Thyroid dysfunction is common in cancer patients treated with pembrolizumab. Reversible destructive thyroiditis and overt hypothyroidism are the most common clinical presentations. The mechanism of thyroid destruction appears independent of thyroid autoantibodies and may include T cell, NK cell, and/or monocyte-mediated pathways. Because the thyroid is a frequent target of anti-PD-1 therapies, patients with therapeutically refractory thyroid cancer may be ideal candidates for this treatment.

Atherosclerotic renovascular disease (RVD) reduces renal blood flow (RBF) and GFR and accelerates poststenotic kidney (STK) tissue injury. Preclinical studies indicate that mesenchymal stem cells (MSCs) can stimulate angiogenesis and modify immune function in experimental RVD. We assessed the safety and efficacy of adding intra-arterial autologous adipose-derived MSCs into STK to standardized medical treatment in human subjects without revascularization. The intervention group (=14) received a single infusion of MSC (1.0 × 10 or 2.5 × 10 cells/kg; =7 each) plus standardized medical treatment; the medical treatment only group (=14) included subjects matched for age, kidney function, and stenosis severity. We measured cortical and medullary volumes, perfusion, and RBF using multidetector computed tomography. We assessed tissue oxygenation by blood oxygen level-dependent MRI and GFR by iothalamate clearance. MSC infusions were well tolerated. Three months after infusion, cortical perfusion and RBF rose in the STK (151.8-185.5 ml/min, =0.01); contralateral kidney RBF increased (212.7-271.8 ml/min,=0.01); and STK renal hypoxia (percentage of the whole kidney with R2*>30/s) decreased (12.1% [interquartile range, 3.3%-17.8%] to 6.8% [interquartile range, 1.8%-12.9%], =0.04). No changes in RBF occurred in medical treatment only subjects. Single-kidney GFR remained stable after MSC but fell in the medical treatment only group (-3% versus -24%,=0.04). This first-in-man dose-escalation study provides evidence of safety of intra-arterial infusion of autologous MSCs in patients with RVD. MSC infusion without main renal artery revascularization associated with increased renal tissue oxygenation and cortical blood flow.

Relationships between genetic measures of mastitis (somatic cell score, score for clinical mastitis, and scores for IMI with major or minor pathogens) and immunological parameters (physiological and molecular markers) were examined for periparturient Holstein cows. Physiological markers included 11 in vitro immunological assays. Molecular markers included the second exon of the DRB3 locus of the bovine major histocompatibility complex, the IgG2 isotype genotype, and the CD18 genotype (the locus responsible for bovine leukocyte adhesion deficiency). A gene substitution model was used to estimate the additive genetic effects of alleles of the three molecular markers on estimated breeding value (EBV) for mastitis measures. Pearson correlation coefficients between EBV for immunological assays and EBV for mastitis measures were computed. Molecular markers explained up to 40% of the variation in EBV for measures of mastitis. The presence of allele DRB3.2*16 was associated with higher EBV for SCS. Allele DRB3.2*8 was associated with increased EBV for clinical mastitis, as was the IgG2b allele and the normal CD18 allele. Alleles DRB3.2*11, *23, IgG2a, and the recessive allele for bovine leukocyte adhesion deficiency were associated with decreased clinical mastitis. A positive genetic association was found between allele DRB3.2*24 and EBV for IMI by major pathogens and between DRB3.2*3 and IMI by minor pathogens. Several correlations between EBV for immunological assays and EBV for mastitis measures were significantly different from 0. Cows with low EBV for SCS tended to have neutrophils that had greater functional ability at maximal immunosuppression, low serum IgG1, and high numbers of circulating mononuclear cells. Immunological parameters, including physiological and molecular markers, are useful aids to understand the genetics of resistance to mastitis.

Lactating Holstein cows (n = 1100) from 93 dairy herds in Iowa, Wisconsin, Minnesota, and Illinois were genotyped at the bovine lymphocyte antigen DRB3.2 locus by a genotyping system that used polymerase chain reaction and restriction fragment length polymorphisms. Milk samples were obtained after routine processing at a Dairy Herd Improvement Association facility and returned to the National Animal Disease Center for DNA extraction. Somatic cells were used to classify cows that had acutely elevated SCC (one test of SCC > 500,000; group 1), or chronically elevated SCC (three consecutive tests of SCC > 300,000 or two consecutive tests of > 500,000; group 2), or that were eligible as controls. For each cow in groups 1 and 2, controls were selected that were matched for breed, lactation, herd, and days in lactation (+/-60 d). A conditional model for stepwise logistic regression was used to determine the relative odds for the 10 alleles with a frequency > 3%. No significant associations were observed when the 292 cows in group 2 were compared with their 292 controls. Allele *16 was associated with an increased risk of disease for cows classified with an acute SCC (258 cases and 258 controls). This study has identified DRB3.2*16 as a potential risk factor for acute intramammary infection and established the use of Dairy Herd Improvement Association milk samples as a source of DNA that is useful for genetic epidemiologic studies.

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