Nivolumab-induced hypothyroidism and selective pituitary insufficiency in a patient with lung adenocarcinoma: a case report and review of the literature.

Immune checkpoint blockade including programmed cell death 1 pathway inhibition with agents such as nivolumab is gaining ground in a wide array of malignancies, so far demonstrating significantly improved survival rates even in metastatic, often multiply pretreated settings. Although targeted in nature and generally well-tolerated compared with conventional anticancer treatments, these agents are often linked to a newly emerged group of adverse reactions, referred to as immune-related adverse events, which can also affect endocrine organs. This is a case report of a patient who received nivolumab for the treatment of recurrent metastatic non-small cell lung cancer and developed primary hypothyroidism and secondary adrenal insufficiency caused by selective pituitary dysfunction (with preservation of all other endocrine functions). After hormone replacement with daily administration of T4, T3 and hydrocortisone, the patient achieved complete recovery. Adequate characterisation of these rare yet potentially severe entities is essential for prompt diagnostic and therapeutic interventions that will permit us to fully benefit from these new agents' therapeutic potential.

Parental alcohol consumption and risk of leukemia in the offspring: a systematic review and meta-analysis.

Parental alcohol consumption before and during pregnancy has been linked to adverse outcomes in the offspring including leukemogenesis. We, therefore, aimed to systematically assess and quantitatively synthesize published data on the association of paternal consumption during preconception and maternal consumption during pregnancy with leukemia risk in childhood (0-14 years). Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we searched PubMed (until February 2016) and the reference lists of the relevant studies. Observational studies examining the association between parental alcohol consumption and childhood leukemia were considered eligible. Data extracted from 39 case-control studies (over 16 000 leukemia cases and 30 000 controls) were pooled and summary-effect estimates were calculated. Subgroup analyses were carried out by main acute leukemia type [lymphoblastic or myeloid), cytogenetics/genetic polymorphisms, and specific alcohol beverages. We found a statistically significant dose-response association of any level of maternal alcohol consumption compared with nondrinking during pregnancy exclusively with acute myeloid leukemia (AML) [odds ratio (OR)moderate consumption: 1.64, 95% confidence intervals (CIs): 1.23-2.17 and ORhigh consumption: 2.36, 95% CI: 1.60-3.49]. In contrast, no association of paternal preconception consumption with any leukemia type was noted. In beverage-specific analyses, only a positive association of maternal wine drinking with childhood AML was found, which was more pronounced in analyses including only studies on infant leukemia (ORwine: 2.12, 95% CI: 1.16-3.90). The largest ever meta-analysis shows a sizeable, statistically significant dose-response association of maternal alcohol consumption during index pregnancy with AML risk. Future research exploring the role of genetic polymorphisms is anticipated to shed light on the underlying pathophysiology.

Association of maternal and index child's diet with subsequent leukemia risk: A systematic review and meta analysis.

BACKGROUND: Exploring the effect of maternal and/or childhood diet on offspring leukemogenesis is challenging, given differences in food group categories, their potentially variable impact depending on time window of exposure and the multiple leukemia subtypes. We opted to quantitatively synthesize published data on the association of maternal/child diet with leukemia risk. METHODS: Medline was searched until June 30th, 2016 for eligible articles on the association of childhood leukemia with consumption of (i) food groups, excluding alcoholic and non-alcoholic beverages, and (ii) specific dietary supplements before/during index pregnancy and childhood. RESULTS: Eighteen studies of case-control design (N=11,720 cases/18,721 controls) were included, of which nine assessed maternal dietary components, five index child's and four both, mainly focusing on acute lymphoblastic leukemia (ALL). Statistically significant inverse estimates for ALL were found (2 studies, 413 cases, 490 controls) for fruit (OR: 0.81, 95% CI: 0.67, 0.99); vegetables (OR: 0.51, 95% CI: 0.28, 0.94); legumes (OR: 0.76, 95% CI: 0.62, 0.94); fish (OR: 0.27, 95% CI: 0.14, 0.53, among the 0-4year old; 2 studies 215 cases, 215 controls); preconception folic acid supplementation (OR: 0.69, 95%CI: 0.50-0.95; published meta analysis plus 2 studies, 3511 cases, 6816 controls); and use of vitamins during pregnancy (OR: 0.81, 95%CI: 0.74-0.88; published meta analysis plus one study, 5967 cases, 8876 controls). The associations (2 studies) of the remaining food groups and maternal dietary supplements consumption during pregnancy as well as of childhood diet and supplements intake (2-4 studies) were non significant. CONCLUSIONS: Maternal consumption of specific food groups comprising"healthy" items of the Mediterranean diet, preconception use of folic acid and intake of vitamins during pregnancy were associated with decreased ALL risk. Further research is needed, however preferably with homogeneous dietary information and data on immunophenotypic/cytogenetic subtypes to also explore the interaction of specific macro- and micronutrients intake with gene polymorphisms.

Maternal and childhood consumption of coffee, tea and cola beverages in association with childhood leukemia: a meta-analysis.

OBJECTIVE: To systematically review studies and meta-analyze the literature on the association of maternal and/or index child's coffee, tea, and cola consumption with subsequent development of childhood leukemia and its major subtypes. METHODS: Eligible studies were identified through a detailed algorithm and hand-search of eligible articles' references; thereafter, summary-effect estimates were calculated by leukemia subtype and dose-response meta-analyses were performed. RESULTS: Twelve case-control studies, comprising a total of 3649 cases and 5705 controls, were included. High maternal coffee consumption was positively associated with acute lymphoblastic leukemia (ALL; OR: 1.43, 95%CI: 1.22-1.68) and acute myeloid leukemia (AML; OR: 2.52, 95%CI: 1.59-3.57). Any or low to moderate maternal cola consumption was also positively associated with overall leukemia (AL) and ALL, A linear trend between coffee and cola consumption and childhood leukemia was observed in the dose-response analyses. On the contrary, low to moderate tea consumption was inversely associated with AL (OR: 0.85, 95%CI: 0.75-0.97), although the trend was non-significant. A null association between offspring's cola consumption and leukemia was noted. CONCLUSIONS: Our findings confirm the detrimental association between maternal coffee consumption and childhood leukemia risk and provide indications for a similar role of maternal cola intake. In contrast, an inverse association with tea was found, implying that other micronutrients contained in this beverage could potentially counterbalance the deleterious effects of caffeine. Further research should focus on the intake of specific micronutrients, different types of coffee and tea, specific immunophenotypes of the disease, and the modifying effect of genetic polymorphisms.

Nutrition in early life and risk of childhood leukemia: a case-control study in Greece.

PURPOSE: There is a paucity of findings concerning the role of diet in childhood leukemogenesis, whereas the results are equivocal and the studies heterogeneous with regard to food items examined. This case-control study investigates the association of childhood leukemia with food groups, macronutrient consumption, total energy intake and adherence to Mediterranean diet among children aged 5-14 years in Greece. METHODS: A total of 139 consecutive, incident leukemia cases out of which 121 were acute lymphoblastic leukemia were derived from the Nationwide Registry for Childhood Hematological Malignancies along with one : one age- and gender-matched hospital controls. Information on socio-demographic, maternal and child variables and dietary habits was obtained through in-person interviews with the guardians/children. Multiple logistic regression was performed with adjustment for birth weight and possible confounding variables. RESULTS: Higher consumption of added lipids was associated with an increased risk of childhood leukemia, whereas consumption of milk and dairy products with reduced risk. From the macronutrient analysis, a borderline trend linking high protein intake with reduced childhood leukemia risk was observed. CONCLUSION: Consumption of milk and dairy products in the first year of life may protect against childhood leukemia possibly through vitamin D actions, while added lipids may increase the risk through various mechanisms. These results offer a holistic evaluation of children's nutrition and suggest that dietary habits in the early years of life may contribute to the prevention of childhood leukemia.

Maternal diet and acute lymphoblastic leukemia in young children.

Because leukemia clone-specific chromosomal abnormalities are present at birth in children who later develop leukemia, it has been hypothesized that maternal factors, including nutrition during pregnancy, might affect the risk of acute lymphoblastic leukemia (ALL) among young children. We have evaluated this hypothesis in a nationwide case-control study of ALL among children ages 12 to 59 months in Greece. Children (n=131) with ALL were gender and age matched to control children (n=131) hospitalized for minor conditions between 1999 and 2003. The mothers of the children were interviewed in person by trained interviewers who used an extensive food frequency questionnaire addressing diet during the index pregnancy. The analysis was done by modeling the data through conditional logistic regression, also controlling for total energy intake and possible confounding factors. Odds ratios (OR) and 95% confidence intervals (95% CI) were expressed per quintile increase of maternal intake during pregnancy of the specified food group. The risk of ALL in the offspring was lower with increased maternal intake of fruits (OR, 0.72; 95% CI, 0.57-0.91), vegetables (OR, 0.76; 95% CI, 0.60-0.95), and fish and seafood (OR, 0.72; 95% CI, 0.59-0.89) and higher with increased maternal intake of sugars and syrups (OR, 1.32; 95% CI, 1.05-1.67) and meat and meat products (OR, 1.25; 95% CI, 1.00-1.57). Children of women who tend to consume during their pregnancies what is currently considered to be a healthy diet maybe at lower risk of ALL.

The mosaic of equestrian-related injuries in Greece.

BACKGROUND: This study aims to estimate the burden and describe the profile of equestrian injuries in Greece, where horses, donkeys, and mules are still used in agriculture and where horse riding is a popular leisure activity. METHODS: Prospectively collected information on 140,823 injuries reported in the national Emergency Department Injury Surveillance System was examined and 244 equestrian-related injuries that occurred during farming, equestrian sports, or horse racing were analyzed. RESULTS: The estimated countrywide injury incidence for farming and equestrian sports combined was 21 per 100,000 person-years, but it was 160 times higher for horse-racing personnel. Men had higher rates of racing injuries and women had higher rates of equestrian sport injuries. Fractures accounted for 39.0% of injuries in horse racing and 30.5% in farming; head injuries accounted for approximately 50% of injuries among farmers. Farming injuries were more serious, with 25% requiring hospitalization. Analysis through the Barell matrix pointed to the role of spurs in the causation of ankle fractures and dislocations and the likely contribution of helmets in preventing traumatic brain injuries. CONCLUSION: Equestrian-related injuries are a serious but underappreciated health problem and merit targeted prevention efforts for each category affected.