Cancer stigma has undergone an important transformation in recent decades. In general, this disease no longer fits squarely into Goffman’s classic taxonomy of stigmatized conditions. This review will demonstrate that, with important adaptations, an identity-threat model of stigma can be used to organize cancer stigma research post-Goffman. This adapted model postulates that one’s personal attributions, responses to situational threat, and disease/treatment characteristics can be used to predict identity threat and well-being of individuals with cancer. Implications for further research and clinical practice are discussed.

Background: Acute kidney injury (AKI) is a significant complication of Coronavirus Disease 2019 (COVID-19), with no effective therapy. Niacinamide, a vitamin B3 analog, has some evidence of efficacy in non-COVID-19-related AKI. The objective of this study is to evaluate the association between niacinamide therapy and outcomes in patients with COVID-19-related AKI. Methods: We implemented a quasi-experimental design with non-random, prospective allocation of niacinamide in 201 hospitalized adult patients, excluding those with baseline estimated glomerular filtration rate <15 ml/min/1.73m2 on or off dialysis, with COVID-19-related AKI by Kidney Disease Improving Global Outcomes (KDIGO) criteria, in two hospitals with identical COVID-19 care algorithms, one of which additionally implemented treatment with niacinamide for COVID-19-related AKI. Patients on the niacinamide protocol (B3 patients) were compared against patients at the same institution before protocol commencement and contemporaneous patients at the non-niacinamide hospital (collectively, non-B3 patients). The primary outcome was a composite of death or renal replacement therapy (RRT). Results: 38/90 B3 patients and 62/111 non-B3 patients died or received RRT. Using multivariable Cox proportional hazard modeling, niacinamide was associated with a lower risk of RRT or death (HR 0.64, 95% CI 0.40 to 1.00, p=0.05), an association driven by patients with KDIGO stage 2/3 AKI (HR 0.29, 95% CI 0.13 to 0.65, p=0.03; p interaction with KDIGO stage 0.03). Total mortality also followed this pattern (HR 0.17, 95% CI 0.05-0.52 in KDIGO 2/3 patients, p=0.002). Serum creatinine following AKI increased by 0.20 (SE 0.08) mg/dL/day among non-B3 patients with KDIGO 2/3 AKI but was stable among comparable B3 patients (+0.01 (SE 0.06) mg/dL/day; p interaction 0.03). Conclusions: Niacinamide was associated with lower risk of RRT/death and improved creatinine trajectory among patients with severe COVID-19-related AKI. Larger randomized studies are necessary to establish a causal relationship.

Type 1 Diabetes (T1D) has a strong genetic component. The Insulin dependent diabetes 22 (Idd22) locus was identified in crosses of T1D-susceptible NOD mice with the strongly T1D-resistant ALR strain. The NOD-Idd22 recombinant congenic mouse strain was generated where NOD mice carry the full Idd22 confidence interval. NOD-Idd22 mice exhibit almost complete protection from spontaneous T1D and a significant reduction in insulitis. Our goal was to unravel the mode of Idd22 based protection using in vivo and in vitro models. We determined that Idd22 did not impact immune cell diabetogenicity or β-cell resistance to cytoxicity in vitro. However, NOD-Idd22 mice were highly protected against adoptive transfer of T1D. Transferred CTL trafficked to the pancreatic lymph node (PLN) and proliferated to the same extent in NOD and NOD-Idd22 mice yet, the accumulation of pathogenic CTL in the islets was significantly reduced in NOD-Idd22 mice, correlating with disease resistance. Pancreatic endothelial cells from NOD-Idd22 animals expressed lower levels of adhesion molecules, even in response to inflammatory stimuli. Lower adhesion molecule expression resulted in weaker adherence of T cells to NOD-Idd22 endothelium as compared to NOD derived endothelium. Taken together, these results provide evidence that Idd22 regulates the ability of β-cell autoreactive T cells to traffic into the pancreatic islets and may represent a new target for pharmaceutical intervention to potentially prevent T1D.

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