Systemic sclerosis is associated with increased in-patient mortality in patients hospitalized for heart failure.

AIMS: We aimed to analyse the characteristics and in-hospital outcomes of patients hospitalized for heart failure (HF) with co-morbid systemic sclerosis (SSc) and compare them to those without SSc, using data from the National Inpatient Sample from years 2016 to 2019. METHODS AND RESULTS: International Classification of Diseases, Tenth Revision diagnosis codes were used to identify hospitalized patients with a primary diagnosis of HF and secondary diagnoses of SSc from the National Inpatient Sample database from 2016 to 2019. Patients were divided into two groups: those with and without a secondary diagnosis of SSc. Baseline characteristics including demographics and co-morbidities, outcomes of mortality, length of stay (LOS), and costs were compared between the two groups. Multivariable logistic regression analysis was performed to adjust for confounders and assess the impact of SSc on in-hospital mortality, cost, and LOS. A total of 4 709 724 hospitalizations for HF were identified, with 8150 (0.17%) having a secondary diagnosis of SSc. These patients were predominantly female (82.3% vs. 47.8%; P = 0.01), younger (mean age of 67.4 vs. 71.4; P < 0.01), and had significantly lower rates of traditional cardiovascular risk factors such as coronary artery disease (35.8% vs. 50.6%; P < 0.01), hyperlipidaemia (39.1% vs. 52.9%; P < 0.01), diabetes (22.5% vs. 49.1%; P < 0.01), obesity (13.2% vs. 25.0%; P < 0.01), and hypertension (20.2% vs. 23.8%; P < 0.01). Higher rates of co-morbid pulmonary disease in the form of interstitial lung disease (23.1% vs. 2.0%; P < 0.01) and pulmonary hypertension (36.6% vs. 12.7%; P < 0.01) were noted in the SSc cohort. Unadjusted in-hospital mortality was significantly higher in the HF with SSc group [5.1% vs. 2.6%; odds ratio: 1.99; 95% confidence interval (CI): 1.60-2.48; P < 0.001]. Unadjusted mortality was also higher among female (86.7% vs. 47.0%; P < 0.01), Black (15.7% vs. 13.0%; P < 0.01), and Hispanic (13.3% vs. 6.9%; P < 0.01) patients in the SSc cohort. After adjusting for potential confounders, SSc remained independently associated with higher in-hospital mortality (adjusted odds ratio: 1.81; 95% CI: 1.44-2.28; P < 0.001). Patients with HF and SSc also had longer LOS (6.4 vs. 5.4; adjusted mean difference [AMD]: 0.37, 95% CI: 0.05-0.68; P = 0.02) and higher hospitalization costs ($67 363 vs. $57 128; AMD: 198.9; 95% CI: -4780 to 5178; P = 0.93). CONCLUSIONS: In patients hospitalized for HF, those with SSc were noted to have higher odds of in-hospital mortality than those without SSc. Patients with HF and SSc were more likely to be younger, female, and have higher rates of co-morbid interstitial lung disease and pulmonary hypertension at baseline with fewer traditional cardiovascular risk factors.

Artificial intelligence in rheumatoid arthritis: potential applications and future implications.

The widespread adoption of digital health records, coupled with the rise of advanced diagnostic testing, has resulted in an explosion of patient data, comparable in scope to genomic datasets. This vast information repository offers significant potential for improving patient outcomes and decision-making, provided one can extract meaningful insights from it. This is where artificial intelligence (AI) tools like machine learning (ML) and deep learning come into play, helping us leverage these enormous datasets to predict outcomes and make informed decisions. AI models can be trained to analyze and interpret patient data, including physician notes, laboratory testing, and imaging, to aid in the management of patients with rheumatic diseases. As one of the most common autoimmune diseases, rheumatoid arthritis (RA) has attracted considerable attention, particularly concerning the evolution of diagnostic techniques and therapeutic interventions. Our aim is to underscore those areas where AI, according to recent research, demonstrates promising potential to enhance the management of patients with RA.

Further characterization of clinical and laboratory features in VEXAS syndrome: large-scale analysis of a multicentre case series of 116 French patients.

BACKGROUND: A new autoinflammatory syndrome related to somatic mutations of UBA1 was recently described and called VEXAS syndrome ('Vacuoles, E1 Enzyme, X-linked, Autoinflammatory, Somatic syndrome'). OBJECTIVES: To describe clinical characteristics, laboratory findings and outcomes of VEXAS syndrome. METHODS: One hundred and sixteen patients with VEXAS syndrome were referred to a French multicentre registry between November 2020 and May 2021. The frequency and median of parameters and vital status, from diagnosis to the end of the follow-up, were recorded. RESULTS: The main clinical features of VEXAS syndrome were found to be skin lesions (83%), noninfectious fever (64%), weight loss (62%), lung involvement (50%), ocular symptoms (39%), relapsing chondritis (36%), venous thrombosis (35%), lymph nodes (34%) and arthralgia (27%). Haematological disease was present in 58 cases (50%): myelodysplastic syndrome (MDS; n = 58) and monoclonal gammopathy of unknown significance (n = 12; all patients with MGUS also have a MDS). UBA1 mutations included p.M41T (45%), p.M41V (30%), p.M41L (18%) and splice mutations (7%). After a median follow-up of 3 years, 18 patients died (15·5%; nine of infection and three due to MDS progression). Unsupervised analysis identified three clusters: cluster 1 (47%; mild-to-moderate disease); cluster 2 (16%; underlying MDS and higher mortality rates); and cluster 3 (37%; constitutional manifestations, higher C-reactive protein levels and less frequent chondritis). The 5-year probability of survival was 84·2% in cluster 1, 50·5% in cluster 2 and 89·6% in cluster 3. The UBA1 p.Met41Leu mutation was associated with a better prognosis. CONCLUSIONS: VEXAS syndrome has a large spectrum of organ manifestations and shows different clinical and prognostic profiles. It also raises a potential impact of the identified UBA1 mutation.

Aurolab aqueous drainage implant in the vitreous cavity: Our modifications over the conventional technique of glaucoma implant surgery.

Glaucoma drainage devices (GDDs) are used for managing refractory glaucoma due to failed trabeculectomy, neovascular glaucoma, traumatic glaucoma, and secondary glaucoma post keratoplasty. Aurolab aqueous drainage implant (AADI) is a nonvalved drainage implant conventionally implanted with the tube placed in the anterior chamber. Studies about the outcome of the various aqueous drainage devices implanted in the anterior chamber have reported complications such as tube extrusion, migration, blockage, erosion, and corneal decompensation. We propose modifying the conventional GDD implantation technique by placing the tube in the vitreous cavity, thereby negating the risk of anterior segment complications in patients with refractory glaucoma whose anterior segment is already compromised. Another novel approach implemented in this technique was making a scleral tunnel instead of using a scleral or corneal patch graft to cover the tube to prevent its migration. This article describes the surgical steps of this technique and its advantages, along with a surgical video.

Comparison between chloral hydrate and propofol-ketamine as sedation regimens for pediatric auditory brainstem response testing / Comparação entre o uso de hidrato de cloral e propofol-quetamina como formas de sedação para exames de potenciais evocados auditivos de tronco encefálico

Abstract Introduction: The use of diagnostic auditory brainstem response testing under sedation is currently the "gold standard" in infants and young children who are not developmentally capable of completing the test. Objective: The aim of the study is to compare a propofol-ketamine regimen to an oral chloral hydrate regimen for sedating children undergoing auditory brainstem response testing. Methods: Patients between 4 months and 6 years who required sedation for auditory brainstem response testing were included in this retrospective study. Drugs doses, adverse effects, sedation times, and the effectiveness of the sedative regimens were reviewed. Results: 73 patients underwent oral chloral hydrate sedation, while 117 received propofol-ketamine sedation. 12% of the patients in the chloral hydrate group failed to achieve desired sedation level. The average procedure, recovery and total nursing times were significantly lower in the propofol-ketamine group. Propofol-ketamine group experienced higher incidence of transient hypoxemia. Conclusion: Both sedation regimens can be successfully used for sedating children undergoing auditory brainstem response testing. While deep sedation using propofol-ketamine regimen offers more efficiency than moderate sedation using chloral hydrate, it does carry a higher incidence of transient hypoxemia, which warrants the use of a highly skilled team trained in pediatric cardio-respiratory monitoring and airway management.

Resumo Introdução: O uso de testes diagnósticos de potencial evocado auditivo de tronco encefálico sob sedação é atualmente o padrão-ouro em lactentes e crianças pequenas que não têm desenvolvimento suficiente para realizar o exame. Objetivo: O objetivo do estudo foi comparar a sedação de crianças submetidas a testes de potencial evocado auditivo de tronco encefálico com propofol-quetamina e com hidrato de cloral por via oral. Método: Pacientes entre 4 meses e 6 anos de idade que necessitaram de sedação para a realização do potencial evocado auditivo de tronco encefálico foram incluídos nesse estudo retrospectivo. Foram revisadas as doses dos medicamentos, os efeitos adversos, os tempos de sedação e a eficácia das formas de sedação. Resultados: 73 pacientes foram submetidos à sedação oral com hidrato de cloral, enquanto 117 receberam sedação com propofol-quetamina; 12% dos pacientes do grupo hidrato de cloral não alcançaram o nível desejado de sedação. Os tempos médios de procedimento, recuperação e o tempo total de cuidados de enfermagem foram significativamente menores no grupo propofol-quetamina, entretanto este grupo experimentou maior incidência de hipoxemia transitória. Conclusão: Ambos os regimes de sedação podem ser utilizados com sucesso para sedar crianças para realização do exame de potencial evocado de tronco encefálico. Embora a sedação profunda com propofol e quetamina ofereça mais eficiência do que a sedação moderada com hidrato de cloral, ela apresenta maior incidência de hipoxemia transitória, o que requer uma equipe altamente qualificada, treinada em monitoramento cardiorrespiratório pediátrico e manejo de vias aéreas.

Comparison between chloral hydrate and propofol-ketamine as sedation regimens for pediatric auditory brainstem response testing.

INTRODUCTION: The use of diagnostic auditory brainstem response testing under sedation is currently the "gold standard" in infants and young children who are not developmentally capable of completing the test. OBJECTIVE: The aim of the study is to compare a propofol-ketamine regimen to an oral chloral hydrate regimen for sedating children undergoing auditory brainstem response testing. METHODS: Patients between 4 months and 6 years who required sedation for auditory brainstem response testing were included in this retrospective study. Drugs doses, adverse effects, sedation times, and the effectiveness of the sedative regimens were reviewed. RESULTS: 73 patients underwent oral chloral hydrate sedation, while 117 received propofol-ketamine sedation. 12% of the patients in the chloral hydrate group failed to achieve desired sedation level. The average procedure, recovery and total nursing times were significantly lower in the propofol-ketamine group. Propofol-ketamine group experienced higher incidence of transient hypoxemia. CONCLUSION: Both sedation regimens can be successfully used for sedating children undergoing auditory brainstem response testing. While deep sedation using propofol-ketamine regimen offers more efficiency than moderate sedation using chloral hydrate, it does carry a higher incidence of transient hypoxemia, which warrants the use of a highly skilled team trained in pediatric cardio-respiratory monitoring and airway management.

High Yield of Recombinant Protein in Shaken E. coli Cultures with Enzymatic Glucose Release Medium EnPresso B.

Expression of recombinant proteins in sufficient quantities is essential for protein structure-function studies. The most commonly used method for recombinant protein production is overexpression in E. coli cultures. However, producing high yields of functional proteins in E. coli can be a challenge in conventional shaken cultures. This is often due to nonoptimal growth conditions, which result in low cell yields and insoluble or incorrectly folded target protein. To overcome the shortcomings of shake flask cultivation, we present a cultivation method based on enzymatic glucose delivery. This system mimics the fed-batch principle used in bioreactor cultivations and provides high yields of biomass and recombinant proteins in shaken cultivations.

Insulin regulates Rab3-Noc2 complex dissociation to promote GLUT4 translocation in rat adipocytes.

AIMS/HYPOTHESIS: The glucose transporter GLUT4 is present mainly in insulin-responsive tissues of fat, heart and skeletal muscle and is translocated from intracellular membrane compartments to the plasma membrane (PM) upon insulin stimulation. The transit of GLUT4 to the PM is known to be dependent on a series of Rab proteins. However, the extent to which the activity of these Rabs is regulated by the action of insulin action is still unknown. We sought to identify insulin-activated Rab proteins and Rab effectors that facilitate GLUT4 translocation. METHODS: We developed a new photoaffinity reagent (Bio-ATB-GTP) that allows GTP-binding proteomes to be explored. Using this approach we screened for insulin-responsive GTP loading of Rabs in primary rat adipocytes. RESULTS: We identified Rab3B as a new candidate insulin-stimulated G-protein in adipocytes. Using constitutively active and dominant negative mutants and Rab3 knockdown we provide evidence that Rab3 isoforms are key regulators of GLUT4 translocation in adipocytes. Insulin-stimulated Rab3 GTP binding is associated with disruption of the interaction between Rab3 and its negative effector Noc2. Disruption of the Rab3-Noc2 complex leads to displacement of Noc2 from the PM. This relieves the inhibitory effect of Noc2, facilitating GLUT4 translocation. CONCLUSIONS/INTERPRETATION: The discovery of the involvement of Rab3 and Noc2 in an insulin-regulated step in GLUT4 translocation suggests that the control of this translocation process is unexpectedly similar to regulated secretion and particularly pancreatic insulin-vesicle release.