Enteral feeding of intrauterine growth restriction preterm infants: theoretical risks and practical implications

Intrauterine growth restriction (IUGR) infants are thought to have impaired gut function after birth secondary to intrauterine redistribution of the blood flow, due to placental insufficiency, with a consequent reduction of gut perfusion. For this reason, infants complicated by IUGR have been considered at higher risk of feeding intolerance. Postnatal evaluation of splanchnic perfusion, through Doppler of the superior mesenteric artery, and of splanchnic oxygenation, through near infrared spectroscopy measurements, may be useful in evaluating the persistence (or not) of the redistribution of blood flow occurred in utero

MicroRNA-21/PDCD4 proapoptotic signaling from circulating CD34+ cells to vascular endothelial cells:a potential contributor to adverse cardiovascular outcomes in patients with critical limb ischemia

Dataset related to the article with title: MicroRNA-21/PDCD4 proapoptotic signaling from circulating CD34+ cells to vascular endothelial cells: a potential contributor to adverse cardiovascular outcomes in patients with critical limb ischemia By:Gaia Spinetti1, Elena Sangalli1, Elena Tagliabue1, Davide Maselli1, Ornella Colpani1, David Ferland-McCollough2, Franco Carnelli1, Patrizia Orlando1, Agostino Paccagnella3, Anna Furlan3, Piero Maria Stefani3, Luisa Sambado3, Maria Sambataro3, and Paolo Madeddu2. 1IRCCS MultiMedica, Milan, Italy; 2University of Bristol, Bristol, UK, 3Ca Foncello Hospital, Treviso, Italy. Diabetes Care. 2020 Jul;43(7):1520-1529. doi: 10.2337/dc19-2227. Epub 2020 May 1. Abstract Objective. In patients with type 2 diabetes (T2D) and critical limb ischemia (CLI), migration of circulating CD34+ cells predicted cardiovascular mortality at 18 months post-revascularization. This study aimed to provide long-term validation and mechanistic understanding of the biomarker. Research Design and Methods. The association between CD34+ cell migration and cardiovascular mortality was reassessed at 6 years post-revascularization. In a new series of T2D-CLI and control subjects, immuno-sorted bone marrow (BM)-CD34+ cells were profiled for microRNA expression and assessed for apoptosis and angiogenesis activity. The differentially regulated microRNA-21, and its pro-apoptotic target PDCD4, were titrated to verify their contribution in transferring damaging signals from CD34+ cells to endothelial cells. Results. Multivariable regression analysis confirmed CD34+ cell migration forecasts long-term cardiovascular mortality. CD34+ cells from T2D-CLI patients were more apoptotic and less proangiogenic than controls and featured microRNA-21 downregulation, modulation of several long non-coding RNAs acting as microRNA-21 sponges, and upregulation of the microRNA-21 proapoptotic target PDCD4. Silencing miR-21 in control CD34+ cells phenocopied the T2D-CLI cell behavior. In coculture, T2D-CLI CD34+ cells imprinted naïve endothelial cells, increasing apoptosis, reducing network formation, and modulating the TUG1 sponge/microRNA-21/PDCD4 axis. Silencing PDCD4 or scavenging ROS protected endothelial cells from the negative influence of T2D-CLI CD34+ cells Conclusions. Migration of CD34+ cells predicts long-term cardiovascular mortality in T2D-CLI patients. An altered paracrine signalling conveys anti-angiogenic and pro-apoptotic features from CD34+ cells to the endothelium. This damaging interaction may increase the risk for life-threatening complications

Anthropometric characteristics and non-Hodgkin’s lymphoma and multiple myeloma risk in the European Prospective Investigation into Cancer and Nutrition (EPIC)

Background: The incidences of non-Hodgkin's lymphoma and multiple myeloma are increasing steadily. It has been hypothesized that this may be due, in part, to the parallel rising prevalence of obesity. It is biologically plausible that anthropometric characteristics can infuence the risk of non-Hodgkin's lymphoma and multiple myeloma. Design and Methods: In the context of the European Prospective Investigation into Cancer and Nutrition (EPIC), anthropometric characteristics were assessed in 371,983 cancer-free individuals at baseline. During the 8.5 years of follow-up, 1,219 histologically confirmed incident cases of non-Hodgkin's lymphoma and multiple myeloma occurred in 609 men and 610 women. Gender-specific proportional hazards models were used to estimate relative risks and 95% confidence intervals (95% CI) of development of non-Hodgkin's lymphoma and multiple myeloma in relation to the anthropometric characteristics. Results: Height was associated with overall non-Hodgkin's lymphoma and multiple myeloma in women (RR 1.50,95% CI 1.14-1.98) for highest versus lowest quartile; p-trend <0.01) but not in men. Neither obesity (weight and body mass index) nor abdominal fat (waist-to-hip ratio, waist or hip circumference) measures were positively associated with overall non-Hodgkin's lymphoma and multiple myeloma. Relative risks for highest versus lowest body mass index quartile were 1.09 (95% CI 0.85-1.38) and 0.92 (95% CI 0.71-1.19) for men and women, respectively. Women in the upper body mass index quartile were at greater risk of diffuse large B-cell lymphoma (RR 2.18, 95% CI 1.05-4.53) and taller women had an elevated risk of follicular lymphoma (RR 1.25, 95% CI 0.59-2.62). Among men, height and body mass index were non-significantly, positively related to follicular lymphoma. Multiple myeloma risk alone was elevated for taller women (RR 2.34, 95% CI 1.29-4.21) and heavier men (RR 1.77, 95% CI 1.02-3.05). Conclusions: The EPIC analyses support an association between height and overall non-Hodgkin's lymphoma and multiple myeloma among women and suggest heterogeneous subtype associations. This is one of the first prospective studies focusing on central adiposity and non-Hodgkin's lymphoma subtypes

The Italian Network for Tumor Biotherapy (NIBIT): Getting together to push the field forward

As for a consolidated tradition, the 5th annual meeting of the Italian Network for Cancer Biotherapy took place in the Certosa of Pontignano, a Tuscan monastery, on September 20–22, 2007. The congress gathered more than 40 Italian leading groups representing academia, biotechnology and pharmaceutical industry. Aim of the meeting was to share new advances in cancer bio-immunotherapy and to promote their swift translation from pre-clinical research to clinical applications. Several topics were covered including: a) molecular and cellular mechanisms of tumor escape; b) therapeutic antibodies and recombinant constructs; c) clinical trials up-date and new programs; d) National Cooperative Networks and their potential interactions; e) old and new times in cancer immunology, an "amarcord". Here, we report the main issues discussed during the meeting

Seeing touches early in life

Addabbo M, Longhi E, Bolognini N, et al. Seeing touches early in life. PLoS ONE. 2015;10(9): e0134549

The Pyrimidine Nucleotide Biosynthetic Pathway Modulates Production of Biofilm Determinants in Escherichia coli

Bacteria are often found in multicellular communities known as biofilms, which constitute a resistance form against environmental stresses. Extracellular adhesion and cell aggregation factors, responsible for bacterial biofilm formation and maintenance, are tightly regulated in response to physiological and environmental cues. We show that, in Escherichia coli, inactivation of genes belonging to the de novo uridine monophosphate (UMP) biosynthetic pathway impairs production of curli fibers and cellulose, important components of the bacterial biofilm matrix, by inhibiting transcription of the csgDEFG operon, thus preventing production of the biofilm master regulator CsgD protein. Supplementing growth media with exogenous uracil, which can be converted to UMP through the pyrimidine nucleotide salvage pathway, restores csgDEFG transcription and curli production. In addition, however, exogenous uracil triggers cellulose production, particularly in strains defective in either carB or pyrB genes, which encode enzymes catalyzing the first steps of de novo UMP biosynthesis. Our results indicate the existence of tight and complex links between pyrimidine metabolism and curli/cellulose production: transcription of the csgDEFG operon responds to pyrimidine nucleotide availability, while cellulose production is triggered by exogenous uracil in the absence of active de novo UMP biosynthesis. We speculate that perturbations in the UMP biosynthetic pathways allow the bacterial cell to sense signals such as starvation, nucleic acids degradation, and availability of exogenous pyrimidines, and to adapt the production of the extracellular matrix to the changing environmental conditions

ITALIAN CANCER FIGURES - REPORT 2015: The burden of rare cancers in Italy = I TUMORI IN ITALIA - RAPPORTO 2015: I tumori rari in Italia

OBJECTIVES: This collaborative study, based on data collected by the network of Italian Cancer Registries (AIRTUM), describes the burden of rare cancers in Italy. Estimated number of new rare cancer cases yearly diagnosed (incidence), proportion of patients alive after diagnosis (survival), and estimated number of people still alive after a new cancer diagnosis (prevalence) are provided for about 200 different cancer entities. MATERIALS AND METHODS: Data herein presented were provided by AIRTUM population- based cancer registries (CRs), covering nowadays 52% of the Italian population. This monograph uses the AIRTUM database (January 2015), which includes all malignant cancer cases diagnosed between 1976 and 2010. All cases are coded according to the International Classification of Diseases for Oncology (ICD-O-3). Data underwent standard quality checks (described in the AIRTUM data management protocol) and were checked against rare-cancer specific quality indicators proposed and published by RARECARE and HAEMACARE (www.rarecarenet.eu; www.haemacare.eu). The definition and list of rare cancers proposed by the RARECAREnet "Information Network on Rare Cancers" project were adopted: rare cancers are entities (defined as a combination of topographical and morphological codes of the ICD-O-3) having an incidence rate of less than 6 per 100,000 per year in the European population. This monograph presents 198 rare cancers grouped in 14 major groups. Crude incidence rates were estimated as the number of all new cancers occurring in 2000-2010 divided by the overall population at risk, for males and females (also for gender-specific tumours).The proportion of rare cancers out of the total cancers (rare and common) by site was also calculated. Incidence rates by sex and age are reported. The expected number of new cases in 2015 in Italy was estimated assuming the incidence in Italy to be the same as in the AIRTUM area. One- and 5-year relative survival estimates of cases aged 0-99 years diagnosed between 2000 and 2008 in the AIRTUM database, and followed up to 31 December 2009, were calculated using complete cohort survival analysis. To estimate the observed prevalence in Italy, incidence and follow-up data from 11 CRs for the period 1992-2006 were used, with a prevalence index date of 1 January 2007. Observed prevalence in the general population was disentangled by time prior to the reference date (≤2 years, 2-5 years, ≤15 years). To calculate the complete prevalence proportion at 1 January 2007 in Italy, the 15-year observed prevalence was corrected by the completeness index, in order to account for those cancer survivors diagnosed before the cancer registry activity started. The completeness index by cancer and age was obtained by means of statistical regression models, using incidence and survival data available in the European RARECAREnet data. RESULTS: In total, 339,403 tumours were included in the incidence analysis. The annual incidence rate (IR) of all 198 rare cancers in the period 2000-2010 was 147 per 100,000 per year, corresponding to about 89,000 new diagnoses in Italy each year, accounting for 25% of all cancer. Five cancers, rare at European level, were not rare in Italy because their IR was higher than 6 per 100,000; these tumours were: diffuse large B-cell lymphoma and squamous cell carcinoma of larynx (whose IRs in Italy were 7 per 100,000), multiple myeloma (IR: 8 per 100,000), hepatocellular carcinoma (IR: 9 per 100,000) and carcinoma of thyroid gland (IR: 14 per 100,000). Among the remaining 193 rare cancers, more than two thirds (No. 139) had an annual IR &lt;0.5 per 100,000, accounting for about 7,100 new cancers cases; for 25 cancer types, the IR ranged between 0.5 and 1 per 100,000, accounting for about 10,000 new diagnoses; while for 29 cancer types the IR was between 1 and 6 per 100,000, accounting for about 41,000 new cancer cases. Among all rare cancers diagnosed in Italy, 7% were rare haematological diseases (IR: 41 per 100,000), 18% were solid rare cancers. Among the latter, the rare epithelial tumours of the digestive system were the most common (23%, IR: 26 per 100,000), followed by epithelial tumours of head and neck (17%, IR: 19) and rare cancers of the female genital system (17%, IR: 17), endocrine tumours (13% including thyroid carcinomas and less than 1% with an IR of 0.4 excluding thyroid carcinomas), sarcomas (8%, IR: 9 per 100,000), central nervous system tumours and rare epithelial tumours of the thoracic cavity (5%with an IR equal to 6 and 5 per 100,000, respectively). The remaining (rare male genital tumours, IR: 4 per 100,000; tumours of eye, IR: 0.7 per 100,000; neuroendocrine tumours, IR: 4 per 100,000; embryonal tumours, IR: 0.4 per 100,000; rare skin tumours and malignant melanoma of mucosae, IR: 0.8 per 100,000) each constituted &lt;4% of all solid rare cancers. Patients with rare cancers were on average younger than those with common cancers. Essentially, all childhood cancers were rare, while after age 40 years, the common cancers (breast, prostate, colon, rectum, and lung) became increasingly more frequent. For 254,821 rare cancers diagnosed in 2000-2008, 5-year RS was on average 55%, lower than the corresponding figures for patients with common cancers (68%). RS was lower for rare cancers than for common cancers at 1 year and continued to diverge up to 3 years, while the gap remained constant from 3 to 5 years after diagnosis. For rare and common cancers, survival decreased with increasing age. Five-year RS was similar and high for both rare and common cancers up to 54 years; it decreased with age, especially after 54 years, with the elderly (75+ years) having a 37% and 20% lower survival than those aged 55-64 years for rare and common cancers, respectively. We estimated that about 900,000 people were alive in Italy with a previous diagnosis of a rare cancer in 2010 (prevalence). The highest prevalence was observed for rare haematological diseases (278 per 100,000) and rare tumours of the female genital system (265 per 100,000). Very low prevalence (&lt;10 prt 100,000) was observed for rare epithelial skin cancers, for rare epithelial tumours of the digestive system and rare epithelial tumours of the thoracic cavity. COMMENTS: One in four cancers cases diagnosed in Italy is a rare cancer, in agreement with estimates of 24% calculated in Europe overall. In Italy, the group of all rare cancers combined, include 5 cancer types with an IR&gt;6 per 100,000 in Italy, in particular thyroid cancer (IR: 14 per 100,000).The exclusion of thyroid carcinoma from rare cancers reduces the proportion of them in Italy in 2010 to 22%. Differences in incidence across population can be due to the different distribution of risk factors (whether environmental, lifestyle, occupational, or genetic), heterogeneous diagnostic intensity activity, as well as different diagnostic capacity; moreover heterogeneity in accuracy of registration may determine some minor differences in the account of rare cancers. Rare cancers had worse prognosis than common cancers at 1, 3, and 5 years from diagnosis. Differences between rare and common cancers were small 1 year after diagnosis, but survival for rare cancers declined more markedly thereafter, consistent with the idea that treatments for rare cancers are less effective than those for common cancers. However, differences in stage at diagnosis could not be excluded, as 1- and 3-year RS for rare cancers was lower than the corresponding figures for common cancers. Moreover, rare cancers include many cancer entities with a bad prognosis (5-year RS &lt;50%): cancer of head and neck, oesophagus, small intestine, ovary, brain, biliary tract, liver, pleura, multiple myeloma, acute myeloid and lymphatic leukaemia; in contrast, most common cancer cases are breast, prostate, and colorectal cancers, which have a good prognosis. The high prevalence observed for rare haematological diseases and rare tumours of the female genital system is due to their high incidence (the majority of haematological diseases are rare and gynaecological cancers added up to fairly high incidence rates) and relatively good prognosis. The low prevalence of rare epithelial tumours of the digestive system was due to the low survival rates of the majority of tumours included in this group (oesophagus, stomach, small intestine, pancreas, and liver), regardless of the high incidence rate of rare epithelial cancers of these sites. This AIRTUM study confirms that rare cancers are a major public health problem in Italy and provides quantitative estimations, for the first time in Italy, to a problem long known to exist. This monograph provides detailed epidemiologic indicators for almost 200 rare cancers, the majority of which (72%) are very rare (IR&lt;0.5 per 100,000). These data are of major interest for different stakeholders. Health care planners can find useful information herein to properly plan and think of how to reorganise health care services. Researchers now have numbers to design clinical trials considering alternative study designs and statistical approaches. Population-based cancer registries with good quality data are the best source of information to describe the rare cancer burden in a population

Enteral nutrition for preterm infants: by bolus or continuous? An update

Optimization of nutritional management of preterm infants is crucial for achievement of their long-term health. Enteral nutrition is preferred to total parenteral nutrition (TPN) because the former avoids complications related to vascular catheterization, sepsis, adverse effects of TPN, and fasting. Due to the lack of ability of preterm infants to coordinate suckling, swallowing, and breathing, tube feeding is necessary for most infants less than 1500 g to ensure sufficient feeding tolerance, to support optimal growth and to reduce the risk of aspiration. Therefore, feeding by orogastric or nasogastric tube using either continuous or intermittent bolus delivery of formula or human milk is common practice for these infants. Theoretical risks and benefits of both continuous nasogastric milk feeding and intermittent bolus milk feeding have been proposed. According to the literature, continuous nutrition could be preferred in smaller infants (as those with a birthweight below 1250 g) or hemodynamically impaired infants; in stable growing infants nutrition can be administered intermittently as in healthy term infants