Assessing the behavior of a hybrid model of the knee with contact surrogate under parameter uncertainties.

Modeling the knee is an important factor in increasing the quality of life of both healthy individuals and patients. Nevertheless, the intricate nature of the knee makes this problem complicated. In this study, an extension to an established planar knee joint model with Hertzian contact pairs is proposed with contact mechanics based on polynomial chaos expansion surrogate. Firstly, the finite element (FE) model is made representing a contact pair of sphere-to-plane type with two layers on both bodies, corresponding to the cartilage and the bone. Five variables corresponding to both geometry and material parameters are used to parametrize this model. Then, 128 distinct variants of the FE model are created based on a quasi-Monte Carlo sequence. This dataset is used to train and validate the surrogate. The trained surrogate is proven to have predictive capabilities with an average nRMSE of 0.2% in randomized test/train splits. When included in a model of the knee and tested under parameter uncertainties in Monte Carlo simulations, it results in nRMSE of 58% for angular coordinate compared to the original model with Hertzian pair. This signifies the high influence of contact formulation on the model output and the need for more physically based models in knee contact modeling.

Breast Implant-Associated Anaplastic Large Cell Lymphoma: Where Hematology and Plastic Surgery Meet.

Breast implant insertion for breast reconstruction or breast augmentation is a developing procedure, with high demand worldwide-being the second most common plastic surgery in the US as of 2022. Breast-implant-associated anaplastic large cell lymphoma (BIA-ALCL) is T-cell, non-Hodgkin lymphoma, typically CD30+, ALK-, presenting with fluid collection in the inner aspect of the peri-implant capsule in most patients, with the onset exceeding 1-year after implantation. The mean time between breast implant insertion and BIA-ALCL development is 7-10 years. The main risk factor is the use of textured implants because of their susceptibility to triggering local inflammation and immune stimulation finally leading to lymphoproliferation. Genetic predispositions to hereditary breast cancer increase the risk of disease development as well. BIA-ALCL seems to be underestimated in many countries and the initial symptom-seroma might be overlooked and misdiagnosed. Despite its rarity, the awareness of the disease should be improved among patients and medical professionals. This paper summarizes epidemiology, etiopathogenesis, differential diagnosis, and treatment-both surgical and hematological approaches.

Immunogenetic Aspects of Sarcopenic Obesity.

Sarcopenic obesity (SO) is a combination of obesity and sarcopenia, with diagnostic criteria defined as impaired skeletal muscle function and altered body composition (e.g., increased fat mass and reduced muscle mass). The mechanism of SO is not yet perfectly understood; however, the pathogenesis includes aging and its complications, chronic inflammation, insulin resistance (IR), and hormonal changes. Genetic background is apparent in the pathogenesis of isolated obesity, which is most often polygenic and is characterized by the additive effect of various genetic factors. The genetic etiology has not been strictly established in SO. Still, many data confirm the existence of pathogenic gene variants, e.g., Fat Mass and Obesity Associated Gene (FTO), beta-2-adrenergic receptor (ADRB2) gene, melanocortin-4 receptor (MC4R) and others with obesity. The literature on the role of these genes is scarce, and their role has not yet been thoroughly established. On the other hand, the involvement of systemic inflammation due to increased adipose tissue in SO plays a significant role in its pathophysiology through the synthesis of various cytokines such as monocyte chemoattractant protein-1 (MCP-1), IL-1Ra, IL-15, adiponectin or CRP. The lack of anti-inflammatory cytokine (e.g., IL-15) can increase SO risk, but further studies are needed to evaluate the exact mechanisms of implications of various cytokines in SO individuals. This manuscript analyses various immunogenetic and non-genetic factors and summarizes the recent findings on immunogenetics potentially impacting SO development.

Impact of Cardiac Magnetic Resonance on the Diagnosis of Left Ventricular Noncompaction-A 15-Year Experience.

The aim of this study was to assess the impact of cardiac magnetic resonance (CMR) on the diagnosis in patients with known or suspected left ventricular noncompaction (LVNC). We retrospectively reviewed the medical charts of 12,811 consecutive patients who had CMR studies between 2008 and 2022 in a large tertiary center. We included patients referred for CMR because of known or suspected LVNC. The study sample consisted of 333 patients, 193 (58.0%) male, median age 39.0 (26.8-51.0) years. Among 74 patients fulfilling the echocardiographic LVNC criteria, the diagnosis was confirmed in 54 (73.0%) cases. In 259 patients with ultrasound-based suspicion of LVNC, CMR led to an LVNC diagnosis in 82 (31.7%) patients. In both groups, CMR led to a new diagnosis in 89 cases (10 (13.5%) and 79 (30.5%)). A quantity of 38 (5.4%) patients were diagnosed with dilated cardiomyopathy, 11 (1.4%) patients were diagnosed with hypertrophic cardiomyopathy, and 21 (4.1%) patients were diagnosed with unclassified cardiomyopathy. In four patients with suspected LVNC, a myocardial trabeculation was a secondary result of dilatation due to coronary heart disease. In five cases, valvular heart disease was found. Four patients were diagnosed with athlete's heart. Other diagnoses (arrhythmogenic right ventricular cardiomyopathy, peripartum cardiomyopathy, hypokinetic non-dilated cardiomyopathy, sarcoidosis, amyloidosis, and ventricular septum defect) were found in six patients. CMR is a valuable tool in the evaluation of cardiac muscle and in differentiating LVNC and other cardiac diseases.

Superior sagittal sinus thrombosis in the course of mixed phenotype acute leukaemia treated with acute lymphoblastic leukaemia-like therapy-a case report.

Mixed phenotype acute leukaemia (MPAL) is associated with worse overall survival, compared with other acute leukaemias in adults. Lack of clear treatment guidelines makes the therapy challenging. ALL-like induction and consolidation treatment followed by allo-HSCT is the preferred first-line treatment. We present a case of a 36-year-old woman diagnosed with MPAL (EGIL Myelo/B) with KMT2A rearrangement, treated with the PALG-ALL-7 (including PEG-asparaginase) protocol. On day 25 after the induction therapy initiation, numbness of limbs and dizziness were observed. Therefore, the imaging studies (CT and MRI) were performed and a diagnosis of thrombosis of superior sagittal sinus of the brain was established. Routinely performed blood coagulation tests showed prolonged APTT and PT, decreased antithrombin III activity and decreased free protein S concentration. LMWH treatment and substitutional therapy with antithrombin III were started, which resulted in a significant reduction in the thrombosis associated symptoms and improvement of the neurological status after 3 days. After induction and consolidation therapy, the patient obtained complete haematological remission and negative measurable residual disease. Six months after the diagnosis, allo-HSCT was successfully performed. During the 4 months follow-up, the patient remained MRD negative and thrombotic symptoms free. To the best of our knowledge, our communication has been the first report of such complication in an MPAL patient treated with PEG-asparaginase containing protocol in adults. We recommend increased vigilance in patients manifesting any mild neurological symptoms and early decision about the MRI study performance.

Clinical features, etiology, and survival in patients with restrictive cardiomyopathy: A single-center experience.

BACKGROUND: Numerous prognostic factors have been proposed for cardiac amyloidosis (CA). The knowledge about other subtypes of restrictive cardiomyopathy (RCM) is scant. AIMS: This study aimed to elucidate the etiology and prognostic factors of RCM as well as assess cardiac biomarkers: high-sensitive troponin T (hs-TnT), growth differentiation factor-15 (GDF-15), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and soluble suppression of tumorigenicity 2, as mortality predictors in RCM. METHODS: We enrolled 36 RCM patients in our tertiary cardiac department. All patients were screened for CA. Genetic testing was performed in 17 patients without CA. RESULTS: Pathogenic or likely pathogenic gene variants were found in 86% of patients, including 5 novel variants. Twenty patients died, and 4 had a heart transplantation during the study. Median overall survival was 29 months (8-55). The univariate Cox models analysis indicated that systolic and diastolic blood pressure, GDF-15, hs-TnT, NT-proBNP, left ventricular stroke volume, the ratio of the transmitral early peak velocity (E) estimated by pulsed wave Doppler over the early mitral annulus velocity (e'), tricuspid annulus plane systolic excursion, early tricuspid valve annular systolic velocity, the presence of pulmonary hypertension, and pericardial effusion influenced survival (P <0.05). A worse prognosis was observed in patients with GDF-15 >1316 pg/ml, hs-TnT >42 ng/l, NT-proBNP >3383 pg/ml, and pericardial effusion >3.5 mm (Kaplan-Meier analysis, log-rank test, P <0.001). CONCLUSIONS: Genetic testing should be considered in every RCM patient where light-chain amyloidosis has been excluded. Survival remains poor regardless of etiology. Increased concentrations of GDF-15, hs-TNT, NT-proBNP, and pericardial effusion are associated with worse prognosis. Further studies are warranted.

C-Reactive Protein and Albumin Levels as Useful Tools for Predicting In-Hospital Outcomes in Polish Nonagenarians.

Purpose: The admissions of nonagenarians to internal medicine wards are rising. The aim of this study was to analyse the causes of ward admission and blood and renal parameters as potential mortality predictors in this age group. Patients and Methods: Out of 1140 patients, 111 nonagenarians aged 90+ admitted to the Internal Medicine Ward in one general hospital in Poznan in 2019 were studied. Medical records of these patients were analysed to find factors attributable to the hospitalisation. Results: The leading causes of admission were infections and cardiovascular diseases, and the main causes of death were cardiovascular diseases. Elevated C-reactive protein (CRP) level was a statistically significant death predictor. Equally, decreased albumin level was found to be a mortality predictor. No such relationships were obtained for haematological or renal parameters. Conclusion: Our study uniquely analysed a relatively large group of hospitalised nonagenarians and identified those who need particular attention in the ward by identifying those with the highest risk of death. CRP and albumin levels may serve as useful indicators of in-hospital mortality in this age group.

Diagnosis and treatment of transthyretin amyloidosis cardiomyopathy: A position statement of the Polish Cardiac Society.

Considering the rare incidence of transthyretin amyloidosis cardiomyopathy (ATTR-CM) in Poland, patients encounter difficulties at the stages of diagnosis and treatment. For successful diagnosis, it is vital to raise the suspicion of ATTR-CM, that is, to identify typical clinical scenarios such as heart failure with preserved ejection fraction or the red flags of amyloidosis. In most cases, it is possible to establish the diagnosis on the basis of noninvasive tests. This article presents the recommended diagnostic algorithms including laboratory workup, imaging tests (in particular, isotope scanning), and genetic tests. Since ATTR-CM should be differentiated from light chain amyloidosis, we also discuss aspects related to hematological manifestations and invasive diagnosis. We describe neurological signs and symptoms in patients with amyloidosis and present therapeutic options, including the causative treatment of ATTR-CM with the only currently approved drug, tafamidis. We also discuss drugs that are being assessed in ongoing clinical trials. We outline differences in the symptomatic treatment of heart failure in ATTR-CM and recommendations for nonpharmacological treatment and monitoring of the disease. Finally, we underline the need for providing access to the causative treatment with tafamidis as part of a drug program, as in other rare diseases, so that patients with ATTR-CM can be treated according to the European Society of Cardiology guidelines on heart failure and cardiomyopathy.

Positive antiphospholipid antibodies: observation or treatment?

Antiphospholipid antibodies (APLAs) are  primarily directed toward phospholipid-binding proteins and are responsible for thrombotic events. APLAs include anti-ß2Glycoprotein I (anti-ß2GPI), anticardiolipin (anti-CL) antibodies, and lupus anticoagulant. These antibodies are typical markers of antiphospholipid syndrome (APS) and are a part of its diagnostic criteria. Many data underline the presence of APLAs in other rheumatic diseases (e.g., systemic lupus erythematosus, systemic sclerosis, Sjögren's syndrome, rheumatoid arthritis and Behçet's disease). However, they are also detected in patients with cancer, infection, and neurological disorders. Furthermore, healthy individuals may be carriers of APLAs. Chronic asymptomatic APLAs presence is most common in the elderly and subjects with chronic diseases (including malignancies). Specific kinds of APLAs are considered markers of oncological progression. These antibodies occur in 6% of pregnant women (without diagnosed APS) and are related to many pregnancy complications. Of worth, various types of APLAs are reported to have different prothrombotic properties. The risk of thrombotic events in APLA-positive but clinically naïve patients raises many questions in clinical practice. This manuscript analyses various clinical situations and consequences of the APLAs' presence, particularly in patients without diagnosed APS. The prevalence, etiology, molecular background, and prothrombotic properties of numerous APLAs are broadly discussed. The new management approach in different clinical conditions and organ complications is present in the context of recent recommendations. Discussed data underlines that adequate and timely introduced thromboprophylaxis can decrease the risk of thrombus formation and prevent increased morbidity.

Emicizumab: a novel drug in hemophilia A prophylaxis - a narrative review.

INTRODUCTION: Hemophilia A is a genetically conditioned disease leading to hemostatic disorders due to factor VIII (FVIII) deficiency. The treatment of hemophilia has evolved throughout the past years and has significantly changed. One of the newest drugs for prophylactic treatment is the humanized bispecific IgG antibody - emicizumab, which binds with factor IXa and factor X, bridging those factors and thus mimicking the activity of factor VIII. AREAS COVERED: The literature search was done via the PubMed database, with the emphasis on clinical trials and case reports, describing the off-label emicizumab use. This review presents an extensive summary and considers the advantages and disadvantages (side-effects) of emicizumab, describing additional clinical situations, where emicizumab has been successfully used. In our review, we cover information about the mechanisms of action, indications, and efficacy and discuss some chosen case reports about off-label emicizumab use. EXPERT OPINION: Its convenient administration method (subcutaneous) and frequency of injections (from once a week to once a month) makes it a more comfortable treatment, limiting injection-site reactions, hospital stays, costs of prophylaxis, and significantly increasing patients' quality of life. Adverse effects are scarce and rarely serious - the most common ones are reactions at the injection-site and upper respiratory tract infections.

Correlation of Bone Material Model Using Voxel Mesh and Parametric Optimization.

The authors present an algorithm for determining the stiffness of the bone tissue for individual ranges of bone density. The paper begins with the preparation and appropriate mechanical processing of samples from the bovine femur and their imaging using computed tomography and then processing DICOM files in the MIMICS system. During the processing of DICOM files, particular emphasis was placed on defining basic planes along the sides of the samples, which improved the representation of sample geometry in the models. The MIMICS system transformed DICOM images into voxel models from which the whole bone FE model was built in the next step. A single voxel represents the averaged density of the real sample in a very small finite volume. In the numerical model, it is represented by the HEX8 element, which is a cube. All voxels were divided into groups that were assigned average equivalent densities. Then, the previously prepared samples were loaded to failure in a three-point bending test. The force waveforms as a function of the deflection of samples were obtained, based on which the global stiffness of the entire sample was determined. To determine the stiffness of each averaged voxel density value, the authors used advanced optimization analyses, during which numerical analyses were carried out simultaneously, independently mapping six experimental tests. Ultimately, the use of genetic algorithms made it possible to select a set of stiffness parameters for which the error of mapping the global stiffness for all samples was the smallest. The discrepancies obtained were less than 5%, which the authors considered satisfactory by the authors for such a heterogeneous medium and for samples collected from different parts of the bone. Finally, the determined data were validated for the sample that was not involved in the correlation of material parameters. The stiffness was 7% lower than in the experimental test.

Imaging Features of Pediatric Left Ventricular Noncompaction Cardiomyopathy in Echocardiography and Cardiovascular Magnetic Resonance.

Background: Left ventricular noncompaction (LVNC) is a distinct cardiomyopathy characterized by the presence of a two-layer myocardium with prominent trabeculation and deep intertrabecular recesses. The diagnosis of LVNC can be challenging because the diagnostic criteria are not uniform. The aim of our study was to evaluate echocardiographic and CMR findings in a group of children with isolated LVNC. Methods: From February 2008 to July 2021, pediatric patients under 18 years of age at the time of diagnosis with echocardiographic evidence of isolated LVNC were prospectively enrolled. The patients underwent echocardiography and contrast-enhanced cardiovascular magnetic resonance (CMR) with late gadolinium enhancement to assess myocardial noncompaction, ventricular size, and function. Results: A total of 34 patients, with a median age of 11.9 years, were recruited. The patients were followed prospectively for a median of 5.1 years. Of the 31 patients who met Jenni's criteria in echocardiography, CMR was performed on 27 (79%). Further comprehensive analysis was performed in the group of 25 patients who met the echocardiographic and CMR criteria for LVNC. In echocardiography, the median NC/C ratio in systole was 2.60 and in diastole 3.40. In 25 out of 27 children (93%), LVNC was confirmed by CMR, according to Petersen's criteria, with a median NC/C ratio of 3.27. Conclusions: (1) Echocardiography precisely identifies patients with LVNC. (2) Echocardiography is a good method for monitoring LV systolic function, but CMR is indicated for the precise assessment of LV remodeling and RV size and function, as well as for the detection of myocardial fibrosis.

Identification of muscle movements and activity by experimental methods for selected cases - stage #2.

PURPOSE: The aim of the performed tests and static measurements was to determine the torque and to determine the activity curve for individual muscle heads during the flexion-extension movement in the elbow joint. METHODS: Both heads of the biceps branchial muscle and the triceps muscle of the arm - long head and lateral head - were examined. Static measurements were carried out for four selected positions of the upper limb. For each pose, a measurement series consisting of five attempts of ten seconds of effort was performed. Isometric contraction was performed as 100% of the maximum voluntary MVC contraction. Dynamic measurements were carried out when working in isokinetic conditions. In both stages, an EMG and a Biodex isokinetic dynamometer were used. RESULTS: During the analyses, it was assumed that the average value of the torque is equal to the approximate value of the torque of a given head under static conditions. The value of the torque of the biceps brachial muscle, long head was 48.04 Nm and for the short head - 45.82 Nm. For the triceps muscle of the long head, this value was 52.52 Nm and for the lateral head - 38.06 Nm. On the basis of dynamic measurements, four activation curves were determined for each of the heads during the 7-second task. For the curves, the sum value of muscle activity in a given period of time was calculated as the area under the curve. CONCLUSIONS: Both parts of the series of articles present a series of experimental studies conducted in order to determine the parameters for one patient, for whom a personalized numerical model of the upper limb was ultimately created. Static measurements were carried out to determine the maximum values of the moments of forces. Dynamic measurements allowed for the determination of activity curves during the movement of the upper limb.

Role of cardiac magnetic resonance in heart failure of initially unknown etiology: A 10-year observational study.

BACKGROUND: The heart failure (HF) population is estimated to be 64.3 million people worldwide and continues to grow. Identifying the underlying cause of HF is crucial for patient management and prognosis. AIMS: We sought to evaluate the role of cardiac magnetic resonance (CMR) imaging to identify the etiology of HF and to evaluate the impact of CMR on diagnosis and patient management. METHODS: We retrospectively reviewed the medical charts of 8630 consecutive patients referred for CMR in a large tertiary center between 2008 and 2017 (10 years). In this study, we only included patients referred for CMR due to HF of unknown etiology whose diagnostic workup had not revealed suspicion of any specific cardiac disease leading to HF. We also analyzed changes in patient management that were guided by the CMR findings, which were defined as changes in treatment and/or the necessity of further tests. RESULTS: The study sample included 243 patients: 173 (71.2%) patients were male, and the mean (SD) age was 44.0 (15.2) years. All patients underwent contrast-enhanced CMR. Late gadolinium enhancement (LGE) was detected in 74.9% of cases. In 94 patients (38.7%), CMR led to a new diagnosis. In 41 patients (16.9%), patient management was changed by CMR. The latter group comprised patients with coronary artery disease, amyloidosis, valvular disease, and cardiomyopathies other than dilated, namely hypertrophic, restrictive, and left ventricular noncompaction. CONCLUSIONS: Our study strongly suggests that CMR imaging is a valuable tool for determining the etiology of HF and affects patient management.

Identification of muscle movements and activity by experimental methods for selected cases - stage#1.

PURPOSE: The aim of this study was to determine the position where the most activated and isolated individual muscles were. In the next steps, the selected limb positions will be used to determine the maximum values of isometric forces of the individual muscle heads based on the Hill model. METHODS: In order to determine the sought muscle activation, an electromyograph was used. Isometric contraction measurements were carried out for seven series of tests. Isometric contraction was performed as 100% MVC. RESULTS: For the long head of the biceps muscle, in the case of bending in the shoulder joint, angle of 75° was selected and for abduction in the shoulder joint - 90°. Internal rotation in the shoulder joint was omitted because of lower activation values. For the short head of the biceps muscle, the angle characterized by the greatest activity of the head was the angle of 115° in flexion at the elbow joint. The selected angle was 30° for shoulder extension and 110° for shoulder adduction. For the lateral head of the triceps brachial muscle, measurements showed that the angle at which the lateral head was most activated is 115°. CONCLUSIONS: The aim of this study was to determine the positions of the arm muscles that activate and isolate individual heads the most. The research presented and achieved results concern one specific person for whom a personalized numerical model was developed to represent the flexion-extension movement at the elbow joint. The performed tests can also be a preliminary assessment of the upper limb positions, for which wider conclusions could be drawn in the case of measurements on a larger number of participants.

Cardiovascular Magnetic Resonance in Peripartum Cardiomyopathy: Comparison with Idiopathic Dilated Cardiomyopathy.

BACKGROUND: Peripartum (PPCM) and dilated (DCM) cardiomyopathies are distinct forms of cardiac disease that share certain aspects in clinical presentation. AIM: We hypothesized that different cardiac structural changes underlie PPCM and DCM, and we aimed to investigate them with cardiovascular magnetic resonance (CMR). METHODS: We included 21 PPCM patients (30.5 ± 5.9 years) and 30 female DCM patients (41.5 ± 16.8 years) matched for left ventricular ejection fraction. Biventricular and biatrial volumetric and functional parameters were assessed along with ventricular and atrial strain indices based on feature-tracking techniques. The presence of late gadolinium enhancement (LGE) was also assessed. RESULTS: In PPCM, the left ventricular (LV) stroke volume index was lower (p = 0.04), right atrial (RA) minimal and pre-systolic volumes were higher (p < 0.01 and p = 0.02, respectively), and the total RA ejection fraction was lower (p = 0.02) in comparison to DCM. Moreover, in PPCM, the LV global longitudinal strain (p = 0.03), global circumferential strain rate (p = 0.04), and global longitudinal strain rate (p < 0.01) were less impaired than in DCM. Both PPCM and DCM patients with LGE had more dilated ventricles and more impaired LV and left atrial function than in PPCM and DCM patients without LGE. CONCLUSIONS: Subtle differences appear on CMR between PPCM and DCM. Most importantly, the RA is larger and more impaired, and LV global longitudinal strain is less reduced in PPCM than in DCM. Furthermore, similarly to DCM, PPCM patients with LGE have more dilated and impaired ventricles than patients without LGE.

Comparison of mitral regurgitation severity assessments based on magnetic resonance imaging and echocardiography in patients with hypertrophic cardiomyopathy.

Mitral regurgitation (MR), which is one of the factors responsible for heart failure symptoms and the development of atrial fibrillation, is an important feature of hypertrophic cardiomyopathy (HCM), and its presence affects which treatment options are chosen. Although cardiac magnetic resonance imaging (MRI) is considered the reference standard for assessing the regurgitant volume (RV) and fraction (RF), echocardiography is the most common method for assessing MR severity. Accordingly, the aim of this study was to compare the results of echocardiography and cardiac MRI for assessing MR severity in a cohort of patients with HCM. MR severity was assessed in 53 patients using cardiac MRI by determining the mitral RV (MRV) and mitral RF (MRF). The results were graded according to thresholds recommended in current guidelines. MR severity assessed by echocardiography was graded by integrating indices of severity. Greater than mild MR, as assessed using echocardiography, was present in 22 patients (41.5%) with HCM and in none of the control patients (p = 0.001). In all, 31 patients (58.5%) had no more than mild MR. When MR severity was assessed using different methods, either moderate (kappa = 0.44, 95% confidence interval = 0.21-0.67), poor or no agreement was found between MRI-derived and echocardiography-derived grades. HCM patients with echocardiography-derived moderate and severe MR had similar median MRVs and MRFs (p = 0.59 and p = 0.11, respectively). In HCM patients, cardiac MRI and echocardiography were at most in modest agreement in assessing MR severity. Importantly, echocardiography-derived moderate and severe MR were not distinguishable by either MRV or MRF.