Screening vs no screening for preterm delivery in low risk singleton pregnancies

Introduction: To compare the effect of a policy of screening for spontaneous preterm delivery (SPD) by transvaginal cervical length (CL) measurement versus a no screening policy in the prevention of severe prematurity. Methods: Retrospective study on low risk singleton pregnancies examined at 20-24 weeks. Two cohorts one with SPD screening and the other without screening were matched using propensity analysis to create the study groups. Women with short CL were treated with vaginal progesterone and/or cervical cerclage/pessary. The outcomes examined were SPD<32 weeks (SPD 32) and SPD between 20 and 32 weeks (SPD 20-32). Results: Screening for SPD was associated with a significant reduction in the rate of SPD at less than 32 weeks (0.3% vs 0.8%, p=0.001 in the screened and no screened pregnancies respectively) and in the rate of SPD 20-32 (0.3% vs 0.9%, p=0.005 in the screened and no screened pregnancies respectively). After adjusting for maternal age, parity, body mass index, smoking and mode of conception, the screening group had significantly lower hazard for SPD 20-32 (HR=0.36, 95% CI: 0.18-0.75, p=0.006) and SPD32 (HR=0.39, 95% CI: 0.19-0.82, p=0.013). Conclusion: Screening for SPD by transvaginal CL measurement in mid pregnancy may reduce the incidence of severe prematurity in low risk singleton pregnancies.

Prediction of allosteric sites and signalling: insights from benchmarking datasets

Allostery is a pervasive mechanism which regulates the activity of proteins in living systems through binding of a molecule at a distant site from the orthosteric site of the protein. The universality of allosteric regulation complemented by the benefits of highly specific, potentially non-toxic and protein activity modulating allosteric drugs makes uncovering allosteric sites on proteins invaluable for drug discovery. However, there are few computational methods to effectively predict them. Bond-to-bond propensity analysis, a recently developed method, has successfully predicted allosteric sites for a diverse group of proteins with only the knowledge of the orthosteric sites and the corresponding ligands in 19 of 20 cases. The method is based on an energy-weighted atomistic protein graph and allows for computationally highly efficient analysis in atomistic detail. We here extended the analysis onto 432 structures of 146 proteins from two existing benchmarking datasets for allosteric proteins: ASBench and CASBench. We further refined the metrics to account for the cumulative effect of residues with high propensities and the crucial residues in a given site with two additional measures. The allosteric site is recovered for 95/113 proteins (99/118 structures) from ASBench and 32/33 proteins (304/314 structures) from CASBench, with the only a priori knowledge being the orthosteric site residues. Knowing the orthosteric ligands of the protein, the allosteric site is identified for 32/33 proteins (308/314 structures) from CASBench.

Whatever happens, two mammary is better than one

It is well known that the left internal mammary artery (LIMA) should be the first conduit of choice. Similarly, especially in patients younger than 70 years, other conduits should be search among arterial grafts such as right internal mammary artery (RIMA) or radial artery (RA). If the RA can be harvested in the meanwhile of LIMA harvesting without time consuming, it is well established that former one has to be grafted only on presence of a good run-off. One of the main criticisms moved to the use of RIMA are linked to technical difficulties in its harvesting it. Edgar Aranda-Michel and coworkers tried to answer to the age-old question is “RIMA has to be used in situ or free-graft?” In a retrospective study on 667 patients (442 had free RIMA and 245 had free RIMA) that were also matched through propensity analysis (202 patients per group), they did not find any differences between the two groups in the major outcomes, including heart failure specific readmissions. This finding is consistent with the literature, hence the take-home message is whatever happens, two mammary is better than one.

Characteristics, management, and prognosis of elderly patients with COVID-19 admitted in the ICU during the first wave: insights from the COVID-ICU study

Background The COVID-19 pandemic is a heavy burden in terms of health care resources. Future decision-making policies require consistent data on the management and prognosis of the older patients (> 70 years old) with COVID-19 admitted in the intensive care unit (ICU). Methods Characteristics, management, and prognosis of critically ill old patients (> 70 years) were extracted from the international prospective COVID-ICU database. A propensity score weighted-comparison evaluated the impact of intubation upon admission on Day-90 mortality. Results The analysis included 1199 (28% of the COVID-ICU cohort) patients (median [interquartile] age 74 [72–78] years). Fifty-three percent, 31%, and 16% were 70–74, 75–79, and over 80 years old, respectively. The most frequent comorbidities were chronic hypertension (62%), diabetes (30%), and chronic respiratory disease (25%). Median Clinical Frailty Scale was 3 (2–3). Upon admission, the PaO2/FiO2 ratio was 154 (105–222). 740 (62%) patients were intubated on Day-1 and eventually 938 (78%) during their ICU stay. Overall Day-90 mortality was 46% and reached 67% among the 193 patients over 80 years old. Mortality was higher in older patients, diabetics, and those with a lower PaO2/FiO2 ratio upon admission, cardiovascular dysfunction, and a shorter time between first symptoms and ICU admission. In propensity analysis, early intubation at ICU admission was associated with a significantly higher Day-90 mortality (42% vs 28%; hazard ratio 1.68; 95% CI 1.24–2.27; p < 0·001). Conclusion Patients over 70 years old represented more than a quarter of the COVID-19 population admitted in the participating ICUs during the first wave. Day-90 mortality was 46%, with dismal outcomes reported for patients older than 80 years or those intubated upon ICU admission.

Thin Strut CoCr Biodegradable Polymer Biolimus A9-Eluting Stents versus Thicker Strut Stainless Steel Biodegradable Polymer Biolimus A9-Eluting Stents: Two-Year Clinical Outcomes

Background. While thinner struts are associated with improved clinical outcomes in bare-metal stents (BMS), reducing strut thickness may affect drug delivery from drug-eluting stents (DES) and there are limited data comparing otherwise similar thin and thick strut DES. We assessed 2-year outcomes of patients treated with a thin strut (84–88um) cobalt-chromium, biodegradable polymer, Biolimus A9-eluting stent (CoCr-BP-BES) and compared these to patients treated with a stainless steel, biodegradable polymer, Biolimus A9-eluting stent (SS-BP-BES). Methods. In total, 1257 patients were studied: 400 patients from 12 centres receiving ≥1 CoCr-BP-BES in the prospective Biomatrix Alpha registry underwent prespecified comparison with 857 patients who received ≥1 Biomatrix Flex SS-BP-BES in the LEADERS study (historical control). The primary outcome was major adverse cardiac events (MACE)—cardiac death, myocardial infarction (MI), or clinically driven target vessel revascularization (cd-TVR). Propensity analysis was used to adjust for differences in baseline variables and a landmark analysis at day-3 to account for differences in periprocedural MI definitions. Results. MACE at 2 years occurred in 6.65% CoCr-BP-BES versus 13.23% SS-BP-BES groups (unadjusted HR 0.48 [0.31–0.73]; P = 0.0005 ). Following propensity analysis, 2-year adjusted MACE rates were 7.4% versus 13.3% (HR 0.53 [0.35–0.79]; P = 0.004 ). Definite or probable stent thrombosis, adjudicated using identical criteria in both studies, occurred less frequently with CoCr-BP-BES (1.12% vs. 3.22%; adjusted HR 0.32 [0.11–0.9]; P = 0.034 ). In day-3 landmark analysis, the difference in 2-year MACE was no longer significant but there was a lower patient-orientated composite endpoint (11.7% vs. 18.4%; HR 0.6 [0.43–0.83]; P = 0.006 ) and a trend to lower target vessel failure (5.8% vs. 9.1%; HR 0.63 [0.4–1.00]; P = 0.078 ). Conclusion. At 2-year follow-up, propensity-adjusted analysis showed the thin strut (84–88um) Biomatrix Alpha CoCr-BP-BES was associated with improved clinical outcomes compared with the thicker strut (114–120um) Biomatrix Flex SS-BP-BES.