Polymorphisms and circulating levels in the insulin-like growth factor system and risk of breast cancer: a systematic review.

We reviewed all English-language articles on associations among circulating levels of the insulin-like growth factors (IGF) and their binding proteins (IGFBP), polymorphisms in their genes, and breast cancer risk. In premenopausal women, five of eight IGF-I studies and four of six IGFBP-3 studies of circulating levels found that women in the highest quantile had more than twice the risk of developing breast cancer of those in the lowest, although in some this effect was only apparent at young ages. In postmenopausal women, however, there was no consistent effect. A simple sequence length polymorphism 1 kb 5' to IGF-I was examined in relation to circulating levels of IGF-I (12 studies) or breast cancer risk (4 studies), but there was no convincing evidence of any effect. For an A/C polymorphism 5' to IGFBP-3, all three studies were consistent with a modest effect on circulating levels, but no evidence of a direct effect on breast cancer risk was seen in the only relevant study. Variation within the reference range of IGF-I and IGFBP-3 may confer only modest increases in breast cancer risk, and any single polymorphism may only account for a small proportion of that variation. Nevertheless, population attributable fractions for high circulating levels of IGF-I and IGFBP-3 and for common genetic variants could be substantial. Further large studies, or combined analysis of data from existing studies, are needed to quantify these effects more precisely.     

Diagnostic performance and impact on patient management of [68Ga]Ga-DOTA-TOC PET/CT in colorectal neuroendocrine tumors derived from hindgut

The main purpose of this retrospective study was to determine the diagnostic performance of [⁶⁸Ga]Ga-DOTA-D-Phe1-Try3-octreotide(DOTA-TOC) positron emission tomography/computed tomography (PET/CT) in patients with well-differentiated colorectal Neuroendocrine Tumours (NETs) originating from the hindgut. The other aims were to assess the impact of the examination on patient management and to analyze the results of 2-[¹⁸F]FDG and/or 6-[¹⁸F]FDOPA PET/CT when they were performed. [⁶⁸Ga]Ga-DOTA-TOC PET/CT and clinical data from 30 patients with biopsy-proven well-differentiated NETs originating from the hindgut were retrospectively reviewed and analyzed by comparing the [⁶⁸Ga]Ga-DOTA-TOC PET/CT findings with pathological and/or follow-up data. We also compared the [⁶⁸Ga]Ga-DOTA-TOC PET/CT results with 2-[¹⁸F]FDG and/or 6-[¹⁸F]FDOPA PET/CT results in 6 patients. The impact on management was determined in hindsight by comparing the patient management decided before and after the TEP examination based on data from multidisciplinary team meetings. On a patient basis, [⁶⁸Ga]Ga-DOTA-TOC PET/CT was accurate in 30 of the 30 examinations. [⁶⁸Ga]Ga-DOTA-TOC PET/CT correctly identified the primary tumor in all patients with primary tumors not resected before the examination and allowed the detection of unexpected distant metastases in 36% of the patients referred for initial staging. [⁶⁸Ga]Ga-DOTA-TOC PET/CT findings affected patient management in 57% of cases with generally major intermodality changes. Intraindividual comparison of the results of the different PET radiopharmaceuticals showed a clear superiority of [⁶⁸Ga]Ga-DOTA-TOC PET/CT considering both the number of lesions and the intensity of uptake. [⁶⁸Ga]Ga-DOTA-TOC PET/CT is an accurate imaging modality for the assessment of well-differentiated colorectal NETs that highly impact patient management. Thus, we suggest that [⁶⁸Ga]Ga-DOTA-TOC PET/CT be employed as a first choice for the assessment of these tumors in nuclear medicine.     

Interlayer and Intralayer Excitons in AlN/WS2 Heterostructure

The study of intra and interlayer excitons in 2D semiconducting vdW heterostructures is a very hot topic not only from a fundamental but also an applicative point of view. Due to their strong light–matter interaction, Transition Metal Dichalcogenides (TMD) and group-III nitrides are particularly attractive in the field of opto-electronic applications such as photo-catalytic and photo-voltaic ultra-thin and flexible devices. Using first-principles ground and excited-state simulations, we investigate here the electronic and excitonic properties of a representative nitride/TMD heterobilayer, the AlN/WS2. We demonstrate that the band alignment is of type I, and low energy intralayer excitons are similar to those of a pristine WS2 monolayer. Further, we disentangle the role of strain and AlN dielectric screening on the electronic and optical gaps. These results, although they do not favor the possible use of AlN/WS2 in photo-catalysis, as envisaged in the previous literature, can boost the recently started experimental studies of 2D hexagonal aluminum nitride as a good low screening substrate for TMD-based electronic and opto-electronic devices. Importantly, our work shows how the inclusion of both spin-orbit and many-body interactions is compulsory for the correct prediction of the electronic and optical properties of TMD/nitride heterobilayers.     

The impact of COVID‐19 on clinical outcomes among acute myocardial infarction patients undergoing early invasive treatment strategy

BackgroundThe implications of coronavirus disease 2019 (COVID‐19) infection on outcomes after invasive therapeutic strategies among patients presenting with acute myocardial infarction (AMI) are not well studied.HypothesisTo assess the outcomes of COVID‐19 patients presenting with AMI undergoing an early invasive treatment strategy.MethodsThis study was a cross‐sectional, retrospective analysis of the National COVID Cohort Collaborative database including all patients presenting with a recorded diagnosis of AMI (ST‐elevation myocardial infarction (MI) and non‐ST elevation MI). COVID‐19 positive patients with AMI were stratified into one of four groups: (1a) patients who had a coronary angiogram with percutaneous coronary intervention (PCI) within 3 days of their AMI; (1b) PCI within 3 days of AMI with coronary artery bypass graft (CABG) within 30 days; (2a) coronary angiogram without PCI and without CABG within 30 days; and (2b) coronary angiogram with CABG within 30 days. The main outcomes were respiratory failure, cardiogenic shock, prolonged length of stay, rehospitalization, and death.ResultsThere were 10 506 COVID‐19 positive patients with a diagnosis of AMI. COVID‐19 positive patients with PCI had 8.2 times higher odds of respiratory failure than COVID‐19 negative patients (p = .001). The odds of prolonged length of stay were 1.7 times higher in COVID‐19 patients who underwent PCI (p = .024) and 1.9 times higher in patients who underwent coronary angiogram followed by CABG (p = .001).ConclusionThese data demonstrate that COVID‐19 positive patients with AMI undergoing early invasive coronary angiography had worse outcomes than COVID‐19 negative patients.