Safety and efficacy of colchicine in crystal-induced arthritis flare in 54 patients with severe chronic kidney disease.

INTRODUCTION: Colchicine, commonly used in gout flare, is contraindicated in severe chronic kidney disease (CKD) (estimated glomerular filtration rate <30 mL/min). However, in this context, there are few alternatives, and colchicine use persists. We evaluated the tolerance of colchicine and its efficacy in patients with severe CKD. PATIENTS AND METHODS: All prescriptions of colchicine for managing crystal-induced arthritis flare (gout or calcium pyrophosphate deposition (CPPD) disease) in a hospitalised patient with severe CKD were screened from September 2020 to September 2021. After patient consent and treatment information, clinical and biological safety and efficacy data were prospectively collected from day 1 (D1) to D11. RESULTS: We included 54 patients (median age 75 years (IQR 67-83)) with 62 colchicine prescriptions (cases). Twelve (22%) patients were on dialysis. The main reason for hospitalisation was heart failure (31.5%), acute renal failure (22.2%), infection (18.5%) or an acute joint episode (9.3%). In total, 59.3% of patients had diabetes. The prescriptions concerned 58 cases of gout flares, 1 case of CPPD and 3 cases of both. Initial colchicine dosages were ≤0.5 mg/day in 47/62 (75.8%) cases; no dosage exceeded 1 mg/day (median duration of 6 days (IQR 3-11)). Colchicine was well tolerated in 47/61 (77%) cases. No serious adverse event was reported. Colchicine was considered completely effective by the medical team in 48/58 (83%) of cases. CONCLUSION: The use of colchicine, at reduced doses, was mostly effective to treat crystal-induced arthritis flare in 54 patients with severe CKD and was well tolerated, without any serious adverse events.

Acute Pulmonary Embolism in Patients with and without COVID-19.

INTRODUCTION: Acute pulmonary embolism (APE) is a frequent condition in patients with COVID-19 and is associated with worse outcomes. Previous studies suggested an immunothrombosis instead of a thrombus embolism, but the precise mechanisms remain unknown. OBJECTIVE: To assess the determinants and prognosis of APE during COVID-19. METHODS: We retrospectively included all consecutive patients with APE confirmed by computed tomography pulmonary angiography hospitalized at Strasbourg University Hospital from 1 March to 31 May 2019 and 1 March to 31 May 2020. A comprehensive set of clinical, biological, and imaging data during hospitalization was collected. The primary outcome was transfer to the intensive care unit (ICU). RESULTS: APE was diagnosed in 140 patients: 59 (42.1%) with COVID-19, and 81 (57.9%) without COVID-19. A 812% reduction of non-COVID-19 related APE was registered during the 2020 period. COVID-19 patients showed a higher simplified pulmonary embolism severity index (sPESI) score (1.15 ± 0.76 vs. 0.83 ± 0.83, p = 0.019) and were more frequently transferred to the ICU (45.8% vs. 6.2%, p < 0.001). No difference regarding the most proximal thrombus localization, Qanadli score (8.1 ± 6.9 vs. 9.0 ± 7.4, p = 0.45), the proportion of subsegmental (10.2% vs. 11.1%, p = 0.86), and segmental pulmonary embolism (35.6% vs. 24.7%, p = 0.16) was evidenced between COVID-19 and non-COVID-19 APE. In COVID-19 patients with subsegmental or segmental APE, thrombus was, in all cases (27/27 patients), localized in areas with COVID-19-related lung injuries. Marked inflammatory and prothrombotic biological markers were associated with COVID-19 APE. CONCLUSIONS: APE patients with COVID-19 have a particular clinico-radiological and biological profile and a dismal prognosis. Our results emphasize the preeminent role of inflammation and a prothrombotic state in these patients.

COVID-19: Mental Health Prevention and Care for Healthcare Professionals.

The Coronavirus Disease 2019 (COVID-19) pandemic exposed health professionals to high stress levels inducing significant psychological impact. Our region, Grand Est, was the most impacted French region during the first COVID-19 wave. In this context, we created CoviPsyHUS, local mental health prevention and care system dedicated explicitly to healthcare workers affected by the COVID-19 pandemic in one of this region's tertiary hospitals. We deployed CoviPsyHUS gradually in 1 month. To date, CoviPsyHUS comprises 60 mental health professionals dedicated to 4 complementary components: (i) a mental health support hotline (170 calls), (ii) relaxation rooms (used by 2,120 healthcare workers with 110 therapeutic workshops offered), (iii) mobile teams (1,200 contacts with healthcare staff), and (iv) a section dedicated to patients and their families. Among the critical points to integrate mental health care system during a crisis, we identified: (i) massive dissemination of mental health support information with multimodal communication, (ii) clear identification of the mental health support system, (iii) proactive mobile teams to identify healthcare professionals in difficulty, (iv) concrete measures to relieve the healthcare professionals under pressure (e.g., the relay in communication with families), (v) support for primary needs (body care (physiotherapy), advice and first-line therapy for sleep disorders), and (vi) psychoeducation and emotion management techniques. The different components of CoviPsyHUS are vital elements in meeting the needs of caregivers in situations of continuous stress. The organization of 4 targeted, modular, and rapidly deployable components makes CoviPsyHUS an innovative, reactive, and replicable mental health prevention and care system that could serve as a universal support model for other COVID-19 affected teams or other exceptional health crises in the future.

Value of Cardiac Biomarkers in the Early Diagnosis of Takotsubo Syndrome.

BACKGROUND: Bedside diagnosis between Takotsubo syndrome (TTS) and ST elevation (STEMI) and non-ST elevation (NSTEMI) myocardial infarction remains challenging. We sought to determine a cardiac biomarker profile to enable their early distinction. METHODS: 1100 patients (TTS n = 314, STEMI n = 452, NSTEMI n = 334) were enrolled in two centers. Baseline clinical and biological characteristics were compared between groups. RESULTS: At admission, cut-off values of BNP (B-type natriuretic peptide)/TnI (Troponin I) ratio of 54 and 329 distinguished respectively STEMI from NSTEMI, and NSTEMI from TTS. Best differentiation was obtained by the use of BNP/TnI ratio at peak (cut-of values of 6 and 115 discriminated respectively STEMI from NSTEMI, and NSTEMI from TTS). We developed a score including five parameters (age, gender, history of psychiatric disorders, LVEF, and BNP/TnI ratio at admission) enabling good distinction between TTS and STEMI (77% specificity and 92% sensitivity, AUC 0.93). For the distinction between TTS and NSTEMI, a four variables score (gender, history of psychiatric disorders, LVEF, and BNP at admission) achieved a good diagnostic performance (89% sensitivity, 85% specificity, AUC 0.94). CONCLUSION: A distinctive cardiac biomarker profile enables at an early stage a differentiation between TTS and ACS. A four (NSTEMI) or five variables score (STEMI) permitted a better discrimination.

Acute Myopericarditis in a Patient With Mild SARS-CoV-2 Respiratory Infection.

Herein is presented a case of a 71-year-old woman with mild SARS-CoV-2 respiratory infection who experienced acute myopericarditis diagnosed using clinical, biological, and electrocardiogram data and cardiac magnetic resonance imaging. The presented case highlights the risk of cardiac involvement, even in the absence of severe respiratory COVID-19 infection. The mechanisms involved in acute myocardial injury in SARS-CoV-2 infection are not well known and requires further studies to determine whether it is related to direct myocardial damage by the virus or to a systemic condition.

Nous présentons le cas d'une femme de 71 ans qui présentait une infection respiratoire légère causée par le virus SRAS-CoV-2 et qui a subi une myopéricardite aiguë diagnostiquée à partir de données cliniques, biologiques et électrocardiographiques et d'un examen d'imagerie par résonance magnétique cardiaque. Ce cas met en lumière le risque d'atteinte cardiaque chez les patients atteints de COVID-19, même en l'absence d'infection respiratoire grave. On ne connaît pas bien les mécanismes qui participent à l'atteinte myocardique aiguë chez les patients infectés par le virus SRAS-CoV-2, et des recherches plus poussées sont nécessaires pour déterminer si cette atteinte est causée directement par le virus ou si elle est due à un trouble systémique.

Minimally invasive surgery for left ventricular assist device implantation is safe and associated with a decreased risk of right ventricular failure.

BACKGROUND: Right ventricular failure (RVF) after left ventricular assist device (LVAD) implantation is associated with significant mortality and morbidity. The objective of this study was to determine pre- and postoperative risk factors associated with the occurrence of RVF after LVAD implantation. METHODS: This retrospective study included 68 patients who received LVADs between 2010 and 2018 either for bridge to transplant (40 patients, 58.8%) or bridge to destination therapy (28 patients, 41.2%). RVF after LVAD implantation was defined according to the INTERMACS classification. The primary endpoint was the occurrence of RVF. The secondary endpoints were hospital mortality and morbidity and long-term survival. RESULTS: The majority of patients (61.8%) had an INTERMACS profile 1 (36.8%) or 2 (25.0%). The LVAD was implanted either by sternotomy (37 patients, 54.4%) or thoracotomy (31 patients, 45.6%). RVF after LVAD implantation was observed in 32 patients (47.1%). In univariate analysis, an elevated serum glutamic oxaloacetic transaminase (SGOT) (P=0.028) and a high preoperative vasoactive inotropic score (VIS) (P=0.028) were significantly associated with an increased risk of RVF, whereas the implantation of LVAD through a thoracotomy approach was associated with a significant reduction in this risk (P=0.006). The multivariate analysis demonstrated that only the thoracotomy approach was significantly associated with decreased risk of RVF (odds ratio =0.33, 95% confidence interval: 0.17-0.96; P=0.042). Hospital mortality was 53.1% and 5.6% in the RVF and control groups, respectively (P<0.0001). The incidence of stroke and postoperative acute renal failure were significantly increased in the RVF group compared with the control group. The survival after LVAD implantation was 33.5%±9.0% and 85.4%±6.0% at 1 year in the RVF and control groups, respectively (P<0.0001). CONCLUSIONS: LVAD implantation by thoracotomy significantly reduced the risk of postoperative RVF. This surgical approach should, therefore, be favored.

Evaluation of the French National Program on Home Return of Patients with Chronic Heart Failure (PRADO-IC): Pilot Study of 91 Patients During Its Deployment in the Bas Rhin Area.

OBJECTIVE: The main objective of this study was to evaluate the impact of the French national program on home return of chronic heart failure patients (PRADO-IC) in terms of re-hospitalizations for heart failure (HF) during its deployment in the Bas-Rhin (France). PATIENTS AND METHODS: This was a pilot, descriptive, quantitative, retrospective, and bi-centric study (University Hospitals of Strasbourg and Haguenau Hospital Center, France). It included all patients included in the PRADO-IC program from these centers between January 1, 2015 and December 31, 2015. The primary endpoint of our study was the evaluation of the number of 1-year, 6-month, and 30-day re-admissions to the hospital in relation to an acute HF episode, before and after the inclusion of patients in the PRADO-IC program. The secondary endpoints were the number of overall re-hospitalizations (all-cause); the number of days of hospitalization for HF; the time to first re-hospitalization and the average length of hospital stay, before and after inclusion in PRADO-IC; and the overall and cardiovascular mortality rates. RESULTS: 91 patients out of 271 (33,6%) with a mean age of 79.2 years (67-94) were included. They all had chronic HF, essentially class II-III NYHA (90.1%), mostly of ischemic origin (41.9%), with altered left ventricular ejection fraction in 71.4% of cases. A reduction in the mean number of hospitalizations for HF per patient at 30 days, 6 months and 1 year was observed, respectively, from 0.18 ± 0.42 per patient before inclusion to 0.15 ± 0.36 after inclusion (p = 0.56); 0.98 ± 1.04 hospitalizations to 0.53 ± 0.81 at 6 months (p < 0.01); and 1.64 ± 1.14 hospitalizations 1.04 ± 1.05 at 1 year (p < 0.001). Patients were hospitalized less overall after inclusion in the PRADO-IC program. The number of days of hospitalization for HF was reduced after inclusion of patients from 18.02 ± 7.78 days before inclusion to 14.28 ± 11.57 days for the 6 month follow-up (p = 0.006), and from 22.07 ± 10.33 days before inclusion to 16.39 ± 15.94 days for the 1 year follow-up (p < 0.001). In contrast, inclusion in PRADO-IC statistically increased the mean time to first re-hospitalization for HF from mean 99.36 ± 72.39 days before inclusion to 148.11 ± 112.77 days after inclusion (p < 0.001). CONCLUSION: This study seems to demonstrate that the PRADO-IC program could improve the management of chronic HF patients in ambulatory care, particularly regarding HF re-hospitalization. However, due to the limitations of the methodology used and the small number of patients, it is advisable to consolidate its initial results with a randomized controlled study on a larger number of patients. In our opinion, its results need to be communicated because, to our knowledge, no equivalent study exists.

Does Transcatheter Aortic Valve Replacement Modulate the Kinetic of Superoxide Anion Generation?

Reactive oxygen species (ROS) are central bioenergetic markers linked to aortic stenosis (AS) development and severity. We sought to evaluate the time course and impact of ROS assessed by plasmatic superoxide anion (SA) among patients undergoing transcatheter aortic valve replacement (TAVR). Among 106 patients, SA significantly decreased after TAVR. Dropped values were measured 10 min after TAVR (0.590 ± 0.181 vs. 0.648 ± 0.193; p < 0.001) and persistent at 3 days (0.611 ± 0.0.228 vs. 0.646 ± 0.199; p = 0.033) and 30 days follow-up (0.572 ± 0.207 vs. 0.639 ± 0.199; p = 0.005). Increased baseline SA (>75 percentile) was continuously associated with higher postprocedural SA values 10 min after valve expansion (p < 0.001), at 3 days (p < 0.001) and 30 days (p < 0.001). Higher baseline SA was linked to higher inflammatory response assessed by higher C-reactive protein values at day 1 and day 3. The composite endpoint of all-cause mortality and/or stroke and/or pacemaker implantation and/or significant paravalvular aortic regurgitation ≥mild at 30 days did not differ significantly according to SA baseline values (p = 0.055). This is the first report identifying a decrease in oxidative stress level after TAVR. Our observation leads to the hypothesis that oxidative stress biomarkers may survive the journey from bench to bedside in AS and TAVR and become new biomarkers with both diagnostic and prognostic values. Antioxid. Redox Signal. 31, 420-426.

A Prokineticin-Driven Epigenetic Switch Regulates Human Epicardial Cell Stemness and Fate.

Epicardial adipose tissues (EATs) and vascular tissues may both belong to the mesoepithelial lineage that develops from epicardium-derived progenitor cells (EPDCs) in developing and injured hearts. Very little is known of the molecular mechanisms of EPDC contribution in EAT development and neovascularization in adult heart, which the topic remains a subject of intense therapeutic interest and scientific debate. Here we studied the epigenetic control of stemness and anti-adipogenic and pro-vasculogenic fate of human EPDCs (hEPDCs), through investigating an angiogenic hormone, prokineticin-2 (PK2) signaling via its receptor PKR1. We found that hEPDCs spontaneously undergoes epithelial-to-mesenchymal transformation (EMT), and are not predestined for the vascular lineages. However, PK2 via a histone demethylase KDM6A inhibits EMT, and induces asymmetric division, leading to self-renewal and formation of vascular and epithelial/endothelial precursors with angiogenic potential capable of differentiating into vascular smooth muscle and endothelial cells. PK2 upregulates and activates KDM6A to inhibit repressive histone H3K27me3 marks on promoters of vascular genes (Flk-1 and SM22α) involved in vascular lineage commitment and maturation. In PK2-mediated anti-adipogenic signaling, KDM6A stabilizes and increases cytoplasmic ß-catenin levels to repress peroxisome proliferator-activated receptor-γ expression and activity. Our findings offer additional molecular targets to manipulate hEPDCs-involved tissue repair/regeneration in cardiometabolic and ischemic heart diseases. Stem Cells 2018;36:1589-1602.

CT-ADP Point-of-Care Assay Predicts 30-Day Paravalvular Aortic Regurgitation and Bleeding Events following Transcatheter Aortic Valve Replacement.

BACKGROUND: Paravalvular aortic regurgitation (PVAR) remains a frequent postprocedural concern following transcatheter aortic valve replacement (TAVR). Persistence of flow turbulence results in the cleavage of high-molecular-weight von Willebrand multimers, primary haemostasis dysfunction and may favour bleedings. Recent data have emphasized the value of a point-of-care measure of von Willebrand factor-dependent platelet function (closure time [CT] adenosine diphosphate [ADP]) in the monitoring of immediate PVAR. This study examined whether CT-ADP could detect PVAR at 30 days and bleeding complications following TAVR. METHODS: CT-ADP was assessed at baseline and the day after the procedure. At 30 days, significant PVAR was defined as a circumferential extent of regurgitation more than 10% by transthoracic echocardiography. Events at follow-up were assessed according to the Valve Academic Research Consortium-2 consensus classification. RESULTS: Significant PVAR was diagnosed in 44 out of 219 patients (20.1%). Important reduction of CT-ADP could be found in patients without PVAR, contrasting with the lack of CT-ADP improvement in significant PVAR patients. By multivariate analysis, CT-ADP > 180 seconds (hazard ratio [HR]: 5.1, 95% confidence interval [CI]: 2.5-10.6; p < 0.001) and a self-expandable valve were the sole independent predictors of 30-day PVAR. At follow-up, postprocedural CT-ADP >180 seconds was identified as an independent predictor of major/life-threatening bleeding (HR: 1.7, 95% CI [1.0-3.1]; p = 0.049). Major/life-threatening bleedings were at their highest levels in patients with postprocedural CT-ADP > 180 seconds (35.2 vs. 18.8%; p = 0.013). CONCLUSION: Postprocedural CT-ADP > 180 seconds is an independent predictor of significant PVAR 30 days after TAVR and may independently contribute to major/life-threatening bleedings.

Can prokineticin prevent obesity and insulin resistance?

PURPOSE OF REVIEW: Because of its increasing prevalence and morbi-mortality, obesity is a major health problem. Obesity etiology includes a combination of excess dietary calories and decreased physical activity, coupled with either predisposing genetic factors or metabolic disorders such as insulin resistance. Adipose tissue secretes several metabolically important proteins known as 'adipokines' that play a major role in obesity and insulin resistance. High levels of a newly identified group of adipokines, called prokineticins, have been found in obese adipose tissues. Prokineticins are peptide hormones released principally from macrophages and reproductive organs. They act on the G protein-coupled receptors PKR1 and PKR2. This review aims to provide an overview of current knowledge of the role of prokineticins and their receptors in the development of obesity and insulin resistance. RECENT FINDINGS: The principal biological effect of prokineticins in the central nervous system is the control of food intake. Nevertheless, peripheral biological effects of prokineticin are associated with increasing insulin sensitivity and suppressing the adipose tissue expansion. SUMMARY: We outline the biological significance of the central and peripheral effects of prokineticins, and the potential of their receptors as targets for the treatment of obesity and insulin resistance.