Exploring Patients' Trust from a New Perspective. A Text-Analysis Study.

The concept of trust has been extensively studied within the field of medicine. Yet, a list of factors that clearly influence patients' trust is still under debate. Moreover, the methodological approaches found in literature have been reported to be lacking in their assessments and measurements of trust relationships in the medical field although trust between a patient and medical provider has been proven to increase adherence and improve health outcomes. Hence, adding data to this debate and exploring a reliable method to explore the construct of trust is relevant. This study collects new evidence of the most salient indicators of patient trust by using a narrative approach and highlighting the potential of this method in collecting indicators that could be used to build training that aims to increase patients' trust. We used the Linguistic Inquiry and Word Count software for text analysis to examine the spontaneous narrations of episodes of trust and distrust within the doctor-patient relationship with a sample of 82 adult patients. Results demonstrate the role of the emotional aspects of the doctor-patient relationship. Data highlights the importance of doctors' benevolence toward patients, and positive emotions seem to be deeply connected with any experience of trust, which leads patients to feel more secure. Methods are presented to use these insights to construct mechanisms that establish medical trust and allow providers to implement effective interventions.

Time Course and Management of Protracted Anaphylaxis Due to PEG-Asparaginase.

Polyethylene glycosylated (PEG)-asparaginase is a cornerstone of treatment for acute lymphoblastic leukemia (ALL), and effective administration is associated with better outcomes. PEG-asparaginase is associated with a uniphasic hypersensitivity reaction in ∼10% to 20% of patients. We present a 17-year-old male individual diagnosed with very high-risk pre-B-ALL, who experienced protracted anaphylaxis 1 hour following administration of his second PEG-asparaginase dose. This type of allergic reaction has yet to be described in ALL patients treated with PEG-asparaginase. Here, we outline the time course and successful management of protracted anaphylaxis in an ALL patient.

Asymptomatic Skeletal Cystic Angiomatosis May Be Managed Conservatively With Close Observation.

Cystic angiomatosis (CA) is a rare disease characterized by the proliferation of vascular and lymphatic channels lined by a single layer of endothelial cells. CA may present with isolated skeletal or visceral disease. There is no consensus for the standard of care in these patients, and diverse regimens for CA have been reported, including observation, surgery, radiation, and a variety of medical therapies. We present a case of multifocal, isolated skeletal CA, treated with close observation alone and review the literature. We suggest that these cases may be safely followed without intervention and may be stable for prolonged periods of time.

Non-Coding RNA Signatures of B-Cell Acute Lymphoblastic Leukemia.

Non-coding RNAs (ncRNAs) comprise a diverse class of non-protein coding transcripts that regulate critical cellular processes associated with cancer. Advances in RNA-sequencing (RNA-Seq) have led to the characterization of non-coding RNA expression across different types of human cancers. Through comprehensive RNA-Seq profiling, a growing number of studies demonstrate that ncRNAs, including long non-coding RNA (lncRNAs) and microRNAs (miRNA), play central roles in progenitor B-cell acute lymphoblastic leukemia (B-ALL) pathogenesis. Furthermore, due to their central roles in cellular homeostasis and their potential as biomarkers, the study of ncRNAs continues to provide new insight into the molecular mechanisms of B-ALL. This article reviews the ncRNA signatures reported for all B-ALL subtypes, focusing on technological developments in transcriptome profiling and recently discovered examples of ncRNAs with biologic and therapeutic relevance in B-ALL.

The role of cell adhesion in hematopoiesis and leukemogenesis.

The cells of the bone marrow microenvironment are emerging as important contributors and regulators of normal hematopoiesis. This microenvironment is perturbed during leukemogenesis, and evidence points toward a bidirectional communication between leukemia cells and the normal cells of the bone marrow, mediated by direct cell-cell contact as well as soluble factors. These interactions are increasingly appreciated to play a role in leukemogenesis and possibly in resistance to chemotherapy. In fact, several compounds that specifically target the bone marrow microenvironment, including inhibitors of cell adhesion, are being tested as adjuncts to leukemia therapy.

Isolated Central Nervous System Chloroma as a Presenting Sign of Relapsed Pediatric Acute Lymphoblastic Leukemia.

Central nervous system (CNS) chloromas are an exceedingly rare presentation of CNS relapse in acute lymphoblastic leukemia (ALL). We report a relapsed ALL patient who presented with 2 separate chloromas and cerebrospinal fluid lymphoblastocytosis, and outline a treatment plan of systemic chemotherapy and CNS-directed radiation therapy. A review of the literature indicates that multiagent chemotherapy combined with CNS radiotherapy is effective, with hematopoietic stem cell transplantation used in half of reported cases. We conclude that intensive systemic multiagent chemotherapy with CNS-directed radiation therapy can be successfully used to treat relapsed pediatric ALL with CNS lymphoblastic chloroma.

Successful treatment of pediatric histiocytic sarcoma using abbreviated high-risk leukemia chemotherapy.

Histiocytic sarcoma (HS) is a malignant tumor composed of proliferating cells of histiocytic origin. True HS is exceedingly rare, particularly in pediatric patients. These tumors are frequently aggressive, and outcome for patients with HS has traditionally been poor. There is currently no consensus on the optimal management of these tumors, with the literature consisting largely of case reports and small case series utilizing a wide variety of therapies. We describe a case of HS in an 8-year-old female who was successfully treated with an abbreviated leukemia chemotherapy regimen.

Creation of a quality improvement collaborative to address adolescent and young adult cancer clinical trial enrollment: ATAQI (AYA trial access quality initiative).

Adolescent and young adult (AYA) participation in cancer clinical trials (CCTs) is suboptimal, hindering further improvements in survival, quality of life, and basic understanding of cancer pathophysiology in this population. Prior studies have identified barriers and facilitators to AYA CCT enrollment; however, few interventional studies have attempted to address these barriers and measure tangible changes. In September 2020, a task force was established to address CCT enrollment barriers at a multi-institutional level utilizing a quality improvement collaborative model for improvement. The AYA Trial Access Quality Initiative was developed with the goal of bring multidisciplinary teams together across multiple sites to learn, apply and share their methods of improvement. It uses a structured process of learning sessions lead by quality improvement and clinical experts who help facilitate learning and problem solving which are followed by action phases. During the pilot phase of the collaboration, one key driver of CCT enrollment in AYA's will be addressed: communication between adult and pediatric oncology by implementation of various interventions at sites. The number of AYAs screened for and enrolled on CCTs will be tracked over the course of the collaborative along with the process measures. It is expected that the interventions will promote engagement of stakeholders in the process of screening AYA oncology patients for eligibility on CCTs. This will hopefully create a favorable environment conducive for increasing enrollment on CCTs and lead to the development of a system-wide quality improvement framework to improve AYA CCT enrollment.

Successful treatment of disseminated cryptococcal infection in a pediatric acute lymphoblastic leukemia patient during induction.

Disseminated cryptococcal infection is rarely reported in the setting of pediatric acute leukemia, despite the immunocompromised state of these patients. However, when present, disseminated cryptococcal infection poses treatment challenges and is associated with significant morbidity and mortality. Treatment of invasive fungal disease in a child with acute leukemia requires a delicate balance between antifungal and antineoplastic therapy. This balance is particularly important early in the course of leukemia, as both the underlying disease and overwhelming infection can be life threatening. We describe the successful management of life-threatening disseminated cryptococcosis in a child with acute lymphoblastic leukemia during induction therapy.

Evaluation of soft tissue attachments to a novel intra-abdominal prosthetic in a rabbit model.

BACKGROUND: Laparoscopic ventral hernia repair requires placement of an intraperitoneal prosthetic. Composite mesh types have been developed to address the shortcomings of standard meshes. The authors evaluated the host reaction to intraperitoneal placement of a novel composite material. MATERIALS AND METHODS: A comparison of an innovative polypropylene/polylactide composite mesh was made to parietex composite (PCO), Proceed, and DualMesh. Eighteen meshes per group were implanted on intact peritoneum in New Zealand white rabbits. The main outcome measures included the formation of visceral adhesions, adhesion tenacity, tensiometric measurements, and histological analysis. Evaluations of adhesions were made at 1, 4, and 16 weeks using a 2-mm minilaparoscopy. RESULTS: There were no significant differences in the mean adhesion scores between the composite mesh types at week 1 (P = .15) and week 16 (P = .06). At 4 weeks, PCO had significantly fewer adhesions when compared with the other 3 mesh types (P = .02). Adhesion tenacity was also equivalent within the group at 16 weeks (P = .06). Tensiometry and histological analysis revealed no statistically significant differences between the mesh types. CONCLUSIONS: Four different composite mesh types had equivalent intra-abdominal soft tissue attachments in a rabbit model after a 16-week implantation period. PCO demonstrated the lowest mean adhesion score of each mesh type. Each mesh exhibited equivalent stiffness and energy to failure after explantation. The 4 composite mesh types demonstrated the successful formation of a neoperitoneum and comparable host biocompatibility as evidenced by similar degrees of inflammation.

Use of Communication Technology to Improve Clinical Trial Participation in Adolescents and Young Adults With Cancer: Consensus Statement From the Children's Oncology Group Adolescent and Young Adult Responsible Investigator Network.

Adolescents and young adults (AYAs; age 15-39 years) with cancer are under-represented in cancer clinical trials because of patient, provider, and institutional barriers. Health care technology is increasingly available to and highly used among AYAs and has the potential to improve cancer care delivery. The COVID-19 pandemic forced institutions to rapidly adopt novel approaches for enrollment and monitoring of patients on cancer clinical trials, many of which have the potential for improving AYA trial participation overall. This consensus statement from the Children's Oncology Group AYA Oncology Discipline Committee reviews opportunities to use technology to optimize AYA trial enrollment and study conduct, as well as considerations for widespread implementation of these practices. The use of remote patient eligibility screening, electronic informed consent, virtual tumor boards, remote study visits, and remote patient monitoring are recommended to increase AYA access to trials and decrease the burden of participation. Widespread adoption of these strategies will require new policies focusing on reimbursement for telehealth, license portability, facile communication between electronic health record systems and advanced safeguards to maintain patient privacy and security. Studies are needed to determine optimal approaches to further incorporate technology at every stage of the clinical trial process, from enrollment through study completion.

Epigenetic-Mediated Regulation of Gene Expression for Biological Control and Cancer: Fidelity of Mechanisms Governing the Cell Cycle.

The cell cycle is governed by stringent epigenetic mechanisms that, in response to intrinsic and extrinsic regulatory cues, support fidelity of DNA replication and cell division. We will focus on (1) the complex and interdependent processes that are obligatory for control of proliferation and compromised in cancer, (2) epigenetic and topological domains that are associated with distinct phases of the cell cycle that may be altered in cancer initiation and progression, and (3) the requirement for mitotic bookmarking to maintain intranuclear localization of transcriptional regulatory machinery to reinforce cell identity throughout the cell cycle to prevent malignant transformation.

Epigenetic-Mediated Regulation of Gene Expression for Biological Control and Cancer: Cell and Tissue Structure, Function, and Phenotype.

Epigenetic gene regulatory mechanisms play a central role in the biological control of cell and tissue structure, function, and phenotype. Identification of epigenetic dysregulation in cancer provides mechanistic into tumor initiation and progression and may prove valuable for a variety of clinical applications. We present an overview of epigenetically driven mechanisms that are obligatory for physiological regulation and parameters of epigenetic control that are modified in tumor cells. The interrelationship between nuclear structure and function is not mutually exclusive but synergistic. We explore concepts influencing the maintenance of chromatin structures, including phase separation, recognition signals, factors that mediate enhancer-promoter looping, and insulation and how these are altered during the cell cycle and in cancer. Understanding how these processes are altered in cancer provides a potential for advancing capabilities for the diagnosis and identification of novel therapeutic targets.

The addition of lysostaphin dramatically improves survival, protects porcine biomesh from infection, and improves graft tensile shear strength.

BACKGROUND: Lysostaphin (LS), a naturally occurring Staphylococcal endopeptidase, has the ability to penetrate biofilm, and has been identified as a potential antimicrobial to prevent mesh infection. The goals of this study were to determine if LS adhered to porcine mesh (PM) can impact host survival, reduce the risk of long-term PM infection, and to analyze lysostaphin bound PM (LS-PM) mesh-fascial interface in an infected field. METHODS: Abdominal onlay PMs measuring 3×3 cm were implanted in select groups of rats (n=75). Group assignments were based on bacterial inoculum and presence of LS on mesh. Explantation occurred at 60 d. Bacterial growth and mesh-fascial interface tensile strength were analyzed. Standard statistical analysis was performed. RESULTS: Only one out of 30 rats with bacterial inoculum not treated with LS survived. All 30 LS treated rats survived and had normal appearing mesh, including 20 rats with a bacterial inoculum (10(6) and 10(8) CFU). Mean tensile strength for controls and LS and no inoculum samples was 3.47±0.86 N versus 5.0±1.0 N (P=0.008). LS groups inoculated with 10(6) and 10(8) CFU exhibited mean tensile strengths of 4.9±1.5 N and 6.7±1.6 N, respectively (P=0.019 and P<0.001 compared with controls). CONCLUSION: Rats inoculated with S. aureus and not treated with LS had a mortality of 97%. By comparison, LS treated animals completely cleared S. aureus when challenged with bacterial concentrations of 1×10(6) and 1×10(8) with maintenance of mesh integrity at 60 d. These findings strongly suggest the clinical use of LS-treated porcine mesh in contaminated fields may translate into more durable hernia repair.

Collagen-elastin ratio predicts burst pressure of arterial seals created using a bipolar vessel sealing device in a porcine model.

BACKGROUND: Bipolar electrosurgical devices are used to generate rapid and efficient hemostasis in a wide range of surgical procedures. Of the factors that influence seal integrity, vessel (artery) diameter has been considered the most important variable. In this study we hypothesized that the relative ratio of the components that form the seal (collagen and elastin) determine the degree of vessel distensibility and play an equally important role in defining seal strength. METHODS: Porcine carotid, renal, iliac, and femoral arteries were sealed using a bipolar electrosurgical device in vivo. Following removal, arterial diameter was measured and vessels' seals tested for arterial burst pressure (ABPr). Samples were then analyzed histologically and biochemically for collagen and elastin content. RESULTS: Arteries with the highest collagen-elastin ratio (C/E) (renal) consistently demonstrated significantly higher burst pressures than those arteries with lower C/E ratios (iliac and femoral) independent of artery diameter. CONCLUSION: Using arteries of distinct anatomical origin and physiological function, we demonstrate that total collagen content, and more specifically C/E ratio, in porcine arteries is a more accurate predictor of ABPr than vessel size alone.

Evaluation of composite mesh for ventral hernia repair.

INTRODUCTION: Composite mesh prostheses incorporate the properties of multiple materials for ventral hernia repair. This study evaluated a polypropylene/ePTFE composite mesh with a novel internal polydioxanone (PDO) absorbable ring. METHODS: Composite mesh was placed intraperitoneally in 16 pigs through an open laparotomy and explanted at 2, 4, 8, and 12 weeks. Intraabdominal adhesions were measured laparoscopically. Host tissue in-growth was assessed histologically and tensiometrically. Degradation of the internal PDO ring component was also measured tensiometrically. Appropriate statistical tests were used, and P ≤.05 indicated significance. RESULTS: No adhesions were formed in 50% of the grafts explanted at 8 weeks and 25% of grafts explanted at 12 weeks. There were significantly more vascular structures at 8 weeks, 73.5 ± 28, compared with 2 weeks, 6.75 ± 2 (P ≤.01). The T-peel force at the mesh-host tissue interface was not significantly different among time points. The absorbable PDO ring underwent complete degradation by 12 weeks. CONCLUSIONS: This composite mesh was associated with minimal intraabdominal adhesions, progressive in-growth of host tissues, and complete degradation of a novel internal PDO ring that aided mesh positioning. This composite hernia mesh showed a favorable performance in a porcine model of open ventral hernia repair.

CXCR4 Mediates Enhanced Cell Migration in CALM-AF10 Leukemia.

Leukemia transformed by the CALM-AF10 chromosomal translocation is characterized by a high incidence of extramedullary disease, central nervous system (CNS) relapse, and a poor prognosis. Invasion of the extramedullary compartment and CNS requires leukemia cell migration out of the marrow and adherence to the cells of the local tissue. Cell adhesion and migration are increasingly recognized as contributors to leukemia development and therapeutic response. These processes are mediated by a variety of cytokines, chemokines, and their receptors, forming networks of both secreted and cell surface factors. The cytokines and cytokine receptors that play key roles in CALM-AF10 driven leukemia are unknown. We find high cell surface expression of the cytokine receptor CXCR4 on leukemia cells expressing the CALM-AF10 oncogenic protein, contributing to the migratory nature of this leukemia. Our discovery of altered cytokine receptor expression and function provides valuable insight into the propagation and persistence of CALM-AF10 driven leukemia.

Effect of bacterial exposure on acellular human dermis in a rat ventral hernia model.

BACKGROUND: Effectiveness of acellular human dermis (AHD) as an alternative to synthetic mesh in contaminated fields has been described. Cellular migration after implantation and corresponding strength of attachment is not well documented. Our aim is to correlate AHD vascularization, fibroblast migration, and strength of attachment with presence of inflammatory cells in clean and contaminated fields. MATERIALS AND METHODS: Lewis rats were randomized to a control and three experimental groups. AHD was placed as an onlay over the intact abdominal wall. Experimental groups (n=72) were exposed to Staphylococcus aureus at 1 x 10(4), 1 x 10(5), or 1 x 10(6) by direct application; controls (n=12) were not exposed. At 5 and 28 d, abdominal walls were explanted and tissue ingrowth assessed via tensiometry measuring energy (E) and max stress (MS) at the AHD-tissue interface. Vascularity, fibroblast migration, and inflammatory cell migration were compared using light microscopy. RESULTS: Shear strength reported as energy and max stress were significantly greater at 28 versus 5 d in all experimental groups, remaining unchanged in controls. Plasma cells and histiocytes significantly increased in all groups; macrophages increased in experimental groups only. Vascular ingrowth increased significantly in all groups; fibroblast migration was greater in controls and 1 x 10(6) exposed group only. CONCLUSIONS: Contamination of AHD results in inflammatory cell influx and a surprising increase in shear strength. Interestingly, shear strength does not increase without contamination. Inflammation stimulates vascular ingrowth, but not equally significant fibroblast migration. Longer survivals are required to determine if energy and max stress of controls increase, and fibroblast migration follows vascular ingrowth.

Spontaneous resolution of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis.

Secondary hemophagocytic lymphohistiocytosis (sHLH) is a reactive, proliferative disorder of the immune system resulting in lymphohistiocytic proliferation, hemophagocytosis, and cytokine dysregulation. The most common infectious trigger in sHLH is Epstein-Barr virus (EBV-HLH). Current treatment protocols for EBV-HLH have a cure rate of approximately 75%; however, there are significant toxicities associated with these therapies. We present two patients with EBV-HLH who experienced spontaneous resolution of their disease prior to the initiation of therapy, suggesting there may be a subgroup of patients with EBV-HLH who do well with conservative management and can avoid potentially toxic therapies.

Pushing the envelope in biomaterial research: initial results of prosthetic coating with stem cells in a rat model.

BACKGROUND: Coating prosthetic for hernia repair with a patient's own cells could improve biocompatibility by decreasing inflammation and adhesion formation and by increasing tissue ingrowth and resistance to infection. The objective of this study was to prove the feasibility of prosthetic coating with stem cells and to assess its resistance to adhesion formation when implanted in an animal model. METHODS: Adult Lewis rat bone marrow stem cells were harvested and cultured. Stem cells were then implanted on three different prosthetics. The prosthetic with the best stem cell adherence was implanted intraperitoneally into six adult rats. Untreated prosthetic was implanted in control animals (n = 12). After 2 weeks, intra-abdominal adhesions were graded using an adhesion scoring scale by two surgeons who were blinded to the animal group. Data were analyzed using the Wilcoxon rank-sum test. RESULTS: Stem cells demonstrated the best adherence and growth on polyglactin prosthetics. After implantation, the stem cell-coated polyglactin prosthetic had <25% of its surface area covered with adhesions in five (83%) samples, whereas the control polyglactin group had only one sample (8.3%) with <25% adhesions, and seven of its samples (58.3%) had >50% surface area adhesions (p < 0.05). CONCLUSIONS: The feasibility of hernia prosthetic coating with stem cells was demonstrated. Furthermore, stem-cell coated polyglactin prosthetic exhibited improved biocompatibility by decreasing adhesion formation in an animal model. Further study is needed to determine the factors that promote stem cell adherence to prosthetics and the in vivo prosthetic biomechanics after stem cell coating. This work is underway in our laboratory.