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Carlo Bouchè,1 Uri Wiesenfeld,1 Luca Ronfani,1 Roberto Simeone,2 Paolo Bogatti,1 Kristina Skerk,1 Giuseppe Ricci1,2 1Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Trieste, Italy; 2Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy Background/aim: Clinical data with respect to the impact of meconium on the risk of maternal hemorrhage are scarce. Therefore, in this study, we aimed to determine whether meconium-stained amniotic fluid (MSAF) represents a risk factor for postpartum hemorrhage (PPH) after vaginal delivery in a large unselected population. Patients and methods: A retrospective cohort study evaluated 78,542 consecutive women who had a vaginal delivery between 24th and 44th weeks of gestation. The women who had undergone cesarean section were excluded to avoid possible bias. Postpartum blood loss was measured with graduated blood sack. Postpartum blood loss between 1,000 and 2,000 mL and >2,000 mL were classified as moderate and severe PPH, respectively. Results: A total of 74,144 patients were available for analysis. According to the color of amniotic fluid (AF), two groups of patients were identified: MSAF (n=10,997) and clear AF (n=63,147). The rates of severe and massive PPH were found to be significantly higher in the MSAF group than that of clear AF group (OR=1.3, 95% CI: 1.2–1.5, p

Obesity is a negative prognosis factor for breast cancer. Yet, the biological mechanisms underlying this effect are still largely unknown. An emerging hypothesis is that the transfer of free fatty acids (FFA) between adipocytes and tumor cells might be altered under obese conditions, contributing to tumor progression. Currently there is a paucity of models to study human mammary adipocytes (M-Ads)-cancer crosstalk. As for other types of isolated white adipocytes, herein, we showed that human M-Ads die within 2-3 days by necrosis when grown in 2D. As an alternative, M-Ads were grown in a fibrin matrix, a 3D model that preserve their distribution, integrity and metabolic function for up to 5 days at physiological glucose concentrations (5 mM). Higher glucose concentrations frequently used in in vitro models promote lipogenesis during M-Ads culture, impairing their lipolytic function. Using transwell inserts, the matrix embedded adipocytes were cocultured with breast cancer cells. FFA transfer between M-Ads and cancer cells was observed, and this event was amplified by obesity. Together these data show that our 3D model is a new tool for studying the effect of M-Ads on tumor cells and beyond with all the components of the tumor microenvironment including the immune cells., (© 2023. The Author(s).)

Background: Although widely used, slow freezing considerably modifies the functions of human spermatozoa. Cryopreservation induces nuclear sperm alterations and cryo-capacitation, reducing the chances of pregnancy. Hypotaurine is naturally present in the male and female genital tracts and has capacitating, osmolytic and anti-oxidant properties. The analysis were performed on surplus semen of men with normal (n = 19) or abnormal (n = 14) sperm parameters. Spermatozoa were selected by density gradient centrifugation before slow freezing. For each sample, these steps were performed in parallel with ("H+" arm) or without ("H-" arm) hypotaurine supplementation. After thawing, we measured total and progressive mobility, vitality, acrosome integrity, markers of capacitation signaling pathway and nuclear quality. For the latter, we focused on sperm chromatin packaging, DNA fragmentation and the presence of vacuoles in the sperm nucleus., Results: Post-thaw spermatozoa selected and frozen in the presence of hypotaurine had a higher vitality (+ 16.7%, p < 0.001), progressive and total motility (+ 39.9% and +  21.6% respectively, p < 0.005) than spermatozoa from the control "H-" arm. Hypotaurine also reduced the non-specific phosphorylation of the capacitation protein markers P110 and P80 (p < 0.01), indicating a decrease in cryo-capacitation. Hypotaurine supplementation reduced chromatin decondensation, measured by chromomycin A3 (- 16.1%, p < 0.05), DNA fragmentation (- 18.7%, p < 0.05) and nuclear vacuolization (- 20.8%, p < 0.05)., Conclusion: Our study is the first to demonstrate beneficial effects of hypotaurine supplementation in preparation and freezing procedures on human spermatozoa sperm fertilization capacity and nucleus quality. Hypotaurine supplementation limited cryo-capacitation, increased the proportion of live and progressively motile spermatozoa and reduces the percentage of spermatozoa showing chromatin decondensation, DNA fragmentation and nuclear vacuolation., Trial Registration: Clinical Trial, NCT04011813 . Registered 19 May 2019 - Retrospectively registered., (© 2021. The Author(s).)

A variety of neuropsychiatric complications has been described in association with COVID-19 infection. Large scale studies presenting a wider picture of these complications and their relative frequency are lacking. The objective of our study was to describe the spectrum of neurological and psychiatric complications in patients with COVID-19 seen in a multidisciplinary hospital centre over 6 months. We conducted a retrospective, observational study of all patients showing neurological or psychiatric symptoms in the context of COVID-19 seen in the medical and university neuroscience department of Assistance Publique Hopitaux de Paris-Sorbonne University. We collected demographic data, comorbidities, symptoms and severity of COVID-19 infection, neurological and psychiatric symptoms, neurological and psychiatric examination data and, when available, results from CSF analysis, MRI, EEG and EMG. A total of 249 COVID-19 patients with a de novo neurological or psychiatric manifestation were included in the database and 245 were included in the final analyses. One-hundred fourteen patients (47%) were admitted to the intensive care unit and 10 (4%) died. The most frequent neuropsychiatric complications diagnosed were encephalopathy (43%), critical illness polyneuropathy and myopathy (26%), isolated psychiatric disturbance (18%) and cerebrovascular disorders (16%). No patients showed CSF evidence of SARS-CoV-2. Encephalopathy was associated with older age and higher risk of death. Critical illness neuromyopathy was associated with an extended stay in the intensive care unit. The majority of these neuropsychiatric complications could be imputed to critical illness, intensive care and systemic inflammation, which contrasts with the paucity of more direct SARS-CoV-2-related complications or post-infection disorders., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain.)

Objective: The aim of this retrospective cohort study is to evaluate the concordance between the preoperative MRI and histology data with the final histopathological examination., Method: This is a retrospective observational study of 183 patients operated for endometrioid cancer between January 2009 and December 2019 in the surgical oncology department of the Lorraine Cancer Institute (ICL) in Vandœuvre-lès-Nancy. The patients included are all women operated on for endometrioid-type endometrial cancer over this period. The exclusion criteria are patients for whom the pre-therapy check-up does not include pelvic MRI and those who have not had first-line surgery. The final anatomopathological results were compared with preoperative imaging data and with endometrial biopsy data., Results: For the myometrial infiltration, the sensitivity of MRI was of 37% and the specificity of 54%. To detect nodal metastases, the sensitivity of MRI was of 21% and the specificity of 93%. We observed an under estimation of the FIGO classification ( p = 0.001) with the MRI in 42.7% of cases (n = 76) and an overestimation in 24.2% of cases (n = 43). There was a concordance in 33.1% of cases (n = 59). We had a poor agreement between the MRI and final histopathological examination with an adjusted kappa (κ) of 0.12 [95% IC (0.02; 0.24)]. There was a moderate concordance on the grade between the pretherapeutic biopsy and the final histopathological examination on excised tissue with an adjusted kappa of 0.52 [95% IC 0.42-0.62)]. Endometrial biopsy underestimated the tumor grade in 28.9% of cases (n = 50) ( p < 0.001), overestimated the tumor grade in 6.9% of cases (n = 12) and we observed a concordance in 64.2% of cases (n = 111)., Conclusion: The pre-operative assessment of endometrial cancer is inconsistent with the results obtained on final histopathological examination. A study with a systematic review should be done to assess the performance of MRI, only in expert centers, in order to consider a a specific care management for endometrial cancer patients: patients who have had an MRI in an outpatient center should have their imaging systematically reviewed, with the possibility of a new examination in case of incomplete sequences, by expert radiologists, and discussed in multidisciplinary concertation meeting in expert centers, before any therapeutic decision. The sentinel node biopsy must be used for low and intermediate risk endometrial cancer.

This prospective study aimed to determine the effects of dry nitrogen cryostorage on human sperm characteristics in comparison with liquid nitrogen cryostorage. For this purpose, 42 men undergoing routine semen analysis (21 normozoospermia and 21 with altered semen parameters) were analyzed. After slow freezing, half of the straws of each sample were randomly stored in liquid and dry tanks, at the top and bottom levels of the latter. After 6 months storage, thawed samples were treated by density gradient centrifugation and sperm characteristics were compared. There was no difference in sperm progressive motility (15.1% ± 14.2% vs. 15.1% ± 12.7%; p = 0.76), sperm vitality (25.5% ± 17.7% vs. 26.2% ± 19%; p = 0.71), percentages of acrosome-reacted spermatozoa (38% ± 8.5% vs. 38.5% ± 7.4%; p = 0.53) and DNA fragmentation spermatozoa (27.3% ± 12.4% vs. 28.5% ± 12.9%, p = 0.47) after cryostorage in the dry or the liquid nitrogen tank. Moreover, we did not observe differences between either cryostorage system for normal and altered sperm samples. This lack of difference was also observed whatever the floor level of cryostorage in the dry tank. The temperature measurement of the dry tank showed a stable temperature at -194 °C throughout storage whatever the storage floor level, guaranteeing the stability of the low temperatures suitable for human sperm storage. Because of its greater safety, dry storage without contact with the liquid phase should be preferred and can be a useful alternative for the cryostorage of human sperm samples., Competing Interests: Declaration of competing interest There was no external funding for this study and all the authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Immune checkpoint inhibitors have improved survival in numerous advanced malignancies, but are associated with a number of immune-related adverse events, including endocrinopathies. Endogenous Cushing's syndrome (CS) is a rare disorder resulting from exposure to high levels of circulating cortisol. CS can be caused either by adrenal cortex tumors or hyperplasia or by pituitary or extra-pituitary tumors over-secreting ACTH (known as ACTH-dependent CS). We report the first case of transient ACTH-dependent CS, which appeared after combined ipilimumab and nivolumab therapy. Our patient presented typical clinical features of CS after three infusions of combined therapy, high serum and daily urinary free cortisol, and high serum ACTH levels. Pituitary MRI showed an enlargement of the pituitary gland suggesting ACTH secretion of pituitary origin, which was confirmed by inferior petrosal sinus sampling. The pituitary findings were preceded by thyroiditis. The evolution was characterized by spontaneous CS regression and subsequent appearance of severe corticotroph deficiency consistent with destructive hypophysitis. Immunotherapy is a novel cause of CS.

A prospective study on randomized patients was conducted to determine how morphokinetic parameters are altered in embryos grown in sequential versus global culture media. Eleven morphokinetic parameters of 160 single embryos transferred were analyzed by time lapse imaging involving two University-affiliated in vitro fertilization (IVF) centers. We found that the fading of the two pronuclei occurred earlier in global (22.56±2.15 hpi) versus sequential media (23.63±2.71 hpi; p=0.0297). Likewise, the first cleavage started earlier at 24.52±2.33 hpi vs 25.76±2.95 hpi (p=0.0158). Also, the first cytokinesis was shorter in global medium, lasting 18±10.2 minutes in global versus 36±37.8 minutes in sequential culture medium (p <0.0001). We also observed a significant shortening in the duration of the 2-cell stage in sequential medium: 10.64 h±2.75 versus 11.66 h±1.11 in global medium (p=0.0225) which suggested a faster progression of the embryos through their first mitotic cell cycle. In conclusion, morphokinetic analysis of human embryos by Time lapse imaging reveals significant differences in five kinetic variables according to culture medium. Our study highlights the need to adapt morphokinetic analysis accordingly to the type of media used to best support human early embryo development.