Aggregation of childhood leukemia in geographic areas of Greece)

A total of 872 children aged up to 14 years, who were diagnosed withleukemia in Greece during the decade 1980-89, were allocated by place ofresidence to the 601 administrative districts of the country. Evaluation ofspatial clustering was done using the Potthoff-Whittinghill method, whichvalidly assesses heterogeneity of leukemia risk among districts with variableexpected numbers of cases. There was highly significant evidence for spatialclustering occurring particularly among children living in urban and, to alesser extent, semi-urban areas. The evidence was stronger for childrenyounger than 10 years old, applied also to children in different five-yearage groups, and persisted when cases of acute lymphoblastic leukemia wereanalyzed separately. These findings provide support to the hypothesis thatlocalized environmental exposures could contribute to the etiology ofchildhood leukemia, but they cannot distinguish between exposures of physicalor chemical nature, nor can they exclude socially conditioned patterns ofexposure to infectious agents.     

The relationship between dietary fat intake and risk of colorectal cancer: evidence from the combined analysis of 13 case-control studies

The objective of this study was to examine the effects of the intakeof dietary fat upon colorectal cancer risk in a combined analysis of datafrom 13 case-control studies previously conducted in populations withdiffering colorectal cancer rates and dietary practices. Original datarecords for 5,287 cases of colorectal cancer and 10,470 controls werecombined. Logistic regression analysis was used to estimate odds ratios (OR)for intakes of total energy, total fat and its components, and cholesterol.Positive associations with energy intake were observed for 11 of the 13studies. However, there was little, if any, evidence of anyenergy-independent effect of either total fat with ORs of 1.00, 0.95, 1.01,1.02, and 0.92 for quintiles of residuals of total fat intake (P trend =0.67) or for saturated fat with ORs of 1.00, 1.08, 1.06, 1.21, and 1.06 (Ptrend = 0.39). The analysis suggests that, among these case-control studies,there is no energy-independent association between dietary fat intake andrisk of colorectal cancer. It also suggests that simple substitution of fatby other sources of calories is unlikely to reduce meaningfully the risk ofcolorectal cancer.     

Randomized phase IIB trial of BLP25 liposome vaccine in stage IIIB and IV non-small-cell lung cancer.

PURPOSE: To evaluate the effect of BLP25 liposome vaccine (L-BLP25) on survival and toxicity in patients with stage IIIB and IV non-small-cell lung cancer (NSCLC). Secondary objectives included health-related quality of life (QOL) and immune responses elicited by L-BLP25. PATIENTS AND METHODS: Patients with an Eastern Cooperative Oncology Group performance status of 0 to 2 and stable or responding stage IIIB or IV NSCLC after any first-line chemotherapy were prestratified by stage and randomly assigned to either L-BLP25 plus best supportive care (BSC) or BSC alone. Patients in the L-BLP25 arm received a single intravenous dose of cyclophosphamide 300 mg/m2 followed by eight weekly subcutaneous immunizations with L-BLP25 (1,000 microg). Subsequent immunizations were administered at 6-week intervals. RESULTS: The survival results indicate a median survival time of 4.4 months longer for patients randomly assigned to the L-BLP25 arm (88 patients) compared with patients assigned to the BSC arm (83 patients; adjusted hazard ratio [HR] = 0.739; 95% CI, 0.509 to 1.073; P = .112). The greatest effect was observed in stage IIIB locoregional (LR) patients, for whom the median survival time for the L-BLP25 arm has not yet been reached compared with 13.3 months for the BSC arm (adjusted HR = 0.524; 95% CI, 0.261 to 1.052; P = .069). No significant toxicity was observed. QOL was maintained longer in patients on the L-BLP25 arm. CONCLUSION: L-BLP25 maintenance therapy in patients with advanced NSCLC is feasible with minimal toxicity. The survival difference of 4.4 months observed with the vaccine did not reach statistical significance. In the subgroup of patients with stage IIIB LR disease, a strong trend in 2-year survival in favor of L-BLP25 was observed.     

A pooled analysis of case-control studies of thyroid cancer¶ I. Methods

Objective: Because the etiology of thyroid cancer is not well described, we conducted a pooled analysis of all published case- control studies, as well as two identified unpublished studies. This paper describes the major characteristics of the 14 studies included in the analysis, as well as the statistical methods employed. Four studies were conducted in the United States (1 each in Washington State, California, Connecticut and Hawaii), 8 in Europe (3 in Sweden, 2 in Norway, 1 in Switzerland, 1 in Italy and 1 in Greece), and 2 in Asia (1 in China and 1 in Japan).Methods: The original datasets were obtained and restructured in a uniform format. Data on socio-demographic characteristics, anthropometric measures, smoking and alcohol consumption, history of benign thyroid diseases and of other selected medical conditions and treatments, family history of cancer and of benign thyroid conditions, occupation, residence in endemic goitre areas, and dietary habits were analyzed. For women, we also analyzed menstrual and reproductive factors and use of female hormones. Radiotherapy and, in Japan, exposure to the A-bombs were considered as potential confounding factors.Results: A total of 2,725 cases (2,247 females and 478 males) and 4,776 controls (3,699 females and 1,077 males) were included in this study. Of the cases, 79% were classified as papillary thyroid carcinomas, 14% as follicular, 2% medullary, 1% anaplastic, 1% other histologies, and 3% histological type unknown. Each of the datasets was checked for outliers and consistency. Data were analysed separately by study center, gender, and the two major histologic types (papillary, follicular). Frequency tables and simple statistics were computed for each variable under study. Conditional logistic regression was used to compute odds ratios. For matched studies, the original matching was preserved, whereas, for unmatched ones, five-year age groups were used for matching. Study-specific analyses were computed, and then the data from all the studies were pooled conditioning on study. Heterogeneity between studies, geographic areas and study designs was assessed, and the modifying effect of age was also evaluated.     

Exclusive Breastfeeding for at Least Four Months Is Associated with a Lower Prevalence of Overweight and Obesity in Mothers and Their Children after 2–5 Years from Delivery

Introduction: Obesity is a current public health concern. Higher body weight is influenced by genetic and environmental parameters, and their interplay and is associated with a greater risk for several chronic diseases. Breastfeeding has been suggested as a preventive measure against obesity, which can further reduce long-term negative health outcomes for both women and children. Aim: The aim of the present study was to evaluate the role of breastfeeding on maternal and childhood overweight and obesity. Materials and Methods: This is a cross-sectional study conducted on 2515 healthy mothers and their children, aged 2–5 years, enrolled from nine different Greek rural and urban regions. Validated, standardized questionnaires were administrated that included anthropometric indices, socio-demographic characteristics of mothers and children, as well as breastfeeding practices. Results: Overall, 68% of participated women exclusively breastfed their children for at least 4 months. Mothers that exclusively breastfed showed a significantly lower prevalence of overweight and obesity after 2–5 years from delivery (p < 0.0001). Children that had exclusively been breastfed showed a significantly lower prevalence of overweight and obesity at the age of 2–5 years (p < 0.0001). Using multivariate regression analysis, exclusive breastfeeding for at least 4 months was associated with a two-fold lower risk for maternal and childhood overweight and obesity after 2–5 years from delivery, independent from maternal age, educational and economic status, and smoking habits (p < 0.0001). Conclusion: Exclusive breastfeeding for at least 4 months had a positive effect on childhood overweight and obesity, also contributing beneficially to post-natal maternal weight control. The beneficial effects of breastfeeding should be communicated to future and new mothers, while supportive actions for all mothers to initiate and continue breastfeeding their offspring should be implemented.     

PROTEIN AI Advisor: A Knowledge-Based Recommendation Framework Using Expert-Validated Meals for Healthy Diets

AI-based software applications for personalized nutrition have recently gained increasing attention to help users follow a healthy lifestyle. In this paper, we present a knowledge-based recommendation framework that exploits an explicit dataset of expert-validated meals to offer highly accurate diet plans spanning across ten user groups of both healthy subjects and participants with health conditions. The proposed advisor is built on a novel architecture that includes (a) a qualitative layer for verifying ingredient appropriateness, and (b) a quantitative layer for synthesizing meal plans. The first layer is implemented as an expert system for fuzzy inference relying on an ontology of rules acquired by experts in Nutrition, while the second layer as an optimization method for generating daily meal plans based on target nutrient values and ranges. The system’s effectiveness is evaluated through extensive experiments for establishing meal and meal plan appropriateness, meal variety, as well as system capacity for recommending meal plans. Evaluations involved synthetic data, including the generation of 3000 virtual user profiles and their weekly meal plans. Results reveal a high precision and recall for recommending appropriate ingredients in most user categories, while the meal plan generator achieved a total recommendation accuracy of 92% for all nutrient recommendations.     

Immunotherapy for advanced hepatocellular carcinoma: From clinical trials to real-world data and future advances

Hepatocellular carcinoma (HCC) is a leading cause of cancer-associated mortality worldwide. HCC is an inflammation-associated immunogenic cancer that frequently arises in chronically inflamed livers. Advanced HCC is managed with systemic therapies; the tyrosine kinase inhibitor (TKI) sorafenib has been used in 1^st-line setting since 2007. Immunotherapies have emerged as promising treatments across solid tumors including HCC for which immune checkpoint inhibitors (ICIs) are licensed in 1^st- and 2^nd-line treatment setting. The treatment field of advanced HCC is continuously evolving. Several clinical trials are investigating novel ICI candidates as well as new ICI regimens in combination with other therapeutic modalities including systemic agents, such as other ICIs, TKIs, and anti-angiogenics. Novel immunotherapies including adoptive cell transfer, vaccine-based approaches, and virotherapy are also being brought to the fore. Yet, despite advances, several challenges persist. Lack of real-world data on the use of immunotherapy for advanced HCC in patients outside of clinical trials constitutes a main limitation hindering the breadth of application and generalizability of data to this larger and more diverse patient cohort. Consequently, issues encountered in real-world practice include patient ineligibly for immunotherapy because of contraindications, comorbidities, or poor performance status; lack of response, efficacy, and safety data; and cost-effectiveness. Further real-world data from high-quality large prospective cohort studies of immunotherapy in patients with advanced HCC is mandated to aid evidence-based clinical decision-making. This review provides a critical and comprehensive overview of clinical trials and real-world data of immunotherapy for HCC, with a focus on ICIs, as well as novel immunotherapy strategies underway.     

Antitubercular activity of Arctium lappa and Tussilago farfara extracts and constituents

Ethnopharmacological relevance

Arctium lappa and Tussilago farfara (Asteraceae) are two plant species used traditionally as antitubercular remedies. The aim of this study was (i) to screen Arctium lappa and Tussilago farfara extracts for activity against Mycobacterium tuberculosis and (ii) to isolate and identify the compound(s) responsible for this reputed anti-TB effect.

Materials and methods

The activity of extracts and isolated compounds was determined against Mycobacterium tuberculosis H₃₇R_v using a high throughput spot culture growth inhibition (HT-SPOTi) assay.

Results

The n-hexane extracts of both plants, the ethyl acetate extract of Tussilago farfara and the dichloromethane phase derived from the methanol extract of Arctium lappa displayed antitubercular activity (MIC 62.5 μg/mL). Further chemical investigation of Arctium lappa led to the isolation of n-nonacosane (1), taraxasterol acetate (2), taraxasterol (3), a (1:1) mixture of β sitosterol/stigmasterol (4), isololiolide (5), melitensin (6), trans-caffeic acid (7), kaempferol (8), quercetin (9), kaempferol-3-O-glucoside (10). Compounds isolated from Tussilago farfara were identified as a (1:1) mixture of β sitosterol/stigmasterol (4), trans-caffeic acid (7), kaempferol (8), quercetin (9), kaempferol-3-O-glucoside (10), loliolide (11), a (4:1) mixture of p-coumaric acid/4-hydroxybenzoic acid (12), p-coumaric acid (13). All compounds were identified following analyses of their physicochemical and spectroscopic data (MS, ¹H and ¹³C-NMR) and by comparison with published data. This is the first report of the isolation of n-nonacosane (1), isololiolide (5), melitensin (6) and kaempferol-3-O-glucoside (10) from Arctium lappa, and of loliolide (11) from Tussilago farfara. Amongst the isolated compounds, the best activity was observed for p-coumaric acid (13) (MIC 31.3 μg/mL or 190.9 μM) alone and in mixture with 4-hydroxybenzoic acid (12) (MIC 62.5 μg/mL).

Conclusions

The above results provide for the first time some scientific evidence to support, to some extent, the ethno-medicinal use of Arctium lappa and Tussilago farfara as traditional antitubercular remedies.     

Fetal stroke and cerebrovascular disease: Advances in understanding from lenticulostriate and venous imaging,alloimmune thrombocytopaenia and monochorionic twins

Fetal stroke is an important cause of cerebral palsy but is difficult to diagnose unless imaging is undertaken in pregnancies at risk because of known maternal or fetal disorders. Fetal ultrasound or magnetic resonance imaging may show haemorrhage or ischaemic lesions including multicystic encephalomalacia and focal porencephaly. Serial imaging has shown the development of malformations including schizencephaly and polymicrogyra after ischaemic and haemorrhagic stroke. Recognised causes of haemorrhagic fetal stroke include alloimmune and autoimmune thrombocytopaenia, maternal and fetal clotting disorders and trauma but these are relatively rare. It is likely that a significant proportion of periventricular and intraventricular haemorrhages are of venous origin. Recent evidence highlights the importance of arterial endothelial dysfunction, rather than thrombocytopaenia, in the intraparenchymal haemorrhage of alloimmune thrombocytopaenia. In the context of placental anastomoses, monochorionic diamniotic twins are at risk of twin twin transfusion syndrome (TTTS), or partial forms including Twin Oligohydramnios Polyhydramnios Sequence (TOPS), differences in estimated weight (selective Intrauterine growth Retardation; sIUGR), or in fetal haemoglobin (Twin Anaemia Polycythaemia Sequence; TAPS). There is a very wide range of ischaemic and haemorrhagic injury in a focal as well as a global distribution. Acute twin twin transfusion may account for intraventricular haemorrhage in recipients and periventricular leukomalacia in donors but there are additional risk factors for focal embolism and cerebrovascular disease. The recipient has circulatory overload, with effects on systemic and pulmonary circulations which probably lead to systemic and pulmonary hypertension and even right ventricular outflow tract obstruction as well as the polycythaemia which is a risk factor for thrombosis and vasculopathy. The donor is hypovolaemic and has a reticulocytosis in response to the anaemia while maternal hypertension and diabetes may influence stroke risk. Understanding of the mechanisms, including the role of vasculopathy, in well studied conditions such as alloimmune thrombocytopaenia and monochorionic diamniotic twinning may lead to reduction of the burden of antenatally sustained cerebral palsy.