Patient-specific Treatment Plans Research Articles

Efficacy of Targeted Therapies in the Management of Head-and-Neck Cancers: A Focus on Genetic Mutations and Patient Outcomes

ABSTRACT Background: Head-and-neck cancers (HNCs) present a significant global health challenge, often associated with high morbidity and mortality. Traditional treatment modalities, including surgery, radiation, and chemotherapy, have limitations in efficacy and adverse effects. Recent advances in targeted therapies, particularly those addressing specific genetic mutations, offer promising alternatives. This study evaluates the efficacy of targeted therapies in managing HNCs, focusing on genetic mutations and patient outcomes. Materials and Methods: A retrospective analysis was conducted on 150 patients diagnosed with HNCs between 2018 and 2023. Patients were stratified based on genetic mutation profiles (e.g., epidermal growth factor receptor [EGFR], PIK3CA, and TP53) identified through next-generation sequencing. Two groups were compared: Group A (n = 75) received targeted therapies tailored to their genetic mutations, whereas Group B (n = 75) received standard chemotherapy. Patient outcomes, including progression-free survival (PFS), overall survival (OS), and quality of life (QoL), were evaluated over a 24-month follow-up period. Results: Group A exhibited significantly improved outcomes compared to Group B. The median PFS was 18 months for Group A versus 12 months for Group B (P < 0.05). The median OS was 24 months for Group A, compared to 16 months for Group B (P < 0.05). In addition, patients in Group A reported better QoL scores, with a 30% reduction in severe adverse effects compared to Group B (P < 0.01). Targeted therapies demonstrated particular efficacy in patients with EGFR and PIK3CA mutations. Conclusion: Targeted therapies offer a substantial improvement in managing HNCs, particularly in patients with specific genetic mutations. These therapies not only enhance survival outcomes but also improve the QoL by reducing adverse effects. Future research should focus on expanding the genetic profiling of HNCs to identify additional therapeutic targets and optimize patient-specific treatment plans.

Safety and therapeutic effects of personalized transcranial direct current stimulation based on electrical field simulation for prolonged disorders of consciousness: study protocol for a multi-center, double-blind, randomized controlled trial.

Disorders of consciousness (DOC) resulting from acquired brain injury (ABI) increase the mortality rate of patients, complicate rehabilitation, and increase the physical and economic burden that DOC imposes on patients and their families. Thus, treatment to promote early awakening from DOC is vital. Transcranial direct current stimulation (tDCS) has shown great potential for promoting neuro-electrochemical activity. However, previous tDCS studies did not consider structural damage or head and brain lesions, so the applicability of the results to all DOC patients was limited. In this study, to establish a patient-specific tDCS treatment plan considering the brain lesions of and damage sustained by DOC patients, we considered the electric field calculated by a the "finite electric" three-dimensional brain model based on magnetic resonance images. This protocol was developed to aid tDCS treatment of actual patients, and to verify its safety and effectiveness. Twenty-four patients with DOC after ABI will be enrolled in this cross-over trial. All participants will receive typical rehabilitation combined with sham tDCS and typical rehabilitation plus personalized tDCS (P-tDCS). Each interventional period will last 2 weeks (30 min/day, 5 days/week). The primary outcome [score on the Korean version of the Coma Recovery Scale-Revised (K-CRS-R)] will be assessed at baseline and the end of the first day of the intervention. Secondary outcomes (K-CRS-R at 1 week and 2 weeks after experimental session and quantitative EEG changes quantitative electroencephalography changes) will be measured at baseline and the end of week 4. Adverse events will be recorded during each treatment session. For patients with neurological disorders, tDCS has served as a painless, non-invasive, easily applied, and effective therapy for several decades, and there is some evidence that it can improve the level of consciousness of patients with DOC. However, variability in the effects on consciousness among subjects have been reported and personalized strategies are lacking. This protocol is for a randomized controlled trial designed to validate the effectiveness and safety of P-tDCS combined with typical rehabilitation for DOC. https://cris.nih.go.kr, identifier KCT0007157.

Elevating Aesthetics: Patient-Specific Treatment with Hyaluronic Acid Fillers to Improve Appearance and Psychosocial Wellbeing

Perception of beauty is changing from a rigid concept (i.e., the universal idea of beauty) to a multifaceted and personalised view of one’s appearance. One of the main concerns of patients is looking artificial and losing their unique facial expressions, which encourages them to seek aesthetic procedures that yield the most natural results. Patients also wish to increase their self-esteem and, ultimately, improve their quality of life. It is now well-established that treatment with hyaluronic acid (HA)-based dermal fillers improves the psychosocial state of patients. The assessment of facial anatomy and patient needs, accompanied by the proven holistic benefit and good safety profile of HA dermal filler treatment, is also a key factor for an optimal outcome. In addition, clear communication between patient and physician is crucial to manage patient expectations, maximise satisfaction, and minimise procedural risks. The availability of a wide range of HA dermal fillers, customised for specific anatomical areas and facial movements, allows physicians to develop patient-specific treatment plans. This review of the ‘Elevating Aesthetics’ symposium held at the International Master Course on Aging Science (IMCAS) 2023 shares insights into the patient’s facial anatomy and possible danger zones presented during a cadaver workshop. Several successful treatment plans tailored to different patient profiles (i.e., patients seeking full-face aesthetic improvement, patients with facial asymmetry, low lip volume in mature and millennial women) were also implemented live. A comprehensive and patient-specific HA dermal filling treatment should be considered by physicians to achieve natural outcomes and improve the general wellbeing of the patient.

A FRAMEWORK FOR THE ANALYSIS OF COMORBID CONDITIONS USING INTELLIGENT EXTRACTION OF MULTIPLE FLUID BIOMARKERS

Fluid biomarkers extracted from many types of body fluids provide significant information that serve as indicators of the underlying physiological and pathological conditions of the human body. Analysis of multiple fluid biomarkers could help improve the early identification and progression of comorbid conditions to enhance the diagnostic accuracy, which can help in developing patient-specific treatment plans. In this work, an attempt has been made to differentiate the co-occurrence of diabetes, hypertension and cardiovascular disease (comorbid conditions) from non-comorbid using multiple fluid biomarkers. Fluid biomarkers are obtained from a public dataset under comorbid ([Formula: see text]) and non-comorbid ([Formula: see text]) conditions. Five features, such as serum creatinine, serum sodium, platelet count, creatine phosphokinase and ejection fraction, are extracted for further analysis. Machine learning algorithms namely, [Formula: see text]-nearest neighbor and linear discriminant analysis (LDA) are used to classify comorbid and non-comorbid conditions. The results show an increase in platelet count in comorbid subjects. This feature also exhibits significant difference ([Formula: see text]) between both the conditions. This study also uses the random undersampling technique to reduce bias associated with data imbalance. LDA classifier yields a maximum accuracy of 54.30% in classifying these two conditions. Further study can be carried out to improve the accuracy and might be helpful in clinical practice for prediction of comorbid conditions.

Assessing the Risk of Postoperative Complications for Proximal Humeral Fractures Treated by Open Reduction and Internal Fixation in Patients With Diabetes and Chronic Kidney Disease

The prevalence of diabetes mellitus (DM) and chronic kidney disease (CKD) has markedly risen over the past three decades. Patients with DM and CKD are at increased risk of infection, immune dysfunction, as well as bone and mineral disorders. Although we know that patients with DM and CKD have these risks, we do not know how these translate to proximal humeral fracture (PHF) healing. We sought to analyze whether these established comorbidities had increased rates of complications after open reduction and internal fixation (ORIF) for PHF treatment. Using a national insurance database, 72,365 patients with PHF managed with ORIF were identified using records from 2010 to 2022. Patients were initially split into those with DM and those without and were further stratified by the presence or absence of CKD. For our comparison baseline cohort, patients were not diagnosed with either DM or CKD. Post-ORIF complication rates were assessed looking specifically at nonunion, postoperative infection, and all-cause revision surgery. A logistic regression statistical analysis was also conducted. Of the 72,365 patients with PHF treated by ORIF, 41,047 were non-DM without CKD (comparison); 17,025 had DM alone (no CKD); 11,729 had DM and CKD; and 2564 had CKD alone (non-DM). Multivariate analysis indicated that patients with DM and/or CKD were at increased risk of developing nonunion (odds ratio [OR] = 1.37, 1.48, 1.23) and all-cause revision surgery (OR = 1.21, 1.11, 1.18) after ORIF for PHF compared with our comparison cohort. In addition, all patients with DM alone (non-CKD) and DM with CKD had an increased risk of postoperative infection (OR = 1.39, 1.26). The management of PHF is a controversial topic, particularly regarding the degree of intervention and optimal treatment choice. Regardless, using a pragmatic design and reviewing a national insurance database, this study provides information for patients in high-risk populations, specifically patients with DM and CKD, and may prove beneficial when selecting a patient-specific treatment plan. Additional studies are needed to assess varying stages of both DM and CKD in patients who sustain PHF treated by ORIF along with postoperative strategies to minimize complications.

Longitudinal deep network for consistent OCT layer segmentation.

Retinal layer thickness is an important bio-marker for people with multiple sclerosis (PwMS). In clinical practice, retinal layer thickness changes in optical coherence tomography (OCT) are widely used for monitoring multiple sclerosis (MS) progression. Recent developments in automated retinal layer segmentation algorithms allow cohort-level retina thinning to be observed in a large study of PwMS. However, variability in these results make it difficult to identify patient-level trends; this prevents patient specific disease monitoring and treatment planning using OCT. Deep learning based retinal layer segmentation algorithms have achieved state-of-the-art accuracy, but the segmentation is performed on each individual scan without utilizing longitudinal information, which can be important in reducing segmentation error and reveal subtle changes in retinal layers. In this paper, we propose a longitudinal OCT segmentation network which achieves more accurate and consistent layer thickness measurements for PwMS.

Nondestructive Evaluation of Mechanical and Histological Properties of the Human Aorta With Near-Infrared Spectroscopy

IntroductionAscending aortic dilatation is a well-known risk factor for aortic rupture. Indications for aortic replacement in its dilatation concomitant to other open-heart surgery exist; however, cut-off values based solely on aortic diameter may fail to identify patients with weakened aortic tissue. We introduce near-infrared spectroscopy (NIRS) as a diagnostic tool to nondestructively evaluate the structural and compositional properties of the human ascending aorta during open-heart surgeries. During open-heart surgery, NIRS could provide information regarding tissue viability in situ and thus contribute to the decision of optimal surgical repair. Materials and methodsSamples were collected from patients with ascending aortic aneurysm (n = 23) undergoing elective aortic reconstruction surgery and from healthy subjects (n = 4). The samples were subjected to spectroscopic measurements, biomechanical testing, and histological analysis. The relationship between the near-infrared spectra and biomechanical and histological properties was investigated by adapting partial least squares regression. ResultsModerate prediction performance was achieved with biomechanical properties (r = 0.681, normalized root-mean-square error of cross-validation = 17.9%) and histological properties (r = 0.602, normalized root-mean-square error of cross-validation = 22.2%). Especially the performance with parameters describing the aorta's ultimate strength, for example, failure strain (r = 0.658), and elasticity (phase difference, r = 0.875) were promising and could, therefore, provide quantitative information on the rupture sensitivity of the aorta. For the estimation of histological properties, the results with α-smooth muscle actin (r = 0.581), elastin density (r = 0.973), mucoid extracellular matrix accumulation(r = 0.708), and media thickness (r = 0.866) were promising. ConclusionsNIRS could be a potential technique for in situ evaluation of biomechanical and histological properties of human aorta and therefore useful in patient-specific treatment planning.

Radiographic Parameters of Adult Hip Dysplasia.

As knowledge about the origin and morphologic characteristics of hip pain in the young adult has evolved, so too has the clinician's ability to assess for various pathologies of the hip on radiographs, magnetic resonance imaging (MRI)/magnetic resonance arthrography (MRA), and computed tomography (CT). Because there is no algorithm at this time directly indicating what to do in more subtle hip morphologies, such as microinstability and borderline hip dysplasia (BHD), a skilled hip preservation specialist must use multiple imaging sources and know how to interpret them correctly. Imaging parameters used in the workup for hip dysplasia and BHD include the lateral center-edge angle, Tönnis angle, iliofemoral line, and presence of an upsloping lateral sourcil or everted labrum, among many others. The purpose of this narrative review was to detail various established criteria and parameters on anteroposterior pelvis plain radiographs, MRI/MRA, and CT that assist in defining the nature and severity of instability present in a dysplastic hip, thereby aiding in the development of patient-specific surgical treatment plans.

A Review of Conventional and Novel Treatments for Osteoporotic Hip Replacements

Osteoporosis is a skeletal disease that severely affects the mechanical properties of bone. It increases the porosity of cancellous bone and reduces the resistance to fractures. It has been reported in 2009 that there are approximately 500 million osteoporotic patients worldwide. Patients who suffer fractures due to fragility cost the National Healthcare Systems in the United Kingdom £4.4 billion in 2018, in Europe €56 billion in 2019, and in the United States $57 billion in 2018. Thus, osteoporosis is problematic for both patients and healthcare systems. This review is conducted for the purpose of presenting and discussing all articles introducing or investigating treatment solutions for osteoporotic patients undergoing total hip replacement. Searches were implemented using three databases, namely Scopus, PubMed, and Web of Science to extract all relevant articles. Predetermined eligibility criteria were used to exclude articles out of the scope of the study. 29 articles out of 183 articles were included in this review. These articles were organised into three sections: (i) biomechanical properties and structure of osteoporotic bones, (ii) hip implant optimisations, and (iii) drug, cells, and bio-activators delivery through hydrogels. The findings of this review suggest that diagnostic tools and measurements are crucial for understanding the characteristics of osteoporosis in general and for setting patient-specific treatment plans. It was also found that attempts to overcome complications associated with osteoporosis included design optimisation of the hip implant; however, only short-term success was reported, while the long-term stability of implants was compromised by the progressive nature of osteoporosis. Finally, it was also found that targeting implantation sites with cells, drugs, and growth factors has been outworked using hydrogels, where promising results have been reported regarding enhanced osteointegration and inhibited bacterial and osteoclastic activities. These results may encourage investigations that explore the effects of these impregnated hydrogels on osteoporotic bones beyond metallic scaffolds and implants.

Integration of Cutaneous Functional Units Principles in Burn Rehabilitation: A Diffusion of Innovations Assessment.

Early recognition of contractures can lead to a more targeted therapy regimen, potentially preventing range of motion losses and improving function and quality of life. Cutaneous functional units (CFUs) allow therapists to explain motion limitations and formulate patient-specific treatment plans. Evidence-based research demonstrates the potential of using these principles to improve the current standard of care. Still, the consistent use of these principles has been slow to diffuse through burn care. Occupational and physical therapists were surveyed to determine the degree to which CFU principles are being integrated into clinical practice. Respondents (297) were occupational therapists (52%) and physical therapists (49%) working in burn units (81%) in North America (70.7%). Most respondents (78.4%) report familiarity with CFU principles. Of those familiar, most respondents reported their knowledge (66.7%) and ability to apply (65.7%) at an intermediate level or greater. A slight majority (59.3%) responded that the concepts influenced their practice, while 40.7% said the concepts did not influence their practice. Forty percent to sixty-nine percent of respondents correctly answered knowledge questions, but only 15% of respondents correctly completed CFUs identification questions. Respondents (77%) report barriers, including difficulty incorporating into practice, time constraints, and the need for more education. Results suggest that diffusion can be improved by developing tools to assist therapists in understanding and incorporating CFUs' principles.

A quasi-static biomechanical model of the human myocardium based on Cardiac Magnetic Resonance images

The left ventricle (LV) has an important mechanical part in pumping blood throughout the body and it is generally sensitive to the failure. Heart failure is one of the world's leading causes of death and has reached the epidemic rate. For the study of heart failure, there are several diagnostic methods, but computational biomechanical models of human myocardium would be a practical tool in diagnostics and patient specific treatment planning. These models help in classifying myocardium pathologies. In this paper, we developed a quasi-static biomechanical model of the LV for healthy subjects based on Cardiac Magnetic Resonance (CMR) acquisition. Estimation LV strain is done using Finite Element (FE) software Abaqus and clinical assessment measured from 20 healthy subjects, such as End Systole (ES) and End Diastole (ED) volumes, ED wall thickness and wall thickening. We acquired LV End Systole strain component is within one standard deviation of the measurements made in the equatorial region of LV. The results of this study suggest that the proposed FE model of LV describes the physiological function of the heart and can differentiate between normal and pathological cardiac function.

A phase-field model for non-small cell lung cancer under the effects of immunotherapy.

Formulating mathematical models that estimate tumor growth under therapy is vital for improving patient-specific treatment plans. In this context, we present our recent work on simulating non-small-scale cell lung cancer (NSCLC) in a simple, deterministic setting for two different patients receiving an immunotherapeutic treatment. At its core, our model consists of a Cahn-Hilliard-based phase-field model describing the evolution of proliferative and necrotic tumor cells. These are coupled to a simplified nutrient model that drives the growth of the proliferative cells and their decay into necrotic cells. The applied immunotherapy decreases the proliferative cell concentration. Here, we model the immunotherapeutic agent concentration in the entire lung over time by an ordinary differential equation (ODE). Finally, reaction terms provide a coupling between all these equations. By assuming spherical, symmetric tumor growth and constant nutrient inflow, we simplify this full 3D cancer simulation model to a reduced 1D model. We can then resort to patient data gathered from computed tomography (CT) scans over several years to calibrate our model. Our model covers the case in which the immunotherapy is successful and limits the tumor size, as well as the case predicting a sudden relapse, leading to exponential tumor growth. Finally, we move from the reduced model back to the full 3D cancer simulation in the lung tissue. Thereby, we demonstrate the predictive benefits that a more detailed patient-specific simulation including spatial information as a possible generalization within our framework could yield in the future.

Deep Learning-Based Segmentation of Head and Neck Organs-at-Risk with Clinical Partially Labeled Data.

Radiotherapy is one of the main treatments for localized head and neck (HN) cancer. To design a personalized treatment with reduced radio-induced toxicity, accurate delineation of organs at risk (OAR) is a crucial step. Manual delineation is time- and labor-consuming, as well as observer-dependent. Deep learning (DL) based segmentation has proven to overcome some of these limitations, but requires large databases of homogeneously contoured image sets for robust training. However, these are not easily obtained from the standard clinical protocols as the OARs delineated may vary depending on the patient's tumor site and specific treatment plan. This results in incomplete or partially labeled data. This paper presents a solution to train a robust DL-based automated segmentation tool exploiting a clinical partially labeled dataset. We propose a two-step workflow for OAR segmentation: first, we developed longitudinal OAR-specific 3D segmentation models for pseudo-contour generation, completing the missing contours for some patients; with all OAR available, we trained a multi-class 3D convolutional neural network (nnU-Net) for final OAR segmentation. Results obtained in 44 independent datasets showed superior performance of the proposed methodology for the segmentation of fifteen OARs, with an average Dice score coefficient and surface Dice similarity coefficient of 80.59% and 88.74%. We demonstrated that the model can be straightforwardly integrated into the clinical workflow for standard and adaptive radiotherapy.

Three-dimensional maxillary virtual patient creation by convolutional neural network-based segmentation on cone-beam computed tomography images

ObjectiveTo qualitatively and quantitatively assess integrated segmentation of three convolutional neural network (CNN) models for the creation of a maxillary virtual patient (MVP) from cone-beam computed tomography (CBCT) images.Materials and methodsA dataset of 40 CBCT scans acquired with different scanning parameters was selected. Three previously validated individual CNN models were integrated to achieve a combined segmentation of maxillary complex, maxillary sinuses, and upper dentition. Two experts performed a qualitative assessment, scoring-integrated segmentations from 0 to 10 based on the number of required refinements. Furthermore, experts executed refinements, allowing performance comparison between integrated automated segmentation (AS) and refined segmentation (RS) models. Inter-observer consistency of the refinements and the time needed to create a full-resolution automatic segmentation were calculated.ResultsFrom the dataset, 85% scored 7–10, and 15% were within 3–6. The average time required for automated segmentation was 1.7 min. Performance metrics indicated an excellent overlap between automatic and refined segmentation with a dice similarity coefficient (DSC) of 99.3%. High inter-observer consistency of refinements was observed, with a 95% Hausdorff distance (HD) of 0.045 mm.ConclusionThe integrated CNN models proved to be fast, accurate, and consistent along with a strong interobserver consistency in creating the MVP.Clinical relevanceThe automated segmentation of these structures simultaneously could act as a valuable tool in clinical orthodontics, implant rehabilitation, and any oral or maxillofacial surgical procedures, where visualization of MVP and its relationship with surrounding structures is a necessity for reaching an accurate diagnosis and patient-specific treatment planning.

Treatment of Pediatric Femoral Shaft Fractures.

Diaphyseal femur fractures are common in pediatric orthopaedic settings. A patient-specific treatment plan incorporates several factors, including age, weight, fracture pattern, associated injuries, and social considerations. Nonaccidental trauma should be considered in children younger than 3 years. In general, young children are treated with noninvasive immobilization (Pavlik harness or early hip spica casting) while school-aged children are treated with internal fixation. Internal fixation options include flexible intramedullary nails, rigid locked intramedullary nails, and plate osteosynthesis. Flexible intramedullary nails have the best outcomes in children of appropriate weight, aged 5 to 11 years, with stable fracture patterns. Lateral-entry rigid intramedullary nails have been designed for use in older children. External fixation is usually reserved for complex scenarios. Regarding all treatment methods, surgeons should be aware of several technical factors necessary to optimize outcomes.

Individualization of Radionuclide Therapies: Challenges and Prospects.

Simple SummaryCurrently, patient-specific treatment plans and dosimetry calculations are not routinely performed for radionuclide therapies. In external beam radiotherapy, it is quite the opposite. As a result, a small fraction of patients receives optimal radioactivity. This conservative approach provides “radiation safety” to healthy tissues but delivers a lower than indicated absorbed dose to the tumors, resulting in a lower response rate and a higher disease relapse rate. Evidence shows that better and more predictable outcomes can be achieved with patient-individualized dose assessment. Therefore, the incorporation of individual planning into radionuclide therapies is a high priority for nuclear medicine physicians and medical physicists alike. Internal dosimetry is used in tumor therapy to optimize the absorbed dose to the target tissue. The main reasons for the difficulties in incorporating patients’ internal dosimetry into routine clinical practice are discussed. The article presents the prospects for the routine implementation of personalized radionuclide therapies.The article presents the problems of clinical implementation of personalized radioisotope therapy. The use of radioactive drugs in the treatment of malignant and benign diseases is rapidly expanding. Currently, in the majority of nuclear medicine departments worldwide, patients receive standard activities of therapeutic radiopharmaceuticals. Intensively conducted clinical trials constantly provide more evidence of a close relationship between the dose of radiopharmaceutical absorbed in pathological tissues and the therapeutic effect of radioisotope therapy. Due to the lack of individual internal dosimetry (based on the quantitative analysis of a series of diagnostic images) before or during the treatment, only a small fraction of patients receives optimal radioactivity. The vast majority of patients receive too-low doses of ionizing radiation to the target tissues. This conservative approach provides “radiation safety” to healthy tissues, but also delivers lower radiopharmaceutical activity to the neoplastic tissue, resulting in a low level of response and a higher relapse rate. The article presents information on the currently used radionuclides in individual radioisotope therapies and on radionuclides newly introduced to the therapeutic market. It discusses the causes of difficulties with the implementation of individualized radioisotope therapies as well as possible changes in the current clinical situation.

Development of an abdominal phantom for the validation of an oligometastatic disease diagnosis workflow.

The liver is a common site for metastatic disease, which is a challenging and life-threatening condition with a grim prognosis and outcome. We propose a standardized workflow for the diagnosis of oligometastatic disease (OMD), as a gold standard workflow has not been established yet. The envisioned workflow comprises the acquisition of a multimodal image data set, novel image processing techniques, and cone beam computed tomography (CBCT)-guided biopsy for subsequent molecular subtyping. By combining morphological, molecular, and functional information about the tumor, a patient-specific treatment planning is possible. We designed and manufactured an abdominal liver phantom that we used to demonstrate multimodal image acquisition, image processing, and biopsy of the OMD diagnosisworkflow. The anthropomorphic abdominal phantom contains a rib cage, a portal vein, lungs, a liver with six lesions, and a hepatic vessel tree. This phantom incorporates three different lesion types with varying visibility under computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography CT (PET-CT), which reflects clinical reality. The phantom is puncturable and the size of the corpus and the organs is comparable to those of a real human abdomen. By using several modern additive manufacturing techniques, the manufacturing process is reproducible and allows to incorporate patient-specific anatomies. As a first step of the OMD diagnosis workflow, a preinterventional CT, MRI, and PET-CT data set of the phantom was acquired. The image information was fused using image registration and organ information was extracted via image segmentation. A CBCT-guided needle puncture experiment was performed, where all six liver lesions were punctured with coaxial biopsy needles. Qualitative observation of the image data and quantitative evaluation using contrast-to-noise ratio (CNR) confirms that one lesion type is visible only in MRI and not CT. The other two lesion types are visible in CT and MRI. The CBCT-guided needle placement was performed for all six lesions, including those visible only in MRI and not CBCT. This was possible by successfully merging multimodal preinterventional image data. Lungs, bones, and liver vessels serve as realistic inhibitions during needle pathplanning. We have developed a reusable abdominal phantom that has been used to validate a standardized OMD diagnosis workflow. Utilizing the phantom, we have been able to show that a multimodal imaging pipeline is advantageous for a comprehensive detection of liver lesions. In a CBCT-guided needle placement experiment we have punctured lesions that are invisible in CBCT using registered preinterventional MRI scans for needle pathplanning.

Biomedical applications of three-dimensional bioprinted craniofacial tissue engineering.

Anatomical complications of the craniofacial regions often present considerable challenges to the surgical repair or replacement of the damaged tissues. Surgical repair has its own set of limitations, including scarcity of the donor tissues, immune rejection, use of immune suppressors followed by the surgery, and restriction in restoring the natural aesthetic appeal. Rapid advancement in the field of biomaterials, cell biology, and engineering has helped scientists to create cellularized skeletal muscle-like structures. However, the existing method still has limitations in building large, highly vascular tissue with clinical application. With the advance in the three-dimensional (3D) bioprinting technique, scientists and clinicians now can produce the functional implants of skeletal muscles and bones that are more patient-specific with the perfect match to the architecture of their craniofacial defects. Craniofacial tissue regeneration using 3D bioprinting can manage and eliminate the restrictions of the surgical transplant from the donor site. The concept of creating the new functional tissue, exactly mimicking the anatomical and physiological function of the damaged tissue, looks highly attractive. This is crucial to reduce the donor site morbidity and retain the esthetics. 3D bioprinting can integrate all three essential components of tissue engineering, that is, rehabilitation, reconstruction, and regeneration of the lost craniofacial tissues. Such integration essentially helps to develop the patient-specific treatment plans and damage site-driven creation of the functional implants for the craniofacial defects. This article is the bird's eye view on the latest development and application of 3D bioprinting in the regeneration of the skeletal muscle tissues and their application in restoring the functional abilities of the damaged craniofacial tissue. We also discussed current challenges in craniofacial bone vascularization and gave our view on the future direction, including establishing the interactions between tissue-engineered skeletal muscle and the peripheral nervous system.

Biomarkers as Predictive Factors of Anti-VEGF Response.

Age-related macular degeneration is the main cause of irreversible vision in developed countries, and intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections are the current gold standard treatment today. Although anti-VEGF treatment results in important improvements in the course of this disease, there is a considerable number of patients not responding to the standardized protocols. The knowledge of how a patient will respond or how frequently retreatment might be required would be vital in planning treatment schedules, saving both resource utilization and financial costs, but today, there is not an ideal biomarker to use as a predictive response to ranibizumab therapy. Whole blood and blood mononuclear cells are the samples most studied; however, few reports are available on other important biofluid samples for studying this disease, such as aqueous humor. Moreover, the great majority of studies carried out to date were focused on the search for SNPs in genes related to AMD risk factors, but miRNAs, proteomic and metabolomics studies have rarely been conducted in anti-VEGF-treated samples. Here, we propose that genomic, proteomic and/or metabolomic markers could be used not alone but in combination with other methods, such as specific clinic characteristics, to identify patients with a poor response to anti-VEGF treatment to establish patient-specific treatment plans.

In vivo assessment of corneal biomechanics under a localized cross-linking treatment using confocal air-coupled optical coherence elastography.

The localized application of the riboflavin/UV-A collagen cross-linking (UV-CXL) corneal treatment has been proposed to concentrate the stiffening process only in the compromised regions of the cornea by limiting the epithelium removal and irradiation area. However, current clinical screening devices dedicated to measuring corneal biomechanics cannot provide maps nor spatial-dependent changes of elasticity in corneas when treated locally with UV-CXL. In this study, we leverage our previously reported confocal air-coupled ultrasonic optical coherence elastography (ACUS-OCE) probe to study local changes of corneal elasticity in three cases: untreated, half-CXL-treated, and full-CXL-treated in vivo rabbit corneas (n = 8). We found a significant increase of the shear modulus in the half-treated (>450%) and full-treated (>650%) corneal regions when compared to the non-treated cases. Therefore, the ACUS-OCE technology possesses a great potential in detecting spatially-dependent mechanical properties of the cornea at multiple meridians and generating elastography maps that are clinically relevant for patient-specific treatment planning and monitoring of UV-CXL procedures.