commercial foods ranged from 47.4 to 100.1 ng/mL with an overall median of 67.9 ng/ml (CV 29%). Analysis for differences among manufacturers was significant (P = 0.0006). Serum 25(OH)D concentrations amongst dogs fed homemade diets had the largest range (9.5-129 ng/mL) and the lowest value (9.5 ng/mL). Dogs receiving salmon oil as a supplement (n = 22) had significantly higher serum 25(OH)D (on average a 19.6 ng/mL increase) than those not receiving a supplement (P = 0.007). CONCLUSIONS: Serum 25(OH)D concentrations in dogs vary widely which likely reflects varying dietary vitD content. Notable differences exist among manufacturers and brands and may reflect differences in proprietary formulations. Given the variability of measured serum 25(OH)D concentrations in dogs and the importance vitD appears to have on health status, dietary vitD content should be optimized.