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Aims: Patient dissatisfaction is not uncommon following primary total knee arthroplasty. One proposed method to alleviate this is by improving knee kinematics. Therefore, we aimed to answer the following research question: are there significant differences in knee kinematics based on the design of the tibial insert (cruciate-retaining (CR), ultra-congruent (UC), or medial congruent (MC))? Methods: Overall, 15 cadaveric knee joints were examined with a CR implant with three different tibial inserts (CR, UC, and MC) using an established knee joint simulator. The effects on coronal alignment, medial and lateral femoral roll back, femorotibial rotation, bony rotations (femur, tibia, and patella), and patellofemoral length ratios were determined. Results: No statistically significant differences were found regarding coronal alignment (p = 0.087 to p = 0.832). The medial congruent insert demonstrated restricted femoral roll back (mean medial 37.57 mm; lateral 36.34 mm), while the CR insert demonstrated the greatest roll back (medial 42.21 mm; lateral 37.88 mm; p < 0.001, respectively). Femorotibial rotation was greatest with the CR insert with 2.45° (SD 4.75°), then the UC insert with 1.31° (SD 4.15°; p < 0.001), and lowest with the medial congruent insert with 0.8° (SD 4.24°; p < 0.001). The most pronounced patella shift, but lowest patellar rotation, was noted with the CR insert. Conclusion: The MC insert demonstrated the highest level of constraint of these inserts. Femoral roll back, femorotibial rotation, and single bony rotations were lowest with the MC insert. The patella showed less shifting with the MC insert, but there was significantly increased rotation. While the medial congruent insert was found to have highest constraint, it remains uncertain if this implant recreates native knee kinematics or if this will result in improved patient satisfaction. Cite this article: Bone Jt Open 2024;5(7):592–600.

Background: Coronary functional disorders (CFD) are significant contributors to angina with non-obstructed coronary arteries (ANOCA). Various endotypes, such as epicardial or microvascular spasm and/or coronary microvascular dysfunction (CMD), have been identified. Previous studies have shown a high prevalence of CFD in ANOCA cases, but often lacked comprehensive coronary functional testing (CFT), which ideally includes coronary spasm provocation testing and CMD assessment. This study aims to investigate the prevalence of CFD and to characterise endotypes in ANOCA patients using comprehensive CFT. Methods: A total of 89 consecutive ANOCA patients (mean age 64, 69% women) who underwent comprehensive CFT were enrolled. CFT comprised acetylcholine (ACh) spasm provocation testing and assessment of coronary flow reserve (CFR) and hyperaemic microvascular resistance using Doppler technique. Results: CFT identified at least one coronary vasomotion disorder in 91% of patients with ANOCA. Among them, microvascular spasm was the most common endotype (61%), followed by CMD (43%). Only 9% of patients had isolated CMD with the remaining CMD patients also showing coronary spasm. Low CFR was mainly associated with high resting coronary flow rather than impaired hyperaemic flow (R −0.60, p

Background: Electrocardiograms (ECGs) recorded with wearable devices and additional smartphone apps play an increasing role in cardiology. Case summaries: We present two cases in which it was possible to record an ECG during cardiac-related symptoms using the patients' smartphones. Previous standard resting and 24-hour ECGs had revealed no pathologies. In one case, AV nodal reentry tachycardia was detected and treated accordingly. In the second case, ischemic ECG changes were recorded in a young woman without cardiovascular risk factors during a chest pain episode. Suspecting a coronary vasomotion disorder, an invasive diagnostic procedure was performed. The acetylcholine spasm provocation test revealed coronary microvascular spasm and appropriate therapy was initiated. Discussion: Smartphone-based ECG systems which can be used by the patient independently while experiencing cardiac-related symptoms are a modern diagnostic tool. Considering the use of these systems is beneficial for early diagnosis and appropriate treatment for paroxysmal arrhythmias and coronary vasomotion disorders.

BackgroundCoronary artery spasm (CAS), encompassing epicardial and microvascular spasm, is increasingly recognized as cause of angina in patients with non-obstructive coronary artery disease (ANOCA). However, various spasm provocation testing protocols and diagnostic criteria are used, making diagnosis and characterization of these patients difficult and interpretation of study results cumbersome. This review provides a structured overview of the prevalence, characterization and prognosis of CAS worldwide in men and women.MethodsA systematic review identifying studies describing ANOCA patients with CAS was performed. Multiple outcomes (prevalence, clinical features, and prognosis) were assessed. Data, except for prognosis were pooled and analysed using random effects meta-analysis models.ResultsTwenty-five publications (N = 14.554) were included (58.2 years; 44.2% women). Percentages of epicardial constriction to define epicardial spasm ranged from >50% to >90%. Epicardial spasm was prevalent in 43% (range 16–73%), with a higher prevalence in Asian vs. Western World population (52% vs. 33%, p = 0.014). Microvascular spasm was prevalent in 25% (range 7–39%). Men were more likely to have epicardial spasm (61%), women were more likely to have microvascular spasm (64%). Recurrent angina is frequently reported during follow-up ranging from 10 to 53%.ConclusionCAS is highly prevalent in ANOCA patients, where men more often have epicardial spasm, women more often have microvascular spasm. A higher prevalence of epicardial spasm is demonstrated in the Asian population compared to the Western World. The prevalence of CAS is high, emphasizing the use of unambiguous study protocols and diagnostic criteria and highlights the importance of routine evaluation of CAS in men and women with ANOCA.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=272100.

Our understanding of the timing of stress responses and specific roles of different regulatory pathways that drive stress responses is incomplete. In particular, the regulation of appetite genes as a consequence of exposure to different stressors has not been studied in sufficient detail in fish. Therefore, a stress trial was conducted with koi carp, aiming at identifying typical effects of stress on regulation of appetite genes. The stressors tank manipulation, air exposure and feed rewarding were chosen. The responses to these stressors were evaluated 10, 30 and 60 min after the stressors were applied. Orexigenic and anorexigenic genes were investigated in four different brain regions (telencephalon, hypothalamus, optic tectum and rhombencephalon). The results show that, apart from the typical appetite regulation in the hypothalamus, the different brain regions also display pronounced responses of appetite genes to the different stressors. In addition, several genes in the serotonergic, dopaminergic and gaba-related pathways were investigated. These genes revealed that rearing in pairs of two and opening of the tank lid affected anorexigenic genes, such as cart and cck, which were not changed by air exposure or feed rewarding. Moreover, distress and eustress led to limited, but distinguishable gene expression pattern changes in the investigated brain regions.

Background: Vaccination is considered the key to overcome the COVID pandemic. For the first time mRNA-based vaccinations are used in humans. Case series suggested an increased risk of myocarditis after vaccination. This study sought to describe CMR findings in patients with suspected mRNA-vaccine associated myocarditis. Methods: A total of 33 consecutive patients referred for CMR work-up of suspected myocarditis associated with mRNA-based vaccination were included. A historical cohort of 135 consecutive patients referred for suspected myocarditis in the pre-COVID era served as control group. All patients underwent multi-parametric CMR including CINE and late gadolinium enhancement (LGE) imaging as well as parametric T1/T2 mapping of the left ventricular myocardium. Results: Patients referred for suspected vaccination-related myocarditis were more often female (55 % vs 32 %, p = 0.015) and demonstrated smaller LV dimensions as well as a better LV function compared to patients of the control group. CMR revealed a lower prevalence of non-ischemic LGE in patients with suspected vaccination-myocarditis (6 % vs 22 %, p = 0.04). However, among patients without LGE we observed a higher prevalence of an abnormal T1/T2 mapping result in patients with suspected vaccination-myocarditis compared to the control group (45 % vs 18 %, p = 0.010). Conclusion: In this small single-centre study, compared to myocarditis referrals in the pre-COVID era, patients currently referred for CMR work-up of suspected mRNA-vaccination-associated myocarditis demonstrated lower prevalence of LGE but higher prevalence of abnormal T1/T2 mapping. These hypothesis-generating observations may point towards a rather subtle myocardial damage and support the routine use of T1/T2 mapping in this indication.

Coronary spasm is a frequent cause of angina despite unobstructed coronary arteries, and symptom control with recommended drugs is limited. We report the case of a 77-year-old woman who had refractory angina despite conventional antianginal treatment. Repurposing riociguat, a soluble guanylate cyclase stimulator, resulted in improvement of symptoms and prevention of spasm. (Level of Difficulty: Intermediate.)

Abstract Barth syndrome is a rare X‐linked recessive disorder characterized by a broad spectrum of clinical features including cardiac and skeletal myopathy, neutropenia, exercise intolerance, and growth delay. Most affected patients are diagnosed during childhood, and mortality is highest in the first years of life. As a consequence, Barth syndrome is often considered a paediatric disease. Here, we report a case where the diagnosis was established in a 39‐year‐old patient with left ventricular non‐compaction and neutropenia. The clinical course of the patient presented here was relatively benign. This suggests that the prevalence of Barth syndrome in adults may be underestimated. Barth syndrome should be considered in the differential diagnosis of male patients with cardiomyopathy and neutropenia.

Abstract We here present the case of a 55‐year old woman who presented with recurrent angina at rest followed by presyncopal attacks and nausea to our clinic. Her only cardiovascular risk factor was arterial hypertension. High‐sensitive troponin T was 3 pg/ml (n

Coronary functional abnormalities are frequent causes of angina pectoris, particularly in patients with unobstructed coronary arteries. There is a spectrum of endotypes of functional coronary abnormalities with different mechanisms of pathology including enhanced vasoconstriction (i.e. coronary artery spasm) or impaired vasodilatation, such as impaired coronary flow reserve or increased microvascular resistance. These vasomotor abnormalities can affect various compartments of the coronary circulation such as the epicardial conduit arteries and/or the coronary microcirculation. Unequivocal categorisation and nomenclature of the broad spectrum of disease endotypes is crucial both in clinical practice as well as in clinical trials. This article describes the definitions of coronary functional abnormalities with currently accepted cut-off values, as well as diagnostic methods to identify and distinguish endotypes. The authors also provide a summary of contemporary data on the prevalence of the different endotypes of coronary functional abnormalities and their coexistence.

Slow coronary flow is frequently seen during angiography in patients with angina and unobstructed coronary arteries. However, the pathophysiology of this finding remains largely unclear. We report a case of a 52-year-old woman with slow coronary flow caused by acetylcholine-induced microvascular spasm, as confirmed by intracoronary flow measurements. (Level of Difficulty: Beginner.)

Abstract Background Adenosine is used in stress perfusion cardiac imaging to reveal myocardial ischemia by its vasodilator effects. Caffeine is a competitive antagonist of adenosine. However, previous studies reported inconsistent results about the influence of caffeine on adenosine's vasodilator effect. This study assessed the impact of caffeine on the myocardial perfusion reserve index (MPRI) using adenosine stress cardiovascular magnetic resonance imaging (CMR). Moreover, we sought to evaluate if the splenic switch-off sign might be indicative of prior caffeine consumption. Methods Semiquantitative perfusion analysis was performed in 25 patients who underwent: 1) caffeine-naïve adenosine stress CMR demonstrating myocardial ischemia and, 2) repeat adenosine stress CMR after intake of caffeine. MPRI (global; remote and ischemic segments), and splenic perfusion ratio (SPR) were assessed and compared between both exams. Results Global MPRI after caffeine was lower vs. caffeine-naïve conditions (1.09 ± 0.19 vs. 1.24 ± 0.19; p

Coronary vasomotion disorders represent a frequent cause of angina and/or dyspnoea in patients with non-obstructed coronary arteries. The highly sophisticated interplay of vasodilatation and vasoconstriction can be assessed in an interventional diagnostic procedure. Established parameters characterising adequate vasodilatation are coronary blood flow at rest, and, after drug-induced vasodilation, coronary flow reserve, and microvascular resistance (hyperaemic microvascular resistance, index of microcirculatory resistance). An increased vasoconstrictive potential is diagnosed by provocation testing with acetylcholine or ergonovine. This enables a diagnosis of coronary epicardial and/or microvascular spasm. Ischaemia associated with microvascular spasm can be confirmed by ischaemic ECG changes and the measurement of lactate concentrations in the coronary sinus. Although interventional diagnostic procedures are helpful for determining the mechanism of the angina, which may be the key to successful medical treatment, they are still neither widely accepted nor applied in many medical centres. This article summarises currently well-established invasive methods for the diagnosis of coronary functional disorders causing angina pectoris.

The body of evidence for the use of coronary physiology assessments to guide percutaneous coronary intervention (PCI) has been growing continuously in recent decades. Two studies presented during TCT Connect 2020 added insights into the prognostic value of coronary physiology measurements in pre- and post-PCI settings. The first study, TARGET FFR, assessed whether a post-PCI fractional flow reserve (FFR)-guided incremental optimisation strategy (PIOS) was superior to angiography-guided PCI. The second study, DEFINE-FLOW, assessed the course of stenoses with fractional and coronary flow reserve (FFR+/CFR−) discordance when treated medically. This article summarises the main results from the TARGET FFR and the DEFINE-FLOW trials and puts them into the context of the existing literature.

BackgroundCollagen cross-links contribute to the mechanical resilience of the intervertebral disc (IVD). UVA-light-activated riboflavin-induced collagen crosslinking (UVA-CXL) is a well-established and effective ophthalmological intervention that increases the mechanical rigidity of the collagen-rich corneal matrix in Keratoconus. This study explores the feasibility, safety and efficacy of translating this intervention in reinforcing the IVD.MethodsAnnulus fibrosus (AF) cells were isolated from bovine IVDs and treated with different combinations of riboflavin (RF) concentrations (0.05-8 mM) and UVA light intensities (0.3-4 mW/cm2). Metabolic activity (resazurin assay), cell viability (TUNEL assay), and gene expression of apoptosis regulators C-FOS and PT5 were assessed immediately and 24 hours after treatment. Biomechanical effects of UVA-CXL on IVDs were measured by indentation analysis of changes in the instantaneous modulus and by peel-force delamination strength analysis of the AF prior and after treatment.ResultsDifferent intensities of UVA did not impair the metabolic activity of AF cells. However, RF affected metabolic activity (p < 0.001). PT53 expression was similar in all RF conditions tested while C-FOS expression decreased 24 hours after treatment. Twenty-four hours after treatment, no apoptotic cells were observed in any condition tested. Biomechanical characterizations showed a significant increase in the annular peel strength of the UVA-CXL group, when compared to controls of UVA and RF alone (p < 0.05). UVA-CXL treated IVDs showed up to 152% higher (p < 0.001) instantaneous modulus values compared to the untreated control.ConclusionThis is the first study on UVA-CXL treatment of IVD. It induced significantly increased delamination strength and instantaneous modulus indentation values in intact IVD samples in a structure-function relationship. RF concentrations and UVA intensities utilized in ophthalmological clinical protocols were well tolerated by the AF cells. Our findings suggest that UVA-CXL may be a promising tool to reinforce the IVD matrix.

Background There is scarce data about the long‐term mortality as well as the prognostic value of cardiovascular magnetic resonance and late gadolinium enhancement (LGE) in patients with biopsy‐proven viral myocarditis. We sought to investigate: (1) mortality and (2) prognostic value of LGEcardiovascular magnetic resonance (location, pattern, extent, and distribution) in a >10‐year follow‐up in patients with biopsy‐proven myocarditis. Methods and Results Two‐hundred three consecutive patients with biopsy‐proven viral myocarditis and cardiovascular magnetic resonance were enrolled; 183 patients were eligible for standardized follow‐up. The median follow‐up was 10.1 years. End points were all‐cause death, cardiac death, and sudden cardiac death (SCD). We found substantial long‐term mortality in patients with biopsy‐proven myocarditis (39.3% all cause, 27.3% cardiac, and 10.9% SCD); 101 patients (55.2%) demonstrated LGE. The presence of LGE was associated with a more than a doubled risk of death (hazard ratio [HR], 2.40; 95% CI], 1.30–4.43), escalating to a HR of 3.00 (95% CI, 1.41–6.42) for cardiac death, and a HR of 14.79 (95% CI, 1.95–112.00) for SCD; all P≤0.009. Specifically, midwall, (antero‐) septal LGE, and extent of LGE were highly associated with death, all P

Patients with angina pectoris, the cardinal symptom of myocardial ischaemia, yet without significant flow-limiting epicardial artery stenosis represent a diagnostic and therapeutic challenge. Coronary artery spasm (CAS) is an established cause for anginal chest pain in patients with angiographically unobstructed coronary arteries. CAS may occur at the epicardial level and/or in the microvasculature. Although the underlying pathophysiological mechanisms of CAS are still largely unclear, endothelial dysfunction and vascular smooth muscle cell (VSMC) hyperreactivity seem to be involved as major players, although their contribution to induce CAS is still seen as controversial. This article will look at the role and possible mechanistic interplay between an impaired endothelial and VSMC function in the pathogenesis of CAS.

Abstract Background Adenosine stress cardiovascular magnetic resonance (CMR) can detect significant coronary artery stenoses with high diagnostic accuracy. Caffeine is a nonselective competitive inhibitor of adenosine2A-receptors, which might hamper the vasodilator effect of adenosine stress, potentially yielding false-negative results. Much controversy exists about the influence of caffeine on adenosine myocardial perfusion imaging. Our study sought to investigate the effects of caffeine on ischemia detection in patients with suspected or known coronary artery disease (CAD) undergoing adenosine stress CMR. Methods Thirty patients with evidence of myocardial ischemia on caffeine-naïve adenosine stress CMR were prospectively enrolled and underwent repeat adenosine stress CMR after intake of 200 mg caffeine. Both CMR exams were then compared for evaluation of ischemic burden. Results Despite intake of caffeine, no conversion of a positive to a negative stress study occurred on a per patient basis. Although we found significant lower ischemic burden in CMR exams with caffeine compared to caffeine-naïve CMR exams, absolute differences varied only slightly (1 segment based on a 16-segment model, 3 segments on a 60-segment model, and 1 ml in total ischemic myocardial volume, p

Background Acute complete occlusion of a coronary artery results in progressive ischemia, moving from the endocardium to the epicardium (ie, wavefront). Dependent on time to reperfusion and collateral flow, myocardial infarction (MI) will manifest, with transmural MI portending poor prognosis. Late gadolinium enhancement cardiac magnetic resonance imaging can detect MI with high diagnostic accuracy. Primary percutaneous coronary intervention is the preferred reperfusion strategy in patients with ST‐segment–elevation MI with 121 minutes demonstrated increased infarct size, transmurality index, and transmurality grade (all P121 minutes causes a high grade of transmural necrosis. In this pure ST‐segment–elevation MI population, time to reperfusion to salvage myocardium was less than suggested by current guidelines.

Welfare in animal husbandry includes considerations of biology, ethics, ecology, law and economics. These diverse aspects must be translated into common quantifiable parameters and applicable methods to objectively assess welfare in animals. To assist this process in the field of aquaculture, where such methods are largely missing, we developed a model to assess fish welfare. A network of information was created to link needs, i.e., fundamental requirements for welfare, with parameters, i.e., quantifiable aspects of welfare. From this ontology, 80 parameters that are relevant for welfare, have practicable assessment methods and deliver reliable results were selected and incorporated into a model. The model, named MyFishCheck, allows the evaluation of welfare in five distinct modules: farm management, water quality, fish group behaviour, fish external and fish internal appearance, thereby yielding five individual grades categorising welfare ranging from critical, to poor, to acceptable, and good. To facilitate the use of the model, a software application was written. With its adaptability to different fish species, farming systems, regulations and purposes as well as its user-friendly digital version, MyFishCheck is a next step towards improved fish welfare assessment and provides a basis for ongoing positive developments for the industry, the farmers and the fish.

A 43-year-old woman with recurrent atypical angina underwent invasive coronary angiography including intracoronary Doppler blood flow assessment and coronary spasm provocation testing. While obstructive epicardial disease could be ruled-out angiographically, the patient experienced reproduction of her angina symptoms after intracoronary administration of acetylcholine (100 µg) during spasm provocation testing. Simultaneously, the ECG showed new-onset ST-segment depression in the absence of epicardial spasm. In addition, coronary flow velocity was significantly reduced after acetylcholine compared to the baseline condition. Following intracoronary administration of nitroglycerine (200 µg), the patient’s symptoms as well as the ECG changes and coronary flow reduction were reversed. Considering the ongoing challenges in appropriate evaluation of the pathophysiological mechanisms of coronary microvascular dysfunction, simultaneous intracoronary Doppler flow measurement during spasm testing – as shown in this case – may provide objective evidence for microvascular spasm in addition to the standardized diagnostic criteria, especially if they are ambiguous.

A coronary-pulmonary artery fistula with giant aneurysmal dilatation is an extremely rare clinical constellation. The natural course of this disease and the incidence of complications are unknown. Hence, optimal treatment, particularly in asymptomatic patients, is still a matter of debate. Here we report a case of a 71-year-old asymptomatic woman with a diastolic murmur. Comprehensive cardiovascular assessments including cardiac computed tomography and invasive coronary angiography revealed a coronary-pulmonary artery fistula with giant aneurysmal dilatation. The patient was managed conservatively and has now been followed up for 5 years without any events.