Short-term neonatal outcomes in vaginal breech delivery: Results of a retrospective single-centre study.

BACKGROUND: Vaginal breech delivery (VBD) has been widely discouraged over the last two decades due to associated neonatal risks. However, many gynaecologists are still challenging this approach, at least in selected settings. OBJECTIVE: To study short-term neonatal outcomes in singleton pregnancies undergoing VBD. MATERIALS AND METHODS: Retrospective cohort study conducted on singleton pregnancies who delivered in breech presentation between 2012 and 2019. Neonatal complications in terms of mortality, umbilical artery (UA) pH, 5-min Apgar score, and postnatal admission to neonatal intensive care unit (NICU) were evaluated. RESULTS: Overall, 804 breech deliveries were considered. Of these, 53.86 % had VBD, 26.62 % had emergency caesarean sections (CS) and 19.53 % had elective CS. No perinatal deaths were reported. After multivariate adjustment, VBD was associated with higher incidence of UA pH < 7.10 compared with both elective and emergency CS. No significant associations were found between VBD and UA pH < 7.00 or 5-min Apgar score < 3 or < 7. No significant differences in NICU hospitalization were observed for different modes of delivery. Gestational age was inversely correlated with UA pH < 7.00, 5-min Apgar score < 3 and < 7, and NICU hospitalization. CONCLUSIONS: VBD in an experienced setting does not increase the risk of negative short-term perinatal outcomes significantly. Gestational age was the most important risk factor for low UA pH or 5-min Apgar score and NICU hospitalization, independent of mode of delivery.

Autologous CD34+ Cell Therapy for Refractory Angina: 2-Year Outcomes From the ACT34-CMI Study.

An increasing number of patients have refractory angina despite optimal medical therapy and are without further revascularization options. Preclinical studies indicate that human CD34+ stem cells can stimulate new blood vessel formation in ischemic myocardium, improving perfusion and function. In ACT34-CMI (N = 167), patients treated with autologous CD34+ stem cells had improvements in angina and exercise time at 6 and 12 months compared to placebo; however, the longer-term effects of this treatment are unknown. ACT34 was a phase II randomized, double-blind, placebo-controlled clinical trial comparing placebo, low dose (1 × 105 CD34/kg body weight), and high dose (5 × 105 CD34/kg) using intramyocardial delivery into the ischemic zone following NOGA® mapping. To obtain longer-term safety and efficacy in these patients, we compiled data of major adverse cardiac events (MACE; death, myocardial infarction, acute coronary syndrome, or heart failure hospitalization) up to 24 months as well as angina and quality of life assessments in patients who consented for 24-month follow-up. A total of 167 patients with class III-IV refractory angina were randomized and completed the injection procedure. The low-dose-treated patients had a significant reduction in angina frequency (p = 0.02, 0.035) and improvements in exercise tolerance testing (ETT) time (p = 0.014, 0.017) compared to the placebo group at 6 and 12 months. At 24 months, patients treated with both low-and high-dose CD34+ cells had significant reduction in angina frequency (p = 0.03). At 24 months, there were a total of seven deaths (12.5%) in the control group versus one (1.8%) in the low-dose and two (3.6%) in the high-dose (p = 0.08) groups. At 2 years, MACE occurred at a rate of 33.9%, 21.8%, and 16.2% in control, low-, and high-dose patients, respectively (p = 0.08). Autologous CD34+ cell therapy was associated with persistent improvement in angina at 2 years and a trend for reduction in mortality in no-option patients with refractory angina.

Intramyocardial, autologous CD34+ cell therapy for refractory angina.

RATIONALE: A growing number of patients with coronary disease have refractory angina. Preclinical and early-phase clinical data suggest that intramyocardial injection of autologous CD34+ cells can improve myocardial perfusion and function. OBJECTIVE: Evaluate the safety and bioactivity of intramyocardial injections of autologous CD34+ cells in patients with refractory angina who have exhausted all other treatment options. METHODS AND RESULTS: In this prospective, double-blind, randomized, phase II study (ClinicalTrials.gov identifier: NCT00300053), 167 patients with refractory angina received 1 of 2 doses (1×10(5) or 5×10(5) cells/kg) of mobilized autologous CD34+ cells or an equal volume of diluent (placebo). Treatment was distributed into 10 sites of ischemic, viable myocardium with a NOGA mapping injection catheter. The primary outcome measure was weekly angina frequency 6 months after treatment. Weekly angina frequency was significantly lower in the low-dose group than in placebo-treated patients at both 6 months (6.8±1.1 versus 10.9±1.2, P=0.020) and 12 months (6.3±1.2 versus 11.0±1.2, P=0.035); measurements in the high-dose group were also lower, but not significantly. Similarly, improvement in exercise tolerance was significantly greater in low-dose patients than in placebo-treated patients (6 months: 139±151 versus 69±122 seconds, P=0.014; 12 months: 140±171 versus 58±146 seconds, P=0.017) and greater, but not significantly, in the high-dose group. During cell mobilization and collection, 4.6% of patients had cardiac enzyme elevations consistent with non-ST segment elevation myocardial infarction. Mortality at 12 months was 5.4% in the placebo-treatment group with no deaths among cell-treated patients. CONCLUSIONS: Patients with refractory angina who received intramyocardial injections of autologous CD34+ cells (10(5) cells/kg) experienced significant improvements in angina frequency and exercise tolerance. The cell-mobilization and -collection procedures were associated with cardiac enzyme elevations, which will be addressed in future studies.

Structure elucidation and biological activity of the oversulfated chondroitin sulfate contaminant in Baxter heparin.

From late December 2007 to February 2008, the number of adverse responses to heparin infusions rose noticeably above baseline levels in North America, ultimately resulting in a widespread recall of all heparin vial products made by Baxter Healthcare. Using various analytical techniques and the de novo synthesis of a fully sulfated chondroitin sulfate (FSCS) derivative, the authors have confirmed the identity of the contaminant as an oversulfated chondroitin sulfate (OSCS) and have also defined the heterogeneity and concentration of this contaminant in various lots of heparin. Using both contaminated heparin products and the synthetically produced derivative, the authors have shown that the OSCS produces a dose-dependent hypotension in both pigs and rats and that the response in rats can be abrogated with bradyzide, a rodent-selective B(2) bradykinin receptor antagonist. The no observed effect level (NOEL) for this contaminant appears to be approximately 1 mg/kg, corresponding to a contamination level in finished lots of heparin of approximately 3%. Using human plasma, the OSCS derivative was shown to activate kallikrein. These data provide insight into the etiology of the adverse events, particularly refractory hypotension, observed in patients who were exposed to heparin contaminated with OSCS.

Discriminant learning analysis.

Linear discriminant analysis (LDA) as a dimension reduction method is widely used in classification such as face recognition. However, it suffers from the small sample size (SSS) problem when data dimensionality is greater than the sample size, as in images where features are high dimensional and correlated. In this paper, we propose to address the SSS problem in the framework of statistical learning theory. We compute linear discriminants by regularized least squares regression, where the singularity problem is resolved. The resulting discriminants are complete in that they include both regular and irregular information. We show that our proposal and its nonlinear extension belong to the same framework where powerful classifiers such as support vector machines are formulated. In addition, our approach allows us to establish an error bound for LDA. Finally, our experiments validate our theoretical analysis results.