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Abstract Background Say‐Barber‐Biesecker‐Young‐Simpson (SBBYSS) variant of Ohdo syndrome is a rare, autosomal dominant and clinically heterogenous disorder, caused by pathogenic variants in the KAT6B gene located on chromosome 10q22.2. KAT6B encodes a highly conserved histone acetyltransferase belonging to the MYST family. Currently, diseases caused by pathogenic variants in KAT6B (KAT6B‐related disorders) comprise two allelic entities: SBBYSS variant of Ohdo syndrome and genitopatellar syndrome (GPS). Increase in the number of cases with overlapping GPS/SBBYSS phenotype which makes it necessary to redefine this group of phenotypes as KAT6B‐related disorders or KAT6B spectrum disorders. Individuals with SBBYSS usually present with facial abnormalities, hypotonia, joint laxity, feeding problems, and long thumbs/great toes. This syndrome also typically involves skeletal problems including patellar hypoplasia/agenesis. Methods Here we report six SBBYS syndrome patients with the same dysmorphic features but a different course of the disease. One known and five novel KATB6 pathogenic variants were identified by molecular diagnostics using Next Generation Sequencing (NGS). Results We present a detailed phenotypic analysis of six individuals with KAT6B‐related disorders, in whom a heterozygous pathogenic variant in KAT6B gene was found. In all of our patients facial dysmorphism as well as developmental and speech delay were present. Additionally, all but one patients presented with hypotonia, ocular abnormalities and long thumbs. Most of our probands showed blepharophimosis and skeletal (mainly knee) defects. Contrary to previously reported severe patellar defects (hypoplasia/agenesis) anomalies presented by our patients were less severe (dysplasia, habitual dislocation, subluxation) referring to KAT6B‐related disorders. Conclusion While most of the anomalies found in our patients comply with SBBYSS criteria, phenotypic differences in our probands support a broader spectrum of the disease phenotype. To establish the range of this spectrum, a detailed analysis of clinical variability among patients with SBBYSS requires further investigation.

Humanoid robots have shown to provide interesting perspectives for autistic children. Yet, few studies have looked at educators' point of view on the use of such robots in educational settings. This paper presents a case study of the use of a humanoid robot, NAO, in a French preschool class dedicated to autistic children. Our work focuses on the perspectives of the adults working with these children. We interviewed the professional staff about changes in their teaching due to the presence of the robot, about the effects on the pupils' behaviour, and about the collaboration between the special needs teacher, the special needs support worker and the operational specialist from the digital education department of the district academic head office. Four themes were identified: joint reflection and collaboration when working with NAO, working with NAO, impact of NAO on pupils, impact of NAO on adults. The professionals underscored the necessity of adopting certain attitudes, in particular, the most neutral facial expression possible, so as not to disturb the children's learning process. They were under the impression that the robot had a beneficial effect on the pupils in terms of learning and social skills, and that it facilitated collaboration among them.

We present results from the Cosmic Evolution Early Release Survey on the stellar population parameters for 28 galaxies with redshifts 4 < z < 9 using imaging data from the James Webb Space Telescope (JWST) Mid-Infrared Instrument (MIRI) combined with data from the Hubble Space Telescope and the Spitzer Space Telescope. The JWST/MIRI 5.6 and 7.7 μ m data extend the coverage of the rest-frame spectral energy distribution to nearly 1 μ m for galaxies in this redshift range. By modeling the galaxies’ SEDs the MIRI data show that the galaxies have, on average, rest-frame UV (1600 Å)— I -band colors 0.4 mag bluer than derived when using photometry that lacks MIRI. Therefore, the galaxies have lower ratios of stellar mass to light. The MIRI data reduce the stellar masses by $\langle {\rm{\Delta }}\mathrm{log}{M}_{* }\rangle =0.25$ dex at 4 < z < 6 and 0.37 dex at 6 < z < 9. This also reduces the star formation rates (SFRs) by 〈ΔlogSFR〉 = 0.14 dex at 4 < z < 6 and 0.27 dex at 6 < z < 9. The MIRI data also improve constraints on the allowable stellar mass formed in early star formation. We model this using a star formation history that includes both a “burst” at z _f = 100 and a slowly varying (“delayed- τ ”) model. The MIRI data reduce the allowable stellar mass by 0.6 dex at 4 < z < 6 and by ≈1 dex at 6 < z < 9. Applying these results globally, this reduces the cosmic stellar-mass density by an order of magnitude in the early Universe ( z ≈ 9). Therefore, observations of rest-frame ≳1 μ m are paramount for constraining the stellar-mass buildup in galaxies at very high redshifts.

Hypopharyngeal cancer is a poorly characterized type of head and neck squamous cell carcinoma (HNSCC) with bleak prognosis and only few studies focusing specifically on the genomic profile of this type of cancer. We performed molecular profiling of 48 HPV (Human Papilloma Virus)-negative tumor samples including 23 originating from the hypopharynx and 25 from the larynx using a targeted next-generation sequencing approach. Among genes previously described as significantly mutated, TP53, FAT1, NOTCH1, KMT2C, and CDKN2A were found to be most frequently mutated. We also found that more than three-quarters of our patients harbored candidate actionable or prognostic alterations in genes belonging to RTK/ERK/PI3K, cell-cycle, and DNA-damage repair pathways. Using previously published data we compared 67 hypopharyngeal cancers to 595 HNSCC from other sites and found no prominent differences in mutational frequency except for CASP8 and HRAS genes. Since we observed relatively frequent mutations of KTM2C (MLL3) in our dataset, we analyzed their role, in vitro, by generating a KMT2C-mutant hypopharyngeal cancer cell line FaDu with CRISPR-Cas9. We demonstrated that KMT2C loss-of-function mutations resulted in increased colony formation and proliferation, in concordance with previously published results. In summary, our results show that the mutational profile of hypopharyngeal cancers might be similar to the one observed for other head and neck cancers with respect to minor differences and includes multiple candidate actionable and prognostic genetic alterations. We also demonstrated, for the first time, that the KMT2C gene may play a role of tumor suppressor in HNSCC, which opens new possibilities in the search for new targeted treatment approaches.

We use medium- and high-resolution spectroscopy of close pairs of quasars to analyze the circumgalactic medium (CGM) surrounding 32 damped Ly α absorption systems (DLAs). The primary quasar sightline in each pair probes an intervening DLA in the redshift range 1.6 < z _abs < 3.5, such that the secondary sightline probes absorption from Ly α and a large suite of metal-line transitions (including O i , C ii , C iv , Si ii , and Si iv ) in the DLA host galaxy’s CGM at transverse distances 24 kpc ≤ R _⊥ ≤ 284 kpc. Analysis of Ly α in the CGM sightlines shows an anticorrelation between R _⊥ and H i column density ( N _HI ) with 99.8% confidence, similar to that observed around luminous galaxies. The incidences of C ii and Si ii with N > 10 ^13 cm ^−2 within 100 kpc of DLAs are larger by 2 σ than those measured in the CGM of Lyman break galaxies (C _f ( N _C _II ) > 0.89 and ${{\rm{C}}}_{f}({N}_{\mathrm{Si}{\rm\small{II}}})={0.75}_{-0.17}^{+0.12}$ ). Metallicity constraints derived from ionic ratios for nine CGM systems with negligible ionization corrections and N _HI > 10 ^18.5 cm ^−2 show a significant degree of scatter (with metallicities/limits across the range $-2.06\lesssim \mathrm{log}Z/{Z}_{\odot }\lesssim -0.75$ ), suggesting inhomogeneity in the metal distribution in these environments. Velocity widths of C iv λ 1548 and low-ionization metal species in the DLA versus CGM sightlines are strongly (>2 σ ) correlated, suggesting that they trace the potential well of the host halo over R _⊥ ≲ 300 kpc scales. At the same time, velocity centroids for C iv λ 1548 differ in DLA versus CGM sightlines by >100 km s ^−1 for ∼50% of velocity components, but few components have velocities that would exceed the escape velocity assuming dark matter host halos of ≥10 ^12 M _⊙ .

Azomethine ylides are nitrogen-based three-atom components commonly used in [3+2]-cycloaddition reactions with various unsaturated 2π-electron components. These reactions are highly regio- and stereoselective and have attracted the attention of organic chemists with respect to the construction of diverse heterocycles potentially bearing four new contiguous stereogenic centers. This review article complies the most important [3+2]-cycloaddition reactions of azomethine ylides with various olefinic, unsaturated 2π-electron components (acyclic, alicyclic, heterocyclic, and exocyclic ones) reported over the past two decades.

Barrett’s esophagus (BE) is a change in the distal esophageal mucosal lining, whereby metaplastic columnar epithelium replaces squamous epithelium of the esophagus. This change represents a pre-malignant mucosal transformation which has a known association with the development of esophageal adenocarcinoma. Gastroesophageal reflux disease is a risk factor for BE, other risk factors include patients who are Caucasian, age > 50 years, central obesity, tobacco use, history of peptic stricture and erosive gastritis. Screening for BE remains selective based on risk factors, a screening program in the general population is not routinely recommended. Diagnosis of BE is established with a combination of endoscopic recognition, targeted biopsies, and histologic confirmation of columnar metaplasia. We aim to provide a comprehensive review of the epidemiology, pathogenesis, screening and advanced techniques of detecting and eradicating Barrett’s esophagus.

IMPORTANCE:. Factors associated with mortality in coronavirus disease 2019 patients on invasive mechanical ventilation are still not fully elucidated. OBJECTIVES:. To identify patient-level parameters, readily available at the bedside, associated with the risk of in-hospital mortality within 28 days from commencement of invasive mechanical ventilation or coronavirus disease 2019. DESIGN, SETTING, AND PARTICIPANTS:. Prospective observational cohort study by the global Coronavirus Disease 2019 Critical Care Consortium. Patients with laboratory-confirmed coronavirus disease 2019 requiring invasive mechanical ventilation from February 2, 2020, to May 15, 2021. MAIN OUTCOMES AND MEASURES:. Patient characteristics and clinical data were assessed upon ICU admission, the commencement of invasive mechanical ventilation and for 28 days thereafter. We primarily aimed to identify time-independent and time-dependent risk factors for 28-day invasive mechanical ventilation mortality. RESULTS:. One-thousand five-hundred eighty-seven patients were included in the survival analysis; 588 patients died in hospital within 28 days of commencing invasive mechanical ventilation (37%). Cox-regression analysis identified associations between the hazard of 28-day invasive mechanical ventilation mortality with age (hazard ratio, 1.26 per 10-yr increase in age; 95% CI, 1.16–1.37; p < 0.001), positive end-expiratory pressure upon commencement of invasive mechanical ventilation (hazard ratio, 0.81 per 5 cm H2O increase; 95% CI, 0.67–0.97; p = 0.02). Time-dependent parameters associated with 28-day invasive mechanical ventilation mortality were serum creatinine (hazard ratio, 1.28 per doubling; 95% CI, 1.15–1.41; p < 0.001), lactate (hazard ratio, 1.22 per doubling; 95% CI, 1.11–1.34; p < 0.001), Paco2 (hazard ratio, 1.63 per doubling; 95% CI, 1.19–2.25; p < 0.001), pH (hazard ratio, 0.89 per 0.1 increase; 95% CI, 0.8–14; p = 0.041), Pao2/Fio2 (hazard ratio, 0.58 per doubling; 95% CI, 0.52–0.66; p < 0.001), and mean arterial pressure (hazard ratio, 0.92 per 10 mm Hg increase; 95% CI, 0.88–0.97; p = 0.003). CONCLUSIONS AND RELEVANCE:. This international study suggests that in patients with coronavirus disease 2019 on invasive mechanical ventilation, older age and clinically relevant variables monitored at baseline or sequentially during the course of invasive mechanical ventilation are associated with 28-day invasive mechanical ventilation mortality hazard. Further investigation is warranted to validate any causative roles these parameters might play in influencing clinical outcomes.

In this review a short account of our work on the synthesis and biological activity of electrically neutral and charged anti-HIV and anticancer pronucleotides, presented on the background of the contemporary research in this area, is given.

Abstract Background The genetic etiology of intellectual and psychomotor disability without a defined spectrum of dysmorphic features is usually monogenic. As no diagnostic criteria for such diseases are established, the clinical diagnosis becomes to be a challenge. The object of our paper is to present two patients with non‐specific clinical symptoms for whom whole‐exome‐sequencing identified the new SON mutations and thus allowed for establishing the diagnosis of Zhu‐Tokita‐Takenouchi‐Kim (ZTTK) syndrome. In both patients, the same symptoms including hypotonia, developmental and speech delay, feeding difficulties as well as frequent infections of the respiratory tract and internal ear were observed. However, both cases presented also with exceptional symptoms such as in case 1 ventriculomegaly and asymmetry of ventricles, hypoplastic left heart syndrome (HLHS), intellectual disability, intestinal malrotation, gastroparesis, and duodenal atresia and in the case 2 febrile seizures and reduced IgA levels. We will be presenting the patients and comparing them to 30 previously described cases. Methods Whole‐exome sequencing (WES) was performed on the probands’ DNA and paired‐end sequenced (2x100 bp) on HiSeq 1500. Variants considered as disease‐causing were validated in the proband and studied in all available family members by amplicon deep sequencing performed using Nextera XT Kit and sequenced on HiSeq 1500. Results We have identified two new variants in SON gene. In case 1 it has been a heterozygous frameshift variant p.(Ala1340GlnfsTer26), while in case 2 it has been a heterozygous frameshift variant, p.(Asp1640GlyfsTer7). Both variants are described for the first time and up to now, are not mentioned in any database. Conclusion As there are no precise criteria established for the clinical diagnosis of ZTTK, an identification of SON gene mutation by whole‐exome‐sequencing is the best method that allows for a diagnosis of this syndrome.

The article is an overview of various methods of braking and controlling the movement of the piston rod under various load conditions. The purpose of this review is to systematize the state of the art in terms of efficiency, energy consumption and limitations of each method. The article discusses systems with different types of hydraulic actuators, operating under passive, active and variable load during the duty cycle of the piston rod. The existing literature was analysed in terms of applicability, reduction of energy consumption of the systems and even the possibility of energy return. Attention was paid to the costs and the need for additional power sources, as well as the problems and limitations of the presented methods. Based on the simulation model, energy consumption tests were carried out in systems with an actuator loaded with a variable force. There is a comparison of all methods in terms of actuator type, load, energy consumption and the possibility of energy recovery.

This article intends to reflect on object and method in linguistic studies considering the Saussurean point of view. The starting point will be phonic aspect of language, given the importance this reflection has in the initial outlines by the then young linguist Ferdinand de Saussure. We will use two works to do this: Course in General Linguistics, a work regarded as a framework for linguistics, and the Phonétique manuscript, written by the Genevan between 1883-1884 and made public in its entirety for the first time in 1995, by Maria Pia Marchese. Thus, we will address fundamental questions of Saussure's theoretical construction, which go through the problem of linguistic unity – its delimitations and method by which they must be defined. This will lead us to highlight the complexity with which Saussure detailed the differences between what would be the phonetic and phonological point of view to his contemporaries and his own conception of a "Phonétique", starting from the concreteness of discourse and anchored in the abstraction of the linguistic system. --- DOI: http://dx.doi.org/10.22409/gragoata.2017n44a999

Abstract Autosomal recessive diseases (ARD) are typically caused by a limited number of mutations whose identification is challenged by their low prevalence. Our purpose was to develop a novel approach allowing an efficient search for mutations causing ARD and evaluation of their pathogenicity without a control group. We developed Iterative Sequencing and Variant Screening (ISVS) approach based on iterative cycles of gene sequencing and mutation screening, and ISVS Simulator software ( http://zsibio.ii.pw.edu.pl/shiny/isvs/ ) for assessment of detected variants’ significance. As shown by simulations, ISVS efficiently identifies and correctly classifies pathogenic mutations except for cases where the gene of interest has extremely high number of low frequency nonpathogenic variants. By applying ISVS, we found 4 known and 9 novel (p.C73Y, p.S124L, p.C194Mfs*17, c.782 + 2 T > A, c.953-5 A > G, p.L325Q, p.D334Mfs*24, p.R436G, p.M448T) TMPRSS3 variants among deaf patients. For 3 known and 5 novel variants the disease association was supported by ISVS Simulator odds >90:1. Pathogenicity of 6 novel mutations has been supported by in-silico predictions of variants’ deleteriousness. By directly comparing variant prevalence in patients and controls, disease association was demonstrated only for two variants and it was relatively weak (P

NF-κB signaling, acting through NFKB1 dependent canonical and NFKB2 dependent non-canonical pathways plays a critical role in inflammatory and immune responses. Recent studies have associated mutations in these two genes with a common variable immunodeficiency (CVID). While evaluating a female patient seeking a diagnosis explaining her recurrent infections, we found a novel heterozygous c.1831C > T (p.Arg611∗) nonsense mutation in the NFKB2 gene which introduces a Stop codon in the ankyrin repeat domain of p100. Whole exome sequencing (WES) analysis, followed by Sanger sequencing, identified this previously unknown mutation in two other family members. Penetrance of the c.1831C > T variant was assessed by flow-cytometry and protein expression in peripheral blood mononuclear cells (PBMC); whereas, activation of the NF-κB2 signaling pathway was examined through immunoblotting and real-time PCR. Heterozygous c.1831C > T variant led to the expansion of lymphocyte B subpopulations with concomitant reduction of plasmablasts, low IgG levels, and accumulation of p52 in PBMC. On the other hand, tested subjects had normal levels of IgM, IgA, IgE and no impairment in lymphocytes proliferation. Although evaluated patients did not fulfill all clinical features of CVID, their health should be monitored in the future for possible late manifestation of the disease. In conclusion, we showed that NFKB2 haplodeficiency caused by c.1831C > T nonsense mutation is asymptomatic, possibly due to the compensatory mechanisms and allele redundancy.

This review provides a short account of the chemical synthesis of nucleoside di- and triphosphates on a historical background, together with the use of this class of compounds as potential pronucleotides in anti-HIV therapy.

The article presents the experimental investigation of low-lifting capacity hydraulic scissor lift energy consumption. The analysis is based on experimental tests of two individual drives of the scissor lift: the conventional one and the variable-speed electro-hydraulic one. The investigation focuses on the study of the total energy consumption for lifting and lowering the scissor lift with different masses of transported cargo and also power consumptions of each element supplying these systems. Particular attention was paid to the significant impact of power supply on each control component as the main factor of reduction in the energetic efficiency of the low-lifting capacity scissor lift. A comparison of both drives indicated that the mass of transported cargo has a significant influence on the choice of the drive used. Results of the research show that significant energetic savings are obtained, as the modernized propulsion system consumes 67% energy of the standard one. A decrease in the percentage of energy losses with the increase in the mass handled led to the conclusion that the enhancement of propulsion systems in scissor lifts should be especially considered in machines carrying big loads.

Introdução: O Ministério da Saúde incluiu a vacina contra o Papilomavírus Humano (HPV) no calendário básico de imunizações em 2014 com a meta vacinar pelo menos 80% das adolescentes entre 11 e 13 anos de idade. Objetivos: Frente à baixa adesão à campanha nacional de vacinação contra o HPV no município de Maringá, PR, em 2014, o presente estudo teve como objetivos: 1) identificar o nível de conhecimento das adolescentes acerca do vírus e da vacina; e 2) descrever os motivos pelos quais elas não se vacinaram. Métodos: Trata-se de um estudo observacional transversal, do tipo inquérito domiciliar com delineamento descritivo, conduzido com 58 adolescentes que não tomaram a 1ª e/ou a 2ª dose da vacina dentro do prazo estipulado pela campanha vacinal de 2014. Para coleta de dados, foi aplicado questionário por meio de entrevistas face a face. Resultados: 86% das adolescentes já ouviram falar do vírus, 74% sabe que sua transmissão é sexual, 49% conhece sua relação com o câncer de colo de útero e 88% já ouviu falar da vacina. A maior parte das meninas entrevistadas não se vacinou por recusa por parte dos pais. Conclusão: Os resultados do presente estudo sugerem que o desconhecimento sobre a infecção pelo HPV e sobre a campanha de vacinação entre as entrevistadas e seus responsáveis, bem como o medo de efeitos colaterais da vacina, como apontado pela população do estudo, interferiram negativamente na tomada de decisão.

TTN gene truncating variants are common in dilated cardiomyopathy (DCM), although data on their clinical significance is still limited. We sought to examine the frequency of truncating variants in TTN in patients with DCM, including familial DCM (FDCM), and to look for genotype-phenotype correlations. Clinical cardiovascular data, family histories and blood samples were collected from 72 DCM probands, mean age of 34 years, 45.8% FDCM. DNA samples were examined by next generation sequencing (NGS) with a focus on the TTN gene. Truncating mutations were followed up by segregation study among family members. We identified 16 TTN truncating variants (TTN trunc) in 17 probands (23.6% of all cases, 30.3% of FDCM, 17.9% of sporadic DCM). During mean 63 months from diagnosis, there was no difference in adverse cardiac events between probands with and without TTN truncating mutations. Among relatives 29 mutation carriers were identified, nine were definitely affected (31%), eight probably affected (27.6%) one possibly affected (3.4%) and eleven were not affected (37.9%). When relatives with all affected statuses were combined, disease penetrance was still incomplete (62.1%) even after exclusion of unaffected relatives under 40 (82%) and was higher in males versus females. In all mutation carriers, during follow-up, 17.4% had major adverse cardiac events, and prognosis was significantly worse in men than in women. In conclusion, TTN truncating variants were observed in nearly one fourth of young DCM patient population, in vast majority without conduction system disease. Incomplete penetrance suggests possible influence of other genetic and/or environmental factors on the course of cardiotitinopathy. Counseling should take into account sex and incomplete penetrance.

Several trap plasmids (enabling positive selection of transposition events) were used to identify a pool of functional transposable elements (TEs) residing in bacteria of the genus Paracoccus (Alphaproteobacteria). Complex analysis of 25 strains representing 20 species of this genus led to the capture and characterization of (i) 37 insertion sequences (ISs) representing 9 IS families (IS3, IS5, IS6, IS21, IS66, IS256, IS1182, IS1380 and IS1634), (ii) a composite transposon Tn6097 generated by two copies of the ISPfe2 (IS1634 family) containing two predicted genetic modules, involved in the arginine deiminase pathway and daunorubicin/doxorubicin resistance, (iii) 3 non-composite transposons of the Tn3 family, including Tn5393 carrying streptomycin resistance and (iv) a transposable genomic island TnPpa1 (45 kb). Some of the elements (e.g. Tn5393, Tn6097 and ISs of the IS903 group of the IS5 family) were shown to contain strong promoters able to drive transcription of genes placed downstream of the target site of transposition. Through the application of trap plasmid pCM132TC, containing a promoterless tetracycline resistance reporter gene, we identified five ways in which transposition can supply promoters to transcriptionally silent genes. Besides highlighting the diversity and specific features of several TEs, the analyses performed in this study have provided novel and interesting information on (i) the dynamics of the process of transposition (e.g. the unusually high frequency of transposition of TnPpa1) and (ii) structural changes in DNA mediated by transposition (e.g. the generation of large deletions in the recipient molecule upon transposition of ISPve1 of the IS21 family). We also demonstrated the great potential of TEs and transposition in the generation of diverse phenotypes as well as in the natural amplification and dissemination of genetic information (of adaptative value) by horizontal gene transfer, which is considered the driving force of bacterial evolution.

The high-quality cardiothoracic surgery program is primed for mindful effective surgery. The challenge lies in attaining mindful skills and efficiency. Herein is one journey toward high departmental quality over two decades. [ABSTRACT FROM AUTHOR]

Tumours of the urinary tract are the fifth most frequent type of cancer. The most common types are urothelial tumours, among which, non-invasive urothelial neoplasms represent 45% of all cases. The 2016 WHO classification of urinary tract tumours introduced new classifications of non-invasive lesions. Besides urothelial papilloma (UP) and papillary urothelial neoplasm of low malignant potential (PUNLMP), as described in the former classification, the new classification also includes new entities such as urothelial proliferation of uncertain malignant potential (UPUMP) and urothelial dysplasia (UD). Of the aforementioned, UPUMP is the lesion that most commonly progresses, but solely to non-invasive carcinomas. UD is associated with a high risk of progression to invasive carcinoma. Understanding the biological character, and establishing the correct differential diagnosis in cases of non-invasive, non-cancerous lesions of the urinary bladder, will be of importance in establishing outcome predictions for future patients. A systematic review of the current literature allows us to systematize genetic, morphologic and prognostic factors of such lesions. Moreover, the collected data provide the basis for a proposed diagnostic algorithm which facilitates quick and effective differential diagnoses in cases of non-invasive non-cancerous urinary bladder lesions. • The correct diagnosis of urinary bladder lesions is important for outcome prediction. • The type of urinary bladder lesion implicates biological behaviour. • The explanation of genetic and morphologic features helps in clinical proceedings. • Our diagnostic algorithm could simplify differential diagnosis. [ABSTRACT FROM AUTHOR]

Age has traditionally been a limiting factor for advanced heart failure (HF) therapies. Orthotopic heart transplantation (OHT) age guidelines have become less restrictive, and left ventricular assist devices (LVADs) are increasingly utilized as destination therapy for patients ≥65 years. Although indications differ, we assessed outcomes for both modalities in this older population. We reviewed charts of consecutive advanced HF therapy recipients aged ≥65 years at our center from 2012 to 2016. Of 118 patients evaluated, 46 (39%) received an LVAD and 72 (61%) received OHT. Gender, body mass index, and rate of prior sternotomy were similar between groups; OHT recipients were younger, less likely to have diabetes mellitus, and more likely to have HF due to ischemic etiology. Forty-six percent of patients receiving LVADs were urgent need (Interagency Registry for Mechanically Assisted Circulatory Support [INTERMACS] profile 1–2), compared to 29% of patients receiving OHT (United Network for Organ Sharing 1A criteria; P = 0.068). OHT recipients had shorter lengths of stay and better 1-year survival compared to LVAD recipients. Although many centers do not offer advanced HF therapy to patients aged ≥65 years, our results indicate that age alone should not be prohibitive for advanced HF therapy, particularly OHT. [ABSTRACT FROM AUTHOR]