Inadequate Tissue Research Articles

Recent advances in biomimetic aggregation‐induced emission photosensitizers for photodynamic therapy and immunotherapy

AbstractThe development of novel photosensitizers (PSs) with aggregation‐induced emission (AIE) properties has emerged as a crucial advancement in the field of photodynamic therapy (PDT). However, the versatile applications of AIE PSs are limited by low encapsulation efficiency and inadequate target tissue permeability. Biomimetic technology stands out as a promising strategy to overcome these challenges, aiming to enhance AIE PSs tumor penetration efficacy, and their association with antitumor immune responses. In this review, recent advancements in biomimetic AIE PSs for PDT and immunotherapy are summarized. We start with introducing strategies involving biomimetic AIE PSs based on cell membranes and extracellular vesicles for the combined application of PDT and immunotherapy. We then discuss the preparation of biomimetic AIE PSs nanoparticles. Finally, we briefly outline the challenges and prospects associated with biomimetic AIE PSs.

Developing Porous Fibrin Scaffolds with Tunable Anisotropic Features to Direct Myoblast Orientation.

Functional regeneration of anisotropically aligned tissues such as ligaments, microvascular networks, myocardium, or skeletal muscle requires a temporal and spatial series of biochemical and biophysical cues to direct cell functions that promote native tissue regeneration. When these cues are lost during traumatic injuries such as volumetric muscle loss (VML), scar formation occurs, limiting the regenerative capacity of the tissue. Currently, autologous tissue transfer is the gold standard for treating injuries such as VML but can result in adverse outcomes including graft failure, donor site morbidity, and excessive scarring. Tissue-engineered scaffolds composed of biomaterials, cells, or both have been investigated to promote functional tissue regeneration but are still limited by inadequate tissue ingrowth. These scaffolds should provide precisely tuned topographies and stiffnesses using proregenerative materials to encourage tissue-specific functions such as myoblast orientation, followed by aligned myotube formation and recovery of functional contraction. In this study, we describe the design and characterization of novel porous fibrin scaffolds with anisotropic microarchitectural features that recapitulate the native tissue microenvironment and offer a promising approach for regeneration of aligned tissues. We used directional freeze-casting with varied fibrin concentrations and freezing temperatures to produce scaffolds with tunable degrees of anisotropy and strut widths. Nanoindentation analyses showed that the moduli of our fibrin scaffolds varied as a function of fibrin concentration and were consistent with native skeletal muscle tissue. Quantitative morphometric analyses of myoblast cytoskeletons on scaffold microarchitectures demonstrated enhanced cell alignment as a function of microarchitectural morphology. The ability to precisely control the anisotropic features of fibrin scaffolds promises to provide a powerful tool for directing aligned tissue ingrowth and enhance functional regeneration of tissues such as skeletal muscle.

A Guide to the Use of Vasopressors and Inotropes for Patients in Shock.

Shock is a life-threatening circulatory failure that results in inadequate tissue perfusion and oxygenation. Vasopressors and inotropes are vasoactive medications that are vital in increasing systemic vascular resistance and cardiac contractility, respectively, in patients presenting with shock. To be well versed in using these agents is an important skill to have in the critical care setting where patients can frequently exhibit symptoms of shock. In this review, we will discuss the pathophysiological mechanisms of shock and evaluate the current evidence behind the management of shock with an emphasis on vasopressors and inotropes.

Bilateral adrenal neuroblastoma: peculiar pattern of a rare pediatric presentation

BackgroundBilateral suprarenal neuroblastoma (BSN) is a rare presentation. Few previously published literature showed BSN patients to have favorable pattern and prognosis. This study aim was to evaluate clinical and biological features in relation to outcome of Egyptian patients with BSN.MethodsIncluded patients were diagnosed from 2007 to 2017, retrospectively. Tissue biopsy, imaging and bone marrow were evaluated at presentation. Clinical, demographic, biological variables and risk group were determined and analyzed in relation to overall (OS) and event-free-survival (EFS).ResultsBSN patients (n = 33) represented 2% of hospital patients with neuroblastoma during the 10-year study period, 17 were males and 16 were females. Twenty-four patients (72.7%) were infants, and 9 patients (27.3%) were above 1 year of age (range: 1 month to 3 years). Metachronous disease was present in only one patient. Amplified MYCN was found in 10 patients. Initially, most patients (n = 25) had distant metastasis, 6 had stage 3 versus 2 stage 2. Fifteen were high risk (HR), 15 intermediate (IR), 1 low risk (LR) and 2 were undetermined due to inadequate tissue biopsy. Three-year OS for HR and IR patients were 40.5% and 83.9% versus 23.2% and 56.6% EFS; respectively.ConclusionBSN treatment is similar to unilateral disease. A more conservative surgical approach with adrenal tissue preservation on less extensive side should be considered. Biological variables and extent of disease are amongst the most important prognostic determinants. Future studies are warranted to further address the biologic profiling of BSN and highlight prognostic significance of size difference between both adrenal sides.

3D bioprinted aged human post-infarct myocardium tissue model.

Fibrotic tissue formed after myocardial infarction (MI) can be as detrimental as MI itself. However, current in vitro cardiac fibrosis models fail to recapitulate the complexities of post-MI tissue. Moreover, although MI and subsequent fibrosis is most prominent in the aged population, the field suffers from inadequate aged tissue models. Herein, an aged human post-MI tissue model, representing the native microenvironment weeks after initial infarction, is engineered using three-dimensional bioprinting via creation of individual bioinks to specifically mimic three distinct regions: remote, border, and scar. The aged post-MI tissue model is engineered through combination of gelatin methacryloyl, methacrylated hyaluronic acid, aged type I collagen, and photoinitiator at variable concentrations with different cell types, including aged human induced pluripotent stem cell-derived cardiomyocytes, endothelial cells, cardiac fibroblasts, and cardiac myofibroblasts, by introducing a methodology which utilizes three printheads of the bioprinter to model aged myocardium. Then, using cell-specific proteins, the cell types that comprised each region are confirmed using immunofluorescence. Next, the beating characteristics are analyzed. Finally, the engineered aged post-MI tissue model is used as a benchtop platform to assess the therapeutic effects of stem cell-derived extracellular vesicles on the scar region. As a result, high viability (>74%) was observedin each region of the printed model. Constructs demonstrated functional behavior, exhibiting a beating velocity of 6.7 μm/s and a frequency of 0.3 Hz. Finally, the effectiveness of hiPSC-EV and MSC-EV treatment was assessed. While hiPSC-EV treatment showed no significant changes, MSC-EV treatment notably increased cardiomyocyte beating velocity, frequency, and confluency, suggesting a regenerative potential. In conclusion, we envision that our approach of modeling post-MI aged myocardium utilizing three printheads of the bioprinter may be utilized for various applications in aged cardiac microenvironment modeling and testing novel therapeutics.

Echocardiography as a Vital Tool in Assessing Shock: A Comprehensive Review.

Shock is a critical condition characterized by inadequate tissue perfusion, leading to cellular hypoxia and organ dysfunction. Early and accurate assessment is crucial for timely intervention and improved patient outcomes. Echocardiography has emerged as a vital tool in the assessment of shock, offering real-time visualization of cardiac anatomy, function, and hemodynamics. This comprehensive review aims to elucidate the role of echocardiography in shock assessment by providing an overview of its principles, techniques, and clinical applications. We discuss the importance of early diagnosis, identification of underlying pathology, monitoring response to therapy, and prognostic value offered by echocardiography in managing shock. Furthermore, we explore its utility in different types of shock, including hypovolemic, cardiogenic, distributive, and obstructive shock. Challenges and limitations of echocardiography, as well as future directions and innovations, are also discussed. Through a synthesis of current evidence and clinical insights, this review underscores the significance of echocardiography in optimizing shock management and highlights areas for further research and development.

Paraspinous Muscle Flaps in Complex Pediatric Spine Surgeries: A 12-Year Single Institution Experience.

The benefits of paraspinous flaps in adult complex spine surgery patients are established in the literature; however, their use in pediatric patients has not been well described. This study compares clinical outcomes with and without paraspinous muscle flap closure in pediatric patients who have undergone spine surgery. We conducted a retrospective review of all pediatric spine surgeries at the University of California, San Francisco from 2011 to 2022. Patients were divided into 2 cohorts based on whether the plastic surgery service closed or did not close the wound with paraspinous muscle flaps. We matched patients by age, American Society of Anesthesiology classification, prior spinal surgical history, and diagnosis. Surgical outcomes were compared between the 2 cohorts. We identified 226 pediatric patients who underwent at least one spinal surgery, 14 of whom received paraspinous flap closure by plastic surgery. They were matched in a 1:4 ratio with controls (n = 56) that did not have plastic surgery closure. The most common indication for plastic surgery involvement was perceived complexity of disease by the spine surgeon with concern for inadequate healthy tissue coverage (78.6%), followed by infection (21.4%). Postoperative complications were similar between the two groups. The plastic surgery cohort had a higher rate of patients who were underweight (57.1% vs 14.3%, P < 0.01) and had positive preoperative wound cultures (28.6% vs 8.9%, P = 0.05), as well as a higher rate of postoperative antibiotic usage (78.6 vs 17.9%, P < 0.01). There was no difference in recorded postoperative outcomes. Spine surgeons requested paraspinous flap closure for patients with more complex disease, preoperative infections, history of chemotherapy, or if they were underweight. Patients with paraspinous flap coverage did not have increased postoperative complications despite their elevated risk profile. Our findings suggest that paraspinous muscle flaps should be considered in high-risk pediatric patients who undergo spine surgery.

Abstract 3511: iQC: machine-learning-driven prediction of surgery reveals systematic confounds in cancer whole slide images from hospitals by protocol

Abstract Problem: This 21st century has produced an eruption of research using AI for the detection and diagnosis of cancer. Yet, an often-unspoken core premise in this field of computational pathology is that a glass slide suitably represents the patient’s disease. Here, we report systematic confounds may dominate slides from a medical center, such that slides are unsuitable for diagnosis. Methods: We mathematically define high quality data as a whole slide image set where the patient’s surgery may be accurately predicted by an automated system. Our system “iQC” accurately distinguished biopsies (i.e. thin strands of tissue) from nonbiopsies, e.g. transurethral resections (TURPs) or prostatectomies, only when the data appeared high quality, e.g. bright histopathology stains and few artifacts. Thus, when the data are of high quality, iQC (i) accurately classifies pixels as tissue, (ii) accurately generates stats that describe the distribution of tissue, and (iii) accurately predicts surgical procedure from those stats. We compare iQC against the published HistoQC tool. Results: iQC holds all data to the same objective quality standard. We validate this standard in five Veterans Affairs Medical Centers (VAMCs) and the public Automated Gleason Grading Challenge (AGGC) dataset. For the surgery prediction task, we report an AUROC of 0.9966-1.000 at VAMCs that produced high quality data and AUROC=0.9824 for AGGC. In contrast, we report AUROC=0.7115 at the VAMC that produced poor quality data. A pathologist found poor quality may be explained by faded histopathology stains and VAMC protocol differences. Supporting this, iQC's novel stain strength statistic finds this VAMC had weaker stains (p &amp;lt; 2.2e-16, two-tailed Wilcoxon rank-sum test; Cohen's d=1.208) than the VAMC that contributed most of the slides. Additionally, iQC recommended only 2 of 3736 (0.005%) VAMC slides for review due to inadequate tissue. In contrast, HistoQC in its default configuration excluded 89.9% of VAMC slides because tissue was not detected, but we reduced this to 16.7% with our custom HistoQC configuration. Conclusion: Our surgery prediction AUROC may be a quantitative indicator positively associated with data quality for a dataset. Unless data are poor quality, iQC accurately locates tissue in slides and excludes few slides. iQC is, to our knowledge, the first automated system in computational pathology that validates quality against objective evidence, e.g. surgical procedure data available in the EHR/LIMS, which requires no efforts or annotations from anatomic pathologists. Citation Format: Andrew J. Schaumberg, Michael S. Lewis, Ramin Nazarian, Ananta Wadhwa, Nathanael Kane, Graham Turner, Purushotham Karnam, Poornima Devineni, Nicholas Wolfe, Randall Kintner, Matthew B. Rettig, Beatrice S. Knudsen, Isla P. Garraway, Saiju Pyarajan. iQC: machine-learning-driven prediction of surgery reveals systematic confounds in cancer whole slide images from hospitals by protocol [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3511.

Effect of Pre-operative Parenteral Testosterone on Penile Dimensions and Vascularity in Proximal Hypospadias: A Prospective Observational Study.

Severe or proximal hypospadias is associated with inadequate local tissue and small phallus size. Pre-operative androgens have been used to increase phallus size, but there are very few studies on its role in proximal hypospadias. This study aimed to assess the effects of pre-operative intramuscular (IM) testosterone on proximal penile hypospadias in terms of penile morphology and tissue characteristics of penile skin. This prospective observational study was conducted on 27 patients of proximal hypospadias over a period from June 2017 to July 2018. The patients were sequentially enrolled into two groups: Group A and Group B. Group A patients received IM testosterone before surgery, whereas Group B patients were operated without pre-operative testosterone. Outcomes were analysed in terms of change in penile dimensions and effect on vascularity of penile skin. Pre-operative IM testosterone in Group A caused a significant increase in stretched penile length from a mean of 3.058 cm (±0.691) to 3.9 cm (±0.875) ( P = 0.002), penile circumference from a mean of 4.142 cm (±0.772) to 4.667 cm (±1.174) ( P = 0.029) and glans width from a mean of 1.225 cm (±0.245) to 1.750 cm (±0.571) ( P = 0.002). There was higher microvessel density in the preputial skin of Group A (mean: 12.212 [±4.745] blood vessels/high-power field [HPF]) compared to Group B (8.867 [±3.258] blood vessels/HPF) ( P = 0.043). Pre-operative testosterone in proximal hypospadias causes significant changes in penile dimensions and tissue characteristics. Improvement in penile dimensions leads to ease in operability and better tissue handling. However, more studies with large sample size are required to establish the beneficial effects of pre-operative hormone stimulation on urethroplasty.

Fatigue and mental health among patients with heart failure in an outpatient setting

Background: Heart failure is a health problem that occurs in the cardiovascular system which globally is the highest cause of death in the world. Heart Failure is a complex clinical syndrome in which the heart cannot pump blood to meet the body's blood circulation needs for tissue metabolism in certain conditions, due to structural or functional damage to the heart chambers. It is usually characterized by excessive blood volume, inadequate tissue perfusion, poor activity tolerance, and usually easily feels tired, orthopnea and edema. The emergence of various clinical symptoms in heart failure patients will cause nursing problems and interfere with basic human needs, one of which is fatigue. Heart failure sufferers have problems with the heart system which results in a lack of blood and oxygen supply to the brain and muscles, so sufferers often experience fatigue to the point of fainting. Purpose: To determine the relationship between the level of fatigue and the mental health of heart failure patients. Method: This type of quantitative research with a design using a cross sectional approach. Carried out at the heart clinic dr. Moewardi Surakarta, Central Java of the regional general hospital from October to December 2023. The population of heart failure sufferers in this study was 186 people, however by using a purposive sampling technique in sampling, a sample of 148 patients was obtained. The inclusion criteria in this study were patients aged &gt;18 years, New York Heart Association (NYHA) class II and class III heart failure patients, while the exclusion criteria were heart failure patients who were unwilling or unable to take part in this study. The instruments used were the fatigue assessment scale (FAS) and depression anxiety and stress scale 21 (DASS-21) questionnaires. Data analysis used univariate and bivariate with the chi square test. Results: The majority of respondents experienced mild fatigue with anxious conditions, 53 people (53.0%). Meanwhile, 47 patients (47.0%) who complained of severe fatigue showed anxiety, 24 people (85.7%), and 12 people (60.0%) felt stressed. The results of the analysis obtained a significant value with a p-value of 0.001 (&lt;0.05) which indicates that H0 was rejected. So there is a relationship between the level of fatigue and mental health conditions in heart failure sufferers. Conclusion: There is a relationship between the level of fatigue and mental health in heart failure patients. The nursing implication that can be implemented is providing education about fatigue so that patients understand the impact it has on heart failure sufferers so that it does not cause mental health problems.

Three-Dimensional Printing Methods for Bioceramic-Based Scaffold Fabrication for Craniomaxillofacial Bone Tissue Engineering.

Three-dimensional printing (3DP) technology has revolutionized the field of the use of bioceramics for maxillofacial and periodontal applications, offering unprecedented control over the shape, size, and structure of bioceramic implants. In addition, bioceramics have become attractive materials for these applications due to their biocompatibility, biostability, and favorable mechanical properties. However, despite their advantages, bioceramic implants are still associated with inferior biological performance issues after implantation, such as slow osseointegration, inadequate tissue response, and an increased risk of implant failure. To address these challenges, researchers have been developing strategies to improve the biological performance of 3D-printed bioceramic implants. The purpose of this review is to provide an overview of 3DP techniques and strategies for bioceramic materials designed for bone regeneration. The review also addresses the use and incorporation of active biomolecules in 3D-printed bioceramic constructs to stimulate bone regeneration. By controlling the surface roughness and chemical composition of the implant, the construct can be tailored to promote osseointegration and reduce the risk of adverse tissue reactions. Additionally, growth factors, such as bone morphogenic proteins (rhBMP-2) and pharmacologic agent (dipyridamole), can be incorporated to promote the growth of new bone tissue. Incorporating porosity into bioceramic constructs can improve bone tissue formation and the overall biological response of the implant. As such, employing surface modification, combining with other materials, and incorporating the 3DP workflow can lead to better patient healing outcomes.

Role of C4d immunohistochemical marker in the diagnosis of bullous pemphigoid: A cross-sectional study.

Objective To determine the diagnostic utility of C4d immunohistochemical marker in cases of bullous pemphigoid by calculating the sensitivity, specificity, positive predictive value and negative predictive value. Methods We conducted an exploratory study (retrospectively and prospectively) from January 2017 to June 2022. All direct immunofluorescence proven cases of bullous pemphigoid were included in the study while cases with inadequate tissue for immunohistochemistry studies were excluded. Results Among the 57 cases of bullous pemphigoid, 49 showed positivity for C4d marker. All the ten control cases of inflammatory dermatoses were negative for C4d staining. A sensitivity of 86%, a specificity of 100%, a positive predictive value of 100% and a negative predictive value of 55.56% were calculated with a confidence interval of 95%. Limitation It is a single centre study. Selection bias may come into play. Conclusion Direct immunofluorescence on fresh or frozen skin tissue remains the gold standard. But in circumstances where direct immunofluorescence facilities are not available, C4d immunohistochemistry marker staining on formalin-fixed paraffin-embedded material submitted for standard microscopic investigation can, in most cases, confirm the diagnosis of bullous pemphigoid, obviating the need for a second biopsy.

Channel-Boosted and Transfer Learning Convolutional Neural Network-Based Osteoporosis Detection from CT Scan, Dual X-Ray, and X-Ray Images.

Osteoporosis is a word used to describe a condition in which bone density has been diminished as a result of inadequate bone tissue development to counteract the elimination of old bone tissue. Osteoporosis diagnosis is made possible by the use of medical imaging technologies such as CT scans, dual X-ray, and X-ray images. In practice, there are various osteoporosis diagnostic methods that may be performed with a single imaging modality to aid in the diagnosis of the disease. The proposed study is to develop a framework, that is, to aid in the diagnosis of osteoporosis which agrees to all of these CT scans, X-ray, and dual X-ray imaging modalities. The framework will be implemented in the near future. The proposed work, CBTCNNOD, is the integration of 3 functional modules. The functional modules are a bilinear filter, grey-level zone length matrix, and CB-CNN. It is constructed in a manner that can provide crisp osteoporosis diagnostic reports based on the images that are fed into the system. All 3 modules work together to improve the performance of the proposed approach, CBTCNNOD, in terms of accuracy by 10.38%, 10.16%, 7.86%, and 14.32%; precision by 11.09%, 9.08%, 10.01%, and 16.51%; sensitivity by 9.77%, 10.74%, 6.20%, and 12.78%; and specificity by 11.01%, 9.52%, 9.5%, and 15.84%, while requiring less processing time of 33.52%, 17.79%, 23.34%, and 10.86%, when compared to the existing techniques of RCETA, BMCOFA, BACBCT, and XSFCV, respectively.

Cytology Smears of Rapid On-site Evaluation as Supplemental Material for Molecular Testing of Non-small Cell Lung Cancer

The thoracic small biopsy sampling procedure including transbronchial forceps lung biopsy (TBLB) and endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) can be accompanied by rapid on-site evaluation (ROSE) of sample material to provide immediate feedback for the proceduralist. The present study aims to investigate the supplemental effect of ROSE smear samples for lung cancer molecular test. In a retrospective study, 308 patients admitted to our hospital from August 2020 to December 2022 undergoing diagnostic TBLB and EBUS-TBNA with ROSE and subsequently diagnosed as non-small cell lung cancer (NSCLC) were analyzed. The matched formalin-fixed paraffin-embedding (FFPE) tissue section and ROSE smears for tumor cellularity were compared. DNA yields of smears were determined. Real-time polymerase chain reaction (PCR) and next-generation sequencing (NGS) were performed on adequate smear samples. ROSE smear samples were enriched in tumor cells. Among 308 biopsy samples, 78 cases (25.3%) exhibited inadequate FFPE tissue sections, whereas 44 cases (14.3%) yielded adequate smear samples. Somatic mutations detected in the FFPE tissue section samples were also detected in the matching adequate smear sample. ROSE smear samples of the thoracic small biopsies are beneficial supplemental materials for ancillary testing of lung cancer. Combined use of cytology smear samples with traditional FFPE section samples can enhance the detection rate of informative mutations in patients with advanced NSCLC. We recommend that the laboratory could further evaluate the ROSE cell smears of the patient when FFPE tissue sections are inadequate, and that adequate cell smears can be used as a supplemental source for the molecular testing of NSCLC.

Lactate and Lactate Clearance Are Predictive Factors for Mortality in Patients with Extracorporeal Membrane Oxygenation.

Findings of inadequate tissue perfusion might be used to predict the risk of mortality. In this study, we evaluated the effects of lactate and lactate clearance on mortality of patients who had undergone extracorporeal membrane oxygenation (ECMO). Patients younger than 18 years old and who needed venoarterial ECMO support after surgery for congenital heart defects, from July 2010 to January 2019, were retrospectively analyzed. Patients successfully weaned from ECMO constituted Group 1, and patients who could not be weaned from ECMO were in Group 2. Postoperative clinics and follow-ups of the groups including mortality and discharge rates were evaluated. There were 1,844 congenital heart surgeries during the study period, and 55 patients that required ECMO support were included in the study. There was no statistically significant difference between the groups regarding demographics and operative variables. The sixth-, 12th-, and 24th-hour lactate levels in Group 1 were statistically significantly lower than those in Group 2 (P=0.046, P=0.024, and P<0.001, respectively). There were statistically significant differences regarding lactate clearance between the groups at the 24th hour (P=0.009). The cutoff point for lactate level was found as ≥ 2.9, with 74.07% sensitivity and 78.57% specificity (P<0.001). The cutoff point for lactate clearance was determined as 69.44%, with 59.26% sensitivity and 78.57% specificity (P=0.003). Prognostic predictive factors are important to initiate advanced treatment modalities in patients with ECMO support. In this condition, lactate and lactate clearance might be used as a predictive marker.

Chemical approaches to probe and engineer AAV vectors.

Adeno-associated virus (AAV) has emerged as the most promising vector for in vivo human gene therapy, with several therapeutic approvals in the last few years and countless more under development. Underlying this remarkable success are several attractive features that AAV offers, including lack of pathogenicity, low immunogenicity, long-term gene expression without genomic integration, the ability to infect both dividing and non-dividing cells, etc. However, the commonly used wild-type AAV capsids in therapeutic development present significant challenges, including inadequate tissue specificity and the need for large doses to attain therapeutic effectiveness, raising safety concerns. Additionally, significant preexisting adaptive immunity against most natural capsids, and the development of such anti-capsid immunity after the first treatment, represent major challenges. Strategies to engineer the AAV capsid are critically needed to address these challenges and unlock the full promise of AAV gene therapy. Chemical modification of the AAV capsid has recently emerged as a powerful new approach to engineer its properties. Unlike genetic strategies, which can be more disruptive to the delicate capsid assembly and packaging processes, "late-stage" chemical modification of the assembled capsid-whether at natural amino acid residues or site-specifically installed noncanonical amino acid residues-often enables a versatile approach to introducing new properties to the capsid. This review summarizes the significant recent progress in AAV capsid engineering strategies, with a particular focus on chemical modifications in advancing the next generation of AAV-based gene therapies.

Histological Perspectives on Dental Implant Failure: A Case Report and Analysis of Peri-Implant Bone Histology

Peri-implant bone histology plays a crucial role in understanding the mechanisms underlying implant failure. This article presents a case report of a failed dental implant in a 72-year-old male patient, with a focus on the histological evaluation of the peri-implant bone. The patient underwent an All-in-4 implant-based denture treatment plan, which initially showed promising results but later resulted in implant failure. A trephine core biopsy was performed to assess the histology of the failed implant site and determine the cause of failure at the microscopic level. Histological analysis revealed the presence of graft material acting as a scaffold, surrounded by dense fibrosis and chronic inflammatory infiltrate. These findings indicate a failure of osseointegration and suggest possible causes for implant failure, such as inadequate tissue integration and host response. Factors contributing to implant failure, including occlusal overload, peri-implantitis, and systemic conditions, were discussed in the context of the case. Understanding the histological changes associated with implant failure is crucial for improving treatment outcomes and developing preventive strategies. Preoperative assessment, including evaluation of bone density and identification of systemic risk factors, is essential for successful implant placement. Retrieval and histological analysis of failed implants provide valuable insights into tissue responses and areas for improvement in implant design and surgical techniques. This case report highlights the significance of peri-implant bone histology in diagnosing and managing implant failure, with implications for enhancing implant success rates and patient care in implant dentistry. Further research in this field will contribute to advancements in implantology and the development of evidence-based protocols for implant treatment.

Biomarkers of heart failure: advances in omics studies.

Heart failure is a complex syndrome characterized by progressive circulatory dysfunction, manifesting clinically as pulmonary and systemic venous congestion, alongside inadequate tissue perfusion. The early identification of HF, particularly at the mild and moderate stages (stages B and C), presents a clinical challenge due to the overlap of signs, symptoms, and natriuretic peptide levels with other cardiorespiratory pathologies. Nonetheless, early detection coupled with timely pharmacological intervention is imperative for enhancing patient outcomes. Advances in high-throughput omics technologies have enabled researchers to analyze patient-derived biofluids and tissues, discovering biomarkers that are sensitive and specific for HF diagnosis. Due to the diversity of HF etiology, it is insufficient to study the diagnostic data of early HF using a single omics technology. This study reviewed the latest progress in genomics, transcriptomics, proteomics, and metabolomics for the identification of HF biomarkers, offering novel insights into the early clinical diagnosis of HF. However, the validity of biomarkers depends on the disease status, intervention time, genetic diversity and comorbidities of the subjects. Moreover, biomarkers lack generalizability in different clinical settings. Hence, it is imperative to conduct multi-center, large-scale and standardized clinical trials to enhance the diagnostic accuracy and utility of HF biomarkers.

Differential utilization of Impella devices, extracorporeal membrane oxygenation, and combined therapies as escalation and de-escalation strategies

Abstract Cardiogenic shock (CS) is a life-threatening condition characterized by a state of inadequate systemic tissue perfusion caused by cardiac dysfunction. When to implement, change, or remove the use of a temporary mechanical circulatory support (tMCS) in patients with CS is dependent on the aetiology and severity. Here, patient scenarios underlying the need to escalate, de-escalate, wean, or bridge from tMCS devices are taken into consideration by interdisciplinary heart failure and CS teams. This includes a comprehensive review of and focus on the rationale for specific device escalation and de-escalation strategies, device selection, and general management.

Abstract C050: Comprehensive analysis of causes for unsuccessful genomic profiling in a Phase 1 setting

Abstract Purpose: Genomic profiling (GP) has revolutionized personalized cancer therapy, enabling tailored treatment strategies based on individual tumor characteristics. However, despite its widespread use, there are instances where GP fails. Understanding the causes of such failures is important for improving the success rate of GP. Here, we present a comprehensive analysis of unsuccessful GP within a phase 1 clinical setting. Materials and Methods: A prospective, single-center, single-arm open label study (NCT02290522) was conducted, enrolling patients with advanced cancer referred to a phase I unit. Fresh tumor tissue was obtained by core needle biopsy for whole genome- or whole exome sequencing and RNA sequencing. In cases where fresh tumor tissue was unavailable, archival, formalin-fixed, paraffin-embedded tumor tissue or circulating tumor DNA extracted from plasma were obtained. Results: Between March 2013 and December 2021, a total of 2151 patients with advanced cancers and exhausted or almost exhausted treatments options were enrolled in the study. GP was unsuccessful in 281 patients (13%). The reasons for failure were; abstaining from biopsy due to performance decline from the time of consent (115/281= 41%), inadequate tissue quality due to normal tissue or necrosis (52/281= 19%), absence of lesions for tissue biopsy at the time of biopsy (41/281= 15%), patient withdrawal of consent (23/281= 8%), pre-analytical factors preventing tissue or liquid biopsy analysis (14/281= 5%), unsuccessful analyses (13/281= 4%), other treatment initiated at time of planned biopsy (10/281= 4%), unknown reasons (9/281= 3%) or biopsy contraindicated (4/281= 1%). Conclusion: The main cause of unsuccessful GP in this study was pre-analytical factors, primarily linked to performance status decline. Performing the biopsy and GP in earlier treatment lines, may reduce failure rates. Furthermore, considering the risk of rapid performance status decline, prior to biopsy referral, along with reduced lag time from obtaining consent to biopsy, may enhance GP success rates. Citation Format: Cecilie Iden, Laila Belcaid, Ida Jacobsen, Martin Hoejgaard, Iben Spanggaard, Morten Mau-Soerensen, Ulrik Lassen, Christina Westmose Yde, Kristoffer Staal Rohrberg. Comprehensive analysis of causes for unsuccessful genomic profiling in a Phase 1 setting [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr C050.