In-hospital outcomes of transapical versus surgical aortic valve replacement: from the U.S. national inpatient sample

OBJECTIVETo compare the outcomes of transapical transcatheter aortic valve replacement (TA-TAVR) and surgical aortic valve replacement (SAVR) using a large US population sample.METHODSThe U.S. National Inpatient Sample was queried for all patients who underwent TA-TAVR or SAVR during the years 2016−2017. The primary outcome was all-cause in-hospital mortality. Secondary outcomes were in-hospital stroke, pericardiocentesis, pacemaker insertion, mechanical ventilation, vascular complications, major bleeding, acute kidney injury, length of stay, and cost of hospitalization. Outcomes were modeled using multi-variable logistic regression for binary outcomes and generalized linear models for continuous outcomes.RESULTSA total of 1560 TA-TAVR and 44,280 SAVR patients were included. Patients who underwent TA-TAVR were older and frailer. Compared to SAVR, TA-TAVR correlated with a higher mortality (4.5% vs. 2.7%, effect size (SMD) = 0.1) and higher periprocedural complications. Following multivariable analysis, both TA-TAVR and SAVR had a similar adjusted risk for in-hospital mortality. TA-TAVR correlated with lower odds of bleeding with (adjusted OR (aOR) = 0.26; 95% CI: 0.18−0.38;P < 0.001), and a shorter length of stay (adjusted mean ratio (aMR) = 0.77; 95% CI: 0.69−0.84; P < 0.001), but higher cost (aMR = 1.18; 95% CI: 1.10−1.28; P < 0.001). No significant differences in other study outcomes. In subgroup analysis, TA-TAVR in patients with chronic lung disease had higher odds for mortality (aOR = 3.11; 95%CI: 1.37−7.08; P = 0.007). CONCLUSIONThe risk-adjusted analysis showed that TA-TAVR has no advantage over SAVR except for patients with chronic lung disease where TA-TAVR has higher mortality.

Trans-apical aortic valve replacement (TA-TAVR) is typically reserved for patients who have unfavorable transfemoral approach.^[1] Several studies investigated the clinical outcomes of transfemoral-(TF) TAVR vs. surgical aortic valve replacement (SAVR); but there is paucity of data about the outcomes of TA-TAVR compared to SAVR. The STACCATO trial was the first randomized controlled trial to compare TA-TAVR versus SAVR. Though it was small trial (included only 70 operable patients) and was terminated prematurely (due to major adverse events in the TA-TAVR), it heralded a better outcome of SAVR when compared to TA-TAVR.^[2] Current trends in the U.S. show a steady decline in TA-TAVR procedures with a decrease in the rates of TAVR-related complications, such as stroke and need for pacemaker insertion. However, there has been no change in the risk of mortality or other peri-procedural complications.^[3]In this study, we aim to elucidate the applicability and safety of TA-TAVR when compared with SAVR. To our knowledge, this is the first retrospective cohort in the literature that compares the outcomes of TA-TAVR vs. SAVR in a national sample representative of the U.S. population.     

The anti-leukaemic activity of novel synthetic naphthoquinones against acute myeloid leukaemia: induction of cell death via the triggering of multiple signalling pathways

Naphthoquinones, such as menadione, display lower toxicity than anthracyclins used in cancer chemotherapy. Novel anti-leukaemic compounds comprised of chloro-amino-phenyl naphthoquinones with substitutions on the benzoic ring were developed. Structure–activity relationship studies indicated that the analogue with both methyl and amine substitutions (named TW-92) was the most efficient in killing leukaemic cells. Treatment of U-937 promonocytic cells with TW-92 induced apoptotic or necrotic cell death, dependent on incubation and dose conditions. TW-92 induced rapid phosphorylation of p38 mitogen-activated protein kinase (p38^MAPK) and of extracellular signal-regulated protein kinases (ERK1/2). The generation of apoptosis was preceded by intracellular H₂O₂ accumulation accompanied by glutathione depletion, the former inhibited by di-phenyl-iodonium (DPI), an inhibitor of NADPH oxidase. TW-92 induced swelling of isolated rat liver mitochondria, indicative of a direct effect on mitochondria. Apoptosis in intact cells was accompanied by a decrease in mitochondrial membrane potential, cytochrome c release and caspase activation. In addition, the level of Mcl-1, an anti-apoptotic regulatory protein, was down-regulated, whereas the expression of the pro-apoptotic BAX was elevated. Finally, TW-92 exerted strong pro-apoptotic and necrotic effects in primary acute myeloid leukaemia samples when given in submicromolar concentrations. Together, these findings demonstrate that TW-92 may provide an effective anti-leukaemic strategy.     

Airway intervention in adult supraglottitis

Background The timing of aggressive airway intervention in adult epiglottitis is controversial. Aims To correlate Friedman’s staging of epiglottitis on admission with the airway interventions undertaken. Methods A retrospective study of 23 adult patients, mean age 51 years (range 29–81 years), who had been admitted with acute supraglottitis between March 1988 and December 2000 was undertaken. Results Three patients (13%) had airway interventions; two with tracheostomy and one with tracheal intubation. All were Friedman stage III and had rapid symptom progression during the 24 hours prior to admission. Three other stage III patients with symptom progression longer than 24 hours and all the remaining patients (stage II or less) were managed with observation and intravenous therapy. Conclusions Friedman originally advocated airway intervention in any patient stage II or worse, but this intubation threshold should probably be lowered to those patients with rapid-onset stage III (moderate respiratory distress, stridor, respiratory rate >30 per minute, pCO₂ >45mmHg) disease.     

The hematopoietic stem cells of alpha-thalassemic mice

The alpha-thalassemic mouse has a hereditary microcytic anemia, almost certainly has a shortened RBC life span, and is a potential candidate for cell replacement therapy. In a routine study of bone marrow repopulating capacity using hemoglobin as a cell marker, normal donor marrow cells, but not alpha-thalassemic donor marrow cells, completely replaced the host cells. Further analysis showed that at least 30 times more alpha-thalassemic cells were required to outcompete normal donor cells injected simultaneously. The results were more extreme then expected and suggested a defect in a stem cell population as well as in the RBCs. Evidence that the multipotent and erythroid-committed stem cells in alpha-thalassemic mice are not decreased was shown by CFU-S and CFU-E assays. The combined results indicate that the deletion expresses itself most conspicuously in the RBC population. Tests were also performed to analyze repopulation kinetics in the Hbath-J/+ mice. In unirradiated alpha-thalassemic hosts, the hemoglobin from a normal donor persisted but did not replace the host hemoglobin. Sublethally irradiated alpha-thalassemic hosts, on the other hand, were easily repopulated with normal cells. We conclude that the alpha-thalassemic mouse is a good model for cell replacement therapy.     

Relationships of sleep duration with sociodemographic and health‐related factors,psychiatric disorders and sleep disturbances in a community sample of Korean adults

The aim of this study is to examine relationships of sleep duration with sociodemographic and health‐related factors, psychiatric disorders and sleep disturbances in a nationwide sample in Korea. A total of 6510 subjects aged 18–64 years participated in this study. Logistic regression was used to calculate the odd ratios and 95% confidence intervals of the covariates, psychiatric disorders and sleep disturbances across the following sleep duration categories: 5 h or less, 6, 7, 8 and 9 h or more per day. Low levels of education, unemployment and physical illness were associated with sleeping for 5 h or less and 9 h or more. Being older and widowed/divorced/separated, high levels of physical activity, pain/discomfort, obesity and high scores on the General Health Questionnaires were associated with sleeping for 5 h or less. Female, being younger and underweight were associated with sleeping for 9 h or more. Alcohol dependence, anxiety disorder and social phobia were associated significantly with sleeping for 5 h or less and 9 h or more. Other psychiatric disorders were more common in subjects who slept for 5 h or less (e.g. alcohol use disorder, mood disorder, major depressive disorder, dysthymic disorder, obsessive‐compulsive disorder and specific phobia) or 9 h or more (e.g. post‐traumatic stress disorder). In addition, subjects who slept for 5 h or less reported more sleep disturbances than did subjects who slept for 7 h. Short or long sleep is associated with psychiatric disorders and/or sleep disturbance, therefore attention to the mental health of short or long sleepers is needed.     

Copy number variants in patients with short stature

Height is a highly heritable and classic polygenic trait. Recent genome-wide association studies (GWAS) have revealed that at least 180 genetic variants influence adult height. However, these variants explain only about 10% of the phenotypic variation in height. Genetic analysis of short individuals can lead to the discovery of novel rare gene defects with a large effect on growth. In an effort to identify novel genes associated with short stature, genome-wide analysis for copy number variants (CNVs), using single-nucleotide polymorphism arrays, in 162 patients (149 families) with short stature was performed. Segregation analysis was performed if possible, and genes in CNVs were compared with information from GWAS, gene expression in rodents'' growth plates and published information. CNVs were detected in 40 families. In six families, a known cause of short stature was found (SHOX deletion or duplication, IGF1R deletion), in two combined with a de novo potentially pathogenic CNV. Thirty-three families had one or more potentially pathogenic CNVs (n=40). In 24 of these families, segregation analysis could be performed, identifying three de novo CNVs and nine CNVs segregating with short stature. Four were located near loci associated with height in GWAS (ADAMTS17, TULP4, PRKG2/BMP3 and PAPPA). Besides six CNVs known to be causative for short stature, 40 CNVs with possible pathogenicity were identified. Segregation studies and bioinformatics analysis suggested various potential candidate genes.     

The preterm gut microbiota: changes associated with necrotizing enterocolitis and infection

Aim: To describe gut colonization in preterm infants using standard culture and 16S gene rRNA profiling, exploring differences in healthy infants and those who developed NEC/late onset sepsis (LOS). Methods: Ninety‐nine stools from 38 infants of median 27‐week gestation were cultured; 44 stools from 27 infants had their microbial profiles determined by 16S. Ordination analyses explored effects of patient variables on gut communities. Results: Standard microbiological culture identified a mean of two organisms (range 0–7), DGGE 12 (range 3–18) per patient. Enterococcus faecalis and coagulase negative staphylococci (CONS) were most common by culture (40% and 39% of specimens). Meconium was not sterile. No fungi were cultured. Bacterial community structures in infants with NEC and LOS differed from healthy infants. Infants who developed NEC carried more CONS (45% vs 30%) and less Enterococcus faecalis (31% vs 57%). 16S identified Enterobacter and Staphylococcus presence associated with NEC/LOS, respectively. Conclusions: Important differences were found in the gut microbiota of preterm infants who develop NEC/LOS. The relationship of these changes to current practices in neonatal intensive care requires further exploration.