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Introduction: Pre-transplant obesity and weight gain after heart transplantation are both associated with increased risk of poor clinical outcomes. We aimed to assess the association between overweight or obesity, exercise capacity, and health-related quality of life in heart transplant recipients., Methods: This study is based on baseline data from the IronIC trial, in which we randomized 102 heart transplant recipients with iron deficiency to ferric derisomaltose or placebo. We performed cardio pulmonary exercise testing in all participants. To assess quality of life, we used the SF-36v2 questionnaire, using two sum scores: the physical component summary and the mental component summary. A minimal clinically important difference was defined as ≥2 and ≥3 for the physical and the mental component summary, respectively., Results: 24/102 heart transplant recipients (24%) had a body mass index (BMI) ≥30 kg/m 2 . Peak oxygen consumption was 17.3 ± 4.6 ml/kg/min in the obese group vs. 24.7 ± 6.4 ml/kg/min in the group with a BMI <30 for a between-group difference of 7.4 (95% confidence interval 4.7-10.2) ml/kg/min: p  < 0.001. The physical component summary score was on average 5.2 points lower in the patients with a body mass index ≥30 than in the lower weight group ( p  = 0.04)., Conclusion: Almost a quarter of our heart transplant recipients in long-term follow-up had a BMI ≥30 kg/m 2 . These patients had substantially lower exercise capacity and lower quality of life in the physical domain., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Holt, Holmen, Rolid, Englund, Østby, Ravnestad, Andreassen, Gullestad, Gude and Broch.)

Aims: Our aim was to investigate haemodynamics at rest and during exercise in patients with transthyretin cardiomyopathy (ATTR-CM) in light of the 2022 European Society of Cardiology (ESC) and European Respiratory Society (ERS) guidelines on pulmonary hypertension (PH)., Methods and Results: We performed right heart catheterization (RHC) in 57 subjects with ATTR-CM. The proportion of patients with PH was 77% according to the 2022 guidelines versus 47% when applying the 2015 guidelines. Isolated post-capillary PH and combined pre- and post-capillary PH were most prevalent. Thirty-six patients underwent a supine bicycle cardiopulmonary exercise test during RHC. Exercise-induced PH was defined as an increase in mean pulmonary arterial pressure from rest to exercise per increase in cardiac output (ΔmPAP/ΔCO) of > 3 mmHg/L/min. An increase in pulmonary arterial wedge pressure per change in cardiac output (ΔPAWP/ΔCO) from rest to exercise >2 mmHg/L/min was considered suggestive of post-capillary exercise-induced PH. All but two patients who exercised during RHC developed exercise-induced PH. The median ΔmPAP/ΔCO was 7.2 mmHg/L/min and ΔPAWP/ΔCO was 5.1 mmHg/L/min. The median ΔRAP/ΔCO was 3.6 mmHg/L/min and ΔRAP/ΔPAWP was 0.6 mmHg/L/min., Conclusions: Most patients with ATTR-CM have isolated post-capillary or combined pre- and post-capillary PH at rest, and almost all patients develop exercise-induced PH with a large post-capillary component. There was a pronounced, but balanced increase in atrial pressures on exercise., (© 2023 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

A man in his seventies underwent routine heart examinations as part of workup for kidney transplantation. Unexpected findings led to more extensive investigations and revealed two rare systemic diseases as causes of his heart failure.

Background: In approximately 20% of patients with thoracic aortic aneurysms or dissections a heritable thoracic aortic disease (HTAD) is suspected. Several monogenic connective tissue diseases imply high risk of aortic disease, including both non-syndromic and syndromic forms. There are some studies assessing inflammation and extracellular matrix remodeling in patients with non-hereditary aortic disease, but such studies in patients with hereditary diseases are scarce., Aims: To quantify markers of extracellular matrix (ECM) and inflammation in patients with vascular connective tissue diseases versus healthy controls., Methods: Patients with Loeys-Dietz syndrome (LDS, n = 12), Marfan syndrome (MFS, n = 11), and familial thoracic aortic aneurysm 6 (FTAA6, n = 9), i.e., actin alpha 2 (ACTA2) pathogenic variants, were recruited. Exome or genome sequencing was performed for genetic diagnosis. Several markers of inflammation and ECM remodeling were measured in plasma by enzyme immunoassays. Flow cytometry of T-cell subpopulations was performed on a subgroup of patients. For comparison, blood samples were drawn from 14 healthy controls., Results: (i) All groups of HTAD patients had increased levels matrix metalloproteinase-9 (MMP-9) as compared with healthy controls, also in adjusted analyses, reflecting altered ECM remodeling. (ii) LDS patients had increased levels of pentraxin 3 (PTX3), reflecting systemic inflammation. (iii) LDS patients have increased levels of soluble CD25, a marker of T-cell activation., Conclusion: Our data suggest that upregulated MMP-9, a matrix degrading enzyme, is a common feature of several subgroups of HTAD. In addition, LDS patients have increased levels of PTX3 reflecting systemic and in particular vascular inflammation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Seim, Holt, Ratajska, Michelsen, Ringseth, Halvorsen, Skjelland, Kvitting, Lundblad, Krohg-Sørensen, Osnes, Aukrust, Paus and Ueland.)

Background: All-terrain vehicle (ATV) laws regarding helmet use, alcohol involvement, and roadway riding are poorly enforced or largely ignored. We hypothesized that direct surgeon funding and leadership in injury prevention would decrease ATV crashes. To focus prevention efforts, we reviewed a rural level 1 trauma center 11-year experience with ATV crashes comparing helmeted and unhelmeted rider outcomes., Methods: For the latter 6 years of the study period, a trauma surgeon sponsored an injury prevention fund promoting ATV safety using simulators and discussions for area high school students. Helmet use, alcohol avoidance, and safe ATV operating were emphasized. A trauma registry review of ATV admissions from 2009 through 2020 examined demographics, helmet use, and clinical outcomes using chi-square, t-test, and regression analysis., Results: Unhelmeted ATV riders suffered more severe head and neck injuries (OR 19, CI 1.5-1.8, P < .001), worse overall Injury Severity Score (ISS), (OR 25, CI 12.1-14.2, P < .001), and higher mortality rates (OR 4.0, CI .02-.05, P < .001). Helmet use corresponded with an average decrease in AIS and increase in GCS status. Although only 15% of riders were helmeted, ATV crash admissions have decreased in the last 5 years ( P < .001)., Discussion: All-terrain vehicle trauma and mortality is still frequent, especially in unhelmeted riders. The recent decrease in area ATV crashes is encouraging. Trauma surgeons have an opportunity to make a difference in public awareness and education through comprehensive physician-funded and directed injury prevention and research efforts.

Background: Unhelmeted motorcyclists injured in states with lax or poorly enforced helmet safety laws are frequently seen in rural trauma centers. A trauma surgeon started a comprehensive injury prevention and research fund with outreach to a three-state trauma center catchment area promoting injury prevention at area high schools and local communities. We hypothesized that unhelmeted riders would have more severe head injuries and fatalities than helmeted riders., Methods: A trauma registry review of 708 injured motorcycle riders over an 11-year period examined demographics, helmet use, and clinical outcomes of helmeted and unhelmeted riders. A full-time injury prevention coordinator collaborating with law enforcement provided electronic and mechanical simulations with discussions regarding helmet use, alcohol avoidance, and responsible motorcycle riding for area high school students. This program coincided with the second half of our 11-year study. Multiple regression analysis evaluated predictors for head injury and death., Results: Unhelmeted motorcyclists suffered worse head injuries, (OR 8.8, CI 1.6-2.4, P < .001), more severe overall injury (OR 10, CI 12.7-18.6, P < .001), and higher mortality (OR 2.7, CI .02-.15, P < .001). Local motorcycle-related trauma center admissions and deaths have stabilized in recent years while statewide motorcycle crashes have increased ( P < .05)., Discussion: Unhelmeted motorcyclists suffer worse head injuries and mortality rates. Physician-led outreach efforts for injury prevention may be effective. Trauma surgeons have ongoing opportunities to promote responsible motorcycle riding for schools and local communities.

Background: A rural level 1 trauma center underwent a consolidation to level III status in a new trauma network system. A dedicated group of midlevel practitioners emphasizing early mobilization, a geriatric care model, and fall prevention replaced surgical residents in the level 3 center. We hypothesized that outcomes of elderly fall-related injuries may be enhanced with midlevel providers using a geriatric-focused care model., Methods: An IRB-approved trauma registry review of patients over 65 years of age with a fall-related injury admitted to a rural trauma center 1 year prior to and 1 year following a trauma center consolidation from level 1 to level III designation evaluated demographics, anticoagulant use, comorbidities, and clinical outcomes. Statistical analysis included t-test and regression analysis., Results: 327 patients injured by falls were seen over a 2-year study period. The number of patients admitted with a fall-related injury and the injury severity were similar over the study period. Increasing age and anticoagulant use increased length of stay and mortality (both with P < .05). Mortality rates and patient level of independence on discharge were improved in the later period involving midlevel practitioners (both with P < .05)., Discussion: Trauma centers and trauma system networks face increasing challenges to provide resources and providers of care for patients injured by falls, especially for the growing elderly population. Midlevel providers focusing on geriatric clinical issues and goals may enhance care and outcomes of elderly fall-related injuries.

Objective: Dysregulation of the complement system has been described in patients with heart failure (HF). However, data on the alternative pathway are scarce and it is unknown if levels of factor B (FB) and the C3 convertase C3bBbP are elevated in these patients. We hypothesized that plasma levels of FB and C3bBbP would be associated with disease severity and survival in patients with HF., Methods: We analyzed plasma levels of FB, C3bBbP, and terminal C5b-9 complement complex (TCC) in 343 HF patients and 27 healthy controls., Results: Compared with controls, patients with HF had elevated levels of circulating FB (1.6-fold, p < 0.001) and C3bBbP (1.3-fold, p < 0.001). In contrast, TCC, reflecting the terminal pathway, was not significantly increased (p = 0.15 vs controls). FB was associated with NT-proBNP, troponin, eGFR, and i.e., C-reactive protein. FB, C3bBbP and TCC were not associated with mortality in HF during a mean follow up of 4.3 years., Conclusion: Our findings suggest that in patients with HF, the alternative pathway is activated. However, this is not accompanied by activation of the terminal pathway., Competing Interests: NS is currently an employee of Johnson and Johnson; the current work was conducted when she was employed by Oslo University Hospital. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Holt, Michelsen, Shahini, Bjørkelund, Bendz, Massey, Schjalm, Halvorsen, Broch, Ueland, Gullestad, Nilsson, Aukrust, Mollnes and Louwe.)

Inflammation is centrally involved in the development of cardiac hypertrophy and the processes of remodelling. The complement system and Toll-like receptor (TLR) family, two upstream arms of the innate immune system, have previously been reported to be involved in cardiac remodelling. However, the role of complement component 3 (C3), TLR co-receptor CD14 and the synergy between them have not been addressed during pressure overload-induced cardiac remodelling. Here, we examined angiotensin II-induced cardiac hypertrophy and remodelling for 7 days in male C57Bl/6 J mice deficient in C3, CD14, or both (C3CD14), and WT controls. Angiotensin II infusion induced a mild concentric hypertrophic phenotype in WT mice with increased left ventricle weight, wall thicknesses and reduced ventricular internal diameter, associated with increased cardiac fibrosis. However, there were no differences between WT mice and mice deficient for C3, CD14 or C3CD14, as systolic blood pressure, cardiac function and structure and levels of fibrosis were comparable between WT mice and the three other genotypes. C5a did not change in angiotensin II treated mice, whereas Mac2 levels were increased in angiotensin II treated mice, but did not differ between genotypes. The inflammatory IL-6 response was comparable between WT and C3 deficient mice, however, it was decreased in CD14 and C3CD14 deficient mice. We conclude that deficiency in C3, CD14 or C3CD14 had no effect on cardiac remodelling following angiotensin II-induced pressure overload. This suggests that C3 and CD14 are not involved in angiotensin II-induced adverse cardiac remodelling., Competing Interests: Declaration of competing interest None., (Copyright © 2020. Published by Elsevier Inc.)

Objective: The aetiology of thoracic aortic aneurysm (TAA) is largely unknown, but inflammation is likely to play a central role in the pathogenesis. In this present study, we aim to investigate the complement receptors in TAA., Methods: Aortic tissue and blood from 31 patients with non-syndromic TAA undergoing thoracic aortic repair surgery were collected. Aortic tissue and blood from 36 patients with atherosclerosis undergoing coronary artery bypass surgery or aortic valve replacement were collected and served as control material. The expression of the complement anaphylatoxin receptors C3aR1, C5aR1 and C5aR2 in aortic tissue were examined by quantitative RT-PCR and C5aR2 protein by immunohistochemistry. Colocalisation of C5aR2 to different cell types was analysed by immunofluorescence. Complement activation products C3bc and sC5b-9 were measured in plasma., Results: Compared with controls, TAA patients had substantial (73%) downregulated gene expression of C5aR2 as seen both at the mRNA (p=0.005) level and protein (p=0.03) level. In contrast, there were no differences in the expression of C3aR1 and C5aR1 between the two groups. Immunofluorescence examination showed that C5aR2 was colocalised to macrophages and T cells in the aortic media. There were no differences in the degree of systemic complement activation between the two groups., Conclusion: Our findings suggest downregulation of the C5aR2, regarded to act mainly anti-inflammatory, in electively operated TAA as compared with non-aneurysmatic aortas of patients with aortic stenosis and/or coronary artery disease. This may tip the balance towards a relative increase in the inflammatory responses induced by C5aR1 and thus enhance the inflammatory processes in TAA., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)