Background

Melanoma is one of the most common malignancies during pregnancy. There is debate regarding the impact of pregnancy on the prognosis of melanoma. Recent large population-based studies from the United States are lacking.

Objectives

To determine the characteristics and survival of women with pregnancy-associated melanoma.

Methods

This population-based, retrospective cohort study used California Cancer Registry data linked with state-wide hospitalization and ambulatory surgery data to identify 15-44-year-old female patients diagnosed with melanoma in 1994-2015, including pregnant patients. Multivariable logistic regression compared demographic and clinical characteristics between pregnant and non-pregnant women with melanoma. Multivariable cox proportional hazards regression models assessed melanoma-specific and overall survival.

Results

We identified 13 108 patients, of which 1406 were pregnant. Pregnancy-associated melanoma was more frequent in Hispanic compared to non-Hispanic White women. Melanoma occurring post-partum was associated with greater tumour thickness (2.01-4.00 vs. 0.01-1.00 mm, odds ratio 1.75, 95% confidence interval: 1.03-2.98). There were otherwise no significant differences between pregnant and non-pregnant women. Worse survival was associated with Asian, Black and Native American race/ethnicity (vs. non-Hispanic White), lower neighbourhood socio-economic status, public insurance, tumour site, greater tumour thickness and lymph node involvement, but not pregnancy.

Conclusions

Melanoma occurring post-partum was associated with greater tumour thickness, but pregnancy status did not affect survival after melanoma. Race/ethnicity, socio-economic status and health insurance impacted survival, emphasizing the importance of reducing health disparities.

Salmonella invades and disrupts gut epithelium integrity, creating an infection-generated electric field that can drive directional migration of macrophages, a process called galvanotaxis. Phagocytosis of bacteria reverses the direction of macrophage galvanotaxis, implicating a bioelectrical mechanism to initiate life-threatening disseminations. The force that drives direction reversal of macrophage galvanotaxis is not understood. One hypothesis is that Salmonella can alter the electrical properties of the macrophages by modifying host cell surface glycan composition, which is supported by the fact that cleavage of surface-exposed sialic acids with a bacterial neuraminidase severely impairs macrophage galvanotaxis, as well as phagocytosis. Here, we utilize N-glycan profiling by nanoLC-chip QTOF mass cytometry to characterize the bacterial neuraminidase-associated compositional shift of the macrophage glycocalyx, which revealed a decrease in sialylated and an increase in fucosylated and high mannose structures. The Salmonella nanH gene, encoding a putative neuraminidase, is required for invasion and internalization in a human colonic epithelial cell infection model. To determine whether NanH is required for the Salmonella infection-dependent direction reversal, we constructed and characterized a nanH deletion mutant and found that NanH is partially required for Salmonella infection in primary murine macrophages. However, compared to wild type Salmonella, infection with the nanH mutant only marginally reduced the cathode-oriented macrophage galvonotaxis, without canceling direction reversal. Together, these findings strongly suggest that while neuraminidase-mediated N-glycan modification impaired both macrophage phagocytosis and galvanotaxis, yet to be defined mechanisms other than NanH may play a more important role in bioelectrical control of macrophage trafficking, which potentially triggers dissemination.

Background

Long-term sequelae are frequent and often disabling after epidermal necrolysis (Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)). However, consensus on the modalities of management of these sequelae is lacking.

Objectives

We conducted an international multicentric DELPHI exercise to establish a multidisciplinary expert consensus to standardize recommendations regarding management of SJS/TEN sequelae.

Methods

Participants were sent a survey via the online tool "Survey Monkey" consisting of 54 statements organized into 8 topics: general recommendations, professionals involved, skin, oral mucosa and teeth, eyes, genital area, mental health, and allergy workup. Participants evaluated the level of appropriateness of each statement on a scale of 1 (extremely inappropriate) to 9 (extremely appropriate). Results were analyzed according to the RAND/UCLA Appropriateness Method.

Results

Fifty-two healthcare professionals participated. After the first round, a consensus was obtained for 100% of 54 initially proposed statements (disagreement index < 1). Among them, 50 statements were agreed upon as 'appropriate'; four statements were considered 'uncertain', and ultimately finally discarded.

Conclusions

Our DELPHI-based expert consensus should help guide physicians in conducting a prolonged multidisciplinary follow-up of sequelae in SJS-TEN.