FAMILY HISTORY OF CANCER AND FAMILY HISTORY SCORES FOR ASSESSING THE LEVEL OF DISEASE RISK IN FAMILIES

In the last decades genetic factors are playing an increasingly important role in medical research, given the evidence for the existence of a heritable susceptibility for various diseases, including common cancers, based on reports of families with multiple affected relatives. Epidemiologists have utilized family history, usually of first-degree relatives, as a surrogate for genetic risk, aware that family history reflects the consequences of genetic susceptibilities, shared environment, and common behaviors. During my PhD I have dealt with two different aspects of family history, i.e., the role of family history of cancer in epidemiological cancer research (Chapter 1) and the use of complex family history score for assessing the level of disease risk in families (Chapter 2). In particular, I have systematically examined the extent to which a family history of cancer might be a risk factor for cancer within the same cancer site and across multiple cancer sites, analyzing a large and comprehensive dataset based on a network of integrated case-control studies, conducted in Italy and Switzerland since the early 90's. The database included 1468 cases of cancer of the oral cavity and pharynx, 198 of the rhinopharynx, 505 of the esophagus, 230 of the stomach, 2390 of the colorectum, 185 of the liver, 326 of the pancreas, 852 of the larynx, 3034 of the breast, 367 of the endometrium, 1031 of the ovary, 1294 of the prostate, 767 of the renal cell, and a total of 16022 corresponding controls. Unconditional multiple logistic regression models, adjusted for the major possible confounding factors, and a procedure for controlling for multiplicity using a false discovery rate were used. The risk of developing cancer at a particular site was increased, although not always significantly, in subjects with a first-degree relative affected by cancer at the same site, with odds ratios ranging from 1.4 for pancreatic cancer, to 7.4 for ovarian cancer. Several across sites associations emerged, some of which possibly due to shared environmental exposures or lifestyle practices among family members (e.g., alcohol, smoking, unhealthy diet, infections) or to the inheritance of one or more predisposing gene mutations (high penetrance gene mutations, such as BRCA1/2 in breast and ovarian cancer, and/or low penetrance polymorphisms, as those involved in carcinogens metabolism, such as GST genes in oral cancer) or to a combination of both. The analysis I performed confirmed that several associations were stronger for a younger age at diagnosis in relatives. A detailed discussion of the findings is reported in paragraph 4 of Chapter 1. In addition to the investigation of the role of family history of cancer in cancer etiology, I have performed a statistical evaluation of the performance of different family history scores to recommend the measure that performs best. Family history scores summarize familial information and are used for estimating the familiar risk, i.e. the level of risk for a particular disease among members of that family. The simplest and most common family history scores are the dichotomous measure indicator, positive in families that have at least one relative with the disease, the number of affected family members, and the proportion of affected relatives, which takes into account the size of the family. The other family history scores proposed in the literature are statistics that describe the deviation of the observed situation from the expected risk for each family. More detailed information on family members (affected and unaffected) as well as incidence rates of the diseases of interest in strata of selected covariates are needed to compute these more complex family history scores. To evaluate family history scores\u2019 performance I used two different complementary approaches: a data-derived approach, using data from the Italian HI-WATE study, with the aim of examining the power of various family history scores in predicting a particular diseases (i.e., colorectal cancer), and a simulation approach to evaluate their accuracy of predicting the true familial risk. From 200 simulations for 48 different settings, Reed\u2019s score and FHS2 seem to perform slightly better than the other scores. However, the simple proportion of affected relatives is not so far in terms of predictivity of the true familial risk. The use of this simple score seems therefore justified, at least until stronger evidence is brought for the advantages of using a more complex score

Exploring the link between diabetes and pancreatic cancer

Introduction: Epidemiological studies indicate an association between type 2 diabetes and pancreatic cancer but the complex and multidirectional relationship between them remains unclear. Areas covered: We summarized epidemiological evidence on diabetes and pancreatic cancer exploring the time-risk relationship. We described mechanisms linking long-standing diabetes to pancreatic cancer. We discussed pancreatic cancer-associated diabetes and its implication in the early detection of pancreatic cancer. Expert opinion: The markedly increased risk of pancreatic cancer in patients with new-onset diabetes compared with long-standing diabetes indicates a complex and bidirectional connection, with long-standing diabetes being a predisposing factor for pancreatic cancer (increasing the risk of the malignancy 1.5- to 2-fold) and new-onset diabetes an early manifestation of the tumour. Identifying clinical features and biomarkers to distinguish pancreatic cancer-associated diabetes from type 2 diabetes is an important goal to improve management and survival of this cancer. Imaging (MRI) for middle age patients with new-onset diabetes may be considered

Hybrid modeling of a biorefinery separation process to monitor short-term and long-term membrane fouling

Membrane filtration is commonly used in biorefineries to separate cells from fermentation broths containing the desired products. However, membrane fouling can cause short-term process disruption and long-term membrane degradation. The evolution of membrane resistance over time can be monitored to track fouling, but this calls for adequate sensors in the plant. This requirement might not be fulfilled even in modern biorefineries, especially when multiple, tightly interconnected membrane modules are used. Therefore, characterization of fouling in industrial facilities remains a challenge. In this study, we propose a hybrid modeling strategy to characterize both reversible and irreversible fouling in multi-module biorefinery membrane separation systems. We couple a linear data-driven model, to provide high-frequency estimates of trans-membrane pressures from the available measurements, with a simple nonlinear knowledge-driven model, to compute the resistances of the individual membrane modules. We test the proposed strategy using real data from the world's first industrial biorefinery manufacturing 1,4-bio-butanediol via fermentation of renewable raw materials. We show how monitoring of individual resistances, even when done by simple visual inspection, offers valuable insight on the reversible and irreversible fouling state of the membranes. We also discuss the advantage of the proposed approach, over monitoring trans-membrane pressures and permeate fluxes, from the standpoints of data variability, effect of process changes, interaction between module in multi-module systems, and fouling dynamics

Laryngeal mask airway in neonatal stabilization and transport: a retrospective study.

Laryngeal mask airway (LMA) may be considered by health caregivers of level I–II hospitals for neonatal resuscitation and stabilization before and during interhospital care, but literature provides little information on this aspect. This study reviewed the use of LMA during stabilization and transport in a large series of neonates. This is a retrospective study evaluating the use of LMA in infants who underwent emergency transport by the Eastern Veneto Neonatal Emergency Transport Service between January 2003 and December 2021. All data were obtained from transport registry, transport forms, and hospital charts. In total, 64/3252 transferred neonates (2%) received positive pressure ventilation with an LMA, with increasing trend over time (p = 0.001). Most of these neonates were transferred after birth (97%), due to a respiratory or neurologic disease (95%). LMA was used before the transport (n = 60), during the transport (n = 1), or both (n = 3). No device-related adverse effects were recorded. Sixty-one neonates (95%) survived and were discharged/transferred from the receiving center

Osteochondritis dissecans of the knee: Epidemiology, etiology, and natural history.

Osteochondritis dissecans of the knee is a disease that typically affects skeletally immature patients. Clinically manifested with knee pain, limping, and joint disfunction, this condition has remained misunderstood and undervalued for a long period. Although being a rare condition, its awareness is of utmost clinical interest because of the possible severe consequences it can bring when misrecognized or inadequately treated. Its etiology remains unclear and is still debated. Many theories have been proposed, including inflammation, local ischemia, subchondral ossification abnormalities, genetic factors, and repetitive mechanical microtrauma, with a likely interplay of the same. This review article aims to deliver and discuss current and up-to-date concepts on epidemiology, etiology, and natural history of this pediatric condition. Level of evidence: level V

Diabetes risk reduction diet and endometrial cancer risk

Diabetes increases endometrial cancer risk. We investigated the role of a diabetes risk reduction diet (DRRD) on the risk of endometrial cancer using data from a multicentric, Italian hospital-based case–control study (1992–2006) enrolling 454 histologically confirmed cases of endometrial cancer and 908 controls matched by age and center. We derived a DRRD score assigning higher scores for higher intakes of cereal fiber, fruit, coffee, polyunsaturated:saturated fatty acid ratio, and nuts and for lower glycemic load and lower intakes of red/processed meat and sugar-sweetened beverages/fruit juices. The odds ratios (OR) of endometrial cancer according to the DRRD score were derived by multiple conditional logistic regression models. The OR for high (DRRD score >24, i.e., third tertile) versus medium–low adherence to the DRRD was 0.73 (95% confidence interval, CI, 0.55–0.97). Similar results were observed after the exclusion of diabetic women (OR 0.75; 95% CI, 0.56–1.00) and allowance for total vegetable consumption (OR 0.80; 95% CI, 0.60–1.07). Inverse associations were observed in most of the analyzed subgroups. The OR for high DRRD combined with high vegetable consumption was 0.45 (95% CI, 0.28–0.73). Our results suggest that diets able to reduce diabetes risk may also reduce endometrial cancer risk. High vegetable consumption combined with high adherence to the DRRD may provide additional benefit in endometrial cancer prevention

PTX3 shapes profibrotic immune cells and epithelial/fibroblast repair and regeneration in a murine model of pulmonary fibrosis

The long pentraxin 3 (PTX3) is protective in different pathologies but was not analyzed in-depth in Idiopathic Pulmonary Fibrosis (IPF). Here, we have explored the influence of PTX3 in the bleomycin (BLM)-induced murine model of IPF by looking at immune cells (macrophages, mast cells, T cells) and stemness/regenerative markers of lung epithelium (SOX2) and fibro-blasts/myofibroblasts (CD44) at different time points that retrace the progression of the disease from onset at day 14, to full-blown disease at day 21, to incomplete regression at day 28. We took advantage of transgenic PTX3 overexpressing mice (Tie2-PTX3) and Ptx3 null ones (PTX3-KO) in which pulmonary fibrosis was induced. Our data have shown that PTX3 overexpression in Tie2-PTX3 compared to WT or PTX3-KO: reduced CD68+ and CD163+ macrophages and the Tryptase+ mast cells during the whole experimental time; on the contrary, CD4+ T cells are consistently present on day 14 and dramatically decreased on day 21; CD8+ T cells do not show significant differences on day 14, but are significantly reduced on day 21; SOX2 is reduced on days 14 and 21; CD44 is reduced on day 21. Therefore, PTX3 could act on the proimmune and fibrogenic microenvironment to prevent fibrosis in BLM-treated mice

Fruit and vegetables and cancer risk : a review of southern European studies

High intakes of fruit and vegetables may reduce the risk of cancer at several sites. Evidence has been derived mainly from case-control studies. We reviewed the relationship between consumption of vegetables and fruit and the risk of several common cancers in a network of Italian and Swiss case-control studies including over 10 000 cases of fourteen different cancers and about 17 000 controls. Data were suggestive of a protective role of vegetable intake on the risk of several common epithelial cancers. OR for the highest compared with the lowest levels of consumption ranged from 0·2 (larynx, oral cavity and pharynx) to 0·9 (prostate). Inverse associations were found for both raw and cooked vegetables, although for upper digestive tract cancers the former were somewhat stronger. Similar inverse associations were found for cruciferous vegetables. Frequent consumption of allium vegetables was also associated with reduced risk of several cancers. Fruit was a favourable correlate of the risk of several cancers, particularly of the upper digestive tract, with associations generally weaker than those reported for vegetables. A reduced risk of cancers of the digestive tract and larynx was found for high consumption of citrus fruit. Suggestive protections against several forms of cancer, mainly digestive tract cancers, were found for high consumption of apples and tomatoes. High intakes of fibres, flavonoids and proanthocyanidins were inversely related to various forms of cancer. In conclusion, data from our series of case-control studies suggested a favourable role of high intakes of fruit and vegetables in the risk of many common cancers, particularly of the digestive tract. This adds evidence to the indication that aspects of the Mediterranean diet may have a favourable impact not only on CVD, but also on several common (epithelial) cancers, particularly of the digestive tract

Adherence to the Mediterranean diet and nasopharyngeal cancer risk in Italy

Purpose: Few studies investigated the role of diet on nasopharyngeal cancer (NPC) risk in non-endemic areas. The aim of this study was to assess the association between adherence to the traditional Mediterranean diet and NPC risk in a southern European low-risk population. Methods: We conducted a hospital-based case-control study in Italy, including 198 histologically confirmed NPC cases and 594 matched controls. Dietary habits were collected by means of a validated food-frequency questionnaire, including 83 foods, food groups, or beverages. Adherence to the traditional Mediterranean diet was assessed through a Mediterranean Diet Score (MDS), based on nine dietary components characterizing this dietary profile, i.e., high intake of vegetables, fruits and nuts, cereals, legumes, and fish; low intake of dairy products and meat; high monounsaturated to saturated fatty acid ratio; and moderate alcohol intake. We estimated odds ratios (ORs) of NPC, and the corresponding 95% confidence intervals (CIs), for increasing MDS (i.e., increasing adherence) using multiple logistic regression models, adjusted for major confounding factors. Results: As compared to MDS 64 4, the ORs of NPC were 0.83 (95% CI: 0.54\u20131.25) for MDS of 5 and 0.66 (95% CI: 0.44\u20130.99) for MDS 65 6, with a significant trend of decreasing risk (p 0.043). The corresponding population attributable fraction was 22%, indicating that 22% of NPC cases in this population would be avoided by shifting all subjects to a score 656. Conclusions: Our study supports a favorable role of the Mediterranean diet on NPC risk