Obesity has reached pandemic proportion and represents a major risk for several comorbidities. In addition to metabolic and cardiovascular obesity-related diseases, recent evidence suggested that obesity might affect immune system function. Adipose tissue is considered an endocrine organ that actively secretes cytokines also referred to as “adipokines.” Adipokines play an important role in the control of human metabolism. The dysfunctional adipose tissue in obese individuals is characterized by an altered cytokine secretion pattern that promotes chronic low-grade inflammation. Epidemiological evidence highlights the association between obesity and allergic and immune-mediated diseases, such as asthma, allergic rhinitis, rheumatic arthritis, and psoriasis. Less is known about underlying pathogenic mechanisms. However, several recent in vivo and in vitro studies have reported that adipokines are involved in inflammatory and autoimmune disorders by influencing both innate and acquired immune responses. In addition, obesity has been associated with reduced immune surveillance and increased risk of cancer. This paper reviews the evidence regarding the role of adipokines in immune system regulation, with particular emphasis on autoimmune, allergic, and inflammatory disorders. Understanding how obesity affects immune system functions may enable researchers to find new potential therapeutic targets in the management of allergic and autoimmune diseases.

Context Non-alcoholic fatty liver disease (NAFLD) is associated with insulin resistance (IR) and predicts type 2 diabetes. Currently, it is uncertain whether NAFLD may directly cause IR or vice versa. Objective To test the hypothesis that NAFLD is causally related to IR. Design and methods We performed a Mendelian Randomization (MR) in 904 obese children/adolescents, using a NAFLD-related genetic risk score (GRS) as instrumental variable. We assessed NAFLD by ultrasonography and IR by homeostasis model assessment (HOMA-IR). We also interrogated the MAGIC Consortium dataset of 46,186 adults to assess the association between PNPLA3 rs738409 (i.e., the most robust NAFLD-related polymorphism) and HOMA-IR, and we performed a two-sample MR with two large datasets to test reverse causation (HOMA-IR increasing the risk of NAFLD). Results NAFLD prevalence increased by 20% for every increase in the GRS (β-coefficient=0.20,p&0.001). NAFLD was associated with ln-HOMA-IR (β-coefficient=0.28,p&0.001). Thus, the expected increase in ln-HOMA-IR for every increase in the GRS (expected β-coefficient) was 0.056 (0.28*0.20), in the case of complete NAFLD-HOMA-IR causal association, and 0.042 in the case of 75% causality. In our cohort, the GRS did not predict ln-HOMA-IR (β-coefficient=0.007,p=0.75). In the MAGIC cohort, the PNPLA3 rs738409 did not associate with ln-HOMA-IR. The two-sample MR failed to show a causal association between ln-HOMA-IR and NAFLD. Conclusions Our study shows that genetically-influenced NAFLD does not increase HOMA-IR, and genetically-influenced HOMA-IR does not increase the risk of NAFLD. Shared pathogenic pathways or NAFLD subtypes not “captured” by our MR design might underpin the association between NAFLD and HOMA-IR.

Pediatric melanoma is a rare disease especially in children aged younger than 10 years old. Recent estimates report a rise of disease incidence in both adults and children. Diagnostic work-up is challenging in pediatric melanoma, as it displays a wide range of clinical presentations. Immunohistochemical biomarkers have been reported as predictors of malignancy in melanoma, however data specific to pediatric melanoma are poor. Our study aims to contribute to provide evidence of pediatric melanoma clinical features and differential diagnosis in this patient population. We describe our experience with a retrospective case series of pigmented skin lesions including malignant melanoma, atypical spitzoid tumor, and benign nevi in children and adolescents aged less than 16 years. We described the clinical and demographic characteristics of the cohort and evaluated the immunohistochemical expression of the PReferentially expressed Antigen in MElanoma (PRAME) for differential diagnosis of melanoma in children. The series displayed a similar distribution of melanoma between males and females, and the most common site of melanoma onset were the upper and lower limbs. In our cohort, PRAME was negative in most cases. Focal and slight positivity (from 1 to 5% of the neoplastic cells) was observed in four cases (two Spitz nevi and two atypical Spitz tumors). A moderate positivity in 25% of the neoplastic cells was observed in one case of atypical Spitz tumor. Immunohistochemical expression of PRAME might be useful in the differential diagnosis of malignant melanoma.

Laparoscopic surgery has been one of the most common procedures for abdominal surgery at pediatric age during the last few decades as it has several advantages compared to laparotomy, such as shorter hospital stays, less pain, and better cosmetic results. However, it is associated with both local and systemic modifications. Recent evidence demonstrated that carbon dioxide pneumoperitoneum might be modulated in terms of pressure, duration, temperature, and humidity to mitigate and modulate these changes. The aim of this study is to review the current knowledge about animal and human models investigating pneumoperitoneum-related biological and histological impairment. In particular, pneumoperitoneum is associated with local and systemic inflammation, acidosis, oxidative stress, mesothelium lining abnormalities, and adhesion development. Animal studies reported that an increase in pressure and time and a decrease in humidity and temperature might enhance the rate of comorbidities. However, to date, few studies were conducted on humans; therefore, this research field should be further investigated to confirm in experimental models and humans how to improve laparoscopic procedures in the spirit of minimally invasive surgeries.

We first investigated in obese children the protective role of the hydroxysteroid 17-beta dehydrogenase 13 (HSD17B13) rs72613567:TA variant in liver damage. Six hundred eighty-five obese children were genotyped for HSD17B13, patatin-like phospholipase domain containing 3 (PNPLA3), transmembrane 6 superfamily member 2 (TM6SF2), and membrane bound O-acyltransferase domain containing 7 (MBOAT7) polymorphisms and underwent anthropometrical, ultrasonographic, and biochemical evaluation. Indirect measurement of liver fibrosis (Pediatric NAFLD Fibrosis Index [PNFI]) was calculated. The population was clustered in 2 genetic risk groups based on the numbers of steatogenic alleles (low: carriers up to 3 risk alleles, high: 4–6 risk alleles). Carriers of the HSD17B13 rare A allele showed lower percentage of hepatic steatosis and both lower serum transaminase and PNFI levels than noncarriers, even after adjustments for confounders. These findings were also confirmed in both risk groups. We demonstrated the protective effect of the rs72613567:TA HSD17B13 variant in reducing liver damage in obese children regardless of genetic predisposition.