Neutrophil-to-eosinophil ratio as a biomarker for clinical outcomes in advanced stage melanoma patients treated with anti-PD-1 therapy.

Neutrophil-to-lymphocyte ratios (NLR) and eosinophil counts are associated with improved survival in melanoma patients treated with immune checkpoint inhibitors, but no study has investigated neutrophil-to-eosinophil ratios (NER) as a predictive indicator in this population. In this retrospective study evaluating anti-PD-1 treated patients with advanced melanoma, progression-free survival (PFS), overall survival (OS), objective response rates (ORR), and risk of high-grade (grade ≥3) immune-related adverse events (irAEs) were compared between groups defined by median pretreatment NLR and NER as well as median NLR and NER at 1-month post-treatment. Lower baseline NLR and NER were associated with improved OS [HR: 0.504, 95% CI: 0.328-0.773, p = .002 and HR: 0.442, 95% CI: 0.288-0.681, p < .001, respectively] on univariate testing. After accounting for multiple covariates, our multivariate analysis found that lower pretreatment NER was associated with better ORR (by irRECIST) (OR: 2.199, 95% CI: 1.071-4.582, p = .033) and improved OS (HR: 0.480, 95% CI: 0.296-0.777, p = .003). Baseline NLR, 1-month NLR, and 1-month NER were not associated with ORR, PFS, or OS outcomes; but 1-month NER correlated with lower risk of grade ≥3 irAEs (OR: 0.392, 95% CI: 0.165-0.895, p = .029). Our findings suggest baseline NER merits additional investigation as a novel prognostic marker for advanced melanoma patients receiving anti-PD-1-based regimens.

Addressing Social Determinants of Health in a Free Clinic Setting: A Student-Run Free Clinic and Community Resource Navigator Program.

Background: Social determinants of health (SDOH) disproportionately affect medically-underserved populations such as those cared for in student-run free clinics (SRFCs). Community resource programs which address SDOH play an important role in reducing health disparities. The Southside MEDiC Clinic (SMC), a SRFC at the University of Wisconsin School of Medicine and Public Health, partnered with the Community Resource Navigator Program (CRNP), a community resource program focused on addressing SDOH, to remove barriers that prevent positive health outcomes for SMC patients. Aim: Our objective is to describe the partnership between the SMC and the CRNP. We hope this design may be used as a model for addressing SDOH in other SRFCs. Discussion: Partnership goals include improved patient perception of health, increased communication between patients and the clinic, and enhanced opportunities for volunteer action learning. Challenges discussed include adaptation to unique clinics. Future directions and potential advancements in this partnership are also addressed.

Comparison of urine fibrinogen and interleukin-6 concentrations between healthy dogs and dogs with risk factors for enterococcal bacteriuria.

OBJECTIVE: To compare urine concentrations of fibrinogen (uFIB) and interleukin-6 (uIL-6) between dogs with risk factors for enterococcal bacteriuria and healthy dogs. SAMPLE: Banked urine samples with negative aerobic culture results from 8 dogs with urolithiasis, 9 dogs with anatomic abnormalities of the lower portion of the urinary tract (LUT), 10 dogs with LUT neoplasia, and 21 healthy control dogs. PROCEDURES: Urine creatinine concentration (uCrea) was determined by an automated biochemical analyzer, and uFIB and uIL-6 were determined by dog-specific ELISAs. The uFIB:uCrea and uIL-6:uCrea ratios were calculated for each sample to normalize intersample differences in urine concentration and were compared among the 4 experimental groups. RESULTS: Median uFIB:uCrea ratios for dogs with urolithiasis (0.72; interquartile [25th to 75 percentile] range [IQR], 0.46 to 3.48) and LUT neoplasia (6.16; IQR, 3.89 to 12.75), but not for dogs with LUT anatomic abnormalities (0.48; IQR, 0.27 to 0.69), were significantly greater than that for control dogs (0.17; IQR, 0.07 to 0.39). Median uIL-6: uCrea ratios for dogs with urolithiasis (0.48; IQR, 0.18 to 1.61), LUT anatomic abnormalities (0.25; IQR, 0.17 to 0.33), and LUT neoplasia (0.25; IQR, 0.12 to 1.01) were significantly greater than that for control dogs (0.08; IQR, 0.06 to 0.11). CONCLUSIONS AND CLINICAL RELEVANCE: The uFIB and uIL-6 in dogs with risk factors for enterococcal bacteriuria were generally greater than corresponding values in control dogs. Further investigation is necessary to determine the role of fibrinogen in enterococcal colonization of the urinary tract of dogs.

Risk factors for enterococcal bacteriuria in dogs: A retrospective study.

BACKGROUND: In humans, Enterococcus spp. urinary tract infections (UTI) are commonly associated with urinary catheter-induced urothelial inflammation but this is not the case in dogs. HYPOTHESIS/OBJECTIVES: To identify risk factors predisposing dogs to enterococcal bacteriuria. ANIMALS: Seventy dogs with Enterococcus spp. bacteriuria (case) and 70 dogs with Enterococcus coli bacteriuria (control). METHODS: A single center retrospective case-control study with subjects and controls identified by a medical records search for Enterococcus spp. (subject) or E coli (control) bacteriuria from January 1, 2014 to December 31, 2017. Cases and controls were balanced with respect to average age and weight. Binary logistic regression was used to estimate and test whether the odds of having Enterococcus spp. bacteriuria (instead of E coli) were associated with the presence of any given characteristic. RESULTS: A history of recurrent bacteriuria was significantly more common in Enterococcus spp. cases than in E coli controls (odds ratio [OR]: 2.07; 95% confidence interval [CI]: 1.04-4.16, P = .04). Comorbidities associated with the presence of Enterococcus spp. bacteriuria included lower urinary tract (LUT) anatomic abnormalities (OR: 2.94; 95% CI: 1.17-8.10, P = .02), urolithiasis (P = .01), and the presence of LUT neoplasia (P = .04). Small frequencies (n = 12 and n = 6, respectively) compromise our ability to precisely estimate the genuine OR for the latter 2 characteristics. CONCLUSIONS AND CLINICAL IMPORTANCE: If the identified risk factors promote Enterococcus spp. colonization in dogs via induced LUT inflammation similar to people then Enterococcus spp. bacteriuria could be a sentinel for underlying LUT inflammation.

Comparison of commercial manual extraction kits for RNA isolation from canine whole blood.

High quantities of quality RNA are necessary for many veterinary laboratory tests. Several commercial kits are available for RNA isolation from human whole blood; their resultant RNA yield and purity have not been reported for canine whole blood, to our knowledge. We assessed the performance of 4 RNA extraction kits (RiboPure, TRIzol, RNeasy Protect animal blood, and QIAamp RNA blood mini). Whole blood from a healthy dog was stored in the manufacturer-recommended RNA stabilizing buffer as directed. RNA isolation, including DNase treatment, was performed using each kit's manufacturer's protocol. Resultant RNA yield and purity were evaluated using spectrophotometric absorbance, capillary electrophoresis and electropherogram analysis, and a reverse-transcription real-time PCR (RT-rtPCR) assay. The RNeasy Protect animal blood kit extracted the highest, and RiboPure the lowest, concentration of nucleic acid. RNA integrity numbers classified extracted RNA as good quality or better for all kits except RNeasy Protect. All kits had evidence of genomic DNA contamination as assessed by RT-rtPCR. Overall, QIAamp RNA blood mini kit and TRIzol optimized both RNA yield and purity from canine whole blood. These kits extracted high quantities of good quality RNA as evidenced by high RNA integrity numbers and minimal contamination with proteins and solvents.