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.

Vasovagal syncope and severe bradycardia following intranasal dexmedetomidine for pediatric procedural sedation.

We report syncope and bradycardia in an 11-year-old girl following administration of intranasal dexmedetomidine for sedation for a voiding cystourethrogram. Following successful completion of VCUG and a 60-min recovery period, the patient's level of consciousness and vital signs returned to presedation levels. Upon leaving the sedation area, the patient collapsed, with no apparent inciting event. The patient quickly regained consciousness and no injury occurred. The primary abnormality found was persistent bradycardia, and she was admitted to the hospital for telemetric observation. The bradycardia lasted ~2 h, and further cardiac workup revealed no underlying abnormality. Unanticipated and previously unreported outcomes may be witnessed as we expand the use of certain sedatives to alternative routes of administration.

GLUT4 traffic through an ESCRT-III-dependent sorting compartment in adipocytes.

In insulin target tissues, GLUT4 is known to traffic through multiple compartments that may involve ubiquitin- and/or SUMO-dependent targeting. During these trafficking steps, GLUT4 is sorted into a storage reservoir compartment that is acutely released by insulin signalling processes that are downstream of PI 3-kinase associated changes in inositol phospholipids. As ESCRT components have recently been found to influence cellular sorting processes that are related to changes in both ubiquitination and inositol phospholipids, we have examined whether GLUT4 traffic is routed through ESCRT dependent sorting steps. Introduction of the dominant negative inhibitory constructs of the ESCRT-III components CHMP3 (CHMP3(1-179)) and Vps4 (GFP-Vps4(E235Q)) into rat adipocytes leads to the accumulation of GLUT4 in large, coalesced and extended vesicles structures that co-localise with the inhibitory constructs over large parts of the extended structure. A new swollen hybrid and extensively ubiquitinated compartment is produced in which GLUT4 co-localises more extensively with the endosomal markers including EEA1 and transferrin receptors but also with the TGN marker syntaxin6. These perturbations are associated with failure of insulin action on GLUT4 traffic to the cell surface and suggest impairment in an ESCRT-dependent sorting step used for GLUT4 traffic to its specialised reservoir compartment.

[Birt-Hogg-Dubé syndrome and multiple recurrent tumors]. / Syndrome de Birt-Hogg-Dubé et tumeurs multiples récidivantes.

Birt-Hogg-Dubé (SBHD) syndrome is a rare autosomal dominant genodermatosis, predisposing to the occurrence of tumors associated with skin manifestations. We report a male patient who presented with a history of recurrent pneumothorax and was treated by nephrectomy for a left kidney carcinoma at 20 years old. Skin examination disclosed numerous fibrofolliculomas of the scalp. During follow-up, surgical resection of parotid oncocytomas and of a parathyroid adenoma were performed. SBHD was confirmed by molecular biology. In the presence of fibrofolliculomas and kidney tumors and recurrent spontaneous pneumothorax, a diagnosis of SHBD syndrome should be discussed, and tests need to be performed on the whole family.

Heart involvement in Churg-Strauss syndrome: retrospective study in French Burgundy population in past 10 years.

INTRODUCTION: Heart manifestations of Churg-Strauss syndrome (CSS) are varied. In the early stages of the disease, it is difficult to distinguish between lesions that are specific to CSS and those of other etiologies. The aim of our work was to compare the characteristics of patients with heart manifestations linked or not to Churg-Strauss syndrome. MATERIAL AND METHODS: We recorded all clinical symptoms of patients with CSS hospitalized between 1998 and 2008 in Burgundy, France, and determined the possible relationships between heart symptoms and CSS. RESULTS: From a cohort of 31 patients, we found 20 with heart lesions. When heart lesions were present, we noted fewer initial symptoms of digestive disorders (p<0.05), lower levels of lung infiltrates and fewer anti-MPO pANCA (p<0.05). Heart lesions were linked to CSS in 75% of cases. Their patients were thus younger than those in the other cardiac patients (p<0.05), were more likely to have clinical manifestations of heart involvement at diagnosis, were less likely to have lung infiltrates on the X-ray at diagnosis and during flare-ups and less likely to have lung abnormalities on X-rays during flare-ups (p<0.05) and higher level of leucocytes and eosinophils at diagnosis. CONCLUSION: Heart lesions directly attributable to CSS are frequent, severe and probably underestimated. A specific physiopathology that is not mediated by ANCA seems to be involved in the genesis of CSS-related heart lesions.

[Excessive sweating related to hydromorphone]. / Sueurs profuses invalidantes sous hydromorphone.

Diffuse and abundant sweating in a middle age patient evolving for several weeks should raise suspicion of malignant lymphoma and infectious or neuroendocrine disorders before considering a drug origin. We report a patient who presented with severe and invalidating excessive sweating related to hydromorphone therapy for vertebral pain. Amongst their many reported side-effects, excessive sweating disappearing with discontinuation of the drug have been reported with some opiates.

[Recurrent delayed pericarditis after pacemaker implantation: a post-pericardiotomy-like syndrome?]. / Une péricardite retardée récidivante après implantation de pacemaker: un équivalent de syndrome de Dressler?

INTRODUCTION: Pacemaker implantation is a usual technique in cardiology which may be followed by acute pleural effusion and delayed unusual pericarditis. CASE REPORT: We reported the case of a 67 year-old man hospitalized for faintness. Rhythmical auricular disease was diagnosed and pacemaker was implanted without immediate complication. Though pericarditis with tamponade at the day 21 will require emergency pericardiotomy surgery. A recurrent pericarditis at day 45 was treated with anti-inflammatory drugs without relapse at the end of the treatment. DISCUSSION: Repeated delayed pericarditis after pacemaker surgery may be compared to the Dressler syndrome which occurs after myocardial infarction.

[Interest of cotrimoxazole in relapsing idiopathic anterior scleritis: about six cases]. / Intérêt du cotrimoxazole dans les sclérites antérieures idiopathiques récidivantes: à propos de six observations.

INTRODUCTION: Anterior scleritis is defined as an inflammation of the sclera, located anteriorly to the equator of the eye. Cotrimoxazole is an antibiotic with an immunomodulatory action. EXEGESIS: In case of idiopathic anterior scleritis or scleritis associated with autoimmune diseases, immunosuppressive treatment is often required. We report on six patients with anterior idiopathic scleritis non sensitive to local treatment where cotrimoxazole improved or cured the symptoms. CONCLUSION: Cotrimoxazole seems to be an interesting therapeutic treatment in non threatening anterior scleritis.

Laparoscopic resection and ureteroureterostomy for congenital midureteral stricture.

A 16-year-old boy presented with flank pain and was found to have right-sided hydronephrosis and hydroureter on ultrasonography and an intravenous urogram. A retrograde pyelogram revealed a tight, short-segment, non-negotiable stricture in the midureter. A CT scan excluded extrinsic compression. In the absence of any other pathology, the stricture was considered to be congenital. The diseased segment of the ureter was resected laparoscopically, and an intracorporeally sutured ureteroureterostomy was fashioned over a double- J stent. The patient made an uneventful recovery and was well at follow-up 18 months later. To the best of our knowledge, this is the first reported case of laparoscopic resection of a congenital midureteral stricture.