Patient-specific Approach Research Articles

Multidimensional Analysis of Descending Aortic Growth After Acute Type A Aortic Dissection

After repair of acute type A aortic dissection, typical geometric variables of conventional aortic surveillance focus on maximum diameter and its rate of growth, potentially missing important geometric changes elsewhere. We determined additional information provided by a semiautomated, 3-dimensional (3D), nonlinear growth model of the descending thoracic aorta after repair of type A aortic dissection. Computed tomographic angiography data were retrospectively collected after hemiarch repair of type A aortic dissection. The descending aorta was systematically reconstructed to generate a 3D model made up of individual segments. The baseline and follow-up diameters were measured semiautomatically for each segment, and the nonlinear interval growth was determined. The fastest growing segment expanded at a rate of 3.8 mm/y (interquartile range, 2.2 to 5.4 mm/y) vs 0.6 mm/y (interquartile range,-0.3 to 1.7 mm/y) when measured at the original site of maximum diameter (P < .01). The maximum baseline diameter was a poor predictor of location with fastest growth (r= 0.10, P > .1). Using the society recommended growth limits, a greater proportion of patients would be considered "at risk" when assessed by our method vs conventional surveillance measures. Our model identifies areas of rapid aortic growth after repair of type A dissection that would likely be missed using current surveillance techniques. The increased precision, resolution, and reproducibility provided by our technique may improve on limitations of current surveillance techniques, provide novel geometric data on aortic remodeling, and contribute to the pursuit of a comprehensive patient-specific approach to aortic risk stratification.

Biliary Drainage Before and After Liver Resection for Perihilar Cholangiocarcinoma.

Perihilar cholangiocarcinoma (PHC) is a rare tumor that requires surgical resection for a potential cure. The role of preoperative biliary drainage has long been debated, given its treatment of biliary sepsis and decompression of the future liver remnant (FLR), but high procedure-specific morbidity. The indications, methods, and outcomes for preoperative biliary drainage are discussed to serve as a guide for perioperative management of patients with resectable PHC. Multiple studies from the literature related to perihilar cholangiocarcinoma, biliary drainage, and management of the FLR were reviewed. Commonly employed preoperative biliary drainage includes endoscopic biliary stenting and percutaneous transhepatic biliary drainage. Drainage of the FLR remains controversial, with most experts recommending drainage of the only in patients with an FLR <50%. Biliary drainage for resectable PHC requires a patient-specific approach with careful determination of the FLR and balancing of potential morbidity with the benefits of drainage.

Real-time phonocardiogram anomaly detection by adaptive 1D Convolutional Neural Networks

The heart sound signals (Phonocardiogram – PCG) enable the earliest monitoring to detect a potential cardiovascular pathology and have recently become a crucial tool as a diagnostic test in outpatient monitoring to assess heart hemodynamic status. The need for an automated and accurate anomaly detection method for PCG has thus become imminent. To determine the state-of-the-art PCG classification algorithm, 48 international teams competed in the PhysioNet (CinC) Challenge in 2016 over the largest benchmark dataset with 3126 records with the classification outputs, normal (N), abnormal (A) and unsure – too noisy (U). In this study, our aim is to push this frontier further; however, we focus deliberately on the anomaly detection problem while assuming a reasonably high Signal-to-Noise Ratio (SNR) on the records. By using 1D Convolutional Neural Networks trained with a novel data purification approach, we aim to achieve the highest detection performance and real-time processing ability with significantly lower delay and computational complexity. The experimental results over the high-quality subset of the same benchmark dataset show that the proposed approach achieves both objectives. Furthermore, our findings reveal the fact that further improvements indeed require a personalized (patient-specific) approach to avoid major drawbacks of a global PCG classification approach.

Fat Necrosis After DIEP Flap Breast Reconstruction: A Review of Perfusion-Related Causes.

Fat necrosis is a common complication for the deep inferior epigastric perforator (DIEP) flap. A thorough understanding of the factors associated with fat necrosis will aid operative planning for reconstructive surgeons. A systematic review of the literature was performed between January 1989 and April 2019. Studies were included if they reported on fat necrosis in DIEP flap or evaluated the perfusion of the DIEP flap. Twenty-eight out of 312 studies met the inclusion and exclusion criteria. Fat necrosis rates ranged from 12.0 to 45.0% on clinical examination within the literature. The four main perforator-specific factors identified included perforator perfusion zones, perforator location, perforator number and venous congestion. Medial row perforators have a wider perfusion zone, while lateral row perforators have a narrow perfusion zone. Holm zone III has a higher rate of fat necrosis compared to Holm zone II. One to two perforators and more than five perforators and a Type III atypical connection between the superficial and deep venous system had a higher rate of fat necrosis. The DIEP flap should incorporate between two and three perforators of a substantial calibre; Holm zone III should be excluded if able and careful review of the pre-operative imaging should be performed to analyse the connections between the deep and superficial venous system. There are multiple perfusion-related factors to consider when planning the DIEP flap and ultimately a patient-specific approach to the vascular anatomy is essential. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

The Biomechanical Effect of Bone Grafting and Bone Graft Remodeling in Patients With Anterior Shoulder Instability

Background: Individual constitutional differences in glenoid shape and bone remodeling require a patient-specific and longitudinal approach to evaluate the biomechanical effects of glenoid bone grafting in patients with anterior shoulder instability. Purpose: To quantify the longitudinal, in vivo, biomechanical effects of bone grafting, bone graft remodeling, and glenoid shape in patients with anterior shoulder instability by means of patient-specific finite element models. Study Design: Descriptive laboratory study. Methods: In total, 25 shoulders of 24 patients with anterior shoulder instability and anterior glenoid bone loss underwent an arthroscopic iliac crest bone graft transfer (ICBGT) procedure with either autologous or allogenic bone. Patient-specific finite element simulations based on preoperative, postoperative, and follow-up computed tomography scans were used to quantify the bone-mediated stability ratio (SR) and the distance to dislocation. Additionally, the relationship between glenoid morphological parameters and the SR was assessed. Results: The ICBGT procedure significantly increased the SR and distance to dislocation in the 2-, 3-, and 4-o’clock directions immediately after the surgical intervention (P < .01) in both the autograft and the allograft groups. Although the SR and distance to dislocation decreased subsequently, autografts showed long-term effects on SR and dislocation distance in the 3-o’clock direction (P < .01) and on SR in the 4-o’clock direction (P < .01). Allografts showed no significant effect on SR and dislocation distance in long-term follow-up (P > .05). Overall, glenoid retroversion as well as cavity depth predicted stability in all 4 dislocation directions, with glenoid cavity depth showing the highest correlation coefficients (R = 0.71, 0.8, 0.73, and 0.7 for 2-, 3-, 4-, and 5-o’clock, respectively). Conclusion: The autologous ICBGT procedure biomechanically improved anterior shoulder stability in long-term follow-up, whereas the use of allografts did not show any bone-mediated biomechanical effect at follow-up due to resorption. Furthermore, in addition to measurements of defect extent, the glenoid depth and version seem to be useful parameters to determine the biomechanical effect and need for glenoid bone grafting in patients with shoulder instability. Clinical Relevance: This study proposes the use of autologous bone grafts for a successful long-term stabilization effect. Additionally, this study proposes additional glenoid morphological measures to predict shoulder stability.

Microbiotyping the Sinonasal Microbiome.

This study offers a novel description of the sinonasal microbiome, through an unsupervised machine learning approach combining dimensionality reduction and clustering. We apply our method to the International Sinonasal Microbiome Study (ISMS) dataset of 410 sinus swab samples. We propose three main sinonasal “microbiotypes” or “states”: the first is Corynebacterium-dominated, the second is Staphylococcus-dominated, and the third dominated by the other core genera of the sinonasal microbiome (Streptococcus, Haemophilus, Moraxella, and Pseudomonas). The prevalence of the three microbiotypes studied did not differ between healthy and diseased sinuses, but differences in their distribution were evident based on geography. We also describe a potential reciprocal relationship between Corynebacterium species and Staphylococcus aureus, suggesting that a certain microbial equilibrium between various players is reached in the sinuses. We validate our approach by applying it to a separate 16S rRNA gene sequence dataset of 97 sinus swabs from a different patient cohort. Sinonasal microbiotyping may prove useful in reducing the complexity of describing sinonasal microbiota. It may drive future studies aimed at modeling microbial interactions in the sinuses and in doing so may facilitate the development of a tailored patient-specific approach to the treatment of sinus disease in the future.

PROBLEM OF CHRONIC PAIN IN ONCOLOGY AND APPROACHES TO ITS RELIEF

This article reviews modern ideas about the pathogenesis of chronic pain in cancer patients and describes main approaches to its relief. Special attention is focused on factors important for the development of a patient-specific approach to the pathophysiology and management of chronic pain syndrome. These factors include genetics, gender, age, early anamnesis, patients’ immunological and endocrine status, as well as those shedding light on the pathogenetic aspects of chronic pain thus facilitating the choice of an optimal therapeutic approach. The review identifies limitations of pharmacotherapy as the major method of chronic pain management and justifies the need for alternative approaches. The latter include monitoring of the circadian rhythms of pain and various nonspecific effects, such as physical factors, psychological methods or reflex therapy. The experience and possibilities of non–pharmacological methods in the complex pathogenetic therapy of chronic pain are analysed, along with preventive measures permitting the development of chronic pain to be avoided. The pathological disorganizing and stressful role of chronic pain is considered with regard to the theory of functional systems. The pathogenetic significance of chronic pain in carcinogenesis and cancer progression is illustrated by examples from scientific literature. The authors emphasize the necessity of effective pain prevention, including invasive methods, in order to ensure an acceptable quality of life for cancer patients at any stage of the malignant process.

Personalized Dosimetry for Liver Cancer Y-90 Radioembolization Using Computational Fluid Dynamics and Monte Carlo Simulation.

Yttrium-90 (Y-90) transarterial radioembolization uses radioactive microspheres injected into the hepatic artery to irradiate liver tumors internally. One of the major challenges is the lack of reliable dosimetry methods for dose prediction and dose verification. We present a patient-specific dosimetry approach for personalized treatment planning based on computational fluid dynamics (CFD) simulations of the microsphere transport combined with Y-90 physics modeling called CFDose. The ultimate goal is the development of a software to optimize the amount of activity and injection point for optimal tumor targeting. We present the proof-of-concept of a CFD dosimetry tool based on a patient's angiogram performed in standard-of-care planning. The hepatic arterial tree of the patient was segmented from the cone-beam CT (CBCT) to predict the microsphere transport using multiscale CFD modeling. To calculate the dose distribution, the predicted microsphere distribution was convolved with a Y-90 dose point kernel. Vessels as small as 0.45mm were segmented, themicrosphere distribution between the liver segments using flow analysis was predicted,the volumetric microsphere and resulting dose distribution in the liver volume were computed. The patient was imaged with positron emission tomography (PET) 2h after radioembolization to evaluate the Y-90 distribution. The dose distribution was found to be consistent with the Y-90 PET images. These results demonstrate the feasibility of developing a complete framework for personalized Y-90 microsphere simulation and dosimetry using patient-specific input parameters.

Diagnosis of Congestive Heart Failure from HRV signal using SVM classifier and Patient Specific cross validation

Congestive heart failure (CHF) is popularly known fatal cardiac disease that occurs when pumping action of heart is lower than normal case. The purpose of this study is to the accurate diagnosis of CHF by improving classifier performance with effective features extraction and cross validation approach. The identification of significant features in electrocardiogram is highly important to detect congestive heart failure. Therefore ,this paper introduces a classifier based automated detection scheme with a novel approach of feature extraction from Heart rate Variability (HRV) signal for early prediction of CHF. The dynamical characteristics of HRV signal is analysed by computation of Largest Lyapunov Exponent. The statistical features are also evaluated to capture crucial variation in HRV signal to distinguish the abnormal and normal heart condition. The extracted features are subjected to Support Vector machine (SVM) classifier for automated discrimination of CHF from normal ECG signal. Experimental results evaluate the performance of extracted features and estimate the accuracy of the classification using the 10 fold cross validation and patient specific cross validation approach. Our experiment is validated by ECG data of normal and CHF subjects from Physionet database. The proposed system is efficient to the detect CHF with an average accuracy of 98.75%,, sensitivity 98.38%, values and 98.94%. Based on comparative study with the existing scientific research work to diagnose CHF, our proposed approach is found to be reliable and efficient for CHF diagnosis

Mantle Zone Cell Lymphomas. New Opportunities for Diagnosis and Treatment (Epidemiological Research)

Introduction. Mantle cell lymphoma is a rare type of B-cell non-Hodgkin lymphoma. According to statistics the incidence of this disorder amounts to 2-3 per 100,000 people; this is about 6% of all non-Hodgkin lymphomas. It has been established that various molecular genetic characteristics of mantle cell lymphoma patients may present opportunities for a patient-specific approach to the disease prognosis and treatment strategy.Materials and methods. The paper presents a retrospective analysis of 45 mantle cell lymphoma patients treated at the GAUZ RKOD of the Ministry of Healthcare from 2015 until now. The data used in the analysis included clinical examination, lab panels, PET CT, tumour and bone marrow biopsy specimen cytology, histology and immunohistochemistry. We analysed the epidemiological data, the patients’ clinical presentation characteristics, treatment approaches, immediate and long-term outcomes.Results and discussion. We have established that the pathological process most frequently involves bone marrow (44%) and spleen (41%). The MIPI scores distribution was as follows: high in 14 (30%), medium in 20 (45%), low in 11 (41%). Ki67 was recorded at under 30% in four cases, in others it amounted to over 30%. In 2015–2017 patients were treated with the R-CHOP protocol with the following support with rituximab. PFS averaged at 20 months, 8 (17%) of patients remain in lasting remission (since 2015). In 2017 the R-BAC (high dose cytarabine for SCT candidates) and R-B (for the elderly and comorbid patients) became protocols of first line. Since 2018 eight patients have undergone auto-SCT (at the first late recurrence) as a treatment consolidation stage. As of now 13 patients have been examined in federal centres for del17p and the TP53 mutation.Conclusion. We have demonstrated the need for and the option of treatment depending on the results of molecular genetic testing of mantle cell lymphomas.

A Proposal for Determining a Diagnostic Cutoff Value of a New Ultrasonographic Index of Retronychia Inversely Correlating with Disease Severity.

Ultrasonography has demonstrated a shortening of the distance between the origin of the nail plate and the base of the distal phalanx in retronychia. The aim of this study was to analyze the clinical and ultrasonographic features of retronychia. We evaluated the clinical findings in 18 patients with retronychia, along with the ratio of ultrasonographic distance a, extending between the nail plate origin and the base of the distal phalanx, to distance b, perpendicular to distance a, extending between the nail plate origin and the upper margin of the distal phalanx. Retronychia was present in 26 nails. The mean ± SD distance a was 7.66 ± 1.64 mm and distance b was 3.56 ± 1.95 mm. The mean ± SD a/b ratio was 2.59 ± 1.11. There was a significant inverse correlation between a/b ratio and clinical severity (Pearson correlation = -0.668; P < .001). The cutoff value of this ratio was 3.319, with specificity of 90% and sensitivity of 69%. The ratio of distance a/distance b and the cutoff value of this ratio may help in making the diagnosis, in objectively determining the disease severity, and in selecting a patient-specific treatment approach.

Simulated perfusion MRI data to boost training of convolutional neural networks for lesion fate prediction in acute stroke

The problem of final tissue outcome prediction of acute ischemic stroke is assessed from physically realistic simulated perfusion magnetic resonance images. Different types of simulations with a focus on the arterial input function are discussed. These simulated perfusion magnetic resonance images are fed to convolutional neural network to predict real patients. Performances close to the state-of-the-art performances are obtained with a patient specific approach. This approach consists in training a model only from simulated images tuned to the arterial input function of a tested real patient. This demonstrates the added value of physically realistic simulated images to predict the final infarct from perfusion.

The face of remission induction.

Acute myeloid leukaemia (AML) is a heterogeneous disease in which prognosis is determined by cytogenetic and molecular aberrations as well as patient-related factors, including age, prior haematologic disorders, and comorbidities. Despite the diverse disease biology, the standard of care for remission induction therapy has changed very little since its inception in 1973. Next generation sequencing has helped to increase our knowledge of the disease pathogenesis, allowing us to develop targeted and possibly more effective treatment options. Seven new agents have been approved for the treatment of AML since 2017, all of which are directed toward a specific molecular subtype or patient population. With the advent of these therapies, a more optimal, patient-specific approach rather than the historical 'one-size fits all' model can be utilised. This review will discuss the role of these novel therapies in the remission induction setting.

Fracture risk assessment in metastatic femurs: a patient-specific CT-based finite-element approach

Present paper aims to contribute to the definition of an effective strategy for the quantification of fracture risk in metastatic femurs, by means of a finite-element (FE) computational approach based on a refined constitutive description of the bone tissue. Healthy bone and metastatic tissue are described by a linearly poroelastic approach, by accounting for the specific degradation of material properties in the metastatic regions as related to the computed tomography (CT) evidence. The bone-metastasis interaction is also modelled through a Gaussian-shaped graded transition of material properties for the bone around the metastasis. Fracture risk indications are furnished by defining a strain-based local index and by referring to local patterns of strain energy density. Proposed computational strategy is applied to a clinical case related to a patient with both femurs affected by multiple metastases. Subject-specific FE 3D models of right and left femurs are generated from CT images and their mechanical responses are simulated by addressing a functional compressive load. Comparisons with a standard linearly elastic formulation (EL), that simply models the metastases as a pseudo-healthy tissue with low levels of material density and stiffness, are performed. Proposed results highlight that the adopted refined constitutive description identifies higher fracture risk levels with respect to the EL formulation, resulting also in very different patterns of bone regions prone to failure. In the limit of a suitable calibration based on significant experimental evidence, the proposed strategy may improve the strength prediction in metastatic femurs, allowing for an effective assessment of fracture risk useful in clinical practice.

Automatic Segmentation of the Subthalamic Nucleus: A Viable Option to Support Planning and Visualization of Patient-Specific Targeting in Deep Brain Stimulation.

Automatic segmentation is gaining relevancy in image-based targeting of neural structures. To evaluate its feasibility, we retrospectively analyzed the concordance of magnetic resonance imaging (MRI)-based automatic segmentation of the subthalamic nucleus (STN) and intraoperative microelectrode recordings (MERs). Electrodes (n=60) for deep brain stimulation were implanted in the STN of patients (n=30; median age 57 yr) with Parkinson disease (n=29) or rapid-onset dystonia parkinsonism (n=1). Elements (Brainlab, Munich, Germany) were used to segment the STN, using 2 volumetric T1 (±contrast) and volumetric T2 images as input. The stereotactic computed tomography was coregistered with the imaging, and the original stereotactic coordinates were imported. MERs (0.5-1 mm steps) along the anterior, central, and lateral trajectories were used to determine differences between the image-segmented STN boundary and MER-based STN entry and exit. Of 175 trajectories, 105 penetrated or touched (≤0.7 mm) the STN. The overall median deviation between the segmented STN boundary and electrophysiological recordings was 1.1 mm for MER-based STN entry and 2.0 mm for STN exit. Regarding the entry point of the STN, there was no statistically significant difference between MRI-based automatic segmentation and the electrophysiological trajectories analyzed with intraoperative MER. The exit point was significantly different between both methods in the central and lateral trajectories. MRI-based automatic segmentation of the STN is a viable, patient-specific targeting approach that can be used alongside traditional targeting methods in deep brain stimulation to support preoperative planning and visualization of target structures and aid postoperative optimization of programming.

Cardiovascular interventions planning through a three-dimensional printing patient-specific approach: Erratum.

Cardiovascular interventions planning through a three-dimensional printing patient-specific approach: Erratum.

The Lung Physiome and virtual patient models: From morphometry to clinical translation

The understanding or prediction of specific functions of the lung can be made using compact models that have identifiable parameters and that are custom designed to the problem of interest. However, when structure contributes to function-as is the case with most lung pathologies-structure-based, biophysical models become essential. Here we describe the application of structure-based models within the lung Physiome framework to identifying and explaining patient risk in 12patients diagnosed with acute pulmonary embolism. The model integrates perfusion, ventilation, and gas exchange to predict arterial blood gases and pulmonary artery pressure in individual patient models in response to patient-specific blood clot distribution, with full or partial arterial occlusion. The necessity for a patient-specific approach with biophysical models that account for scale-specific structure and function is demonstrated.

Biological rationale for a patient-specific approach in the treatment of breast cancer. Clinical value of novel biomarkers of breast cancer

Breast cancer, being the most common type of malignant diseases, remains a significant challenge for both clinicians and fundamental researchers. The implementation of screening mammography, as well as adjuvant and neoadjuvant systemic therapy has made a significant progress in tackling the disease. The studies aimed at the assessment of novel biomarkers of breast cancer, alternative to standard ones, are becoming increasingly relevant. A number of new markers, such as p53, CK5/6, SMA, p63, PHH3, E-cadherin, EGFR, FOXA1, androgen receptors, TILs etc., have demonstrated their high predictive and/or prognostic value in multiple studies. New findings suggest that evaluation of novel biomarkers in breast cancer requires further thorough analysis.Recent studies have identified the role of biomarkers in choosing an optimal treatment strategy for breast cancer, estimated the prognostic value of biomarkers associated with tumor proliferative activity (including cyclin D1, G1-cyclin-dependent kinases 4 and 6, and cyclin-dependent kinases 8/19), specified the role of phospho-histone H3 (which is a proliferation marker that can be used to determine tumor grade), and evaluated the prognostic value of androgen receptors and other biomarkers. Multiple studies have also analyzed the expression of various biomarkers and their impact on overall and relapse-free survival.

An augmented patient-specific approach to administration of contrast agent for CT renal angiography.

ABSTRACTPurpose This hybrid retrospective and prospective study performed on 200 consecutive patients undergoing renal CTA, investigates the opacification of renal vasculature, radiation dose, and reader confidence.Materials and Methods 100 patients were assigned retrospectively to protocol A and the other 100 were allocated prospectively to protocol B. Both protocols implemented a contrast material and saline flow rate of 4.5 mL/sec. Protocol A utilized a 100 mL of low-osmolar nonionic IV contrast material (Ioversol 350 mg I/mL) while protocol B employed a patient-tailored contrast media formula using iso-osmolar non-ionic (Iodixanol 320 mg I/mL).Results Arterial opacification in the abdominal aorta and in the bilateral main proximal renal arteries demonstrated no statistical significance (p>0.05). Only the main distal renal artery of the left kidney in protocol B was statistically significant (p<0.046). In the venous circulation, the IVC demonstrated a significant reduction in opacification in protocol B (59.39 HU ± 19.39) compared to A (87.74 HU ± 34.06) (p<0.001). Mean CNR for protocol A (22.68 HU ± 13.72) was significantly higher than that of protocol B (14.75 HU ± 5.76 p< 0.0001). Effective dose was significantly reduced in protocol B (2.46 ± 0.74 mSv) compared to A (3.07 ± 0.68 mSv) (p<0.001). Mean contrast media volume was reduced in protocol B (44.56 ± 14.32 mL) with lower iodine concentration. ROC analysis demonstrated significantly higher area under the ROC curve for protocol B (p< 0.0001), with inter-reader agreement increasing from moderate to excellent in renal arterial visualization.Conclusion Employing a patient-tailored contrast media injection protocol shows a significant refinement in the visualization of renal vasculature and reader confidence during renal CTA.

Cardiovascular interventions planning through a three-dimensional printing patient-specific approach

: In recent years, three-dimensional modelling and printing techniques have improved diagnosis and preprocedural planning during percutaneous interventions or surgery in cardiovascular disease. The raw data for the whole process are obtained through medical imaging, where regions of interest, that is heart chambers, valves, aorta, coronary vessels etc., are segmented and converted into three-dimensional digital models, which are then reproduced in physical replica by a three-dimensional printer. In the current article, a freeware patient-specific three-dimensional modelling and printing step-by-step procedure for preprocedural planning for complex heart diseases is presented and applied on four patients. Finally, a general discussion on the potential and future developments of personalized three-dimensional modelling and rapid prototyping for preprocedural planning is also presented.