Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Towards the selection of embryos with the greatest implantation potential

Choosing the most suitable embryo remains challenging as the standard approach to select top-quality embryos for transfer rely on static morphological assessment. It is completed after fertilisation, on days 3 and 5 post oocyte retrieval and evaluates the size and number of blastomeres, presence of nucleation and percentage of fragmentation for cleavage stage embryos. Because of the limited number of observations during the morphological assessment, morphokinetic development of embryos has been implemented. It shows a broader image of embryo behaviour with precise evaluation of the timing of events. Yet, studies are inconsistent and debatable in predicting the parameters to identify chromosomal abnormalities. Pre-implantation genetic testing detects dysmorphic embryos and correlate their developmental potential to the assessed morphology. However, the clinical utility of PGT-aneuploidy remains controversial. The future relies on newly described scoring systems such as artificial intelligence and non-invasive PGT, yet their application and actual success rate still lacks supportive evidence

Practice patterns of obstetric care in twin gestations: the value of MFM consultation

Objectives To evaluate the practice patterns among Lebanese obstetricians regarding obstetric care of twins and to compare selected practice patterns between general obstetricians and maternal fetal medicine physicians. Methods Questionnaires distributed during the annual meeting of the Lebanese Society of Obstetrics and Gynecology. Results Questionnaires were returned by 69.2% of the 296 physicians approached. Ten percent had fellowship training in Maternal Fetal Medicine (MFM). Thirty-nine percent perform cervical length measurement at 20-24 weeks of gestation and 34% recommend vaginal progesterone in case of a short cervix. When comparing selected practice patterns between MFM & general obstetricians, MFM specialists were less likely to perform cervical cerclage in the first trimester (5.9% versus 49%,p = .001), more likely to offer prenatal screening for aneuploidy (66.6% vs 46.4%,p = .03), less likely to use vaginal progesterone in the second trimester in the case of a short cervix (42.1% vs 61.8%,p = .04), less likely to perform serial ultrasound exam in the third trimester to assess fetal growth (50% vs 78%,p = .005) and more likely to deliver monoamniotic twins at 32-34 weeks of gestation (55% vs 37%,p = .05). Conclusion Because of the different background of the Lebanese physicians, MFM specialists are more likely to follow obstetric care guidelines in twin gestation

Treatment of cervical cancer metastatic to the abdominal wall with reconstruction using a composite myocutaneous flap: A case report

A 43-year-old woman treated with radical hysterectomy 1 year ago for cervical cancer presented with a suprapubic abdominal mass. A 15 cm necrotic mass from the abdominal wall along with 2 small bowel loops and the dome of the bladder were resected. The peritoneal defect was reconstructed with a pedicled anterolateral thigh and Vastus Lateralis muscle composite flap. Pathology showed invasive non-keratinizing moderately differentiated squamous cell carcinoma, consistent with metastatic cervical cancer, involving urinary bladder, bowel and soft tissue. With advancement in reconstructive surgery, extensive resection with defect closure in properly selected cases of metastatic cervical cancer to the abdominal wall may be considered in an attempt at improving quality of life and overall survival. Keywords: Abdominal wall lesion, Cervical cancer, Metastasis of cervical cancer, Resection of lesio

The accuracy and clinical impact of intraoperative frozen section in determining the extent of surgical intervention in patients with early stage endometrial cancer

The aim of this study was to compare intraoperative frozen section (FS) with the final pathology (FP), and determine its clinical impact in clinically apparent early stage endometrial cancer (EC) at the American University of Beirut Medical Center (AUBMC). Data for patients 18 years or older, with clinically apparent early stage, grade 1 or 2, endometrioid EC, who underwent hysterectomy ± lymph node dissection (LND) at AUBMC between January 1st 1996 and June 30th 2016 were retrospectively reviewed. 70 patients were included. The overall concordance between FS and FP was 92.3% for histological subtype, 77% for tumour grade, 82% for Myometrial invasion (MI) and 100% for tumour size. At a median follow up of 30 months, 8 recurrences (11.4%) were noted, with a 5-year PFS and OS of 76 and 84% respectively, with a trend towards lower recurrence and improved survival in patients who underwent FS or LND.Impact statement What is already known on this subject? Hysterectomy and bilateral salpingo-oophorectomy is the standard surgery for stage I endometrial cancer (EC). Intraoperative frozen section (FS) facilitates the decision on performing lymph node dissection (LND). However, its accuracy and clinical impact have been questioned. What do the results of this study add? Our objective is to compare FS with the final pathology (FP), and determine its clinical impact in clinically apparent early stage EC at the American University of Beirut Medical Center (AUBMC). There is a lack of standardisation regarding FS use and reporting at AUBMC. What are the implications of these findings for clinical practice and/or further research? The strong correlation between FS and FP can serve as a tool to guide decision to perform LND in patients with apparent early stage disease, where use of sentinel LN biopsy technique is not available

Pancreatic surgery outcomes: multicentre prospective snapshot study in 67 countries

Background: Pancreatic surgery remains associated with high morbidity rates. Although postoperative mortality appears to have improved with specialization, the outcomes reported in the literature reflect the activity of highly specialized centres. The aim of this study was to evaluate the outcomes following pancreatic surgery worldwide.Methods: This was an international, prospective, multicentre, cross-sectional snapshot study of consecutive patients undergoing pancreatic operations worldwide in a 3-month interval in 2021. The primary outcome was postoperative mortality within 90 days of surgery. Multivariable logistic regression was used to explore relationships with Human Development Index (HDI) and other parameters.Results: A total of 4223 patients from 67 countries were analysed. A complication of any severity was detected in 68.7 percent of patients (2901 of 4223). Major complication rates (Clavien-Dindo grade at least IIIa) were 24, 18, and 27 percent, and mortality rates were 10, 5, and 5 per cent in low-to-middle-, high-, and very high-HDI countries respectively. The 90-day postoperative mortality rate was 5.4 per cent (229 of 4223) overall, but was significantly higher in the low-to-middle-HDI group (adjusted OR 2.88, 95 per cent c.i. 1.80 to 4.48). The overall failure-to-rescue rate was 21 percent; however, it was 41 per cent in low-to-middle-compared with 19 per cent in very high-HDI countries.Conclusion: Excess mortality in low-to-middle-HDI countries could be attributable to failure to rescue of patients from severe complications. The authors call for a collaborative response from international and regional associations of pancreatic surgeons to address management related to death from postoperative complications to tackle the global disparities in the outcomes of pancreatic surgery (NCT04652271; ISRCTN95140761)

Cardiac myosin activation with omecamtiv mecarbil in systolic heart failure

BACKGROUND The selective cardiac myosin activator omecamtiv mecarbil has been shown to improve cardiac function in patients with heart failure with a reduced ejection fraction. Its effect on cardiovascular outcomes is unknown. METHODS We randomly assigned 8256 patients (inpatients and outpatients) with symptomatic chronic heart failure and an ejection fraction of 35% or less to receive omecamtiv mecarbil (using pharmacokinetic-guided doses of 25 mg, 37.5 mg, or 50 mg twice daily) or placebo, in addition to standard heart-failure therapy. The primary outcome was a composite of a first heart-failure event (hospitalization or urgent visit for heart failure) or death from cardiovascular causes. RESULTS During a median of 21.8 months, a primary-outcome event occurred in 1523 of 4120 patients (37.0%) in the omecamtiv mecarbil group and in 1607 of 4112 patients (39.1%) in the placebo group (hazard ratio, 0.92; 95% confidence interval [CI], 0.86 to 0.99; P = 0.03). A total of 808 patients (19.6%) and 798 patients (19.4%), respectively, died from cardiovascular causes (hazard ratio, 1.01; 95% CI, 0.92 to 1.11). There was no significant difference between groups in the change from baseline on the Kansas City Cardiomyopathy Questionnaire total symptom score. At week 24, the change from baseline for the median N-terminal pro-B-type natriuretic peptide level was 10% lower in the omecamtiv mecarbil group than in the placebo group; the median cardiac troponin I level was 4 ng per liter higher. The frequency of cardiac ischemic and ventricular arrhythmia events was similar in the two groups. CONCLUSIONS Among patients with heart failure and a reduced ejection, those who received omecamtiv mecarbil had a lower incidence of a composite of a heart-failure event or death from cardiovascular causes than those who received placebo. (Funded by Amgen and others; GALACTIC-HF ClinicalTrials.gov number, NCT02929329; EudraCT number, 2016 -002299-28.)