Nivolumab is a programmed cell death receptor-1 (PD-1) antibody used in the treatment of metastatic or unresectable melanoma. Cutaneous reactions are the most common adverse events reported with these agents and are rarely severe or life-threatening. Here we present a case report describing the clinicopathological findings of a patient with a fatal toxic epidermal necrolysis (TEN) eruption associated with use of nivolumab for treatment of metastatic melanoma. The patient developed a pruritic, morbiliform eruption, which slowly progressed over 3 months to a tender, exfoliative dermatosis. Histology initially showed interface dermatitis and subsequently revealed full thickness epidermal necrosis. The diagnosis of TEN was made. From initial biopsy to TEN presentation, there was an increase in the number of CD8+ lymphocytes within the dermal-epidermal junction and an increase of programmed death ligand 1 (PD-L1) expression in both lymphocytes and keratinocytes. Despite treatment with infliximab, high-dose steroids and intravenous immunoglobulin, the patient expired. Herein we describe what we believe is the second case of TEN associated with anti-PD1 therapy reported in the literature. Increased expression of PD-L1 by immunohistochemistry was observed as the eruption progressed to TEN. Early diagnosis and treatment is necessary in these fatal TEN reactions secondary to the anti-PD-1 antibody therapies.

Objective Although low parent health literacy (HL) has been linked to poor child health outcomes, it is not known whether differences in perceptions related to access to care and provider–parent partnership in care are potential contributing factors. We sought to assess whether parent HL is associated with differences in perceived barriers to care and attitudes regarding participatory decision-making with the provider. Methods This was a cross-sectional analysis of data collected from parents presenting with their child to an urban public hospital pediatric clinic in New York City. Dependent variables were caregiver-reported barriers to care (ability to reach provider at night/on weekends, difficult travel to clinic) and attitudes towards participatory decision-making (feeling like a partner, relying on doctor’s knowledge, leaving decisions up to the doctor, being given choices/asked opinion). The primary independent variable was caregiver HL (Short Test of Functional Health Literacy in Adults [S-TOHFLA]). Results A total of 823 parents were assessed; 1 in 4 (27.0%) categorized as having low HL. Parents with low HL were more likely to report barriers to care than those with adequate HL: trouble reaching provider nights/weekends, 64.9% vs. 49.6%, (p < 0.001, adjusted odds ratio [AOR] 1.7, 95% confidence interval [95% CI] 1.2–2.4); difficult travel, 15.3% vs. 8.0%, (p = 0.004, AOR 1.8, 95% CI 1.1–3.0). Low HL was also associated with not feeling like a partner (28.8% vs. 17.1%; AOR 2.0; 95% CI 1.4–3.0), preference for relying on the doctor’s knowledge (68.9% vs. 52.2%; AOR 1.7; 95% CI 1.2–2.4), and preference for leaving decisions up to the doctor (57.7% vs. 33.3%; AOR 2.2; 95% CI 1.6–3.1). Conclusions Addressing issues of parent HL may be helpful in ameliorating barriers to care and promoting provider-parent partnership in care.

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Background: Infant death in KID syndrome is recognized; its association with specific genotypes and pathophysiology is inadequately understood. Objective: To discover characteristics that account for poor outcomes in lethal KID syndrome. Methods: We collected four new cases and nine previously reported, genotyped cases of lethal KID syndrome. We performed new molecular modeling of the lethal mutants GJB2 p.A88V and GJB2 p.G45E. Results: Infant death occurred in all patients with GJB2 p.G45E and p.A88V; it is unusual with other GJB2 mutations. Early death with those two "lethal" mutations is likely multifactorial: during life all had at least one serious infection; most had poor weight gain and severe respiratory difficulties; many had additional anatomic abnormalities. Structural modeling of GJB2 p.G45E identified no impact on the salt bridge previously predicted to account for abnormal central CO 2 sensing of GJB2 p.A88V. Limitations: Clinical review was retrospective. Conclusion: GJB2 p.G45E and p.A88V are the only KID syndrome mutations associated with uniform early lethality. Those electro-physiologically severe mutations in GJB2 reveal abnormalities in many organs in lethal KID syndrome. All KID syndrome patients may have subtle abnormalities beyond eyes, ears and skin. Early genotyping of KID syndrome births will inform prognostic discussion.