Fetal aortic isthmus Doppler assessment to predict the adverse perinatal outcomes associated with fetal growth restriction: systematic review and meta-analysis.

PURPOSE: Fetal growth restriction (FGR) management and delivery planning is based on a multimodal approach. This meta-analysis aimed to evaluate the prognostic accuracies of the aortic isthmus Doppler to predict adverse perinatal outcomes in singleton pregnancies with FGR. METHODS: PubMed, EMBASE, the Cochrane Library, ClinicalTrials.gov and Google scholar were searched from inception to May 2021, for studies on the prognostic accuracy of anterograde aortic isthmus flow compared with retrograde aortic isthmus flow in singleton pregnancy with FGR. The meta-analysis was registered on PROSPERO and was assessed according to PRISMA and Newcastle-Ottawa Scale. DerSimonian and Laird's random-effect model was used for relative risks, Freeman-Tukey Double Arcsine for pooled estimates and exact method to stabilize variances and CIs. Heterogeneity was quantified using I2 statistics. RESULTS: A total of 2933 articles were identified through the electronic search, of which 6 studies (involving 240 women) were included. The quality evaluation of studies revealed an overall acceptable score for study group selection and comparability and substantial heterogeneity. The risk of perinatal death was significantly greater in fetuses with retrograde Aortic Isthmus blood flow, with a RR of 5.17 (p value 0.00001). Similarly, the stillbirth rate was found to have a RR of 5.39 (p value 0.00001). Respiratory distress syndrome had a RR of 2.64 (p value = 0.03) in the group of fetuses with retrograde Aortic Isthmus blood flow. CONCLUSION: Aortic Isthmus Doppler study may add information for FGR management. However, additional clinical trial are required to assess its applicability in clinical practice.

Prediction of hypertensive disorders after screening at 36 weeks' gestation: comparison of angiogenic markers with competing-risks model.

OBJECTIVE: To compare the performance at 35 + 0 to 36 + 6 weeks' gestation of screening for delivery with pre-eclampsia (PE) at various timepoints, using one of three approaches: placental growth factor (PlGF) concentration, soluble fms-like tyrosine kinase-1 (sFlt-1) to PlGF concentration ratio, or the competing-risks model, which combines maternal risk factors with biomarkers to estimate patient-specific risk. METHODS: This was a prospective observational study of women attending for a routine hospital visit at 35 + 0 to 36 + 6 weeks' gestation at one of two maternity hospitals in England between 2016 and 2022. During the visit, maternal demographic characteristics and medical history were recorded and serum PlGF, serum sFlt-1 and mean arterial pressure (MAP) were measured. Detection rates (DRs) were evaluated for delivery with PE (defined as per American College of Obstetricians and Gynecologists 2019 criteria) within 1 week, within 2 weeks or at any time after screening, using the following strategies: (i) low PlGF (< 10th percentile); (ii) high sFlt-1/PlGF ratio (> 90th percentile); or (iii) the competing-risks model, in which maternal factors were combined with multiples of the median values of PlGF ('single test'), PlGF and sFlt-1 ('double test') or PlGF, sFlt-1 and MAP ('triple test'). Risk cut-offs corresponded to a screen-positive rate of 10%. DRs were compared between tests. RESULTS: Of 34 782 pregnancies, 831 (2.4%) developed PE. In screening for delivery with PE at any time from assessment, the DR at 10% screen-positive rate was 47% by low PlGF alone, 54% by the single test, 55% by high sFlt-1/PlGF ratio, 61% by the double test and 68% by the triple test. In screening for delivery with PE within 2 weeks from assessment, the respective values were 67%, 74%, 74%, 80% and 87%. In screening for delivery with PE within 1 week from assessment, the respective values were 77%, 81%, 85%, 88% and 91%. For prediction of PE at any time, the DR was significantly higher with the triple test compared to PlGF alone or the sFlt-1/PlGF ratio, with a DR difference (95% CI) of 20.1% (16.7-23.0%) and 12.4% (9.7-15.3%), respectively. Similar results were seen for prediction of PE within 2 weeks (20.6% (14.9-26.8%) and 12.9% (7.7-17.5%), respectively) and prediction of PE within 1 week (13.5% (5.4-21.6%) and 5.4% (0.0-10.8%), respectively). The double test was superior to the sFlt-1/PlGF ratio and the single test was superior to PlGF alone in the prediction of PE within 2 weeks and at any time from assessment, but not within 1 week of assessment. CONCLUSION: At 35 + 0 to 36 + 6 weeks' gestation, the performance of screening for PE by the competing-risks model triple test is superior to that of PlGF alone or the sFlt-1/PlGF ratio for the development of disease within 1 week, within 2 weeks and at any time from screening. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Pharmacological and non-pharmacological pain relief for office hysteroscopy: an up-to-date review.

In-office hysteroscopy is considered the standard technique for visualization of the uterine cavity and the diagnosis of intrauterine pathologies. Moreover, nowadays, it is possible to treat a vast number of intracavitary diseases in the office, without the need for the inpatient setting. However, in some cases, pain might occur, and this is the most common reason for not completing the procedure. Over the last 20 years, many efforts have been carried out to miniaturize the instrumentation and to improve the techniques in order to avoid discomfort. Nonetheless, hysteroscopy still provokes distress for many patients. For this reason, pharmacological and non-pharmacological treatments for intraoperative and postoperative pain relief have been widely used for in-office hysteroscopy, with different results in various groups of women. The purpose of this review was to analyze the current literature on pharmacological aids (non-steroidal anti inflammatory drugs, cyclooxygenase-2 inhibitors, antispasmodics, local anesthetics, prostaglandins, opioids) and non-pharmacological interventions (transcutaneous electrical nerve stimulation, uterine stretching, uterine pressure, warming of distension medium, hypnosis, music, vocal-local) and to evaluate their impact on the relief from pain experienced during in-office hysteroscopy.

Clinical and microbiological outcome in septic patients with extremely low 25-hydroxyvitamin D levels at initiation of critical care.

A relationship between vitamin D status and mortality in patients in intensive care units (ICU) has been documented. The present study aims to describe the clinical profile and sepsis-related outcome of critically ill septic patients with extremely low (<7 ng/mL) vitamin D levels at ICU admission. We conducted an observational study in the ICU of a teaching hospital including all patients admitted with severe sepsis/septic shock and undergoing 25-hydroxyvitamin D (25(OH)D) testing within the first 24 hours from admission. We studied 107 patients over 12 months. At ICU admission vitamin D deficiency (≤20 ng/mL) was observed in 93.5% of the patients: 57 (53.3%) showed levels <7 ng/mL. As primary outcome, sepsis-related mortality rate was higher in patients with vitamin D levels <7 ng/mL (50.9% versus 26%). Multivariate regression analysis showed that vitamin D concentration <7 ng/mL on ICU admission (p 0.01) and higher mean SAPS II (p <0.01) score were independent predictors of sepsis-related mortality. Patients with very low vitamin D levels suffered higher rate of microbiologically confirmed infections but a lower percentage of microbiological eradication with respect to patients whose values were >7 ng/mL (80.7% versus 58%, p 0.02; 35.3% versus 68%; p 0.03, respectively). Post hoc analysis showed that, in the extremely low vitamin D group, the 52 patients with pneumonia showed a longer duration of mechanical ventilation (9 days (3.75-12.5 days) versus 4 days (2-9 days), p 0.04) and the 66 with septic shock needed vasopressor support for a longer period of time (7 days (4-10 days) versus 4 days (2-7.25 days), p 0.02). Our results suggest that in critical septic patients extremely low vitamin D levels on admission may be a major determinant of clinical outcome. Benefits of vitamin D replacement therapy in this population should be elucidated.

Effect of rMnSOD on survival signaling in pediatric high risk T-cell acute lymphoblastic leukaemia.

Manganese superoxide dismutase (MnSOD) is a mitochondrial enzyme that defends against oxidative damage due to reactive oxygen species (ROS). A new isoform of MnSOD with cytotoxic activity was recently discovered in liposarcoma cells. Here, we tested the effectiveness of a recombinant form of this isoform (rMnSOD) on leukemic T cells, Jurkat cells, and lymphocytes. Our results confirm that leukemic T cells can internalize rMnSOD and that rMnSOD causes apoptosis of 99% of leukemic cells without showing toxic effects on healthy cells. Using light and electron microscopy, we determined that an rMnSOD concentration of 0.067 µM most effective on apoptosis induction. Western blot analysis showed that treatment with 0.067 µM rMnSOD resulted in high expression of the pro-apoptotic protein Bax and low expression of the anti-apoptotic protein Bcl-2 in leukemia cells. Concerning signal transduction pathway no influence was observed after treatment except for Jurkat cells showing a slightly decreased expression of ERK phosphorylation. These results suggest that rMnSOD may be an effective and non-toxic treatment option for T-cell leukemia.

A conditioned medium from a human liposarcoma-derived cell line induces p53-dependent apoptosis in several tumor cell lines.

A novel cell line, named LSA, has been obtained, stabilized, and characterized from a human liposarcoma. These cells have morphological and biochemical features strongly resembling the adipocytes and were able to grow in the Ham's F12 medium, in presence or absence of FCS. A conditioned medium (LSA-CM) was obtained by growing the LSA cells in the F12 medium in the absence of FCS. LSA-CM had cytostatic and cytotoxic effects (apoptosis and necrosis) associated with down-regulation of c-myc and upregulation of p53 in several human cell lines (breast, lung, glioblastoma, etc. ). The MCF-7 and glioblastoma cells were killed by LSA-CM in 5-6 days, whereas the same cells were killed by LSA-CM co-incubated with low doses of cisplatin in 30 h. LSA-CM peri-tumoral injections for 15 days in Balb-c-fc3H mice affected by mammary tumors, resulted in the rapid disruption of tumors and absence of metastases. In contrast, in the untreated animals the tumor masses were 4 times larger than initial lesions, and numerous metastases were found in the lungs. The toxicity analysis of LSA-CM, performed on three different animal species, showed that LSA-CM is absolutely free of acute, subacute, and subchronic toxicity. The possible use of LSA-CM/cisplatin for cancer treatment is discussed.