Hemodynamic findings in normotensive women with small for gestational age and growth restricted fetuses

INTRODUCTION: Fetal growth restriction (FGR) in most instances results as a consequence of primary placental dysfunction due to inadequate trophoblastic invasion. Maternal cardiac maladaptation to pregnancy has been proposed as a possible determinant of placental insufficiency and impaired fetal growth. This study aimed to compare the maternal hemodynamic parameters between normotensive women with small-for-gestational age (SGA) and FGR fetuses and to evaluate their correlation with neonatal outcome.MATERIAL AND METHODS: observational cohort study including singleton pregnancies referred to our tertiary care center due to fetal smallness. At the time of diagnosis, fetuses were classified as SGA or FGR according to the Delphi consensus criteria and pregnant women underwent hemodynamic assessment by using cardiac output monitor (USCOM 1A Ltd). A group of women with singleton uncomplicated pregnancies ≥35 weeks of gestation were recruited as controls. Cardiac output, systemic vascular resistance, stroke volume and heart rate were measured and compared among the three groups (controls vs. FGR vs. SGA). The correlation between antenatal findings and neonatal outcome was also evaluated by multivariate logistic regression analysis.RESULTS: 51 women with fetal smallness were assessed at 34.8±2.6 weeks. SGA and FGR were diagnosed in 22 and 29 cases, respectively. The control group included 61 women assessed at 36.5±0.8 weeks of gestation. Women with FGR had a lower cardiac output -Z score (respectively, -1.3±1.2 vs. -0.4±0.8 vs. -0.2±1.0; p<.001) and a higher systemic vascular resistance Z-score compared with both SGA and controls (respectively, 1.2±1.2 vs. 0.2±1.1 vs. -0.02±1.2; p<.001), while no difference in the hemodynamic parameters was found between women with SGA and controls. The incidence of NICU admission did not differ between SGA and FGR fetuses (18.2% vs 41.4%; p=0.13), however FGR had a longer hospitalization compared to SGA fetuses (14.2±17.7 vs. 4.5±1.6 days; p=0.02). Multivariate analysis showed that the cardiac output Z-score at diagnosis (p=0.012) and the birthweight Z-Score (p= 0.007) were independent predictors of the length of neonatal hospitalization.CONCLUSIONS: Different maternal hemodynamic profiles characterize women with SGA or FGR fetuses. Furthermore, a negative correlation was found between the maternal cardiac output and the length of neonatal hospitalization

Theranostic biomarkers and PARP-inhibitors effectiveness in patients with non-BRCA associated homologous recombination deficient tumors: Still looking through a dirty glass window?

: Breast cancer susceptibility gene 1 (BRCA1) and breast cancer susceptibility gene 2 (BRCA2) deleterious variants were the first and, still today, the main biomarkers of poly(ADP)ribose polymerase (PARP)-inhibitors (PARPis) benefit. The recent, increased, numbers of individuals referred for counseling and multigene panel testing, and the remarkable expansion of approved PARPis, not restricted to BRCA1/BRCA2-Pathogenic Variants (PVs), produced a strong clinical need for non-BRCA biomarkers. Significant limitations of the current testing and assays exist. The different approaches that identify the causes of Homologous Recombination Deficiency (HRD), such as the germline and somatic Homologous Recombination Repair (HRR) gene PVs, the testing showing its consequences, such as the genomic scars, or the novel functional assays such as the RAD51 foci testing, are not interchangeable, and should not be considered as substitutes for each other in clinical practice for guiding use of PARPi in non-BRCA, HRD-associated tumors. Today, the deeper knowledge on the significant relationship among all proteins involved in the HRR, not limited to BRCA, expands the possibility of a successful non-BRCA, HRD-PARPi synthetic lethality and, at the same time, reinforces the need for enhanced definition of HRD biomarkers predicting the magnitude of PARPi benefit

The Collagen Chaperone HSP47 Is a New Interactor of APP that Affects the Levels of Extracellular Beta-Amyloid Peptides

Alzheimer disease (AD) is a neurodegenerative disorder characterized by progressive decline of cognitive function that represents one of the most dramatic medical challenges for the aging population. Aβ peptides, generated by processing of the Amyloid Precursor Protein (APP), are thought to play a central role in the pathogenesis of AD. However, the network of physical and functional interactions that may affect their production and deposition is still poorly understood. The use of a bioinformatic approach based on human/mouse conserved coexpression allowed us to identify a group of genes that display an expression profile strongly correlated with APP. Among the most prominent candidates, we investigated whether the collagen chaperone HSP47 could be functionally correlated with APP. We found that HSP47 accumulates in amyloid deposits of two different mouse models and of some AD patients, is capable to physically interact with APP and can be relocalized by APP overexpression. Notably, we found that it is possible to reduce the levels of secreted Aβ peptides by reducing the expression of HSP47 or by interfering with its activity via chemical inhibitors. Our data unveil HSP47 as a new functional interactor of APP and imply it as a potential target for preventing the formation and/or growth amyloid plaques

Colorectal Cancer Stage at Diagnosis Before vs During the COVID-19 Pandemic in Italy

IMPORTANCE Delays in screening programs and the reluctance of patients to seek medical attention because of the outbreak of SARS-CoV-2 could be associated with the risk of more advanced colorectal cancers at diagnosis. OBJECTIVE To evaluate whether the SARS-CoV-2 pandemic was associated with more advanced oncologic stage and change in clinical presentation for patients with colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS This retrospective, multicenter cohort study included all 17 938 adult patients who underwent surgery for colorectal cancer from March 1, 2020, to December 31, 2021 (pandemic period), and from January 1, 2018, to February 29, 2020 (prepandemic period), in 81 participating centers in Italy, including tertiary centers and community hospitals. Follow-up was 30 days from surgery. EXPOSURES Any type of surgical procedure for colorectal cancer, including explorative surgery, palliative procedures, and atypical or segmental resections. MAIN OUTCOMES AND MEASURES The primary outcome was advanced stage of colorectal cancer at diagnosis. Secondary outcomes were distant metastasis, T4 stage, aggressive biology (defined as cancer with at least 1 of the following characteristics: signet ring cells, mucinous tumor, budding, lymphovascular invasion, perineural invasion, and lymphangitis), stenotic lesion, emergency surgery, and palliative surgery. The independent association between the pandemic period and the outcomes was assessed using multivariate random-effects logistic regression, with hospital as the cluster variable. RESULTS A total of 17 938 patients (10 007 men [55.8%]; mean [SD] age, 70.6 [12.2] years) underwent surgery for colorectal cancer: 7796 (43.5%) during the pandemic period and 10 142 (56.5%) during the prepandemic period. Logistic regression indicated that the pandemic period was significantly associated with an increased rate of advanced-stage colorectal cancer (odds ratio [OR], 1.07; 95%CI, 1.01-1.13; P = .03), aggressive biology (OR, 1.32; 95%CI, 1.15-1.53; P < .001), and stenotic lesions (OR, 1.15; 95%CI, 1.01-1.31; P = .03). CONCLUSIONS AND RELEVANCE This cohort study suggests a significant association between the SARS-CoV-2 pandemic and the risk of a more advanced oncologic stage at diagnosis among patients undergoing surgery for colorectal cancer and might indicate a potential reduction of survival for these patients

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

The role of immune suppression in COVID-19 hospitalization: clinical and epidemiological trends over three years of SARS-CoV-2 epidemic

Specific immune suppression types have been associated with a greater risk of severe COVID-19 disease and death. We analyzed data from patients >17 years that were hospitalized for COVID-19 at the “Fondazione IRCCS Ca′ Granda Ospedale Maggiore Policlinico” in Milan (Lombardy, Northern Italy). The study included 1727 SARS-CoV-2-positive patients (1,131 males, median age of 65 years) hospitalized between February 2020 and November 2022. Of these, 321 (18.6%, CI: 16.8–20.4%) had at least one condition defining immune suppression. Immune suppressed subjects were more likely to have other co-morbidities (80.4% vs. 69.8%, p < 0.001) and be vaccinated (37% vs. 12.7%, p < 0.001). We evaluated the contribution of immune suppression to hospitalization during the various stages of the epidemic and investigated whether immune suppression contributed to severe outcomes and death, also considering the vaccination status of the patients. The proportion of immune suppressed patients among all hospitalizations (initially stable at <20%) started to increase around December 2021, and remained high (30–50%). This change coincided with an increase in the proportions of older patients and patients with co-morbidities and with a decrease in the proportion of patients with severe outcomes. Vaccinated patients showed a lower proportion of severe outcomes; among non-vaccinated patients, severe outcomes were more common in immune suppressed individuals. Immune suppression was a significant predictor of severe outcomes, after adjusting for age, sex, co-morbidities, period of hospitalization, and vaccination status (OR: 1.64; 95% CI: 1.23–2.19), while vaccination was a protective factor (OR: 0.31; 95% IC: 0.20–0.47). However, after November 2021, differences in disease outcomes between vaccinated and non-vaccinated groups (for both immune suppressed and immune competent subjects) disappeared. Since December 2021, the spread of the less virulent Omicron variant and an overall higher level of induced and/or natural immunity likely contributed to the observed shift in hospitalized patient characteristics. Nonetheless, vaccination against SARS-CoV-2, likely in combination with naturally acquired immunity, effectively reduced severe outcomes in both immune competent (73.9% vs. 48.2%, p < 0.001) and immune suppressed (66.4% vs. 35.2%, p < 0.001) patients, confirming previous observations about the value of the vaccine in preventing serious disease

A História da Alimentação: balizas historiográficas

Os M. pretenderam traçar um quadro da História da Alimentação, não como um novo ramo epistemológico da disciplina, mas como um campo em desenvolvimento de práticas e atividades especializadas, incluindo pesquisa, formação, publicações, associações, encontros acadêmicos, etc. Um breve relato das condições em que tal campo se assentou faz-se preceder de um panorama dos estudos de alimentação e temas correia tos, em geral, segundo cinco abardagens Ia biológica, a econômica, a social, a cultural e a filosófica!, assim como da identificação das contribuições mais relevantes da Antropologia, Arqueologia, Sociologia e Geografia. A fim de comentar a multiforme e volumosa bibliografia histórica, foi ela organizada segundo critérios morfológicos. A seguir, alguns tópicos importantes mereceram tratamento à parte: a fome, o alimento e o domínio religioso, as descobertas européias e a difusão mundial de alimentos, gosto e gastronomia. O artigo se encerra com um rápido balanço crítico da historiografia brasileira sobre o tema