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Childhood obesity is an increasingly severe public health problem, with a prospective impact on health. We propose an exposome approach to identifying actionable risk factors for this condition. Our assumption is that relationships between external exposures and outcomes such as rapid growth, overweight or obesity in children can be better understood through a “meet-in-the-middle” model. This is based on a combination of external and internal exposome-based approaches, i.e. the study of multiple exposures (in our case dietary patterns) and molecular pathways (metabolomics and epigenetics). This may strengthen causal reasoning by identifying intermediate markers that are associated with both exposures and outcomes. Our biomarker-based studies in the STOP consortium suggest (in several ways, including mediation analysis) that Branched-Chain Amino Acids (BCAAs) could be mediators of the effect of dietary risk factors on childhood overweight/obesity. This is consistent with intervention and animal studies showing that higher intake of BCAAs has a positive impact on body composition, glycemia and satiety. Concerning food, of particular concern is the trend of increasing intake of ultra-processed food (UPF), including among children. Several mechanisms have been proposed to explain the impact of UPF on obesity and overweight, including nutrient intake (particularly proteins), changes in appetite or the role of additives. Research from the ALSPAC cohort has shown a relationship between UPF intake and trajectories in childhood adiposity, while UPF was related to lower blood levels of BCAAs. We suggest that an exposome-based approach can help strengthening causal reasoning and support policies. Intake of UPF in children should be restricted to prevent obesity.

BACKGROUND: Recently it has been reported that apremilast might promote melanogenesis and it would therefore not be safe to use this drug in patients with psoriasis who have a history of melanoma. METHODS: From January 2017 to December 2020, we retrospectively identified, within a cohort of 635 patients in follow-up care for melanoma, 16 cases of patients with psoriasis treated with apremilast and history of melanoma. Patients were monitored at our unit for a mean duration of 36 months of follow up. RESULTS: The use of apremilast, in our case series was, thus, effective in managing psoriasis without causing recurrence of previous melanoma or any new suspicious lesions which would need removal. DISCUSSION: It has been speculated that apremilast might not be safe in patients who have a history of melanoma as it would be involved in the stimulation of melanogenesis and consequent possibility of recurrence of previous melanoma. CONCLUSION: Our data show that none of the patients treated with apremilast developed recurrence of melanoma at 36 months of follow-up. Further studies are necessary to confirm the safety of apremilast in a larger number of patients with concurrent malignancies, specifically melanoma, and for a longer follow-up period.

OBJECTIVE: Anaplastic lymphoma kinase (ALK) gene has been demonstrated to be rearranged, mutated or amplified in several haematological and solid tumors. Moreover, the use of ALK inhibitors has recently revolutionized the treatment of ALK-rearranged patients affected by non-small cell lung carcinoma. Herein we review the genetic alterations of ALK in melanocytic neoplasms described in literature, focusing on their potential diagnostic and predictive role. MATERIALS AND METHODS: The Authors reviewed the pertinent literature through research on PubMed server was performed typing the terms "ALK", "Anaplastic lymphoma kinase", "ALKATI", "Melanoma", "Spitz", "Spitzoid". RESULTS: ALK translocations were demonstrated in melanocytic neoplasms, particularly in acral melanoma and spitzoid tumors. ALKATI was described in primary and metastatic melanoma, indicating its early occurrence in oncogenesis, with varying immunohistochemical expression of the protein. CONCLUSIONS: The identification of the specific type of ALK mutations could be interesting for planning biologic therapy of melanoma patients. Further studies are needed to evaluate the possibility to introduce an ALK-targeted therapy in patients affected by malignant melanoma.

Background: Gastrointestinal Stromal Tumors (GISTs) are the most common mesenchymal cancers of the gastrointestinal tract PDGFRA genes. Sporadic Multiple Primary GISTs (MPGs) are a rare entity that could occur in adult patients characterized by multiple synchronous lesions generally located in the same organ and even more rarely by metachronous neoplasms. The differential diagnosis among MPGs and disseminated disease or recurrent primary GIST is critical as it affects clinical management. Case report: Here, we present a case of an 86-year-old female who underwent emergency surgery in June 2016 for a giant GIST of the stomach occupying most of the left side of the abdomen. After two years, during adjuvant imatinib 400 mg daily, emergency sigmoid resection was performed due to subacute obstruction and a colonic GIST carrying the same KIT mutation (deletion 557-558 at exon 11) of the previous gastric neoplasm was detected. In this case, we hypothesized the primary nature of the two tumors despite being metachronous and occurring in different organs. However, the same mutational pattern suggested a clonal relationship between the two neoplasms. The onset of a third duodenal lesion, that could corroborate the assumption of the primary metachronous nature of the disease, still remains an unsolved question since its malignancy was not confirmed. Conclusion: Differentiating among metachronous multiple primary GISTs or relapse on imatinib is relevant for staging and choosing the most proper therapeutic approach. Further investigations are surely needed in order to asses a diagnostic tool that may help clinicians to distinguish this rare entity (both synchronous or metachronous) from recurrences. In this scenario, molecular analysis may add essential data to discriminate sporadic MPGs and recurrent or metastatic GISTs.

OBJECTIVES: to evaluate the implementation of an integrated care model for thyroid disease on thyroid surgery at the University Hospital “Federico II” of Naples (Campania Re-gion, Southern Italy). DESIGN: quasi-experimental design employing an interrupted time series analysis. SETTING AND PARTICIPANTS: all subjects who were admit-ted to the University Hospital “Federico II” for thyroid surgery between January 2008 and December 2018. The integrated care model for thyroid disease was implemented starting from January 2016. MAIN OUTCOME MEASURES: rate of partial thyroidecto-mies over all thyroidectomies; rate of diagnosed thyroid cancers over all diagnosed thyroid tumours; length of stay (LOS). Differences pre-and post-interventions were assessed employing Poisson (for count outcomes) and linear (for continu-ous outcomes) regression models. Models were adjusted for age, gender, tumour diagnosis (none, benign, malignant), Charlson index, and discharge month. RESULTS: data on 4,233 thyroidectomies were included. There was no difference between pre-and post-intervention trends for the rate of partial thyroidectomies over all thy-roidectomies (pre-intervention: IRR 1.00; 95%CI 0.99;1.00 – post-intervention: IRR 1.00; 95%CI 0.98;1.02) and for the rate of diagnosed thyroid cancers over all thyroid tumours (pre-intervention IRR 0.99; 95%CI 0.99;1.00 – post-inter-vention IRR 1.00; 95%CI 0.99;1.01). On the contrary, the LOS reduced from 4.5 (±4.3) days in 2008 to 3.2 (±3.2) days in 2018. The multivariate analysis confirmed this reduction, estimated to be 1.1 days on average in the pre-intervention eight-year period (pre-intervention coefficient-0.01; 95%CI-0.02;-0.01), followed by an even greater reduction in the post-intervention three-year period which was estimated to be 1.1 day (post-intervention: coefficient-0.03; 95%CI-0.05;-0.01). CONCLUSIONS: the implementation of an integrated care model for thyroid disease contributed to reduce the LOS for thyroidectomies, improving the efficiency in the management of thyroid disease. However, this intervention had no impact in reducing the rate of total thyroidectomies.

In the original article, there was a mistake in Figure 2F as published. The wrong image was included due to the incorrect labeling of a file. The correct Figure 2 appears below. In addition, there was a mistake in Figure 7. Incorrect panels were included in Figures 7B, C. The corrected Figure 7 appears below. Finally, there was a mistake in Figure 9 where the first two and last columns were mislabelled. The corrected Figure 9 appears below. The authors apologize for these errors and state that these do not change the scientific meaning and conclusions of the article in any way. The original article has been updated.