Abdominal Aortic Calcification is Associated with Degeneration of The Paraspinal Muscles - A Retrospective cross-sectional Study.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To analyze the relationship of abdominal aortic calcification (AAC) and a reduction in the cross-sectional area (CSA) and the fatty infiltration (FI) of the paravertebral muscles in patients undergoing lumbar fusion surgery. BACKGROUND: Both AAC and paraspinal muscle degeneration have been shown to be associated with poorer outcomes after surgical treatment of degenerative diseases of the lumbar spine. However, there is a lack of data on the association between AAC and paraspinal muscle changes in patients undergoing spine surgery. METHODS: We retrospectively analyzed patients undergoing lumbar fusion for degenerative spinal pathologies. Muscular and spinal degeneration were measured on magnetic resonance imaging (MRI). AAC was classified on lateral lumbar radiographs. The association of AAC and paraspinal muscle composition was assessed by a multivariate regression analysis adjusted for age, sex, body mass index (BMI), comorbidities, and lumbar degeneration. RESULTS: A total of 301 patients was included. Patients with AAC showed significantly higher degrees of intervertebral disc and facet joint degeneration as well as higher total endplate scores at the L3/4 level. The univariable regression analysis showed a significant positive correlation between the degree of AAC and the FI of the erector spinae (b=0.530, P<0.001) and multifidus (b=0.730, P<0.001). The multivariable regression analysis showed a significant positive correlation between the degree of AAC and the FI of the erector spinae (b=0.270, P=0.006) and a significant negative correlation between the degree of AAC and the CSA of the psoas muscle (b=-0.260, P=0.003). CONCLUSION: This study demonstrates a significant and independent association between AAC and degeneration of the erector spinae and the psoas muscles in patients undergoing lumbar fusion. As both AAC and degeneration of paraspinal muscles impact postoperative outcomes negatively, preoperative assessment of AAC may aid in identifying patients at higher risk after lumbar surgery.

The inflammatory spectrum of cardiomyopathies.

Infiltration of the myocardium with various cell types, cytokines and chemokines plays a crucial role in the pathogenesis of cardiomyopathies including inflammatory cardiomyopathies and myocarditis. A more comprehensive understanding of the precise immune mechanisms involved in acute and chronic myocarditis is essential to develop novel therapeutic approaches. This review offers a comprehensive overview of the current knowledge of the immune landscape in cardiomyopathies based on etiology. It identifies gaps in our knowledge about cardiac inflammation and emphasizes the need for new translational approaches to improve our understanding thus enabling development of novel early detection methods and more effective treatments.

Association of abdominal aortic calcification and lower back pain in patients with degenerative spondylolisthesis.

ABSTRACT: Abdominal aortic calcification (AAC) is hypothesized to lead to ischemic pain of the lower back. This retrospective study aims to identify the relationship between AAC and lower back pain (LBP) in patients with degenerative lumbar spondylolisthesis. Lower back pain was assessed preoperatively and 2 years after surgery using the numeric analogue scale. Abdominal aortic calcification was assessed according to the Kauppila classification and was grouped into no, moderate, and severe. A multivariable regression, adjusted for age, sex, body mass index, hypertension, and smoking status, was used to assess the association between AAC and preoperative/postoperative LBP as well as change in LBP after surgery. A total of 262 patients were included in the final analysis. The multivariable logistic regression demonstrated an increased odds ratio (OR) for preoperative LBP ≥ 4 numeric analogue scale (OR = 9.49, 95% confidence interval [CI]: 2.71-40.59, P < 0.001) and postoperative LBP ≥ 4 (OR = 1.72, 95% CI: 0.92-3.21, P = 0.008) in patients with severe AAC compared with patients with no AAC. Both moderate and severe AAC were associated with reduced improvement in LBP after surgery (moderate AAC: OR = 0.44, 95% CI: 0.22-0.85, P = 0.016; severe AAC: OR = 0.41, 95% CI: 0.2-0.82, P = 0.012). This study demonstrates an independent association between AAC and LBP and reduced improvement after surgery. Evaluation of AAC could play a role in patient education and might be considered part of the differential diagnosis for LBP, although further prospective studies are needed.

Case report: Recurrence of inflammatory cardiomyopathy detected by magnetocardiography.

Background: The diagnosis of inflammatory cardiomyopathies remains challenging. Life-threatening conditions such as acute coronary syndrome (ACS) always have to be considered as differential diagnoses due to similarities in presentation. Diagnostic methods for inflammatory cardiomyopathy include endomyocardial biopsy (EMB), cardiac magnetic resonance imaging (CMR), and positron emission tomography-computed tomography (PET-CT). We report a case in whom magnetocardiography (MCG) led to an initial diagnosis of inflammatory cardiomyopathy and in whom MCG was used for subsequent monitoring of treatment response under immunosuppression. Case presentation: A 53-year-old man presented with two recurrent episodes of inflammatory cardiomyopathy within a 2-year period. The patient initially presented with reduced exercise capacity. Echocardiography revealed a moderately reduced left ventricular ejection fraction (LVEF 40%). Coronary angiography ruled out obstructive coronary artery disease (CAD) and an EMB was performed. The EMB revealed inflammatory cardiomyopathy without viral pathogens or replication. Moreover, we performed MCG, which confirmed a pathological Tbeg-Tmax vector of 0.108. We recently established a cutoff value of Tbeg-Tmax of 0.051 or greater for the diagnosis of inflammatory cardiomyopathy. Immunosuppressive therapy with prednisolone was initiated, resulting in clinical improvement and an LVEF increase from 40% to 45% within 1 month. Furthermore, the MCG vector improved to 0.036, which is considered normal based on our previous findings. The patient remained clinically stable for 23 months. During a routine follow-up, MCG revealed an abnormal Tbeg-Tmax vector of 0.069. The patient underwent additional testing including routine laboratory values, echocardiography (LVEF 35%), and PET-CT. PET-CT revealed increased metabolism in the myocardium-primarily in the lateral wall. Therapy with prednisolone and azathioprine was initiated and MCG was used to monitor the effect of immunosuppressive therapy. Conclusion: In addition to diagnostic screening, MCG has the potential to become a valuable method for surveillance monitoring of patients who have completed treatment for inflammatory cardiomyopathy. Furthermore, it could be used for treatment monitoring. While changes in the magnetic vector of the heart are not specific to inflammatory cardiomyopathy, as they may also occur in other types of cardiomyopathies, MCG offers a tool of broad and efficient diagnostic screening for cardiac pathologies without side effects.

Case report: Magnetocardiography as a potential method of therapy monitoring in amyloidosis.

Amyloidosis is characterized by a disorder of protein conformation and metabolism, resulting in deposits of insoluble fibrils in various organs causing functional disturbances. Amyloidosis can also affect the heart. Cardiac amyloidosis tends to have a poor prognostic outcome if diagnosed at a late stage. Therefore, early diagnosis and initiation of therapy as well as monitoring of treatment response are crucial to improve outcomes and to learn more about its pathophysiology and clinical course. We present an 83-year-old woman with cardiac transthyretin amyloidosis (ATTR) who was treated with tafamidis. The patient significantly improved 18 months after initiation of therapy with regards to exercise capacity and quality of life. In addition to standard diagnostic methods, we used magnetocardiography (MCG) to monitor potential treatment response by detecting changes in the magnetic field of the heart. MCG is a non-invasive method that detects the cardiac magnetic field generated by electrical currents in the heart with high sensitivity. We have recently shown that this magnetic field changes in various types of cardiomyopathies may be used as a non-invasive screening tool. We determined previously that an MCG vector ≥0.052 was the optimal threshold to detect cardiac amyloidosis. The patient's MCG was measured at various time points during therapy. At the time of diagnosis, the patient's MCG vector was 0.052. After starting therapy, the MCG vector increased to 0.090, but improved to 0.037 after 4 months of therapy. The MCG vector reached a value of 0.017 after 5 months of therapy with tafamidis, and then increased slightly after 27 months to a value of 0.027 (<0.052). Data from this case support our previous findings that MCG may be used to monitor treatment response non-invasively. Further research is needed to understand the unexpected changes in the MCG vector that were observed at the beginning of therapy and later in the course. Larger studies will be necessary to determine how these changes in the electromagnetic field of the heart are related to structural changes and how they affect clinical outcomes.

Abdominal aortic calcification is independently associated with lumbar endplate degeneration.

BACKGROUND: Abdominal aortic calcification (AAC) is associated with lower back pain, reduced bone mineral density of the spine. Vascular changes could also affect the already sparsely perfused intervertebral endplate and intervertebral disc. METHODS: Lumbar MRIs and lateral radiographs of patients with lower back pain were retrospectively analyzed. AAC was assessed on lateral lumbar radiographs according to the Kauppila score, with a maximum score of 24. Patients were grouped into no (AAC = 0), moderate (AAC 1 to ≤ 4), and severe AAC (AAC ≥ 5). Endplate and disc degeneration were classified according to the total endplate score (TEPS) and Pfirrmann classification. The associations between AAC and degenerative changes was analyzed with a generalized mixed model and was adjusted for age, sex, body mass index as well as diabetes mellitus, and smoking status. RESULTS: A total of 217 patients (47.9% female) were included in the analysis, totaling 1085 intervertebral levels. Of those, 45 (20.7%) patients had moderate, and 39 (18%) had severe AAC. The results of the generalized mixed model showed no significant association between AAC and disc degeneration (p > 0.05). In contrast, a significant positive association between AAC and the severity of TEPS (ß: 0.51, 95% CI: 1.92-2.12, p = 0.004) was observed in the multivariable analysis. CONCLUSIONS: This study demonstrates an independent association between AAC and endplate degeneration. These findings expand our knowledge about the degenerative cascade of the lumbar spine and suggest that AAC might be a modifiable risk factor for endplate changes.

Abdominal aortic calcification is independently associated with increased atrophy and fatty infiltration of the lumbar paraspinal muscles: a retrospective cross-sectional study.

BACKGROUND: Aortic abdominal calcification (AAC) is associated with spine-related conditions, such as lower back pain and reduced bone mineral density. Similar to peripheral vascular disease, AAC possibly reduces blood flow to the lumbar posterior paraspinal muscles (PPM) which may lead to atrophy and increased fatty infiltration. METHODS: Imaging of patients with lower back pain was analyzed. AAC was assessed on lateral lumbar radiographs according to the Kauppila classification. The cross-sectional area of the PPM was measured on a T2-weighted axial MRI sequence and the functional cross-sectional area (fCSA) and fatty infiltration (FI) were calculated with custom software. The association of AAC and FI as well as AAC and fCSA was assessed by multivariable linear regression, adjusted for age, sex, body mass index (BMI), diabetes, and smoking. RESULTS: Two hundred and thirty patients (47.8% female) with a median age of 60 years (IQR 48-68) were analyzed. In patients, without AAC the median FI of the PPM was 33.3% (IQR 29.1-37.6%), compared to 44.6% (IQR 38.5-54.3%) in patients with AAC (p < 0.001). In the multivariable linear regression, both fCSA and FI of the PPM were significantly and independently associated with the degree of AAC (p = 0.037 and p = 0.015, respectively). CONCLUSIONS: This is the first study to demonstrate a significant and independent association between AAC and PPM morphology. The results of this study improve our understanding of the interaction between AAC and spinal musculature, with AAC being a reason for atrophy of the PPM.

Application of Magnetocardiography to Screen for Inflammatory Cardiomyopathy and Monitor Treatment Response.

Background Inflammatory cardiomyopathy is one of the most common causes of sudden cardiac death in young adults. Diagnosis of inflammatory cardiomyopathy remains challenging, and better monitoring tools are needed. We present magnetocardiography as a method to diagnose myocardial inflammation and monitor treatment response. Methods and Results A total of 233 patients were enrolled, with a mean age of 45 (±18) years, and 105 (45%) were women. The primary analysis included 209 adult subjects, of whom 66 (32%) were diagnosed with inflammatory cardiomyopathy, 17 (8%) were diagnosed with cardiac amyloidosis, and 35 (17%) were diagnosed with other types of nonischemic cardiomyopathy; 91 (44%) did not have cardiomyopathy. The second analysis included 13 patients with inflammatory cardiomyopathy who underwent immunosuppressive therapy after baseline magnetocardiography measurement. Finally, diagnostic accuracy of magnetocardiography was tested in 3 independent cohorts (total n=23) and 1 patient, who developed vaccine-related myocarditis. First, we identified a magnetocardiography vector to differentiate between patients with cardiomyopathy versus patients without cardiomyopathy (vector of ≥0.051; sensitivity, 0.59; specificity, 0.95; positive predictive value, 93%; and negative predictive value, 64%). All patients with inflammatory cardiomyopathy, including a patient with mRNA vaccine-related myocarditis, had a magnetocardiography vector ≥0.051. Second, we evaluated the ability of the magnetocardiography vector to reflect treatment response. We observed a decrease of the pathologic magnetocardiography vector toward normal in all 13 patients who were clinically improving under immunosuppressive therapy. Magnetocardiography detected treatment response as early as day 7, whereas echocardiographic detection of treatment response occurred after 1 month. The magnetocardiography vector decreased from 0.10 at baseline to 0.07 within 7 days (P=0.010) and to 0.03 within 30 days (P<0.001). After 30 days, left ventricular ejection fraction improved from 42.2% at baseline to 53.8% (P<0.001). Conclusions Magnetocardiography has the potential to be used for diagnostic screening and to monitor early treatment response. The method is valuable in inflammatory cardiomyopathy, where there is a major unmet need for early diagnosis and monitoring response to immunosuppressive therapy.

Highly multiplexed immune repertoire sequencing links multiple lymphocyte classes with severity of response to COVID-19.

Background: Disease progression of subjects with coronavirus disease 2019 (COVID-19) varies dramatically. Understanding the various types of immune response to SARS-CoV-2 is critical for better clinical management of coronavirus outbreaks and to potentially improve future therapies. Disease dynamics can be characterized by deciphering the adaptive immune response. Methods: In this cross-sectional study we analyzed 117 peripheral blood immune repertoires from healthy controls and subjects with mild to severe COVID-19 disease to elucidate the interplay between B and T cells. We used an immune repertoire Primer Extension Target Enrichment method (immunoPETE) to sequence simultaneously human leukocyte antigen (HLA) restricted T cell receptor beta chain (TRB) and unrestricted T cell receptor delta chain (TRD) and immunoglobulin heavy chain (IgH) immune receptor repertoires. The distribution was analyzed of TRB, TRD and IgH clones between healthy and COVID-19 infected subjects. Using McFadden's Adjusted R2 variables were examined for a predictive model. The aim of this study is to analyze the influence of the adaptive immune repertoire on the severity of the disease (value on the World Health Organization Clinical Progression Scale) in COVID-19. Findings: Combining clinical metadata with clonotypes of three immune receptor heavy chains (TRB, TRD, and IgH), we found significant associations between COVID-19 disease severity groups and immune receptor sequences of B and T cell compartments. Logistic regression showed an increase in shared IgH clonal types and decrease of TRD in subjects with severe COVID-19. The probability of finding shared clones of TRD clonal types was highest in healthy subjects (controls). Some specific TRB clones seems to be present in severe COVID-19 (Figure S7b). The most informative models (McFadden´s Adjusted R2=0.141) linked disease severity with immune repertoire measures across all three cell types, as well as receptor-specific cell counts, highlighting the importance of multiple lymphocyte classes in disease progression. Interpretation: Adaptive immune receptor peripheral blood repertoire measures are associated with COVID-19 disease severity. Funding: The study was funded with grants from the Berlin Institute of Health (BIH).

Increased risk of severe clinical course of COVID-19 in carriers of HLA-C*04:01.

BACKGROUND: Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, there has been increasing urgency to identify pathophysiological characteristics leading to severe clinical course in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Human leukocyte antigen alleles (HLA) have been suggested as potential genetic host factors that affect individual immune response to SARS-CoV-2. We sought to evaluate this hypothesis by conducting a multicenter study using HLA sequencing. METHODS: We analyzed the association between COVID-19 severity and HLAs in 435 individuals from Germany (n = 135), Spain (n = 133), Switzerland (n = 20) and the United States (n = 147), who had been enrolled from March 2020 to August 2020. This study included patients older than 18 years, diagnosed with COVID-19 and representing the full spectrum of the disease. Finally, we tested our results by meta-analysing data from prior genome-wide association studies (GWAS). FINDINGS: We describe a potential association of HLA-C*04:01 with severe clinical course of COVID-19. Carriers of HLA-C*04:01 had twice the risk of intubation when infected with SARS-CoV-2 (risk ratio 1.5 [95% CI 1.1-2.1], odds ratio 3.5 [95% CI 1.9-6.6], adjusted p-value = 0.0074). These findings are based on data from four countries and corroborated by independent results from GWAS. Our findings are biologically plausible, as HLA-C*04:01 has fewer predicted bindings sites for relevant SARS-CoV-2 peptides compared to other HLA alleles. INTERPRETATION: HLA-C*04:01 carrier state is associated with severe clinical course in SARS-CoV-2. Our findings suggest that HLA class I alleles have a relevant role in immune defense against SARS-CoV-2. FUNDING: Funded by Roche Sequencing Solutions, Inc.