Citations

Abstract Aims Cardiovascular disease (CVD) is the leading cause of mortality in chronic kidney disease (CKD). While CKD is known to give rise to systemic inflammation, its inciting factors remain poorly defined. Oxalate, long implicated in rare genetic kidney disorders, accumulates with decreased kidney function and has emerged as a driver of inflammation and independent risk factor for CVD. Here, we investigate the immunological mechanisms linking oxalate nephropathy to systemic inflammation, cardiac damage and kidney injury. Methods and results Oxalate nephropathy was induced in C57BL6/N mice through an oxalate-enriched diet. Oxalate induced systemic immune activation, renal fibrosis, and adverse cardiac remodelling, including pulmonary congestion with systolic and diastolic dysfunction. Flow cytometry analysis identified interleukin (IL)-17A as a dominant inflammatory effector, with expansion of Th17 and Th17-like Treg in the kidney, intestine, and spleen. Bulk mRNA sequencing confirmed these findings in kidney and heart. In line, plasma IL-17A was increased in oxalate-fed mice. Confirming the oxalate-IL-17A relationship, plasma IL-17A was elevated in patients with primary hyperoxaluria. Gut microbiome analysis by 16S amplicon sequencing showed only mild oxalate-induced alterations in mice. However, soluble oxalate directly enhanced Th17 polarization and disrupted mitochondrial respiration in vitro. In vivo, antibody-mediated IL-17A blockade improved kidney function, cardiac fibrosis, reduced neutrophil infiltration, and partially restored cardiac function in oxalate-fed mice. Conclusion Our study identifies oxalate as a systemic immunometabolic stressor and IL-17A as a central mediator of oxalate-induced cardiorenal injury. These findings establish the oxalate-IL-17A axis as a mechanistic link between CKD and CVD and suggest IL-17A inhibition as a potential therapeutic strategy to reduce cardiovascular damage in CKD.

BACKGROUND: No large registries of patients with acute eosinophilic myocarditis (EM) are available. However, EM is perceived as a cardiac disease with high mortality, affecting mainly young and middle-aged adults according to small series and case reports. Awareness of the clinical presentation, associated systemic conditions, treatments, and outcomes of this uncommon condition is an unmet need. METHODS: In this international, multicenter, retrospective cohort study, 53 centers screened 193 patients with histologically proven acute EM between 1992 and 2023. After the exclusion of patients with insufficient data (n=10), symptoms lasting >30 days (n=19), or histological diagnosis not confirmed after review (n=8), 156 patients were included. RESULTS: Median age at presentation was 48 years (first to third quartile, 34–59 years) with male predominance (67.3%), and only 2 were pediatric cases (≤16 years of age; 1.3%). The main signs and symptoms at presentation were dyspnea (75.6%), fever (61.3%), and chest pain (53.2%). Unexpectedly, peripheral eosinophilia was reported in only 57.4% of cases, with a median cell count of 630 eosinophils/μL. The median left ventricular ejection fraction at presentation was 32% (first to third quartile, 25%–48%). The disorders most frequently associated with EM were eosinophilic granulomatosis with polyangiitis (22.4% of cases) and hypersensitivity forms (14.1%). Idiopathic/undefined forms accounted for 44.9% of cases, and miscellaneous causes accounted for 18.6%. In-hospital death or need for heart transplantation (HTx) occurred in 23 patients (14.7%; 22 deaths and 1 HTx), despite 43.6% being treated with temporary mechanical circulatory support and 92.9% being treated with immunosuppressive agents. Estimated rates of death or HTx at 1 and 3 years were 19.0% and 23.8%. Increased age, decreased left ventricular ejection fraction on admission, and no immunosuppressive therapy during hospitalization were independent predictors of death or HTx. A nonsignificant higher occurrence of deaths or HTx was observed in the hypersensitivity form (46.1%) compared with the eosinophilic granulomatosis with polyangiitis–associated form (13.1%) at 3 years ( P =0.15). CONCLUSIONS: Acute EM can often present without peripheral eosinophilia, and rates of in-hospital and midterm mortality or HTx are high. Endomyocardial biopsy is required to reach the final diagnosis of EM because relying on peripheral eosinophilia can lead to missing diagnosis. In-hospital immunosuppression is associated with HTx-free survival, although tailored immunosuppressive therapies are needed to improve outcomes. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT06447935.

Abstract Aims Cardiogenic shock (CS) is often treated with catecholamines titrated to an adequate target mean arterial pressure (MAP) while minimizing adverse effects. We aim to assess the optimal catecholamine dose/MAP balance in heart failure-associated CS (HF-CS). Methods Patients with HF-CS were retrospectively enrolled from 16 tertiary centres in 5 European countries (2016–2021; NCT03313687). Dosage was quantified by inotropic scores (epinephrine, norepinephrine, and dobutamine). Associations of baseline and seven-day summarized dosage with intensive care unit (ICU) discharge (mixed-effects logistic regression) and 30-day mortality (Cox regression) were analysed. Potential catecholamine/MAP target ratios for optimized outcomes were assessed in models adjusted for age, sex, pH, lactate and prior resuscitation, stratified by centre. Results N = 704 patients: median age 63 years, 74% male, 34% post-resuscitation, median lactate 5.2 mmol/l. Of these, 53% were discharged from ICU, 48% died within 30 days. Higher inotropic scores independently predicted a lower probability of ICU discharge (baseline score: OR 0.78 [95%-CI 0.69–0.88]; summarized score: OR 0.46 [0.38–0.56]; both P < .001) and higher risk of 30-day mortality (baseline score: HR 1.27 [1.15–1.40], summarized score HR 1.83 [1.60–2.09]; both P < .001). A score/MAP ratio <0.403 µg/kg/min/mmHg was associated with higher ICU discharge odds (ceiling effect); a < 0.426 µg/kg/min/mmHg with lower 30-day mortality hazards (no ceiling effect). Lowering catecholamine doses by accepting reduced MAP targets was linked to better outcomes. Conclusion In HF-CS, higher catecholamine support independently associates with worse outcomes. Accepting lower blood pressure targets to reduce catecholamine dosage may improve outcomes. Validation in randomized controlled trials is urgently needed.

Objectives: To identify factors associated with short-term mortality among patients receiving microaxial flow pump (mAFP) therapy for acute myocardial infarction-related cardiogenic shock (AMI-CS). Data Sources: We searched four databases (MEDLINE, Embase, CENTRAL, and Scopus) from January 1, 2004, to January 1, 2025. Study Selection: We selected English-language studies that included adults with AMI-CS receiving mAFP and evaluated factors associated with short-term mortality. We excluded patients receiving concurrent venoarterial extracorporeal membrane oxygenation, as well as studies that solely included patients presenting with out-of-hospital cardiac arrest. Data Extraction: Two authors performed citation screening and data extraction. For each factor evaluated in at least two studies, we performed meta-analyses of adjusted odds ratios (aORs) using a random-effects model. Risk of bias was evaluated using the Quality in Prognosis Studies tool, and the certainty of evidence was evaluated using Grading of Recommendations, Assessment, Development, and Evaluations methodology. Data Synthesis: Our primary analysis included 18 studies, encompassing 20,617 patients. Median short-term mortality across studies was 50.7% (interquartile range 38.4–55.3%). Factors associated with short-term mortality based on high-certainty evidence included: increased age (aOR, 1.04 per year [95% CI, 1.03–1.05 per year] or ≥ 65 yr (aOR, 2.42 yr [95% CI, 0.77–7.64 yr]), female sex (aOR, 1.26 [95% CI, 1.09–1.45]), higher body mass index (aOR, 1.05 per point [95% CI, 1.04–1.07 per point]), higher heart rate (aOR, 1.02 per beats/min [95% CI, 1.01–1.02 per beats/min]), higher serum creatinine (aOR, 1.35 per mg/dL [95% CI, 1.08–1.70 per mg/dL]), mechanical ventilation (aOR, 2.53 [95% CI, 1.82–3.53]), vasopressors (aOR, 1.52 [95% CI, 1.11–2.08] for any vasopressors and aOR, 1.37 [95% CI, 1.18–1.58] per each vasopressor), presentation with ST-elevation myocardial infarction (aOR, 1.59 [95% CI, 1.11–2.26]), cardiac arrest (aOR, 2.85 [95% CI, 2.22–3.64]), and hypoxic-ischemic brain injury (aOR, 5.36 [95% CI, 3.03–9.47]). Conclusions: We identified several prognostic factors associated with short-term mortality in AMI-CS patients receiving mAFP support. This work may help inform clinicians, patients, and families regarding utilization of mAFP in AMI-CS.

Abstract Aims The Society for Cardiovascular Angiography and Interventions (SCAI) Classification provides risk stratification of patients with acute myocardial infarction complicated by cardiogenic shock (AMI-CS). This sub-study of the ECLS-SHOCK trial investigates the prognostic impact of SCAI stages in AMI-CS and the influence of SCAI stages on the effect of extracorporeal life support (ECLS) therapy in AMI-CS patients. Methods Patients with AMI-CS enrolled in the multicentre, randomized ECLS-SHOCK trial were included. The outcomes, treatment effect and safety of ECLS were stratified according to SCAI stage at admission using a post-hoc classification. Results From a total of 417 patients enrolled in the ECLS-SHOCK trial between June 2019 and November 2022, 51.6% (n = 215), 13.4% (n = 56) and 35.0% (n = 146) presented in SCAI Stages C, D and E, respectively. SCAI stages were associated with the risk of 30 day all-cause mortality (C vs. D vs. E: 32.6% vs. 67.9% vs. 64.4%, P < 0.001), with rates of renal replacement therapy at 30 days (C vs. D vs. E: 7.0% vs. 19.6% vs. 13.7%, P = 0.03) and with poor neurological outcomes (C vs. D vs. E: 17.2% vs. 44.4% vs. 36.5%, P < 0.001). No interaction was observed between SCAI stage and the treatment effect of ELCS on 30 day all-cause mortality (ELCS vs. control SCAI C: 32.7% vs. 32.4%; SCAI D: 68.4% vs. 66.7%; SCAI E: 59.7% vs. 68.4%, P for interaction = 0.65). Conclusions In AMI-CS patients included in the ECLS-SHOCK trial, SCAI stages at admission were predictive for mortality and for the incidence of safety events. The efficacy of ECLS treatment was not affected by SCAI stage.

ABSTRACT This study aimed to distinguish between essential thrombocythemia (ET) and prefibrotic primary myelofibrosis (pre‐PMF) using routine blood tests, with a focus on white blood cell (WBC) and platelet (PLT) levels. We evaluated the predicted probability of a pre‐PMF diagnosis based on the interaction between WBC and PLT levels using data from a logistic regression model involving 891 patients with ET and 180 patients with pre‐PMF. Patients were divided into four groups based on whether their WBC and PLT values were below or above the respective thresholds of 8.85 × 10 9 /L and 793 × 10 9 /L. The results showed that patients with low levels of both WBCs and PLTs had the lowest predicted probability of pre‐PMF (6%), indicating a profile more typical of ET. When either WBC or PLT levels were elevated, the probability increased to approximately 18%–19%, indicating a potential shift toward pre‐PMF features. Notably, patients with elevated levels of both WBCs and PLTs had the highest probability of a pre‐PMF diagnosis (26%), which was more than four times higher than that of the low–low group. The association between combined WBC/PLT levels and a pre‐PMF diagnosis remained significant ( p < 0.001), even when adjusting for serum lactate dehydrogenase (LDH) and splenomegaly. These findings suggest that elevated WBC and PLT levels together can serve as a practical and accessible diagnostic tool for supporting the differential diagnosis of ET or pre‐PMF in cases of uncertainty, and for deferring bone marrow biopsy in cases of early disease presenting with isolated thrombocytosis.

Acute right ventricular failure (ARVF) is commonly seen in the intensive care unit and constitutes a significant clinical challenge, with associated high in-hospital mortality. Recently, the treatment of ARVF has significantly changed, with the progressive implementation of mechanical circulatory support devices that now represent important tools for clinicians in treating this condition. However, despite recent advancements, the optimal approach for ARVF remains elusive, and precise treatment algorithms and comprehensive management protocols are still lacking. In the present review, we explore the pathophysiology of ARVF, highlighting the different mechanisms that may lead to this clinical entity and emphasizing the left and right heart’s complex interplay. We analyze the different therapeutic options that are now available for short- and long-term management of ARVF, with a particular focus on the advantages and disadvantages of the mechanical circulatory support devices actually used. Furthermore, we propose future directions in the field and a possible flowchart for the treatment of this condition.

Hypertrophic olivary degeneration (HOD) is a rare condition characterized by degeneration and hypertrophy of the inferior olivary nucleus (ION) in the brainstem. This case report presents a 39-year-old woman with HOD undergoing left total shoulder arthroplasty. Despite long-standing concerns about regional anesthesia in patients with central nervous system disorders, an interscalene catheter was placed using ultrasound and nerve stimulation guidance. The patient experienced effective analgesia without new neurologic deficits. This report highlights the safe use of regional anesthesia in patients with HOD and underscores the need for individualized anesthetic management and further research to establish clear guidelines.

Summary Background: Precision prevention involves using biological, behavioral, socioeconomic, and epidemiological data to improve health for a particular individual or group. With almost 63% of the global population using social media, these platforms show promise to deliver tailored messaging and personalized interventions to individuals. Objectives: To describe the personalization elements and behavior components used in a sample of precision prevention interventions delivered through social media. Methods: To identify examples of cases, a search was done on clinicaltrials.gov, searching for ‘other terms: prevention’ + ‘Intervention/Treatment: social media intervention’ + ‘study results: With results. The selected cases were described, personalization elements reported, and their adopted intervention components were coded according to the Behavior Change Wheel (BCW) framework. Results: A total of four cases employing personalization in their interventions were identified. Three of these cases targeted women's health. The intervention period varied from two to eight months, with participant commitment ranging from active involvement on five out of seven days to monthly participation. The BCW interventions of persuasion and incentivization, were most frequently utilized, while education and coercion were used sparingly in the selected cases. Notably, none of the four cases reported the use of training, restrictions, or modeling. Conclusions: Social media has the potential to serve as a tool for digital phenotyping and contribute to the advancement of precision prevention. Challenges include the social media platform set-up and ensuring all ethical considerations are met.