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Introduction Recurrent shoulder dislocations often cause attrition of the labrum and progressive loss of the anterior bony contour of the glenoid. Treatment options for this pathology involve either soft tissue repair or bony augmentation procedure. The optimal management for patients with shoulder instability with subcritical bone loss remains unknown and current clinical practice is highly varied.Methods and analysis The Shoulder instability Trial comparing Arthroscopic stabilisation Benefits compared with Latarjet procedure Evaluation (STABLE) is an ongoing multicentre, randomised controlled trial of 114 patients diagnosed with recurrent anterior shoulder instability and subcritical glenoid bone loss (10%–20%, measured on 3D CT using circle of best fit technique). Patients are randomised either arthroscopic capsuloligamentous repair (Bankart repair+remplissage) or open or arthroscopic coracoid transfer (Latarjet procedure). The primary outcome of this trial will be the between-group difference in the change from baseline to 24 months postintervention in Western Ontario Shoulder Instability Index scores. Secondary outcomes include: (1) rates of recurrent shoulder dislocations and symptoms of instability up to 24 months’ postsurgery; (2) clinical outcomes measured by American Shoulder and Elbow Society score, Shoulder Activity Scale, EQ-5D and Patient Satisfaction Scale; (3) physical examination (range of motion, stability); (4) return to previous level of activity/sport; (5) rate of shoulder-related complications and serious adverse events.Ethics and dissemination This protocol has been reviewed and approved by the Hamilton Integrated Research Ethics Board (HiREB; project number 15998) prior to commencement of the trial. Results from the study will be submitted for publication in a peer-reviewed journal regardless of whether there are statistically significant findings.Trial registration number NCT05705479; this study was prospectively registered on clinicaltrials.gov.

BackgroundIdiopathic pulmonary fibrosis (IPF) is a chronic pulmonary disease that is characterized by an excessive accumulation of extracellular matrix (ECM) proteins (e.g. collagens) in the parenchyma, which ultimately leads to respiratory failure and death. While current therapies exist to slow the progression, no therapies are available to resolve fibrosis.MethodsWe characterized the O-linked N-Acetylglucosamine (O-GlcNAc) transferase (OGT)/O-GlcNAc axis in IPF using single-cell RNA-sequencing (scRNA-seq) data and human lung sections and isolated fibroblasts from IPF and non-IPF donors. The underlying mechanism(s) of IPF were further investigated using multiple experimental models to modulate collagen expression and accumulation by genetically and pharmacologically targeting OGT. Furthermore, we hone in on the transforming growth factor-beta (TGF-β) effector molecule, Smad3, by co-expressing it with OGT to determine if it is modified and its subsequent effect on Smad3 activation.ResultsWe found that OGT and O-GlcNAc levels are upregulated in patients with IPF compared to non-IPF. We report that the OGT regulates collagen deposition and fibrosis resolution, which is an evolutionarily conserved process demonstrated across multiple species. Co-expression of OGT and Smad3 showed that Smad3 is O-GlcNAc modified. Blocking OGT activity resulted in decreased phosphorylation at Ser-423/425 of Smad3 attenuating the effects of TGF-β1 induced collagen expression/deposition.ConclusionOGT inhibition or knockdown successfully blocked and reversed collagen expression and accumulation, respectively. Smad3 is discovered to be a substrate of OGT and its O-GlcNAc modification(s) directly affects its phosphorylation state. These data identify OGT as a potential target in pulmonary fibrosis resolution, as well as other diseases that might have aberrant ECM/collagen accumulation.

Abstract Aims Impact of skin mottling has been poorly studied in patients admitted for cardiogenic shock. This study aimed to address this issue and identify determinants of 30-day and 1-year mortality in a large cardiogenic shock cohort of all etiologies. Methods and results FRENSHOCK is a prospective multicenter observational registry conducted in French critical care units between April and October, 2016. Among the 772 enrolled patients (mean age 65.7 ± 14.9 years; 71.5% male), 660 had skin mottling assessed at admission (85.5%) with almost 39% of patients in cardiogenic shock presenting mottling. The need for invasive respiratory support was significantly higher in patients with mottling (50.2% vs. 30.1%, p

Abstract Background Cardiovascular disease (CVD) is the main cause of mortality in patients with chronic kidney disease (CKD). Although several studies have demonstrated the consistently high prognostic value of stress cardiovascular magnetic resonance (CMR), its prognostic value in patients with CKD is not well established. We aimed to assess the safety and the incremental prognostic value of vasodilator stress perfusion CMR in consecutive symptomatic patients with known CKD. Methods Between 2008 and 2021, we conducted a retrospective dual center study with all consecutive symptomatic patients with known stage 3 CKD, defined by estimated glomerular filtration rate (eGFR) between 30 and 60 ml/min/1.73 m2, referred for vasodilator stress CMR. All patients with eGFR

Summary: Background: Smoking cigarettes produces carbon monoxide (CO), which can reduce the oxygen-carrying capacity of the blood. We aimed to determine whether elevated expiratory CO levels would be associated with a worse prognosis in smokers presenting with acute cardiac events. Methods: From 7 to 22 April 2021, expiratory CO levels were measured in a prospective registry including all consecutive patients admitted for acute cardiac event in 39 centres throughout France. The primary outcome was 1-year all-cause death. Initial in-hospital major adverse cardiac events (MAE; death, resuscitated cardiac arrest and cardiogenic shock) were also analysed. The study was registered at ClinicalTrials.gov (NCT05063097). Findings: Among 1379 patients (63 ± 15 years, 70% men), 368 (27%) were active smokers. Expiratory CO levels were significantly raised in active smokers compared to non-smokers. A CO level >11 parts per million (ppm) found in 94 (25.5%) smokers was associated with a significant increase in death (14.9% for CO > 11 ppm vs. 2.9% for CO ≤ 11 ppm; p 11 ppm was associated with a significant increase in MAE in smokers during initial hospitalisation after adjustment for comorbidities (odds ratio [OR] 15.75, 95% CI [5.56–44.60]) or parameters of in-hospital severity (OR 10.67, 95% CI [4.06–28.04]). In the overall population, CO > 11 ppm but not smoking was associated with an increased rate of all-cause death (HR 4.03, 95% CI [2.33–6.98] and 1.66 [0.96–2.85] respectively). Interpretation: Elevated CO level is independently associated with a 6-fold increase in 1-year death and 10-fold in-hospital MAE in smokers hospitalized for acute cardiac events. Funding: Grant from Fondation Coeur & Recherche.

The role of the beta-adrenergic signaling pathway in heart failure (HF) is pivotal. Early blockade of this pathway with beta-blocker (BB) therapy is recommended as the first-line medication for patients with HF and reduced ejection fraction (HFrEF). Conversely, in patients with severe acute HF (AHF), including those with resolved cardiogenic shock (CS), BB initiation can be hazardous. There are very few data on the management of BB in these situations. The present expert consensus aims to review all published data on the use of BB in patients with severe decompensated AHF, with or without hemodynamic compromise, and proposes an expert-recommended practical algorithm for the prescription and monitoring of BB therapy in critical settings.

Background Parkinson's disease is a degenerative neurological disorder that can cause both motor and nonmotor symptoms. Motor symptoms are associated with increasing the patient's falls risk. Shoulder arthroplasty surgery in this patient cohort is associated with more complications than non-Parkinsonian patients. We sought to identify any increase in complications associated with this patient cohort and any surgical considerations that ought to be taken in light of their disease process. Methods We performed a systematic review of articles using PubMed, MEDLINE, Cochrane Central, and Google Scholar. All studies which included any shoulder arthroplasty surgery for patients with Parkinson's disease were included. Results Complication rates were higher in patients with Parkinson's disease than in the normal arthroplasty cohort in all studies. There was significant heterogeneity between all 8 studies included in the systematic review. Complication rates ranged from 26% to 100%. Complications included subluxation, loosening, malunion, nonunion, scapular notching, stiffness, fracture, baseplate failure, dislocation, and infection. Reoperation rates ranged from 5% to 29%. Conclusion Compared to patients without Parkinson's disease undergoing shoulder arthroplasty, patients with Parkinson's disease achieved similar reductions in pain but inferior clinical function. The range of movement was less predictable, and complication rates were significantly higher in Parkinson's disease patients. This study will aid the surgeon and patient regarding surgical intervention, informed consent, and allow the surgeon to anticipate potential complications of shoulder arthroplasty in this patient cohort.

Abstract Aims Published data on cardiogenic shock (CS) are scarce and are mostly focused on small registries of selected populations. The aim of this study was to examine the current CS picture and define the independent correlates of 30 day mortality in a large non‐selected cohort. Methods and results FRENSHOCK is a prospective multicentre observational survey conducted in metropolitan French intensive care units and intensive cardiac care units between April and October 2016. There were 772 patients enrolled (mean age 65.7 ± 14.9 years; 71.5% male). Of these patients, 280 (36.3%) had ischaemic CS. Organ replacement therapies (respiratory support, circulatory support or renal replacement therapy) were used in 58.3% of patients. Mortality at 30 days was 26.0% in the overall population (16.7% to 48.0% depending on the main cause and first place of admission). Multivariate analysis showed that six independent factors were associated with a higher 30 day mortality: age [per year, odds ratio (OR) 1.06, 95% confidence interval (CI): 1.04–1.08], diuretics (OR 1.74, 95% CI: 1.05–2.88), circulatory support (OR 1.92, 95% CI: 1.12–3.29), left ventricular ejection fraction

Objectives. The aim of this postmarket clinical study was to assess the safety and efficacy of the latest generation polymer-free sirolimus-eluting stents (PF-SES) in an all-comers population comparing outcomes in stable coronary artery disease (CAD) versus acute coronary syndrome (ACS) in France. Background. The efficacy and safety of the first-generation PF-SES have already been demonstrated by randomized controlled trials and “all-comers” observational studies. Methods. For this all-comers observational, prospective, multicenter study, 1456 patients were recruited in 22 French centers. The primary endpoint was target lesion revascularization (TLR) rate at 12 months and secondary endpoints included major adverse cardiac events (MACE) and bleeding. Results. 895 patients had stable CAD and 561 had ACS. At 12 months, 2% of patients had a TLR, with similar rates between stable CAD and ACS (1.9% vs 2.2%, p = 0.7). The overall MACE rate was 5.2% with an expected higher rate in patients with ACS as compared to those with stable CAD (7.3% vs 3.9%, p = 0.007). The overall bleeding event rate was 4.5%, with similar rates in stable CAD as compared to ACS patients (3.8% vs 5.6%, p = 0.3). Dual antiplatelet therapy (DAPT) interruptions prior to the recommended duration occurred in 41.7% of patients with no increase in MACE rates as compared to patients who did not prematurely interrupt DAPT (3.9% vs 6.1%, p = 0.073). Conclusions. The latest generation PF-SES is associated with low clinical event rates in these all-comers patients. There was a high rate of prematurely terminated DAPT, without any effect on MACE at 12 months. This trial is registered with NCT03809715.

BackgroundCardiogenic shock (CS) is a life-threatening condition carrying poor prognosis, potentially triggered by ventricular arrhythmia (VA). Whether the occurrence of VA as trigger of CS worsens the prognosis compared to non-VA triggers remains unclear. The aim of this study was to evaluate 1-year outcomes [mortality, heart transplantation, ventricular assist devices (VAD)] between VA-triggered and non-VA-triggered CS.MethodsFRENSHOCK is a prospective multicenter registry including 772 CS patients from 49 centers. One to three triggers can be identified in the registry (ischemic, mechanical complications, ventricular/supraventricular arrhythmia, bradycardia, iatrogenesis, infection, non-compliance). Baseline characteristics, management and 1-year outcomes were analyzed according to the VA-trigger in the CS population.ResultsWithin 769 CS patients included, 94 were VA-triggered (12.2%) and were compared to others. At 1 year, although there was no mortality difference [42.6 vs. 45.3%, HR 0.94 (0.67–1.30), p = 0.7], VA-triggered CS resulted in more heart transplantations and VAD (17 vs. 9%, p = 0.02). Into VA-triggered CS group, though there was no 1-year mortality difference between ischemic and non-ischemic cardiomyopathies [42.5 vs. 42.6%, HR 0.97 (0.52–1.81), p = 0.92], non-ischemic cardiomyopathy led to more heart transplantations and VAD (25.9 vs. 5%, p = 0.02).ConclusionVA-triggered CS did not show higher mortality compared to other triggers but resulted in more heart transplantation and VAD at 1 year, especially in non-ischemic cardiomyopathy, suggesting the need for earlier evaluation by advanced heart failure specialized team for a possible indication of mechanical circulatory support or heart transplantation.Clinical trial registrationhttps://clinicaltrials.gov, identifier NCT02703038.

Abstract Aim and hypotheses The THEMIS randomized trial compared ticagrelor plus aspirin versus placebo plus aspirin for patients with stable coronary artery disease and type 2 diabetes mellitus (CAD-T2DM), and without prior myocardial infarction (MI) or stroke. The aim of the study was to quantify the size of the CAD-T2DM population without prior MI or stroke population in a real-world setting, and more specifically populations with similar THEMIS selection criteria (THEMIS-like and THEMIS-PCI-like populations), as well as their risk of major outcomes in current practice. Methods A 2-year follow-up cohort study included all CAD-T2DM without MI/stroke prevalent patients on January 1st, 2014 in the SNDS French nationwide claims database. The THEMIS-like population concerned those ≥ 50 years of age with similar THEMIS inclusion and exclusion criteria. Prevalence was standardized to the European population. The cumulative incidence function was used to estimate the incidence of clinical outcomes (MI, ischemic stroke, and major bleeding according to the TIMI classification) with death as competing risk, and the Kaplan–Meier estimate for all-cause death and a composite outcome of MI, stroke and all-cause death. Results From a population of about 50 million adults, the prevalence of CAD-T2DM without MI/stroke, THEMIS-like and THEMIS-PCI-like populations was respectively at 6.04, 1.50 and 0.27 per 1000 adults, with a mean age of 72.7, 72.3 and 70.9 years and less comorbidities and diabetic complications for the THEMIS-like and THEMIS-PCI-like population. The 2-year cumulative incidence was respectively 1.7%, 1.3% and 1.6% for MI, 1.7%, 1.5% and 1.4% for stroke, 4.8%, 3.1% and 2.9% for major bleeding, 13.6%, 9.7% and 6.8% for all-cause death, and 16.2%, 12.0% and 9.5% for the composite outcome. Conclusion THEMIS-like prevalence was estimated at 1.50 per 1,000 adults, representing about a quarter of CAD-T2DM without MI/stroke patients, and 0.27 per 1000 adults for the THEMIS-PCI-like populations. In current French practice, the median age of both these populations was about 5–6 years older than in the THEMIS trial, with a 2-year incidence of major outcomes between two or four time above the ones of the placebo arm of the THEMIS trial using very close definitions. Registration No. EUPAS27402 ( http://www.ENCEPP.eu ).

BackgroundSex hormones associated with both the left atrial (LA) and left ventricular (LV) structures in women, but the association of menopause status with left atrioventricular coupling is not established.AimTo assess the prognostic value of a left atrioventricular coupling index (LACI) in peri-menopausal women without a history of cardiovascular disease (CVD).Materials and methodsIn all women participating in MESA study with baseline cardiovascular MRI, the LACI was measured as the ratio of the LA end-diastolic volume to the LV end-diastolic volume. Cox models were used to assess the association between the LACI and the outcomes of atrial fibrillation (AF), heart failure (HF), coronary heart disease (CHD) death, and hard CVD.ResultsAmong the 2,087 women participants (61 ± 10 years), 485 cardiovascular events occurred (mean follow-up: 13.2 ± 3.3 years). A higher LACI was independently associated with AF (HR 1.70; 95%CI [1.51–1.90]), HF (HR 1.62; [1.33–1.97]), CHD death (HR 1.36; [1.10–1.68]), and hard CVD (HR 1.30; [1.13–1.51], all p < 0.001). Adjusted models with the LACI showed significant improvement in model discrimination and reclassification when compared to traditional models to predict: incident AF (C-statistic: 0.82 vs. 0.79; NRI = 0.325; IDI = 0.036), HF (C-statistic: 0.84 vs. 0.81; NRI = 0.571; IDI = 0.023), CHD death (C-statistic: 0.87 vs. 0.85; NRI = 0.506; IDI = 0.012), hard CVD (C-statistic: 0.78 vs. 0.76; NRI = 0.229; IDI = 0.012). The prognostic value of the LACI had a better discrimination and reclassification than individual LA or LV parameters.ConclusionIn a multi-ethnic population of pre- and post-menopausal women, the LACI is an independent predictor of HF, AF, CHD death, and hard CVD.Clinical trial registration[https://clinicaltrials.gov/], identifier [NCT00005487].

Background: In this study, we aimed to report clinical characteristics and outcomes of patients with and without SARS-CoV-2 infection who were referred for acute coronary syndrome (ACS) during the peak of the pandemic in France. Methods: We included all consecutive patients referred for ST-elevation myocardial infarction (STEMI) or non-STEMI (NSTEMI) during the first 3 weeks of April 2020 in 5 university hospitals (Paris, south, and north of France), all performing primary percutaneous coronary intervention. Results: The study included 237 patients (67 ± 14 years old; 69% male), 116 (49%) with STEMI and 121 (51%) with NSTEMI. The prevalence of SARS-CoV-2-associated ACS was 11% (n = 26) and 11 patients had severe hypoxemia on presentation (mechanical ventilation or nasal oxygen > 6 L/min). Patients were comparable regarding medical history and risk factors, except a higher prevalence of diabetes mellitus in SARS-CoV-2 patients (53.8% vs 25.6%; P = 0.003). In SARS-CoV-2 patients, cardiac arrest on admission was more frequent (26.9% vs 6.6%; P < 0.001). The presence of significant coronary artery disease and culprit artery occlusion in SARS-CoV-2 patients respectively, was 92% and 69.4% for those with STEMI, and 50% and 15.5% for those with NSTEMI. Percutaneous coronary intervention was performed in the same percentage of STEMI (84.6%) and NSTEMI (84.8%) patients, regardless of SARS-CoV-2 infection, but no-reflow (19.2% vs 3.3%; P < 0.001) was greater in SARS-CoV-2 patients. In-hospital death occurred in 7 SARS-CoV-2 patients (5 from cardiac cause) and was higher compared with noninfected patients (26.9% vs 6.2%; P < 0.001). Conclusions: In this registry, ACS in SARS-CoV-2 patients presented with high a percentage of cardiac arrest on admission, high incidence of no-reflow, and high in-hospital mortality. Résumé: Contexte: Notre étude avait pour but d’établir les caractéristiques cliniques et les résultats de patients infectés ou non par le SRAS-CoV-2 qui ont été orientés en raison d’un syndrome coronarien aigu (SCA) pendant la phase aiguë de la pandémie en France. Méthodologie: Nous avons inclus dans l’étude tous les patients consécutifs qui ont présenté un infarctus du myocarde avec sus-décalage du segment ST (STEMI) ou sans sus-décalage du segment ST (NSTEMI) au cours des 3 premières semaines d’avril 2020 et qui ont été orientés vers 5 hôpitaux universitaires (situés à Paris, ainsi que dans le sud et le nord de la France), tous en mesure de réaliser des interventions co-ronariennes percutanées primaires. Résultats: L’étude comprenait 237 patients (âge : 67 ± 14 ans; proportion d’hommes : 69 %); 116 (49 %) présentaient un STEMI et 121 (51 %), un NSTEMI. La prévalence d’un SCA associé à une infection par le SRAS-CoV-2 s’établissait à 11 % (n = 26), et 11 patients étaient en hypoxémie grave (nécessitant une ventilation artificielle ou l’administration d’oxygène par voie nasale à un débit de plus de 6 l/min) à leur arrivée. Les patients présentaient des antécédents médicaux et des facteurs de risque comparables, à l’exception du fait que la prévalence du diabète était plus élevée chez les patients infectés par le SRAS-CoV-2 (53,8 % vs 25,6 %; p = 0,003). Ces derniers avaient plus souvent subi un arrêt cardiaque à leur admission (26,9 % vs 6,6 %; p < 0,001). Chez les patients infectés par le SRAS-CoV-2, une coronaropathie importante et une occlusion de l’artère coupable ont été observées chez respectivement 92 % et 69,4 % des patients présentant un STEMI, et chez 50 % et 15,5 % des patients présentant un NSTEMI. Une intervention coronarienne percutanée a été effectuée dans les mêmes proportions chez les patients subissant un STEMI (84,6 %) que chez ceux présentant un NSTEMI (84,8 %), sans égard à la présence ou à l’absence d’une infection par le SRAS-CoV-2, mais les cas de non-reperfusion (no-reflow) ont été plus fréquents chez les patients infectés que chez les autres patients (19,2 % et 3,3 %, respectivement; p < 0,001). Sept patients infectés par le SRAS-CoV-2 sont morts à l’hôpital (5 de cause cardiaque), ce qui représente un taux de mortalité plus élevé que chez les patients non infectés (26,9 % vs 6,2 %; p < 0,001). Conclusions: Dans le cadre de cette étude, le SCA survenu chez les patients infectés par le SRAS-CoV-2 était associé à un fort pourcentage d’arrêt cardiaque à l’admission, à une fréquence élevée de cas de non-reperfusion et à un taux élevé de mortalité hospitalière.

Abstract Precise descriptions of coronavirus disease 2019 (COVID‐19)‐related cardiac damage as well as underlying mechanisms are scarce. We describe clinical presentation and diagnostic workup of acute myocarditis in a patient who had developed COVID‐19 syndrome 1 month earlier. A healthy 40‐year‐old man suffered from typical COVID‐19 symptoms. Four weeks later, he was admitted because of fever and tonsillitis. Blood tests showed major inflammation. Thoracic computed tomography was normal, and RT–PCR for SARS‐CoV‐2 on nasopharyngeal swab was negative. Because of haemodynamic worsening with both an increase in cardiac troponin and B‐type natriuretic peptide levels and normal electrocardiogram, acute myocarditis was suspected. Cardiac echographic examination showed left ventricular ejection fraction at 45%. Exhaustive diagnostic workup included RT–PCR and serologies for infectious agents and autoimmune blood tests as well as cardiac magnetic resonance imaging and endomyocardial biopsies. Cardiac magnetic resonance with T2 mapping sequences showed evidence of myocardial inflammation and focal lateral subepicardial late gadolinium enhancement. Pathological analysis exhibited interstitial oedema, small foci of necrosis, and infiltrates composed of plasmocytes, T‐lymphocytes, and mainly CD163+ macrophages. These findings led to the diagnosis of acute lympho‐plasmo‐histiocytic myocarditis. There was no evidence of viral RNA within myocardium. The only positive viral serology was for SARS‐CoV‐2. The patient and his cardiac function recovered in the next few days without use of anti‐inflammatory or antiviral drugs. This case highlights that systemic inflammation associated with acute myocarditis can be delayed up to 1 month after initial SARS‐CoV‐2 infection and can be resolved spontaneously.

BackgroundAside from the culprit plaque, the presence of vulnerable plaques in patients with acute coronary syndrome (ACS) may be associated with future cardiac events. A link between calcification and plaque rupture has been previously described.AimTo assess whether analysis of the calcium component of coronary plaques using CT angiography, coronary computed tomographic angiography (CCTA) can help to detect additional vulnerable plaques in patients with non-ST elevation myocardial infarction (NSTEMI).Materials And MethodsCross sectional study of consecutive patients referred for NSTEMI from 30 July to 30 August 2018 with CCTA performed before coronary angiography with systematic optical coherence tomography (OCT) analysis of all coronary arteries within 24 h of clinical onset of NSTEMI. Three types of plaques were defined: culprit plaques defined by angiography (vulnerable culprit plaques–VCP) – plaques with a fibrous cap thickness < 65 microns or thrombus in OCT (vulnerable non-culprit plaque–VNCP) – plaques with a fibrous cap thickness ≥ 65 microns in OCT (stable plaque–SP).ResultsA total of 134 calcified plaques were identified in 29 patients (73% male, 59 ± 14 years) with 29(22%) VCP, 28(21%) VNCP and 77(57%) SP. Using CCTA analysis of the calcium component, factors associated with vulnerable plaques were longer calcification length, larger calcification volume, lower calcium mass, higher Agatston score plaque-specific (ASp), presence of spotty calcifications and an intimal position in the wall. In multivariate analysis, ASp, calcification length and spotty calcifications were independently associated to vulnerable plaques. There was no difference between VCP and VNCP.ConclusionsCCTA analysis of calcium component of the plaque could help to identify additional vulnerable plaques in NSTEMI patients.

In the context of development of standards for forensic science, particularly standards initially developed by the U.S. Organization of Scientific Area Committees for Forensic Science (OSAC), this perspective paper raises concern about the publication of vacuous standards. Vacuous standards generally state few requirements; the requirements they do state are often vague; compliance with their stated requirements can be achieved with little effort – the bar is set very low; and compliance with their stated requirements would not be sufficient to lead to scientifically valid results. This perspective paper proposes a number of requirements that we believe would be essential in order for a standard on validation of forensic-science methods to be fit for purpose.

Background: Although left atrial (LA) and left ventricular (LV) structural and functional parameters have independent prognostic value as predictors of heart failure (HF), the close physiological relationship between the LA and LV suggest that the assessment of LA/LV coupling could better reflect left atrioventricular dysfunction and be a better predictor of HF.Aim: We investigated the prognostic value of a left atrioventricular coupling index (LACI), measured by cardiovascular magnetic resonance (CMR), as well as change in LACI to predict incident HF in the Multi-Ethnic Study of Atherosclerosis (MESA).Materials and Methods: In the MESA, 2,250 study participants, free of clinically recognized HF and cardiovascular disease (CVD) at baseline, had LACI assessed by CMR imaging at baseline (Exam 1, 2000–2002), and 10 years later (Exam 5, 2010–2012). Left atrioventricular coupling index was defined as the ratio of LA to LV end-diastolic volumes. Univariable and multivariable Cox proportional hazard models were used to evaluate the associations of LACI and average annualized change in LACI (ΔLACI) with incident HF after adjustment for traditional MESA-HF risk factors. The incremental risk prediction was calculated using C-statistic, categorical net reclassification index (NRI) and integrative discrimination index (IDI).Results: Among the 2,250 participants (mean age 59.3 ± 9.3 years and 47.6% male participants), 50 incident HF events occurred over 6.8 ± 1.3 years after the second CMR exam. After adjustment, greater LACI and ΔLACI were independently associated with HF (adjusted HR 1.44, 95% CI [1.25–1.66] and adjusted HR 1.55, 95% CI [1.30–1.85], respectively; both p < 0.0001). Adjusted models for LACI showed significant improvement in model discrimination and reclassification compared to currently used HF risk score model for predicting HF incidence (C-statistic: 0.81 vs. 0.77; NRI = 0.411; IDI = 0.043). After adjustment, ΔLACI showed also significant improvement in model discrimination compared to the multivariable model with traditional MESA-HF risk factors for predicting incident HF (C-statistic: 0.82 vs. 0.77; NRI = 0.491; IDI = 0.058).Conclusions: In a multi-ethnic population, atrioventricular coupling (LACI), and coupling change (ΔLACI) are independently associated with incident HF. Both have incremental prognostic value for predicting HF events over traditional HF risk factors.

There is a large heterogeneity among patients presenting with cardiogenic shock (CS). It is crucial to better apprehend this heterogeneity in order to adapt treatments and improve prognoses in these severe patients. Notably, the presence (or absence) of a pre-existing history of chronic heart failure (CHF) at time of CS onset may be a significant part of this heterogeneity, and data focusing on this aspect are lacking. We aimed to compare CS patients with new-onset HF to those with worsening CHF in the multicenter FRENSHOCK registry. Altogether, 772 CS patients were prospectively included: 433 with a previous history of CHF and 339 without. Worsening CHF patients were older (68 +/− 13.4 vs. 62.7 +/− 16.2, p < 0.001) and had a greater burden of extra-cardiac comorbidities. At admission, acute myocardial infarction was predominantly observed in the new-onset HF group (49.9% vs. 25.6%, p < 0.001). When focusing on hemodynamic parameters, worsening CHF patients showed more congestion and higher ventricular filling pressures. Worsening CHF patients experienced higher in-hospital all-cause mortality (31.3% vs. 24.2%, p = 0.029). Our results emphasize the great heterogeneity of the patients presenting with CS. Worsening CHF patients had higher risk profiles, and this translated to a 30% increase in in-hospital all-cause mortality. The heterogeneity of this population prompts us to better determine the phenotype of CS patients to adapt their management.

Introduction: Cocaine users often present with repetitive events of cocaine-associated chest pain (CACP), clinically resembling acute coronary syndromes. The aim of the study is to describe the specific risk factors for CACP.Method: Cocaine users (n = 316) were recruited for a multicenter cross-sectional study. Lifetime CACP history, sociodemographic factors, and lifetime use of cocaine and other substances were assessed. Thirty single nucleotide polymorphisms (SNPs) of NOS3, ROCK2, EDN1, GUCY1A3, and ALDH2 genes, suggested by the literature on coronary spasms, were selected. The associations with CACP history were tested using the chi-square test, Student's t-test and logistic regression.Results: Among the 316 subjects [78.5% men, mean age 37.5 years, (standard-deviation ±8.7)], 190 (60.1%) were daily cocaine users and 103 (32.6%) reported a lifetime CACP history. Among those with a lifetime CACP history, the median was 10 events per individual. In multivariate analysis, lifetime CACP history was associated with daily cocaine use [odds-ratio (OR) 3.24; 95% confidence intervals (1.29–9.33)], rapid route of cocaine use [OR 2.33 (1.20–4.64) vs. intranasal use], and lifetime amphetamine use [daily amphetamine use: OR 2.80 (1.25–6.32) and non-daily amphetamine use: OR 2.14 (1.15–4.04) vs. never used]. Patients with lifetime opioid maintenance treatment (OMT) reported significantly less lifetime CACP history [OR 0.35 (0.16–0.76)]. None of the selected SNPs was associated with CACP history after multiple testing corrections.Conclusions: Clinical variables describing the intensity of stimulant use were positively associated with lifetime CACP history, while OMT was negatively associated with it. Specific harm reduction strategies can target these risk factors.

This Letter to the Editor is a reply to Mohammed et al. (2021) https://doi.org/10.1016/j.fsisyn.2021.100145, which in turn is a response to Morrison et al. (2020) “Vacuous standards – subversion of the OSAC standards-development process” https://doi.org/10.1016/j.fsisyn.2020.06.005.

Purpose: Pathological metastatic fractures in lower-extremity weight bearing bones often require surgical reconstruction. Post-operative radiation is routinely recommended following surgical reconstruction. This study evaluated the clinical outcomes of patients that undergo surgical fixation of an established or an impending pathologic lower extremity fracture without post-operative radiation. Materials and methods: A retrospective chart review of patients at Sunnybrook Health Sciences Center between 2007 and 2019 was performed. Descriptive statistical analyses were performed. Results: A total of 161 surgical reconstruction procedures were identified. Among these cases, 86/161 (53.4%) received post-operative radiation, 75/161 (47%) did not receive post-operative radiation within 12 weeks of their index surgery. Of the 75 patients not receiving post-operative radiation, 40 patients had prior radiation to the surgical site and 35 patients were radiation naïve. 5 patients (6.7%) required a second operation to the index surgical site, with 4 patients (5.3%) requiring a second fixation surgery to stabilize hardware at a median of 6.0 months post-surgery. Post-surgical radiation to the surgical site (at >12 weeks) was administered to 12 patients (16.0%) at a median of 9.1 months post-surgery. Conclusions: The surgical revision rate was low despite absence of immediate post-operative radiation therapy and was similar to prior reports in patients receiving post-operative radiation.

We present data in relation to the article entitled “Description of acute cardiac care in 2014:A French nation-wide database on 277,845 admissions in 270 ICCUs”.(10.1016/j.ijcard.2017.04.002) (Roubille et al., 2017) [1]: the main characteristics of the pathologies managed in the intensive cardiac care units (ICCUs), the details on the interventions performed and the main differences between centers following the size of the centers and a figure presenting the monthly variations of admissions in the ICCUs in France in a total of 277,845 patients in 270 centers admitted at least one time in the ICCUs in 2014 (exhaustive data). Keywords: Acute cardiac care, Database, Emergency, Intensive cardiac care unit, Intensive cardiovascular care unit, Intensive care

Topological constraint theory (TCT) has revealed itself to be a powerful tool in interpreting the behaviors of amorphous solids. The theory predicts a transition between a “rigid” overconstrained network and a “floppy” underconstrained network as a function of connectivity or average coordination number, 〈r〉. The predicted results have been shown experimentally for various glassy materials, the majority of these being based on 4-fold-coordinate networks such as chalcogenide and oxide glasses. Here, we demonstrate the broader applicability of topological constraint theory to uniquely coordinated amorphous hydrogenated boron carbide (a-BC:H), based on 6-fold-coordinate boron atoms arranged into partially hydrogenated interconnected 12-vertex icosahedra. We have produced a substantial set of plasma-enhanced chemical vapor deposited a-BC:H films with a large range of densities and network coordination, and demonstrate a clear threshold in Young's modulus as a function of 〈r〉, ascribed to a rigidity transition. We investigate constraint counting strategies in this material and show that by treating icosahedra as “superatoms,” a rigidity transition is observed within the range of the theoretically predicted 〈r〉c value of 2.4 for covalent solids with bond-stretching and bond-bending forces. This experimental data set for a-BC:H is unique in that it represents a uniform change in connectivity with 〈r〉 and demonstrates a distinct rigidity transition with data points both above and below the transition threshold. Finally, we discuss how TCT can be applied to explain and optimize mechanical and dielectric properties in a-BC:H and related materials in the context of microelectronics applications.

Posttraumatic Stress Disorder (PTSD) is a complex illness, frequently co-morbid with depression, caused by both genetics, and the environment. Alcohol Use Disorder (AUD), which also co-occurs with depression, is often co-morbid with PTSD. To date, very few genes have been identified for PTSD and even less for PTSD comorbidity with AUD, likely because of the phenotypic heterogeneity seen in humans, combined with each gene playing a relatively small role in disease predisposition. In the current study, we investigated whether a genetic model of depression-like behavior, further developed from the depression model Wistar Kyoto (WKY) rat, is a suitable vehicle to uncover the genetics of co-morbidity between PTSD and AUD. The by-now inbred WKY More Immobile (WMI) and the WKY Less Immobile (WLI) rats were generated from the WKY via bidirectional selective breeding using the forced swim test, a measure of despair-like behavior, as the functional selector. The colonies of the WMIs that show despair-like behavior and the control strain showing less or no despair-like behavior, the WLI, are maintained with strict inbreeding over 40 generations to date. WMIs of both sexes intrinsically self-administer more alcohol than WLIs. Alcohol self-administration is increased in the WMIs without sucrose fading, water deprivation or any prior stress, mimicking the increased voluntary alcohol-consumption of subjects with AUD. Prior Stress-Enhanced Fear Learning (SEFL) is a model of PTSD. WMI males, but not females, show increased SEFL after acute restraint stress in the context-dependent fear conditioning paradigm, a sexually dimorphic pattern similar to human data. Plasma corticosterone differences between stressed and not-stressed WLI and WMI male and female animals immediately prior to fear conditioning predict SEFL results. These data demonstrate that the WMI male and its genetically close, but behaviorally divergent control the WLI male, would be suitable for investigating the underlying genetic basis of comorbidity between SEFL and alcohol self-administration.

The Justinianic ‘mirror for princes’, the source of fragments attributed to Philo Judaeus and of passages in Barlaam, stresses the ruler’s need to imitate God and display philanthropia.

ObjectiveEpicardial adipose tissue (EAT) is suggested to correlate with metabolic risk factors and to promote plaque development in the coronary arteries. We sought to determine whether EAT thickness was associated or not with the presence and extent of angiographic coronary artery disease (CAD).MethodsWe measured epicardial fat thickness by computed tomography and assessed the presence and extent of CAD by coronary angiography in participants from the prospective EVASCAN study. The association of EAT thickness with cardiovascular risk factors, coronary artery calcification scoring and angiographic CAD was assessed using multivariate regression analysis.ResultsOf 970 patients (age 60.9 years, 71% male), 75% (n = 731) had CAD. Patients with angiographic CAD had thicker EAT on the left ventricle lateral wall when compared with patients without CAD (2.74±2.4 mm vs. 2.08±2.1 mm; p = 0.0001). The adjusted odds ratio (OR) for a patient with a LVLW EAT value ≥2.8 mm to have CAD was OR = 1.46 [1.03-2.08], p = 0.0326 after adjusting for risk factors. EAT also correlated with the number of diseased vessels (p = 0.0001 for trend). By receiver operating characteristic curve analysis, an EAT value ≥2.8 mm best predicted the presence of>50% diameter coronary artery stenosis, with a sensitivity and specificity of 46.1% and 66.5% respectively (AUC:0.58). Coronary artery calcium scoring had an AUC of 0.76.ConclusionAlthough left ventricle lateral wall EAT thickness correlated with the presence and extent of angiographic CAD, it has a low performance for the diagnosis of CAD.

This Letter to the Editor is a reply to Mohammed et al. (2021) https://doi.org/10.1016/j.fsisyn.2021.100145, which in turn is a response to Morrison et al. (2020) "Vacuous standards - subversion of the OSAC standards-development process" https://doi.org/10.1016/j.fsisyn.2020.06.005.