Fetal electrocardiotocography in labor and neonatal outcome: an observational study in 1889 patients in the French center of Edouard Herriot, Lyon.

BACKGROUND: The STAN methodology has been shown to reduce both operative delivery for fetal distress and the cord artery metabolic acidosis rate. OBJECTIVE: The objective of this study was to monitor delivery modes and perinatal outcomes following the introduction of the STAN methodology and the evolution of its use at our institution. METHODS: Two periods were characterized: June 2000-June 2002 (period 1) and July 2002-April 2005 (period 2). Parity, mode of labor and delivery, ST events, and neonatal outcome (Apgar score and pH of the umbilical cord artery and vein), cases of metabolic acidosis and operative delivery for fetal distress were studied. RESULTS: One thousand eight hundred and eighty-nine women were included in the study. The rate of use of STAN increased from 13.5% to 16% over these two time periods. The rate of metabolic acidosis was low: 0.28% and 0.45%, respectively. No cases of neonatal encephalopathy or of perinatal death were diagnosed. There was a decrease in the rate of operative delivery for fetal distress (163/701 (22.9%) vs. 228/1111 (20.3%), p = 0.26). CONCLUSIONS: According to the literature, our use of the STAN appears to be very successful; the metabolic acidosis rate was 0.38% and the rate of operative delivery for fetal distress decreased. We improved the accuracy of the interpretation of the fetal heart rate.     

ABL mutations in late chronic phase chronic myeloid leukemia patients with up-front cytogenetic resistance to imatinib are associated with a greater likelihood of progression to blast crisis and shorter survival: a study by the GIMEMA Working Party on Chronic Myeloid Leukemia.

PURPOSE: Point mutations within the ABL kinase domain of the BCR-ABL gene have been associated with clinical resistance to imatinib mesylate in chronic myeloid leukemia (CML) patients. To shed further light on the frequency, distribution, and prognostic significance of ABL mutations, we retrospectively analyzed a homogeneous cohort of late chronic phase CML patients who showed primary cytogenetic resistance to imatinib. PATIENTS AND METHODS: Using denaturing high-performance liquid chromatography (D-HPLC) and sequencing, we screened for ABL mutations in a total of 178 bone marrow and/or peripheral blood samples from 40 late chronic phase CML patients homogeneously treated with imatinib 400 mg/d, who did not reach a major cytogenetic response at 12 months. RESULTS: Mutations were found in 19 of 40 patients (48%). Mutations were already detectable by D-HPLC at a median of 3 months from the onset of therapy. The presence of a missense mutation was significantly associated with a greater likelihood of subsequent progression to accelerated phase/blast crisis (P = .0002) and shorter survival (P = .001). Patients carrying mutations falling within the P-loop seemed to have a particularly poor outcome in terms of time to progression (P = .032) and survival (P = .045). CONCLUSION: Our results show that, irrespective of the hematologic response, monitoring for emerging mutations in the first months of therapy may play a role in detecting patients with worse prognosis, for whom a revision of the therapeutic strategy should be considered.     

Melatonin: Antioxidant and modulatory properties in age‐related changes during Trypanosoma cruzi infection

The purpose of this study was to investigate the effects of melatonin on selected biomarkers of innate and humoral immune response as well as the antioxidant/oxidant status (superoxide dismutase—SOD and reduced glutathione levels (GSH) to understand whether age‐related changes would influence the development of acute Trypanosoma cruzi (T. cruzi) infection. Young‐ (5 weeks) and middle‐aged (18 months) Wistar rats were orally treated with melatonin (gavage) (05 mg/kg/day), 9 days after infection. A significant increase in both SOD activity and GSH levels was found in plasma from all middle‐aged melatonin‐treated animals. Melatonin triggered enhanced expression of major histocompatibility class II (MHC‐II) antigens on antigen‐presenting cell (APC) and peritoneal macrophages in all treated animals. High levels of CD4⁺CD28‐negative T cells (*P<.05) were detected in middle‐aged control animals. Melatonin induced a significant reduction (***P<.001) in CD28‐negative in CD4⁺ and CD8⁺ T cells in middle‐aged control animals. Contrarily, the same group displayed upregulated CD4⁺CD28⁺T and CD8⁺CD28⁺T cells. Melatonin also triggered an upregulation of CD80 and CD86 expression in all young‐treated groups. Significant percentages of B and spleen dendritic cells in middle‐aged infected and treated animals were observed. Our data reveal new features of melatonin action in inhibiting membrane lipid peroxidation, through the reduction in 8‐isoprostane, upregulating the antioxidant defenses and triggering an effective balance in the antioxidant/oxidant status during acute infection. The ability of melatonin to counteract the immune alterations induced by aging added further support to its use as a potential therapeutic target not only for T. cruzi infection but also for other immunocompromised states.     

Transcatheter Aortic Valve Replacement for Severe Aortic Regurgitation With Acute Refractory Cardiogenic Shock

From January 2013 to January 2017, 686 consecutive patients were referred to our centre for transcatheter aortic valve replacement, including 5 subjects with severe aortic regurgitation and acute refractory cardiogenic shock. These patients were contraindicated for surgical treatment by the heart team because of high surgical risk (median logistic EuroSCORE: 74.6/Society of Thoracic Surgeons score: 37.9). The success rate of valve implantation was 100% through transfemoral access with self-expandable devices. The observed 30-day mortality rate was 20%. Hence, the transcatheter aortic valve replacement procedure might represent a successful and life-saving intervention for treatment of patients with severe aortic regurgitation who present with acute refractory cardiogenic shock.     

Inhibition of urinary bladder cancer cell proliferation by silibinin

Silibinin, a natural compound extracted from milk thistle, has demonstrated antitumor properties in urinary bladder cancer cells; however, the role of TP53 gene in these effects is unclear. In order to better understand the molecular and antiproliferative mechanisms of this compound, urinary bladder cancer cells with different TP53 gene status, RT4 (low-grade tumor, wild TP53 gene), 5637 (high-grade tumor, Grade 2, mutated TP53 gene), and T24 (high-grade tumor, Grade 3, mutated TP53 gene) were treated with several concentrations of silibinin (1, 5, 10, 50, 100, and 150 μM). Cytotoxicity, prooxidant effect, morphological changes, cell migration, cell cycle progression, global methylation profile, and relative expression of HOXB3, c-MYC, PLK1, SMAD4, SRC, HAT, HDAC, and RASSF1A genes were evaluated. The silibinin presented cytotoxic and prooxidant effects in the three cell lines. In mutated TP53 cells, significant interference in cell migration and cell cycle arrest at the G2/M phase was observed. Additionally, silibinin induced global DNA hypomethylation in the highest grade tumor cells. For wild-type TP53 cells, a sub-G1 apoptotic population was present. Furthermore, there was modulation of gene expression responsible for cell growth (SMAD and c-MYC), migration (SRC), cell cycle kinetics (PLK1), angiogenesis (HOXB3), and of genes associated with epigenetic events such as DNA acetylation (HAT) and deacetylation (HDAC). In conclusion, the silibinin inhibited the urinary bladder tumor cell proliferation independently of TP53 status; however, cell cycle effects, gene expression changes, and alteration of cell migration are dependent on TP53 status. © 2020 Wiley Periodicals, Inc.     

Peak oxygen uptake and ventilatory anaerobic threshold in fibromyalgia

OBJECTIVE: To compare maximum oxygen uptake and anaerobic threshold in patients with fibromyalgia (FM) and healthy sedentary controls matched by sex, age, weight, and body mass index. METHODS: Fifty women with FM aged 18-60 years and 50 healthy sedentary controls were studied. All were submitted to a maximum treadmill incremental test. Expired gas, ventilatory anaerobic threshold, and maximum oxygen uptake (VO2max) were evaluated. The influence of FM on quality of life was evaluated by questionnaires: the Fibromyalgia Impact Questionnaire and the Medical Outcomes Study Short-Form (SF-36). RESULTS: In patients with FM, the anaerobic threshold and peak oxygen uptake were significantly reduced. Maximum heartbeat rate was significantly lower in FM, indicating submaximum effort. Linear regression data showed a correlation between peak VO2 and the "Role-physical" domain of the SF-36. No such correlations were noted with anaerobic threshold. CONCLUSION: These results confirm the hypothesis of lower physical fitness in patients with FM. Considering that patients with FM do not achieve a maximum effort, ventilatory anaerobic threshold should be considered as a better fitness index than VO2max.