Clinical Significance of Exercise Pulmonary Hypertension With a Negative Diastolic Stress Test for Suspected Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Half of patients with heart failure with preserved ejection fraction (HFpEF) remain undiagnosed by resting evaluation alone. Therefore, exercise testing is proposed. The diastolic stress test (DST), however, has limited sensitivity. We aimed to determine the clinical significance of adding the mean pulmonary artery pressure over cardiac output (mPAP/CO) slope to the DST in suspected HFpEF. METHODS AND RESULTS: In this prospective cohort study, consecutive patients (n=1936) with suspected HFpEF underwent exercise echocardiography with simultaneous respiratory gas analysis. These patients were stratified by exercise E over e' (exE/e') and mPAP/CO slope, and peak oxygen uptake, natriuretic peptides (NT-proBNP [N-terminal pro-B-type natriuretic peptide]), and score-based HFpEF likelihood were compared. Twenty-two percent of patients (n=428) had exE/e'<15 despite a mPAP/CO slope>3 mm Hg/L per min, 24% (n=464) had a positive DST (exE/e'≥15), and 54% (n=1044) had a normal DST and slope. Percentage of predicted oxygen uptake was similar in the group with exE/e'<15 but high mPAP/CO slope and the positive DST group (-2% [-5% to +1%]), yet worse than in those with normal DST and slope (-12% [-14% to -9%]). Patients with exE/e'<15 but a high slope had NT-proBNP levels and H2FPEF (heavy, hypertensive, atrial fibrillation, pulmonary hypertension, elder; filling pressure) scores intermediate to the positive DST group and the group with both a normal DST and slope. CONCLUSIONS: Twenty-two percent of patients with suspected HFpEF presented with a mPAP/CO slope>3 mm Hg/L per min despite a negative DST. These patients had HFpEF characteristics and a peak oxygen uptake as low as patients with a positive DST. Therefore, an elevated mPAP/CO slope might indicate HFpEF irrespective of the DST result.

Prevention and Rehabilitation After Heart Transplantation: A Clinical Consensus Statement of the European Association of Preventive Cardiology, Heart Failure Association of the ESC, and the European Cardio Thoracic Transplant Association, a Section of ESOT.

Little is known either about either physical activity patterns, or other lifestyle-related prevention measures in heart transplantation (HTx) recipients. The history of HTx started more than 50 years ago but there are still no guidelines or position papers highlighting the features of prevention and rehabilitation after HTx. The aims of this scientific statement are (i) to explain the importance of prevention and rehabilitation after HTx, and (ii) to promote the factors (modifiable/non-modifiable) that should be addressed after HTx to improve patients' physical capacity, quality of life and survival. All HTx team members have their role to play in the care of these patients and multidisciplinary prevention and rehabilitation programmes designed for transplant recipients. HTx recipients are clearly not healthy disease-free subjects yet they also significantly differ from heart failure patients or those who are supported with mechanical circulatory support. Therefore, prevention and rehabilitation after HTx both need to be specifically tailored to this patient population and be multidisciplinary in nature. Prevention and rehabilitation programmes should be initiated early after HTx and continued during the entire post-transplant journey. This clinical consensus statement focuses on the importance and the characteristics of prevention and rehabilitation designed for HTx recipients.

Prevention and rehabilitation after heart transplantation: A clinical consensus statement of the European Association of Preventive Cardiology, Heart Failure Association of the ESC, and the European Cardio Thoracic Transplant Association, a section of ESOT.

Little is known either about either physical activity patterns, or other lifestyle-related prevention measures in heart transplantation (HTx) recipients. The history of HTx started more than 50 years ago but there are still no guidelines or position papers highlighting the features of prevention and rehabilitation after HTx. The aims of this scientific statement are (i) to explain the importance of prevention and rehabilitation after HTx, and (ii) to promote the factors (modifiable/non-modifiable) that should be addressed after HTx to improve patients' physical capacity, quality of life and survival. All HTx team members have their role to play in the care of these patients and multidisciplinary prevention and rehabilitation programmes designed for transplant recipients. HTx recipients are clearly not healthy disease-free subjects yet they also significantly differ from heart failure patients or those who are supported with mechanical circulatory support. Therefore, prevention and rehabilitation after HTx both need to be specifically tailored to this patient population and be multidisciplinary in nature. Prevention and rehabilitation programmes should be initiated early after HTx and continued during the entire post-transplant journey. This clinical consensus statement focuses on the importance and the characteristics of prevention and rehabilitation designed for HTx recipients.

Toward Ultra-High-Quality-Factor Wireless Masing Magnetic Resonance Sensing.

It has recently been shown that a bolus of hyperpolarized nuclear spins can yield stimulated emission signals similar in nature to maser signals, potentially enabling new ways of sensing hyperpolarized contrast media, including most notably [1-13C]pyruvate that is under evaluation in over 50 clinical trials for metabolic imaging of cancer. The stimulated NMR signal emissions lasting for minutes do not require radio-frequency excitation, offering unprecedented advantages compared to conventional MR sensing. However, creating nuclear spin maser emission is challenging in practice due to stringent fundamental requirements, making practical in vivo applications hardly possible using conventional passive MR detectors. Here, we demonstrate the utility of a wireless NMR maser detector, the quality factor of which was enhanced 22-fold (to 1,670) via parametric pumping. This active-feedback technique breaks the intrinsic fundamental limit of NMR detector circuit quality factor. We show the use of parametric pumping to reduce the threshold requirement for inducing nuclear spin masing at 300 MHz resonance frequency in a preclinical MRI scanner. Indeed, stimulated emission from hyperpolarized protons was obtained under highly unfavorable conditions of low magnetic field homogeneity (T2* of 3 ms). Greater gains of the quality factor of the MR detector (up to 1 million) were also demonstrated.

Prevention and rehabilitation after heart transplantation: A clinical consensus statement of the European Association of Preventive Cardiology, Heart Failure Association of the ESC, and the European Cardio Thoracic Transplant Association, a section of ESOT.

Little is known either about either physical activity patterns, or other lifestyle-related prevention measures in heart transplantation (HTx) recipients. The history of HTx started more than 50 years ago but there are still no guidelines or position papers highlighting the features of prevention and rehabilitation after HTx. The aims of this scientific statement are (i) to explain the importance of prevention and rehabilitation after HTx, and (ii) to promote the factors (modifiable/non-modifiable) that should be addressed after HTx to improve patients' physical capacity, quality of life and survival. All HTx team members have their role to play in the care of these patients and multidisciplinary prevention and rehabilitation programmes designed for transplant recipients. HTx recipients are clearly not healthy disease-free subjects yet they also significantly differ from heart failure patients or those who are supported with mechanical circulatory support. Therefore, prevention and rehabilitation after HTx both need to be specifically tailored to this patient population and be multidisciplinary in nature. Prevention and rehabilitation programmes should be initiated early after HTx and continued during the entire post-transplant journey. This clinical consensus.

Cancer predisposing syndromes in childhood and adolescence pose several challenges necessitating interdisciplinary care in dedicated programs.

Introduction: Genetic disposition is a major etiologic factor in childhood cancer. More than 100 cancer predisposing syndromes (CPS) are known. Surveillance protocols seek to mitigate morbidity and mortality. To implement recommendations in patient care and to ascertain that the constant gain of knowledge forces its way into practice specific pediatric CPS programs were established. Patients and methods: We retrospectively analyzed data on children, adolescents, and young adults referred to our pediatric CPS program between October 1, 2021, and March 31, 2023. Follow-up ended on December 31, 2023. Results: We identified 67 patients (30 male, 36 female, 1 non-binary, median age 9.5 years). Thirty-five patients were referred for CPS surveillance, 32 for features suspicious of a CPS including café-au-lait macules (n = 10), overgrowth (n = 9), other specific symptoms (n = 4), cancer suspicious of a CPS (n = 6), and rare neoplasms (n = 3). CPS was confirmed by clinical criteria in 6 patients and genetic testing in 7 (of 13). In addition, 6 clinically unaffected at-risk relatives were identified carrying a cancer predisposing pathogenic variant. A total of 48 patients were eventually diagnosed with CPS, surveillance recommendations were on record for 45. Of those, 8 patients did not keep their appointments for various reasons. Surveillance revealed neoplasms (n = 2) and metachronous tumors (n = 4) by clinical (n = 2), radiological examination (n = 2), and endoscopy (n = 2). Psychosocial counselling was utilized by 16 (of 45; 35.6%) families. Conclusions: The diverse pediatric CPSs pose several challenges necessitating interdisciplinary care in specified CPS programs. To ultimately improve outcome including psychosocial well-being joint clinical and research efforts are necessary.

Divergent cardiac and renal effects of miR-181c-5p inhibition in a rodent heart failure model.

Aims: MiR-181c-5p overexpression associates with heart failure (HF) and cardiac damage, but the underlying pathophysiology remains unclear. This study investigated the effect of miR-181c-5p inhibition on cardiac function and fibrosis in a rodent model of diastolic dysfunction, and evaluated additional effects on kidney as relevant comorbid organ. Methods and results: Diastolic dysfunction was induced in male C57/BL6J mice (n = 20) by combining high-fat diet, L-NG-nitroarginine methyl ester, and angiotensin II administration, and was compared to sham controls (n = 18). Mice were randomized to subcutaneous miR-181c-5p antagomiR (INH) or scrambled antagomiR injections (40 mg/kg/week). HF mice demonstrated diastolic dysfunction and increased fibrosis, which was attenuated by INH treatment. Remarkably, HF + INH animals had a threefold higher mortality rate (60%) compared to HF controls (20%). Histological examination revealed increased glomerular damage in all INH treated mice, and signs of thrombotic microangiopathy (TMA) in mice who died prematurely. Quantitative polymerase chain reaction demonstrated a miR-181c-5p-related downregulation of cardiac but not renal Tgfbr1 in HF + INH mice, while INH treatment reduced renal but not cardiac Vegfa expression in all mice. Conclusion: This study demonstrates cardiac anti-fibrotic effects of miR-181c-5p inhibition in a rodent HF model through targeting of Tgfbr1 in the heart. Despite improved diastolic function, HF + INH mice had higher mortality due to increased predisposition for TMA, increased renal fibrosis and glomerular damage, associated with Vegfa downregulation in kidneys.

Long-term results of arthroscopic capsulolabral revision repair for failed anterior shoulder instability repair using suture anchors at a minimum of 10 years follow-up.

INTRODUCTION: Arthroscopic revision anterior shoulder instability repair has been proposed, and early clinical results have been promising. However, long-term results after this procedure and the probable risk factors for failure have not been sufficiently discussed in the literature. MATERIALS AND METHODS: Thirty-eight patients who were diagnosed with recurrent anteroinferior shoulder instability after failed Bankart repair, treated with ACRR between September 1998 and November 2003 and able to be contacted were included. Of these patients, 2 were excluded from the study due to the use of SureTak anchors for fixation, and 5 other patients refused to participate in the study due to lack of interest (3 patients) or lack of time (2 patients). The remaining shoulders were clinically examined at a minimum of ten years after surgery via the ASES, Constant, AAOS, Rowe, Dawson and VAS scores for pain and stability. Degenerative arthropathy was assessed with the modified Samilson-Prieto score. RESULTS: All 31 remaining shoulders were evaluated at a mean time of 11.86 years (142.4 months) after surgery. Six patients (19.35%) reported redisolcation after the revision procedure, 4 of whom were affected by a new significant shoulder trauma. The ROWE and Constant scores improved significantly. Moderate to severe dislocation arthropathy was observed in 19.4% of patients. Five patients (16.2%) were not satisfied with the procedure. CONCLUSION: Long-term follow-up after ACRR shows predictable results, with a high degree of patient satisfaction, good to excellent patient-reported outcome scores and minimal radiological degenerative changes. However, with an average recurrence rate of 19.3% after 11.86 years, the redislocation rate appears high. With careful patient selection, recurrence rates can be significantly reduced.

Circulating MicroRNA as Biomarkers of Anthracycline-Induced Cardiotoxicity: JACC: CardioOncology State-of-the-Art Review.

Close monitoring for cardiotoxicity during anthracycline chemotherapy is crucial for early diagnosis and therapy guidance. Currently, monitoring relies on cardiac imaging and serial measurement of cardiac biomarkers like cardiac troponin and natriuretic peptides. However, these conventional biomarkers are nonspecific indicators of cardiac damage. Exploring new, more specific biomarkers with a clear link to the underlying pathomechanism of cardiotoxicity holds promise for increased specificity and sensitivity in detecting early anthracycline-induced cardiotoxicity. miRNAs (microRNAs), small single-stranded, noncoding RNA sequences involved in epigenetic regulation, influence various physiological and pathological processes by targeting expression and translation. Emerging as new biomarker candidates, circulating miRNAs exhibit resistance to degradation and offer a direct pathomechanistic link. This review comprehensively outlines their potential as early biomarkers for cardiotoxicity and their pathomechanistic link.

Effects of transcranial direct current stimulation and sensorimotor training in anterior cruciate ligament patients: a sham-controlled pilot study.

BACKGROUND: Studies showed changes in the central nervous system in patients who sustained an anterior cruciate ligament tear. There is a lack of evidence regarding the effectiveness of transcranial direct-current stimulation in such patients. METHODS: A sham-controlled randomised study. One group of patients (n = 6) underwent 6 weeks of sensorimotor training after an anterior cruciate ligament tear during transcranial direct-current stimulation. The stimulation consisted of 20 minutes (3 sessions/week; 2 weeks) of 2 mA anodal transcranial direct-current stimulation over the primary motor and premotor cortex. The second group (n = 6) received sham stimulation with 6 weeks of sensorimotor training. Centre of pressure deviations in the medio-lateral and anterior-posterior direction and centre of pressure velocity were measured. RESULTS: The results demonstrated a significant effect of sensorimotor training on the centre of pressure in medio-lateral and anterior-posterior direction (p=0.025) (p=0.03) in the leg in which an anterior cruciate ligament tear occurred. The type of training did not affect the results. Post-hoc tests showed no significant effect of training in the subgroups (p≥0.115). CONCLUSION: Sensorimotor training led to a decrease in sway of the centre of pressure in patients who sustained an anterior cruciate ligament tear, but the addition of anodal transcranial direct-current stimulation placed over the primary motor cortex did not potentiate the adaptive responses of the sensorimotor training.

Sepsis induces heterogeneous transcription of coagulation- and inflammation-associated genes in renal microvasculature.

BACKGROUND: Acute kidney injury (AKI) in sepsis patients increases patient mortality. Endothelial cells are important players in the pathophysiology of sepsis-associated AKI (SA-AKI), yet knowledge regarding their spatiotemporal involvement in coagulation disbalance and leukocyte recruitment is lacking. This study investigated the identity and kinetics of responses of different microvascular compartments in kidney cortex in response to SA-AKI. METHODS: Laser microdissected arterioles, glomeruli, peritubular capillaries, and postcapillary venules from kidneys of mice subjected to cecal ligation and puncture (CLP) were analyzed using RNA sequencing. Differential expression and pathway enrichment analyses identified genes involved in coagulation and inflammation. A selection of these genes was evaluated by RT-qPCR in microvascular compartments of renal biopsies from patients with SA-AKI. The role of two identified genes in lipopolysaccharide-induced endothelial coagulation and inflammatory activation were determined in vitro in HUVEC using siRNA-based gene silencing. RESULTS: CLP-sepsis in mice induced altered expression of approximately 400 genes in the renal microvasculature, with microvascular compartments exhibiting unique spatiotemporal responses. In mice, changes in gene expression related to coagulation and inflammation were most extensive in glomeruli at early and intermediate time points, with high induction of Plat, Serpine1, Thbd, Icam1, Stat3, and Ifitm3. In human SA-AKI, PROCR and STAT3 were induced in postcapillary venules, while SERPINE1 expression was diminished. IFITM3 was increased in arterioles and glomeruli. In vitro studies revealed that STAT3 and IFITM3 partly control endothelial coagulation and inflammatory activation. CONCLUSION: Renal microvascular compartments in mice and humans exhibited heterogeneous changes in coagulation- and inflammation-related gene expression in response to SA-AKI. Additional research should aim at understanding the functional consequences of the here described heterogeneous microvascular responses to establish the usefulness of identified genes as therapeutic targets in SA-AKI.

Tibiofemoral Subluxation on Radiograph as a Predictor of Location and Size of Osteochondritis Dissecans Lesions of the Knee.

Background: Lower limb malalignment has been associated with osteochondritis dissecans (OCD). However, the location of the OCD lesion often is not concordant with the mechanical leg axis. Other potentially modifiable alignment parameters may influence the propensity for impingement of the femoral condyles. Purpose: To assess differences in lower limb alignment (LLA) and relative tibiofemoral position between patients with medial (MFC-OCD) or lateral OCD (LFC-OCD) of the femoral condyle. Study Design: Cohort study; Level of evidence, 3. Methods: Patients ≤30 years old who were diagnosed with unicondylar OCD between January 2010 and January 2020 were eligible for this study. Included were 55 patients (age, 20.8 ± 4.5 years)-46 with MFC-OCD and 9 with LFC-OCD. Preoperative standing long-leg radiographs were studied to obtain primary outcomes-including LLA and mechanical alignment analyses-and secondary outcomes-including knee joint obliquity angle; rotation angle; medial, central (c-subluxation), and lateral subluxation (L-subluxation) of the tibia relative to the femur in the coronal plane; and tibiofemoral joint line center distance (TFJCD). Results: With regard to primary outcomes, LLA was significantly different between MFC-OCD (1.7°± 3.1° varus) and LFC-OCD (2.7 ± 3.1° valgus) (P < .001), and 78% (36/46) of patients with MFC-OCD had varus alignment, whereas 78% (7/9) of patients with LFC-OCD had valgus alignment (P < 0.002). With regard to secondary outcomes, patients with MFC-OCD had a more medial tibial position in relation to the femur, with a significantly smaller rotation angle (5.6°± 2.4° vs 9.6°± 3.6°; P < .001), a smaller C-subluxation (7.2 ± 6.6 vs 14.9 ± 8.8 mm; P < .01), a smaller L-subluxation (2.3 ± 2.6 vs 4.4 ± 2.7 mm; P < .05), and reduced TFJCD (3.5 ± 1.7 vs 6.6 ± 1.8 mm; P < .001) compared with the LFC-OCD group. For patients with MFC-OCD, the size of the OCD was significantly correlated with C-subluxation (r = 0.412; P = .006). Conclusion: LLA was significantly different according to OCD location. In patients with MFC-OCD, the tibia was subluxated medially, resulting in a change of joint geometry by approximation of the medial tibial eminence toward the medial femoral condyle, potentially causing excessive pressure overload and microtrauma of the cartilage. Interestingly, the extent of subluxation was correlated with OCD size.

Within- and between-session changes of in-session reflective functioning of mothers in dyadic parent-infant psychotherapy.

This study investigated if in-session reflective functioning (RF) of mothers improved between and within sessions of brief dyadic focused parent-infant psychotherapy (fPIP) for the treatment of regulatory disorders in infants.In-session RF was coded for 44 therapy sessions from N = 11 mothers randomly selected from a RCT on the efficacy of fPIP as part of secondary analyses. A new rating system distinguished self-focused and child-focused in-session RF. Cumulative ordinal regression models were applied to analyze the dynamics of in-session RF within and across sessions, controlling for word count of each statement.While in-session RF improved significantly within sessions, between-session RF improved significantly only in the second session compared to the first with a significant decrease observed in the last session. Child-focused in-session RF was significantly lower than self-focused in-session RF at the beginning of the sessions but improved significantly stronger than self-focused in-session RF during sessions.In-session RF (particularly in child-focused statements) can be regarded as a dynamic change process relevant within each session of dyadic fPIP. Improvements made on a session-by-session basis may not be maintained until the next session. Implications for practitioners and in-session RF research are discussed.

MATRESHCA: Microtesla Apparatus for Transfer of Resonance Enhancement of Spin Hyperpolarization via Chemical Exchange and Addition.

We present an integrated, open-source device for parahydrogen-based hyperpolarization processes in the microtesla field regime with a cost of components of less than $7000. The device is designed to produce a batch of 13C and 15N hyperpolarized (HP) compounds via hydrogenative or non-hydrogenative parahydrogen-induced polarization methods that employ microtesla magnetic fields for efficient polarization transfer of parahydrogen-derived spin order to X-nuclei (e.g., 13C and 15N). The apparatus employs a layered structure (reminiscent of a Russian doll "Matryoshka") that includes a nonmagnetic variable-temperature sample chamber, a microtesla magnetic field coil (operating in the range of 0.02-75 microtesla), a three-layered mu-metal shield (to attenuate the ambient magnetic field), and a magnetic shield degaussing coil placed in the overall device enclosure. The gas-handling manifold allows for parahydrogen-gas flow and pressure control (up to 9.2 bar of total parahydrogen pressure). The sample temperature can be varied either using a water bath or a PID-controlled heat exchanger in the range from -12 to 80 °C. This benchtop device measures 62 cm (length) × 47 cm (width) × 47 cm (height), weighs 30 kg, and requires only connections to a high-pressure parahydrogen gas supply and a single 110/220 VAC power source. The utility of the device has been demonstrated using an example of parahydrogen pairwise addition to form HP ethyl [1-13C]acetate (P13C = 7%, [c] = 1 M). Moreover, the Signal Amplification By Reversible Exchange in SHield Enables Alignment Transfer to Heteronuclei (SABRE-SHEATH) technique was employed to demonstrate efficient hyperpolarization of 13C and 15N spins in a wide range of biologically relevant molecules, including [1-13C]pyruvate (P13C = 14%, [c] = 27 mM), [1-13C]-α-ketoglutarate (P13C = 17%), [1-13C]ketoisocaproate (P13C = 18%), [15N3]metronidazole (P15N = 13%, [c] = 20 mM), and others. While the vast majority of the utility studies have been performed in standard 5 mm NMR tubes, the sample chamber of the device can accommodate a wide range of sample container sizes and geometries of up to 1 L sample volume. The device establishes an integrated, simple, inexpensive, and versatile equipment gateway needed to facilitate parahydrogen-based hyperpolarization experiments ranging from basic science to preclinical applications; indeed, detailed technical drawings and a bill of materials are provided to support the ready translation of this design to other laboratories.

Carbon-13 Radiofrequency Amplification by Stimulated Emission of Radiation of the Hyperpolarized Ketone and Hemiketal Forms of Allyl [1-13C]Pyruvate.

13C hyperpolarized pyruvate is an emerging MRI contrast agent for sensing molecular events in cancer and other diseases with aberrant metabolic pathways. This metabolic contrast agent can be produced via several hyperpolarization techniques. Despite remarkable success in research settings, widespread clinical adoption faces substantial roadblocks because the current sensing technology utilized to sense this contrast agent requires the excitation of 13C nuclear spins that also need to be synchronized with MRI field gradient pulses. Here, we demonstrate sensing of hyperpolarized allyl [1-13C]pyruvate via the stimulated emission of radiation that mitigates the requirements currently blocking broader adoption. Specifically, 13C Radiofrequency Amplification by Stimulated Emission of Radiation (13C RASER) was obtained after pairwise addition of parahydrogen to a pyruvate precursor, detected in a commercial inductive detector with a quality factor (Q) of 32 for sample concentrations as low as 0.125 M with 13C polarization of 4%. Moreover, parahydrogen-induced polarization allowed for the preparation of a mixture of ketone and hemiketal forms of hyperpolarized allyl [1-13C]pyruvate, which are separated by 10 ppm in 13C NMR spectra. This is a good model system to study the simultaneous 13C RASER signals of multiple 13C species. This system models the metabolic production of hyperpolarized [1-13C]lactate from hyperpolarized [1-13C]pyruvate, which has a similar chemical shift difference. Our results show that 13C RASER signals can be obtained from both species simultaneously when the emission threshold is exceeded for both species. On the other hand, when the emission threshold is exceeded only for one of the hyperpolarized species, 13C stimulated emission is confined to this species only, therefore enabling the background-free detection of individual hyperpolarized 13C signals. The reported results pave the way to novel sensing approaches of 13C hyperpolarized pyruvate, potentially unlocking hyperpolarized 13C MRI on virtually any MRI system─an attractive vision for the future molecular imaging and diagnostics.

MR imaging after patellar MACI and MPFL reconstruction: a comparison of isolated versus combined procedures.

OBJECTIVE: To qualitatively and quantitatively evaluate the 2.5-year MRI outcome after Matrix-associated autologous chondrocyte implantation (MACI) at the patella, reconstruction of the medial patellofemoral ligament (MPFL), and combined procedures. METHODS: In 66 consecutive patients (age 22.8 ± 6.4years) with MACI at the patella (n = 16), MPFL reconstruction (MPFL; n = 31), or combined procedures (n = 19) 3T MRI was performed 2.5 years after surgery. For morphological MRI evaluation WORMS and MOCART scores were obtained. In addition quantitative cartilage T2 and T1rho relaxation times were acquired. Several clinical scores were obtained. Statistical analyses included descriptive statistics, Mann-Whitney-U-tests and Pearson correlations. RESULTS: WORMS scores at follow-up (FU) were significantly worse after combined procedures (8.7 ± 4.9) than after isolated MACI (4.3 ± 3.6, P = 0.005) and after isolated MPFL reconstruction (5.3 ± 5.7, P = 0.004). Bone marrow edema at the patella in the combined group was the only (non-significantly) worsening WORMS parameter from pre- to postoperatively. MOCART scores were significantly worse in the combined group than in the isolated MACI group (57 ± 3 vs 88 ± 9, P < 0.001). Perfect defect filling was achieved in 26% and 69% of cases in the combined and MACI group, respectively (P = 0.031). Global and patellar T2 values were higher in the combined group (Global T2: 34.0 ± 2.8ms) and MACI group (35.5 ± 3.1ms) as compared to the MPFL group (31.1 ± 3.2ms, P < 0.05). T2 values correlated significantly with clinical scores (P < 0.005). Clinical Cincinnati scores were significantly worse in the combined group (P < 0.05). CONCLUSION: After combined surgery with patellar MACI and MPFL reconstruction inferior MRI outcomes were observed than after isolated procedures. Therefore, patients with need for combined surgery may be at particular risk for osteoarthritis.

Heart failure with severely reduced ejection fraction after liver transplantation: a case report and review of the literature.

BACKGROUND: Liver transplantation (LT) is a strenuous event for the cardiovascular system. Cardiovascular events (CVE), including heart failure (HF), arrhythmias and myocardial ischemia, are important causes of peri- and post-liver transplantation morbidity and mortality. CASE PRESENTATION: We describe the case of a 45-year-old male patient who developed heart failure with severely reduced ejection fraction (HFrEF) after receiving liver transplantation (LT) for end-stage post-alcoholic liver cirrhosis. Preoperative transthoracic echocardiography (TTE) demonstrated borderline left ventricular ejection fraction (LVEF) of 50% and diastolic dysfunction grade 2. On coronary angiography, the patient had no coronary stenoses. Persistent vasopressor need, increasing creatinine levels and progressive pleural effusion characterized the early postoperative period. TTE on postoperative day 6 revealed a new finding of a markedly reduced LVEF of 15%, accompanied by a discrete increase in hs-TnI and CK-MB without electrocardiographic (ECG) ST-T abnormalities. LVEF did not recover completely (EF 45%) during follow-up. The patient had a sudden death 4.5 months post-liver transplantation. CONCLUSION: Our case demonstrates that the risk of post-LT systolic dysfunction is not excluded by preoperative resting examinations within normal range and highlights the need for preoperative cardiac stress assessment (e.g. dobutamine echocardiography or stress cardiac magnetic resonance imaging) before LT. In addition, patients on a liver-transplant waiting list with cardiac dysfunction should be followed by a multidisciplinary team including a dedicated cardiology team experienced in managing liver-related cardiac pathology.

Chemogenetic activation of CRF neurons as a model of chronic stress produces sex-specific physiological and behavioral effects.

Trauma and chronic stress exposure are the strongest predictors of lifetime neuropsychiatric disease presentation. These disorders often have significant sex biases, with females having higher incidences of affective disorders such as major depression, anxiety, and PTSD. Understanding the mechanisms by which stress exposure heightens disease vulnerability is essential for developing novel interventions. Current rodent stress models consist of a battery of sensory, homeostatic, and psychological stressors that are ultimately integrated by corticotropin-releasing factor (CRF) neurons to trigger corticosteroid release. These stress paradigms, however, often differ between research groups in the type, timing, and duration of stressors utilized. These inconsistencies, along with the variability of individual animals' perception and response to each stressor, present challenges for reproducibility and translational relevance. Here, we hypothesized that a more direct approach using chemogenetic activation of CRF neurons would recapitulate the effects of traditional stress paradigms and provide a high-throughput method for examining stress-relevant phenotypes. Using a transgenic approach to express the Gq-coupled Designer Receptor Exclusively Activated by Designer Drugs (DREADD) receptor hM3Dq in CRF-neurons, we found that the DREADD ligand clozapine-N-oxide (CNO) produced an acute and robust activation of the hypothalamic-pituitary-adrenal (HPA) axis, as predicted. Interestingly, chronic treatment with this method of direct CRF activation uncovered a novel sex-specific dissociation of glucocorticoid levels with stress-related outcomes. Despite hM3Dq-expressing females producing greater corticosterone levels in response to CNO than males, hM3Dq-expressing males showed significant typical physiological stress sensitivity with reductions in body and thymus weights. hM3Dq-expressing females while resistant to the physiological effects of chronic CRF activation, showed significant increases in baseline and fear-conditioned freezing behaviors. These data establish a novel mouse model for interrogating stress-relevant phenotypes and highlight sex-specific stress circuitry distinct for physiological and limbic control that may underlie disease risk.

New Horizons in Hyperpolarized 13C MRI.

Hyperpolarization techniques significantly enhance the sensitivity of magnetic resonance (MR) and thus present fascinating new directions for research and applications with in vivo MR imaging and spectroscopy (MRI/S). Hyperpolarized 13C MRI/S, in particular, enables real-time non-invasive assessment of metabolic processes and holds great promise for a diverse range of clinical applications spanning fields like oncology, neurology, and cardiology, with a potential for improving early diagnosis of disease, patient stratification, and therapy response assessment. Despite its potential, technical challenges remain for achieving clinical translation. This paper provides an overview of the discussions that took place at the international workshop "New Horizons in Hyperpolarized 13C MRI," in March 2023 at the Bavarian Academy of Sciences and Humanities, Munich, Germany. The workshop covered new developments, as well as future directions, in topics including polarization techniques (particularly focusing on parahydrogen-based methods), novel probes, considerations related to data acquisition and analysis, and emerging clinical applications in oncology and other fields.