The HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENE15-HISTONE DEACETYLASE9 complex associates with HYPONASTIC LEAVES 1 to modulate microRNA expression in response to abscisic acid signaling.

The regulation of microRNA (miRNA) biogenesis is crucial for maintaining plant homeostasis under biotic and abiotic stress. The crosstalk between the RNA polymerase II (Pol-II) complex and the miRNA processing machinery has emerged as a central hub modulating transcription and cotranscriptional processing of primary miRNA transcripts (pri-miRNAs). However, it remains unclear how miRNA-specific transcriptional regulators recognize MIRNA loci. Here, we show that the Arabidopsis (Arabidopsis thaliana) HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENE15 (HOS15)-HISTONE DEACETYLASE9 (HDA9) complex is a conditional suppressor of miRNA biogenesis, particularly in response to abscisic acid (ABA). When treated with ABA, hos15/hda9 mutants show enhanced transcription of pri-miRNAs that is accompanied by increased processing, leading to overaccumulation of a set of mature miRNAs. Moreover, upon recognition of the nascent pri-miRNAs, the ABA-induced recruitment of the HOS15-HDA9 complex to MIRNA loci is guided by HYPONASTIC LEAVES 1 (HYL1). The HYL1-dependent recruitment of the HOS15-HDA9 complex to MIRNA loci suppresses expression of MIRNAs and processing of pri-miRNA. Most importantly, our findings indicate that nascent pri-miRNAs serve as scaffolds for recruiting transcriptional regulators, specifically to MIRNA loci. This indicates that RNA molecules can act as regulators of their own expression by causing a negative feedback loop that turns off their transcription, providing a self-buffering system.

HYL1-CLEAVAGE SUBTILASE 1 (HCS1) suppresses miRNA biogenesis in response to light-to-dark transition.

The core plant microprocessor consists of DICER-LIKE 1 (DCL1), SERRATE (SE), and HYPONASTIC LEAVES 1 (HYL1) and plays a pivotal role in microRNA (miRNA) biogenesis. However, the proteolytic regulation of each component remains elusive. Here, we show that HYL1-CLEAVAGE SUBTILASE 1 (HCS1) is a cytoplasmic protease for HYL1-destabilization. HCS1-excessiveness reduces HYL1 that disrupts miRNA biogenesis, while HCS1-deficiency accumulates HYL1. Consistently, we identified the HYL1K154A mutant that is insensitive to the proteolytic activity of HCS1, confirming the importance of HCS1 in HYL1 proteostasis. Moreover, HCS1-activity is regulated by light/dark transition. Under light, cytoplasmic CONSTITUTIVE PHOTOMORPHOGENIC 1 (COP1) E3 ligase suppresses HCS1-activity. COP1 sterically inhibits HCS1 by obstructing HYL1 access into the catalytic sites of HCS1. In contrast, darkness unshackles HCS1-activity for HYL1-destabilization due to nuclear COP1 relocation. Overall, the COP1-HYL1-HCS1 network may integrate two essential cellular pathways: the miRNA-biogenetic pathway and light signaling pathway.

Single center outcomes after temporary mechanical circulatory assist device prior to Heartmate 3 implantation - a retrospective cohort study.

Objectives. Temporary mechanical circulatory support (TMCS) has become a component in the therapeutic strategy for treatment of cardiogenic shock as a bridge-to-decision. TMCS can facilitate recovery of cardiopulmonary function, end-organ function, and potentially reduce the surgical risk of left ventricular assist device (LVAD) implantation. Despite the improvements of hemodynamics and end-organ function, post-LVAD operative morbidity might be increased in these high-risk patients. The aim of the study was to compare outcomes after Heartmate 3 (HM3) implantation in patients with and without TMCS prior to HM3 implant. Methods. In this retrospective cohort study of all HM3 patients in the period between November 2015 and October 2021, patients with and without prior TMCS were compared. Patients' demographics, baseline clinical characteristics, laboratory tests, intraoperative variables, postoperative outcomes, and adverse events were collected from patient records. Results. The TMCS group showed an improvement in hemodynamics prior to LVAD implantation. Median TMCS duration was 19.5 (14-26) days. However, the TMCS group were more coagulopathic, had more wound infections, neurological complications, and more patients were on dialysis compared with patient without TMCS prior to HM3 implantation. Survival four years after HM3 implantation was 80 and 82% in the TMCS (N = 22) and non-TMCS group (N = 41), respectively. Conclusion. Patients on TMCS had an acceptable short and long-term survival and comparable to patients receiving HM3 without prior TMCS. However, they had a more complicated postoperative course.

Dual or single antiplatelet therapy after coronary surgery for acute coronary syndrome (TACSI trial): Rationale and design of an investigator-initiated, prospective, multinational, registry-based randomized clinical trial.

The TACSI trial (ClinicalTrials.gov Identifier: NCT03560310) tests the hypothesis that 1-year treatment with dual antiplatelet therapy with acetylsalicylic acid (ASA) and ticagrelor is superior to only ASA after isolated coronary artery bypass grafting (CABG) in patients with acute coronary syndrome. The TACSI trial is an investigator-initiated pragmatic, prospective, multinational, multicenter, open-label, registry-based randomized trial with 1:1 randomization to dual antiplatelet therapy with ASA and ticagrelor or ASA only, in patients undergoing first isolated CABG, with a planned enrollment of 2200 patients at Nordic cardiac surgery centers. The primary efficacy end point is a composite of time to all-cause death, myocardial infarction, stroke, or new coronary revascularization within 12 months after randomization. The primary safety end point is time to hospitalization due to major bleeding. Secondary efficacy end points include time to the individual components of the primary end point, cardiovascular death, and rehospitalization due to cardiovascular causes. High-quality health care registries are used to assess primary and secondary end points. The patients will be followed for 10 years. The TACSI trial will give important information useful for guiding the antiplatelet strategy in acute coronary syndrome patients treated with CABG.

Validation of a risk prediction model for early chronic kidney disease in patients with type 2 diabetes: Data from the German/Austrian Diabetes Prospective Follow-up registry.

AIM: To validate a recently proposed risk prediction model for chronic kidney disease (CKD) in type 2 diabetes (T2D). MATERIALS AND METHODS: Subjects from the German/Austrian Diabetes Prospective Follow-up (DPV) registry with T2D, normoalbuminuria, an estimated glomerular filtration rate of 60 ml/min/1.73m2 or higher and aged 39-75 years were included. Prognostic factors included age, body mass index (BMI), smoking status and HbA1c. Subjects were categorized into low, moderate, high and very high-risk groups. Outcome was CKD occurrence. RESULTS: Subjects (n = 10 922) had a mean age of 61 years, diabetes duration of 6 years, BMI of 31.7 kg/m2 , HbA1c of 6.9% (52 mmol/mol); 9.1% had diabetic retinopathy and 16.3% were smokers. After the follow-up (~59 months), 37.4% subjects developed CKD. The area under the curve (AUC; unadjusted base model) was 0.58 (95% CI 0.57-0.59). After adjustment for diabetes and follow-up duration, the AUC was 0.69 (95% CI 0.68-0.70), indicating improved discrimination. After follow-up, 15.0%, 20.1%, 27.7% and 40.2% patients in the low, moderate, high and very high-risk groups, respectively, had developed CKD. Increasing risk score correlated with increasing cumulative risk of incident CKD over a median of 4.5 years of follow-up (P < .0001). CONCLUSIONS: The predictive model achieved moderate discrimination but good calibration in a German/Austrian T2D population, suggesting that the model may be relevant for determining CKD risk.

Short-term outcomes after heart transplantation using donor hearts preserved with ex vivo perfusion.

The standard Conventional Cold Storage (CCS) during heart transplantation procurement is associated with time-dependent ischemic injury to the graft, which is a significant independent risk factor for post-transplant early morbidity and mortality - especially when cold ischemic time exceeds four hours. Since 2018, Rigshospitalet (Copenhagen, Denmark) has been utilising ex vivo perfusion (Organ Care System, OCS) in selected cases. The objective of this study was to compare the short-term clinical outcomes of patients transplanted with OCS compared to CCS. Methods: This retrospective single-centre study was based on consecutive patients undergoing a heart transplant between January 2018 and April 2021. Patients were selected for the OCS group when the cold ischemic time was expected to exceed four hours. The primary outcome measure was six-month event-free survival. Results: In total, 48 patients were included in the study; nine were transplanted with an OCS heart. The two groups had no significant differences in baseline characteristics. Six-month event-free survival was 77.8% [95% CI: 54.9-100%] in the OCS group and 79.5% [95% CI: 67.8-93.2%] in the CCS group (p = 0.91). While the OCS group had a median out-of-body time that was 183 min longer (p < 0.0001), the cold ischemic time was reduced by 51 min (p = 0.007). Conclusion: In a Scandinavian setting, our data confirms that utilising OCS in heart procurement allows for a longer out-of-body time and a reduced cold ischemic time without negatively affecting safety or early post-transplant outcomes.

Three decades of heart transplantation: experience and long-term outcome.

Objectives. Heart transplantation (HTx) has become an established treatment option in patients with end-stage heart failure. The aim of this study was to report on long-term outcome over the past three decades. Design. Consecutive adult patients receiving first-time and isolated HTx from October 3, 1990, to November 2, 2020, at Rigshospitalet, Copenhagen, Denmark, were retrospectively evaluated. Data were obtained from the Scandinavian Transplant Registry and patient medical records. Recipients were grouped by time of transplantation (early era: 1990-1999; mid era: 2000-2009; recent era: 2010-2020). Results. A total of 384 recipients (77% men, median age 50 [IQR: 40-57]) were included. Median number of HTx procedures per year was 12 (10-14). Overall, 22% of patients were bridged to HTx with a mechanical circulatory support device. Median survival for the whole cohort was 13.8 years and improved numerically from the early era (12.6 years) to the mid era (14.9 years). Median survival conditional on survival to 1-year follow-up after HTx was 16.1 years. Survival probability by Kaplan-Meier method improved significantly from the mid to the recent era (log-rank p = .02). Conclusions. Heart transplantation remains an excellent treatment for selected patients with end-stage heart failure and long-term outcome has improved significantly over the past decades.

Tolerable Duration of Warm Ischaemia After Circulatory Death Is Safe For At Least One Hour in Porcine Lungs: Functional Assessment with Ex Vivo Lung Perfusion.

BACKGROUND: Lungs from donation after circulatory death (DCD) may be an underused resource for transplantation. The aim was to investigate, with a DCD pig model, if it was possible to recondition lungs exposed for up to 2 h of warm ischaemia with ex vivo lung perfusion (EVLP). METHODS: Danish domestic pigs (N = 17) were randomized into three groups. In the two study groups, lungs were exposed to either 1 or 2 h of warm ischaemia. All lungs were reconditioned and evaluated after 83 ± 38 minutes of perfusion at FiO2 1.0 and 0.21 with EVLP. Outcome measures were gas exchange, pulmonary physiology, inflammatory markers, and histopathologic assessment score. RESULTS: Lungs exposed for 2 h of warm ischaemia did not meet the criteria: PaO2 > 13 kPa required for donation compared with lungs subjected to 0 and 1 h of warm ischaemia (11.0 kPa vs. 14.2 kPa, P < 0.001). These lungs also developed an increased amount of foam and fluid in the airways. No differences in PaCO2, compliance, or pulmonary vascular resistance were observed. CONCLUSION: Results show that while lungs subjected to 0 or 1 h of warm ischaemia meet the criteria for transplantation based on EVLP evaluation, lungs subjected to 2 h of warm ischaemia did not.

Treatment studies with cannabinoids in anorexia nervosa: a systematic review.

INTRODUCTION: Anorexia nervosa (AN) is a psychiatric disorder with a high mortality and unknown etiology, and effective treatment is lacking. For decades, cannabis has been known to cause physical effects on the human body, including increasing appetite, which may be beneficial in the treatment of AN. OBJECTIVE: To systematically review the literature for evidence of an effect of cannabinoids on (1) weight gain, and (2) other outcomes, in AN. METHOD: A systematic review was done using three databases Embase, PubMed and Psychinfo. The review was registered in PROSPERO with ID number CRD42019141293 and was done according to PRISMA guidelines. RESULTS: There were 1288 studies identified and after thorough review and exclusion of copies, 4 studies met the inclusion criteria. Three studies used the same AN population and utilized data from one original study, leaving only two original studies. Both of these were Randomized Controlled Trials that explored the effects of delta-9-tetrahydrocannabinol (Δ9-THC) or dronabinol in AN, whereof one study was properly designed and powered and showed a weight increase of an added 1 kg over 4 weeks over placebo. DISCUSSION AND CONCLUSION: There are few studies and the level of evidence is low. The only properly designed, low bias and highly powered study found a weight increasing effect of dronabinol in AN, while the other, using Δ9-THC at a high dose, found no effect and where the dose may have counteracted the weight gaining effects due to adverse events. More research on cannabinoids in anorexia nervosa is warranted, especially its effects on psychopathology. LEVEL OF EVIDENCE: Level I, systematic review.

Prevalence, management, and outcome of adverse rhythm disorders in takotsubo syndrome: insights from the international multicenter GEIST registry.

One important complication related to takotsubo syndrome (TTS) is adverse rhythm disorders. Our study was conducted to determine the incidence and management of adverse rhythm disorders in TTS and its long-term prognostic impact. We analyzed 906 TTS patients from 9 European centers. Patients were divided into the adverse rhythm disorders group (encompassing ventricular tachycardia, ventricular fibrillation, torsade de pointes, and asystole or complete atrioventricular block) and non-adverse rhythm disorders group. In our study cohort, we identified 67 (7.4%) patients with presence of adverse rhythm disorders. TTS patients were followed up over a period of 2.8 years. In the adverse rhythm disorders group, 18% of patients presented adverse rhythm disorders before hospital admission. Asystole and/or AV block were significantly more presented before admission (13 patients versus 8 patients; p < 0.01), whereas ventricular tachyarrhythmias were more presented in-hospital (4 patients versus 42 patients; p < 0.01). Adverse rhythm disorders patients suffered more frequently from cardiogenic shock (31% versus 7.6%, p < 0.01) and in-hospital death (10.9% versus 3.6%; p < 0.01). Furthermore, the long-term survival was significantly impaired in adverse rhythm disorders patients as compared with non-adverse rhythm disorders patients; (log-rank p < 0.01). Using multivariate Cox regression analysis, cardiogenic shock (HR 2.86, 95% CI 1.1-6.9; p = 0.02) was identified as independent predictors of adverse rhythm disorders. The short- and long-term mortality rate of TTS patients presenting with adverse rhythm disorders was significantly higher than in TTS patients presenting without it. Therefore, TTS patients with adverse rhythm disorders should be carefully monitored during hospital stay and at long-term follow-up.

Male Anabolic Androgenic Steroid Users with Personality Disorders Report More Aggressive Feelings, Suicidal Thoughts, and Criminality.

Background and objectives: Anabolic androgenic steroids (AAS) are mainly used for aesthetic and performance-enhancing reasons. Their use is a growing public health problem and concern for society because of their adverse effects. The primary aim of this study was to identify psychiatric and personality disorders and to measure anxiety and depression in AAS users. Materials and Methods: Fifty-six males who actively contacted the Anti-Doping Hot-Line and wished to stop using AAS were included. Structured Clinical Interviews Diagnosis-I and -II were used to diagnose psychiatric and personality disorders. The Brief Scale for Anxiety and Montgomery Asberg Depression Rating Scale (subscales from the Comprehensive Psychopathological Rating Scale) were used to measure changes in anxiety and depression. Structured Clinical Interviews Diagnosis-I and -II were performed at one time point. Anxiety and depression were measured at inclusion and after six months. Urine samples were collected for an analysis of AAS and drugs of abuse. Results: All participants reported some adverse effects that they associated with AAS use. In total, 56% and 52% of the cohort fulfilled the criteria for Structured Clinical Interviews Diagnosis-I and -II diagnoses, respectively. A significantly increased risk of reporting aggressive feelings/behaviors (Odds Ratio (OR) = 4.9; Confidence Interval (CI) 0.99-25, p = 0.04), suicidal thoughts/attempts (OR = 4.6, CI 95; 0.99-21, p = 0.04) and criminality (OR = 6.5, CI 1-39, p = 0.03) was found among individuals with AAS use fulfilling the criteria for personality disorders compared with those without such AAS use. The Brief Scale for Anxiety score decreased from the median of 15 at inclusion to 10 at the follow-up visit six months later (p = 0.01, n = 19). Conclusions: Our findings indicate that among individuals with AAS use, those with a personality disorder report more aggressive behaviors, suicidal thoughts/suicidal attempts, and criminality than those without a personality disorder.

Malignancies and outcome in Takotsubo syndrome: a meta-analysis study on cancer and stress cardiomyopathy.

Takotsubo syndrome (TTS) can be induced by a large variety of physical/emotional triggers; several cases, however, are related to either an overt or occult malignancy, as shown in retrospective studies and case reports. The aim of this study was therefore to evaluate the clinical outcome of patients with TTS and cancer in a meta-analysis study. In June 2018, a Pubmed systematic research was conducted for studies assessing outcome in patients with TTS and cancer. We assessed Mantel-Haenszel pooled estimates of risk ratios (RRs) and 95% confidence intervals (CIs) for adverse events at follow-up. After paper retrieval, four studies were included in the meta-analysis, with a total of 123,563 patients. The prevalence of current or previous malignancy among patients admitted with TTS was 6.7% (8258 patients). When compared to control patients, patients with cancer showed an increased risk of clinical events (RR 3.24, 95% CI 3.04-3.45, p < 0.01). The risk of in-hospital events was significantly higher in the cancer group (RR 2.08 95% CI, 1.50-2.87, p < 0.01) and was mainly due to higher need for respiratory support (RR 1.67, 95% CI, 1.58-1.77, p < 0.01). The risk of adverse events at follow-up was also higher in the cancer group (RR 3.30, 95% CI 3.09-3.51, p < 0.01). Cancer, either history or active, is associated with an increased risk of adverse events in TTS.

30-day mortality in frail patients undergoing cardiac surgery: the results of the frailty in cardiac surgery (FICS) copenhagen study.

Objectives. Typically, patients referred to cardiac surgery are aged. Because EuroSCORE tend to overestimate and STS tend to underestimate the risk of mortality after cardiac surgery, frailty has become interesting as a potential predictor for mortality after cardiac surgery. Therefore, we conducted a study to identify the number of frail patients undergoing cardiac surgery and describe the risk of short-term complications and mortality. Design. In a prospective observational study, we have compared the surgical outcome in frail versus non-frail patients. Patients aged > 65 years and undergoing non-acute cardiac surgery were included. Frailty was assessed using the comprehensive assessment of frailty (CAF) score. The CAF evaluates the patient's physical condition through performing physical tests. Results. 604 patients included, 477 were men and the median age was 73 years (range, 65-90). Twenty-five percent were deemed frail. Frail patients had a four times higher 30-day mortality. Furthermore, frail patients had higher postoperative complication rates of atrial fibrillation, prolonged ventilation, re-operations, renal failure, transfusion requirements, and increased length of stay. Patients who died within 30 days had a significantly higher CAF score than those who survived (p = .039). Based on ROC curves, the area under the curve (AUC) for CAF score was 0.700, EuroSCORE 0.664 and STS score 0.748. Conclusion. Frailty is common in patients undergoing cardiac surgery and carries increased risk of 30-day mortality and postoperative complications. The AUC indicates similar prediction of mortality for CAF score compared to the existing risk scores. Clinical Trials Registration ID: NCT02992587.

Left ventricular myocardial deformation in Takotsubo syndrome: a cardiovascular magnetic resonance myocardial feature tracking study.

OBJECTIVES: This study assessed the applicability and prognostic value of cardiovascular magnetic resonance (CMR) left ventricular deformation analysis in Takotsubo syndrome (TTS). METHODS: CMR-feature tracking was performed blinded in a core laboratory to determine circumferential (CS), radial (RS) and longitudinal strain (LS) in 141 TTS patients participating in this cohort study. A subgroup of consecutive TTS patients (n = 20) was compared with age- and sex-matched controls with anterior ST-segment elevation myocardial infarction (STEMI) and non-STEMI as well as healthy subjects. RESULTS: Median global CS, RS and LS were -19%, 19% and -12%, respectively. Apical ballooning was associated with significantly lower global CS (p < 0.01) and LS (p < 0.01) compared with midventricular and basal ballooning. Global RS was lowest in patients with basal ballooning (p < 0.01). Segmental analysis resulted in a reliable discrimination of different ballooning patterns using CS and LS. Strain values were significantly lower in TTS compared with non-STEMI patients and healthy subjects, whereas STEMI patients showed similar values. While global CS and RS were not associated with long-term mortality, global LS (cutoff -14.75%) was identified as a potential parameter for long-term risk stratification (mortality rate 17.9% versus 2.5%; p = 0.02). CONCLUSIONS: The transient contraction abnormalities in TTS can be quantitatively assessed with CMR-feature tracking. GLS is a potential determinant of outcome in TTS, which, however, requires further validation. KEY POINTS: • Cardiovascular magnetic resonance myocardial feature tracking enables accurate assessment of regional and global left ventricular dysfunction in Takotsubo syndrome (TTS). • Global strain in TTS is similar to patients with anterior STEMI and lower compared with non-STEMI and healthy subjects. • Global longitudinal strain is a potential tool for risk prediction in TTS patients.

Involvement of Spinal IL-6 Trans-Signaling in the Induction of Hyperexcitability of Deep Dorsal Horn Neurons by Spinal Tumor Necrosis Factor-Alpha.

UNLABELLED: During peripheral inflammation, both spinal TNF-α and IL-6 are released within the spinal cord and support the generation of inflammation-evoked spinal hyperexcitability. However, whether spinal TNF-α and IL-6 act independently in parallel or in a functionally dependent manner has not been investigated. In extracellular recordings from mechanonociceptive deep dorsal horn neurons of normal rats in vivo, we found that spinal application of TNF-α increased spinal neuronal responses to mechanical stimulation of knee and ankle joints. This effect was significantly attenuated by either sgp130, which blocks IL-6 trans-signaling mediated by IL-6 and its soluble receptor IL-6R (sIL-6R); by an antibody to the IL-6 receptor; or by minocycline, which inhibits the microglia. IL-6 was localized in neurons of the spinal cord and, upon peripheral noxious stimulation in the presence of spinal TNF-α, IL-6 was released spinally. Furthermore, TNF-α recruited microglial cells to provide sIL-6R, which can form complexes with IL-6. Spinal application of IL-6 plus sIL-6R, but not of IL-6 alone, enhanced spinal hyperexcitability similar to TNF-α and the inhibition of TNF-α-induced hyperexcitability by minocycline was overcome by coadministration of sIL-6R, showing that sIL-6R is required. Neither minocycline nor the TNF-α-neutralizing compound etanercept inhibited the induction of hyperexcitability by IL-6 plus sIL-6R. Together, these data show that the induction of hyperexcitability of nociceptive deep dorsal horn neurons by TNF-α largely depends on the formation of IL-6/sIL-6R complexes that are downstream of TNF-α and requires the interactions of neurons and microglia orchestrated by TNF-α. SIGNIFICANCE STATEMENT: Both spinal TNF-α and IL-6 induce a state of spinal hyperexcitability. We present the novel finding that the full effect of TNF-α on the development of spinal hyperexcitability depends on IL-6 trans-signaling acting downstream of TNF-α. IL-6 trans-signaling requires the formation of complexes of IL-6 and soluble IL-6 receptor. Spinal TNF-α furthers the release of IL-6 from neurons in the spinal cord during peripheral noxious stimulation and recruits microglial cells to provide soluble IL-6 receptor, which can form complexes with IL-6. Therefore, a specific interaction between neurons and microglia is required for the full development of TNF-α-induced hyperexcitability of nociceptive deep horsal horn neurons.

Transient left atrial dysfunction is a feature of Takotsubo syndrome.

BACKGROUND: Takotsubo syndrome (TTS) is characterized by a transient left and/or right ventricular dysfunction as a consequence of a distinctive pattern of regional wall motion abnormalities. However, a systematic evaluation of the left atrial (LA) function in patients with TTS is lacking. The aim of the present study was therefore to comprehensively assess LA performance indexes and function in patients with TTS. METHODS: We compared LA function assessed by volumetric indexes derived from fractional volume changes in cardiovascular magnetic resonance (CMR) between 125 TTS patients and 125 patients with anterior ST-segment elevation myocardial infarction (STEMI). Furthermore, recovery of LA performance was evaluated in a subgroup of 20 TTS patients with follow-up CMR data. RESULTS: Patients with TTS demonstrated a significantly lower total LA emptying fraction (EF) [44% (interquartile range (IQR) 34-53%) versus 51% (IQR 42-56%); p < 0.01], passive LA-EF [21% (IQR 14-30%) versus 24% (IQR 20-29%); p = 0.03] and active LA-EF [29% (IQR 20-38%) versus 35% (28-42%); p < 0.01] compared to patients with anterior STEMI. Among the 20 TTS patients with serial CMR data, the total LA-EF significantly improved from 42% (IQR 29-48%) at the acute stage to 51% (IQR 46-59%) at follow-up (p < 0.01). Similarly, active LA-EF (p < 0.01) and passive LA-EF (p = 0.02) improved significantly as well. CONCLUSION: Compared to anterior STEMI, TTS patients demonstrated a significantly decreased LA function during the acute/subacute phase of the disease. However, impairment of LA performance seems to be transient in TTS with recovery during follow-up.

Cardiac surgery in patients with end-stage renal disease on dialysis.

OBJECTIVES: Over the past decade, the number of patients on dialysis and with cardiovascular diseases has steadily increased. This retrospective analysis compares the postoperative mortality after cardiac surgery between patients on hemodialysis and peritoneal dialysis. METHODS: Between 1998 and 2015, 136 patients with end-stage renal disease initiating dialysis more than one month before surgery underwent cardiac surgery. Demographics, preoperative hemodynamic and biochemical data were collected from the patient records. Vital status and date of death was retrieved from a national register. RESULTS: Hemodialysis was undertaken in 73% and peritoneal dialysis in 22% of patients aged 59.7 ± 12.9 years, mean EuroSCORE 8.6% ± 3.5. Isolated coronary artery bypass graft was performed in 46%, isolated valve procedure in 29% and combined procedures in 24% with no significant statistical difference between groups. The 30-day mortality was 14% for hemodialysis patients and 3% for peritoneal dialysis patients (p = .056). One-year and 5-year mortality were, 30% and 59% in the hemodialysis group, 30% and 57% in the peritoneal dialysis group (p = .975, p = .852). Independent predictors of total mortality were age (p = .001), diabetes (p = .017) and active endocarditis (p = .012). CONCLUSION: No statistically significant difference in mortality was found between patients in hemo- or peritoneal dialysis. However, we observed that patients with end-stage renal disease on dialysis have two times higher mortality rate than estimated by EuroSCORE.

Coagulopathy in patients with acute pulmonary embolism: a pilot study of whole blood coagulation and markers of endothelial damage.

Whole blood coagulation and markers of endothelial damage were studied in patients with acute pulmonary embolism (PE), and evaluated in relation to PE severity. Twenty-five patients were enrolled prospectively each having viscoelastical analysis of whole blood done using thrombelastography (TEG) and Multiplate aggregometry. Fourteen of these patients were investigated for endothelial damage by ELISA measurements of Syndecan-1 (endothelial glycocalyx degradation), soluble endothelial Selectin (endothelial cell activation), soluble Thrombomodulin (endothelial cell injury) and Histone Complexed DNA fragments (endothelial cytotoxic histones). The mean values of TEG and Multiplate parameters were all within the reference levels, but a significant difference between patients with high and intermediate risk PE was observed for Ly30 (lytic activity) 1.5% [0-10] vs. 0.2% [0-2.2] p = .04, and ADP (platelet reactivity) 92 U [20-145] vs. 59 U [20-111] p = .03. A similar difference was indicated for functional fibrinogen 21 mm [17-29] vs. 18 mm [3-23] p = .05. Analysis of endothelial markers identified a significant difference in circulating levels between high and intermediate risk PE patients for Syndecan-1 118.6 ng/mL [76-133] vs. 36.3 ng/mL [11.8-102.9] p = .008. In conclusion, patients with acute PE had normal whole blood coagulation, but high risk PE patients had signs of increased activity of the haemostatic system and significantly increased level of endothelial glycocalyx degradation.

National clinical guidelines for non-surgical treatment of patients with recent onset neck pain or cervical radiculopathy.

PURPOSE: To summarise recommendations about 21 selected non-surgical interventions for recent onset (<12 weeks) non-specific neck pain (NP) and cervical radiculopathy (CR) based on two guidelines from the Danish Health Authority. METHODS: Two multidisciplinary working groups formulated recommendations based on the GRADE approach. RESULTS: Twelve recommendations were based on evidence and nine on consensus. Management should include information about prognosis, warning signs, and advise to remain active. For treatment, guidelines suggest different types of supervised exercise and manual therapy; combinations of exercise and manual therapy before medicine for NP; acupuncture for NP but not CR; traction for CR; and oral NSAID (oral or topical) and Tramadol after careful consideration for NP and CR. CONCLUSION: Recommendations are based on low-quality evidence or on consensus, but are well aligned with recommendations from guidelines from North America. The working groups recommend intensifying research relating to all aspects of management of NP and CR.

Transit-time flow measurement as a predictor of coronary bypass graft failure at one year angiographic follow-up.

BACKGROUND: Transit-time flow measurement (TTFM) is a commonly used intraoperative method for evaluation of coronary artery bypass graft (CABG) anastomoses. This study was undertaken to determine whether TTFM can also be used to predict graft patency at one year postsurgery. METHODS: Three hundred forty-five CABG patients with intraoperative graft flow measurements and one year angiographic follow-up were analyzed. Graft failure was defined as more than 50% stenosis including the "string sign." Logistic regression analysis was used to analyze the risk of graft failure after one year based on graft vessel type, anastomatic configuration, and coronary artery size. RESULTS: Nine hundred eighty-two coronary anastomoses were performed of which 12% had signs of graft failure at one year angiographic follow-up. In internal mammary arteries (IMAs), analysis showed a 4% decrease in graft failure odds for every 1 mL/min increase in TTFM (OR = 0.96, CI = [0.93; 0.99], p = 0.005). ROC analysis showed good discriminative ability for TTFM alone AUC = 69.5% in IMA grafts. For single-vein grafts the decrease in graft failure odds was 2% for every 1 mL/min increase in TTFM (OR = 0.98; CI = [0.97; 1.00], p = 0.059) and AUC of 59.9%. There were no significant relationships between TTFM and graft failure in other graft types or graft configurations. CONCLUSION: The TTFM method has good discriminative ability for assessing the risk of graft failure in certain graft types within the first year after CABG surgery and is a valuable instrument for intraoperative quality assessment of bypass grafts.