Mapping the Cardiometabolic Patient Experience and Self-Care Behaviors to Inform Design, Implementation, and Persistent Use of Digital Health Care Solutions: Mixed Methods Study.

BACKGROUND: Cardiometabolic conditions including acute coronary syndrome (ACS) and type 2 diabetes (T2D) require comprehensive care and patient engagement in self-care behaviors, and the drivers of those behaviors at the individual and health system level are still poorly understood. OBJECTIVE: We aim to gain insights into self-care behaviors of individuals with cardiometabolic conditions. METHODS: A convenience sample of 98 adult patients with ACS and T2D was recruited in the United States, Germany, and Taiwan to participate in a mixed methods study using ethnographic methods. All participants completed 7-day web-based diaries tracking their level of engagement, and 48 completed 90-minute web-based semistructured interviews between February 4, 2021, and March 27, 2021, focusing on themes including moments of engagement. Qualitative analysis identified factors influencing self-care practices and a Patient Mind States Model prototype. RESULTS: Patient reports indicate that many patients feel social pressure to adhere to treatment. Patients' experience can be understood within 5 categories defined in terms of their degree of engagement and adherence ("ignoring," "struggling," "juggling," "controlling," and "reframing"). CONCLUSIONS: For people living with ACS and T2D, the self-care journey is defined by patterns of patient experiences, which can identify areas that tailored digital health care interventions may play a meaningful role.

A novel acute kidney injury scoring system for renal and clinical outcomes in pediatric heart transplant patients.

BACKGROUND: The development of acute kidney injury (AKI) has been associated with worse outcomes in children after heart transplantation. Our study compares the application of a cumulative six-point Kidney Diseases Improving Global Outcomes (KDIGO) AKI scoring system, utilizing both creatinine and urine output criteria that we term as the AKI-6 criteria, to traditional AKI staging as a predictor for clinical and renal outcomes in the pediatric heart transplant recipients. METHODS: We conducted a retrospective single-center chart review on 155 pediatric patients who underwent heart transplantation from May 2014 to December 2021. The primary independent variable was the presence of severe AKI. Severe AKI by KDIGO was defined as Stage ≥2, whereas severe AKI by AKI-6 was defined as cumulative scores ≥4 or Stage 3 AKI based on either KDIGO criterion alone. Primary outcomes included actuarial survival and renal dysfunction by 1-year post-transplant, defined as an estimated glomerular filtration rate <60 mL/min/1.73 m2 . RESULTS: In total, 140 (90%) patients developed AKI; 98 (63%) patients developed severe AKI by KDIGO, and 60 (39%) by AKI-6. Severe AKI by AKI-6 was associated with worse actuarial survival following heart transplantation compared with KDIGO (p = 0.01). Of the 143 patients with 1-year creatinine data, 6 (11%) patients out of 54 with severe AKI by AKI-6 had evidence of renal dysfunction (p = 0.01), compared with 6 (7%) patients out of 88 by KDIGO (p = 0.3). CONCLUSIONS: AKI-6 scoring provides greater prognostic utility for actuarial survival and renal dysfunction by 1-year post-heart transplantation in pediatric patients than traditional KDIGO staging.

KLF4 recruits SWI/SNF to increase chromatin accessibility and reprogram the endothelial enhancer landscape under laminar shear stress.

Physiologic laminar shear stress (LSS) induces an endothelial gene expression profile that is vasculo-protective. In this report, we delineate how LSS mediates changes in the epigenetic landscape to promote this beneficial response. We show that under LSS, KLF4 interacts with the SWI/SNF nucleosome remodeling complex to increase accessibility at enhancer sites that promote the expression of homeostatic endothelial genes. By combining molecular and computational approaches we discover enhancers that loop to promoters of KLF4- and LSS-responsive genes that stabilize endothelial cells and suppress inflammation, such as BMPR2, SMAD5, and DUSP5. By linking enhancers to genes that they regulate under physiologic LSS, our work establishes a foundation for interpreting how non-coding DNA variants in these regions might disrupt protective gene expression to influence vascular disease.

Fatal nocardiosis infection in a pediatric patient with an immunodeficiency after heart re-transplantation.

BACKGROUND: Nocardia infections are rare opportunistic infections in SOT recipients, with few reported pediatric cases. Pediatric patients with single ventricle congenital heart defects requiring HT may be more susceptible to opportunistic infections due to a decreased T-cell repertoire from early thymectomy and potential immunodeficiencies related to their congenital heart disease. Other risk factors in SOT recipients include the use of immunosuppressive medications and the development of persistent lymphopenia, delayed count recovery and/or lymphocyte dysfunction. METHODS: We report the case of a patient with hypoplastic left heart syndrome who underwent neonatal congenital heart surgery (with thymectomy) prior to palliative surgery and 2 HTs. RESULTS: After developing respiratory and neurological symptoms, the patient was found to be positive for Nocardia farcinica by BAL culture and cerebrospinal fluid PCR. Immune cell phenotyping demonstrated an attenuated T and B-cell repertoire. Despite antibiotic and immunoglobulin therapy, his symptoms worsened and he was subsequently discharged with hospice care. CONCLUSION: Pediatric patients with a history of congenital heart defects who undergo neonatal thymectomy prior to heart transplantation and a long-term history of immunosuppression should undergo routine immune system profiling to evaluate for T- and B-cell deficiency as risk factors for opportunistic infection. Such patients could benefit from long-term therapy with TMP/SMX for optimal antimicrobial prophylaxis, with desensitization as needed for allergies. Disseminated nocardiosis should be considered when evaluating acutely ill SOT recipients, especially those with persistent lymphopenia and known or suspected secondary immunodeficiencies.

Implementation of a Clinical Leadership Curriculum for Pediatric Residents.

Introduction: Clinical leadership is an essential skill for physicians, empowering them to lead and coordinate teams, communicate clearly under various conditions, model positive behaviors, display emotional intelligence, and ultimately improve patient care outcomes. However, there are currently no standardized residency curricula or competency-based assessments for clinical leadership, as residents often assimilate leadership skills through trial-and-error or observation of their clinical faculty. By utilizing a comprehensive needs assessment and synthesizing evidence-based practices, we developed and implemented a longitudinal and skills-based clinical leadership curriculum for pediatric residents. Methods: We modeled our clinical leadership curriculum after Kern's 6-step approach to curricular development and the Accreditation Council for Graduate Medical Education competency requirements for professionalism. We identified topics based on a resident needs assessment and synthesized evidence from published practices. The curriculum was implemented through both monthly facilitated group sessions and independent learning modules. Results: 44 postgraduate year-2 (PGY-2) and PGY-3 pediatric residents participated in at least one monthly session of the clinical leadership curriculum. 27 (61%) completed the survey to evaluate the efficacy of the curriculum. Of the respondents, 23 (85%) residents found the leadership sessions useful, 4 (15%) were neutral, and none (0%) rated the sessions as not useful. 26 (96%) residents reported that the sessions should be continued. Conclusion: The clinical leadership curriculum has been received favorably by senior pediatric residents at our institution. Our next steps are to pilot the curriculum within residency programs of different specialties at our own institution as well as with pediatric residencies at other institutions.

Single-Day Low-Residue Diet Prior to Colonoscopy Demonstrates Improved Bowel Preparation Quality and Patient Tolerance over Clear Liquid Diet: A Randomized, Single-Blinded, Dual-Center Trial.

BACKGROUND AND AIMS: Patients often refer to bowel preparation and associated dietary restrictions as the greatest deterrents to having a colonoscopy completed or performed. Large studies comparing a low-residue diet (LRD) and a clear liquid diet (CLD) are still limited. The aim of this study is to compare LRD and CLD with regard to bowel preparation quality, tolerance, and satisfaction among a diverse patient population. METHODS: This study is a dual-center, randomized, single-blinded, prospective trial involving adult patients undergoing outpatient colonoscopy at the University of California Irvine Medical Center and an affiliated Veterans Administration hospital. Patients were randomized to consume either a CLD or a planned LRD for the full day prior to colonoscopy. Both groups consumed 4L split-dosed PEG-ELS. The adequacy of bowel preparation was evaluated using the Boston Bowel Preparation Score (BBPS). Adequate preparation was defined as a BBPS ≥ 6 with no individual segment less than a score of 2. Hunger and fatigue pre - and post-procedure were graded on a ten-point scale. Nausea, vomiting, bloating, abdominal cramping, overall discomfort, satisfaction with the diet, willingness to repeat the same preparation and overall experience were assessed. RESULTS: A total of 195 subjects who underwent colonoscopy from October 2014 to October 2017 were included. The mean BBPS for the LRD and CLD groups was 8.38 and 7.93, respectively (p = 0.1). There was a significantly higher number of adequate preparations in the LRD group compared to CLD (p = 0.05). Evening hunger scores just before starting the bowel preparation were significantly lower in the LRD than the CLD group, 2.81 versus 5.97, respectively (p = 0.006). Subjects in the LRD group showed significantly less nausea (p = 0.047) and bloating (p = 0.04). Symptom scores for vomiting, abdominal cramping, and overall discomfort were similar between the groups. Satisfaction with diet was significantly higher in the LRD group than CLD, 72% versus 37.66%, respectively (p < 0.001). The overall colonoscopy experience and the satisfaction with the preparation itself were also better reported in the LRD group (p < 0.001 and p = 0.002, respectively). CONCLUSIONS: This study, which included a diverse group of patients, demonstrated that patients using a LRD before colonoscopy achieve a bowel preparation quality that is superior to patients on a CLD restriction. This study shows that a low-residue diet improves patient satisfaction and results in significantly better tolerability of bowel preparation. As a less restrictive dietary regimen, the low-residue diet may help improve patient participation in colorectal cancer screening programs.

Assessment of Clinical Leadership Training Needs in Senior Pediatric Residents.

INTRODUCTION: Although clinical leadership in physicians is associated with improved healthcare, leadership training is rarely integrated into residency training. Our objective was to perform a comprehensive needs assessment of our pediatric residents' existing leadership experiences and knowledge and to identify training gaps within our program. METHODS: First, we held focus groups with senior pediatric residents to understand their clinical leadership experiences and identify training needs. Notes were transcribed and independently coded by 2 researchers, with thematic saturation achieved. Next, we focused each session on 1 leadership content area identified from the aforementioned themes to better understand the specific training needs for each topic. RESULTS: Four major themes were identified: (1) Effective and timely communication with supervisors, learners, ancillary staff, and patients is indispensable in promoting safe patient care, avoiding conflict, and preventing misunderstanding. (2) Training in teaching methods is desired, especially gaining the skills needed to teach various levels of learners, in different settings and under time constraints. (3) Time management, availability of resources, and team logistics were often learned through trial-and-error. (4) Self-care, self-acceptance, emotional regulation, and peer debriefing are relied upon to manage negative emotions; rarely are resilience and wellness strategies employed in "real-time." CONCLUSION: Senior residents currently face gaps in clinical leadership training and may benefit from additional instruction in content areas related to these 4 themes. Our next steps are to utilize the identified themes to develop a longitudinal and skills-based clinical leadership curriculum to address the gap in graduate medical education.

Peer-Developed Modules on Basic Biostatistics and Evidence-Based Medicine Principles for Undergraduate Medical Education.

Introduction: Evidence-based medicine (EBM) is pivotal in shaping patient care, yet it is challenging to incorporate into undergraduate medical education (UME) due to a lack of dedicated resources within the preclinical curriculum. To address this challenge, we used a peer-led approach to explain difficult concepts through language that students can understand at their shared level of understanding. Methods: Four second-year medical students trained in EBM over 18 months by facilitating monthly journal clubs, ultimately leading to their involvement as peer-instructors. With input from a faculty expert, peer-instructors designed integrative PowerPoint modules and interactive problem sets on basic biostatistics and EBM principles. Assessment included formative quizzes with multiple attempts to achieve at least 80% to demonstrate mastery of core learning objectives. Afterwards, students were invited to provide feedback using a 5-point Likert scale survey. Results: Of second-year students who participated, all 151 demonstrated 80% competency on each quiz. Eighty-seven (58%) students completed the survey on which, 77% agreed/strongly agreed that their level of understanding of EBM improved after the peer-led sessions, 76% agreed/strongly agreed that the sessions were more conducive to learning compared to traditional lectures, and 94% agreed/strongly agreed that the material covered was relevant to the USMLE Step 1. Discussion: This peer-led approach has been rated as effective by learners, improving their ability to critically appraise and apply clinical evidence. To promote integration of EBM into UME, we have prepared modules, problem sets, quizzes, and an outline of the problem-solving sessions for universal adoption.

Assessment of methods used for 3-dimensional superimposition of craniofacial skeletal structures: a systematic review.

BACKGROUND: So far, several techniques have been recommended for the assessment of craniofacial changes through skeletal tissue superimposition, but the evidence that supports them remains unexplored. The purpose of the present study is to assess the available literature on skeletal-tissue superimpositions of serial craniofacial CT or CBCT images used to detect morphological changes. MATERIALS AND METHODS: Medline (via Pubmed), EMBASE, Google Scholar, Cochrane Library, Open Grey and Grey Literature Report were searched (last search: 17.11.2019) using specific terms that fulfilled the requirements of each database in the context of the study aim. Hand searches were also performed. The outcomes of interest were the accuracy, precision, or agreement between skeletal-tissue superimposition techniques to assess changes in the morphology of craniofacial structures. Studies of any design with sample size ≥3 were assessed by two authors independently. The study protocol was registered in PROSPERO (ID: CRD42019143356). RESULTS: Out of 832 studies, fifteen met the eligibility criteria. From the 15 included studies, 12 have shown high total risk of bias, one low risk of bias, and two studies have shown unclear risk of bias. Thirteen out of the 15 studies showed high applicability concerns, two unclear and no study had low applicability concerns. There was high heterogeneity among studies regarding the type of participants, sample size, growth status, machines, acquisition parameters, superimposition techniques, assessment techniques and outcomes measured. Fourteen of them were performed on Cone Beam Computed Tomography (CBCT) and one on Computed Tomography (CT) derived 3D models. Most of the studies (eleven) used voxel-based registration, one landmark-based registration and three studies compared different registration techniques, which include the surface-based registration. Concerning the area of interest, nine studies focused on the anterior cranial base and certain facial structures, four on maxillary structures and four on mandibular structures. Non-growing participants were included in six studies, growing in eight, whereas one study had both. CONCLUSION: Most of the available studies had methodological shortcomings and high applicability concerns. At the moment, certain voxel-based and surface-based superimpositions seem to work properly and to be superior to landmark-based superimposition. However, further research in the field is required to develop and properly validate these techniques on different samples, through high quality studies with low applicability concerns.

Multicenter case series of patients with small-bowel angiodysplasias treated with a small-bowel radiofrequency ablation catheter.

BACKGROUND AND AIMS: GI angiodysplasia is the most common cause of small-bowel bleeding. Argon plasma coagulation (APC) is preferred for ablation because of its availability, ease of use, and perceived safety, but it has limitations. An instrument capable of repeated use through the enteroscope, which covers more area of intestinal mucosa per treatment with low risk of damage to healthy mucosa, and which improves ablation, is desirable. A series of patients treated with a through-the-scope radiofrequency ablation (RFA) catheter is reported. METHODS: Patients with a previous diagnosis of small-bowel angiodysplasia (SBA) and ongoing bleeding with melena, hematochezia, or iron-deficiency anemia were eligible for treatment. A small-bowel radiofrequency ablation (SBRFA) catheter was passed through the enteroscope instrument channel. The treatment paddle was pushed against the SBA, achieving coaptive coagulation, and the SBA was treated up to 2 times at standard settings of 10 J/cm2. The patients' demographics, pretreatment and posttreatment hemoglobin levels, time to recurrence of bleeding, and need for more therapy were recorded. This study was approved by the institutional review boards of the respective institutions. RESULTS: Twenty consecutive patients were treated from March until October 2018 and followed up until March 2019. There were 6 women (average age 68 years, standard deviation ± 11.1), and 14 men (average age 73 years, standard deviation ± 10.4). All had undergone at least 1 previous EGD and colonoscopy; 14 patients (70%) had SBA on video capsule endoscopy, and 14 patients had undergone previous endoscopic treatment of SBA with APC. A median of 23 treatments were applied (range, 2-99). The median follow-up time was 195 days (range, 30-240 days). Four patients, including 3 with a left ventricular assist device (LVAD), had recurrent bleeding between 45 and 210 days after treatment, and 2 patients received repeated blood transfusions. Three of those patients underwent repeated endoscopies, including a push enteroscopy and an upper endoscopy with no treatment, and a repeated enteroscopy with SBA treated with APC, respectively. One patient with LVAD underwent arterial embolization. CONCLUSIONS: In this case series, bleeding recurred in 20% of patients in a follow-up time of ≤240 days. Notably, 3 of the 4 patients who had recurrent bleeding had an LVAD. These rates compare favorably with reported bleeding recurrence after APC of SBA. More studies on the benefits of SBRFA, which may include reduced risk of recurrent bleeding or prolonging the time to recurrent bleeding, resource utilization, and factors associated with bleeding recurrence are needed.

Artificial intelligence using convolutional neural networks for real-time detection of early esophageal neoplasia in Barrett's esophagus (with video).

BACKGROUND AND AIMS: The visual detection of early esophageal neoplasia (high-grade dysplasia and T1 cancer) in Barrett's esophagus (BE) with white-light and virtual chromoendoscopy still remains challenging. The aim of this study was to assess whether a convolutional neural artificial intelligence network can aid in the recognition of early esophageal neoplasia in BE. METHODS: Nine hundred sixteen images from 65 patients of histology-proven early esophageal neoplasia in BE containing high-grade dysplasia or T1 cancer were collected. The area of neoplasia was masked using image annotation software. Nine hundred nineteen control images were collected of BE without high-grade dysplasia. A convolutional neural network (CNN) algorithm was pretrained on ImageNet and then fine-tuned with the goal of providing the correct binary classification of "dysplastic" or "nondysplastic." We developed an object detection algorithm that drew localization boxes around regions classified as dysplasia. RESULTS: The CNN analyzed 458 test images (225 dysplasia and 233 nondysplasia) and correctly detected early neoplasia with sensitivity of 96.4%, specificity of 94.2%, and accuracy of 95.4%. With regard to the object detection algorithm for all images in the validation set, the system was able to achieve a mean average precision of .7533 at an intersection over union of .3 CONCLUSIONS: In this pilot study, our artificial intelligence model was able to detect early esophageal neoplasia in BE images with high accuracy. In addition, the object detection algorithm was able to draw a localization box around the areas of dysplasia with high precision and at a speed that allows for real-time implementation.

Successful Curative Cryoablation of an Esophageal Gastrointestinal Stromal Tumor.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. The most common location of GIST is the stomach; however, occurrences of GIST in the esophagus are also possible albeit rare. Although the current standard of care for gastric and intestinal GIST involves surgery and tyrosine kinase inhibitors, this case report focuses on the potential of treating esophageal GIST through a novel means of cryoablation therapy.

EUS-guided through-the-needle biopsy for pancreatic cystic lesions.

BACKGROUND AND AIMS: Differentiating pancreatic cystic lesions remains a challenge when the current technique of EUS-guided FNA is used. Recently, a miniaturized biopsy forceps with an outer diameter of 0.8 mm has been developed, thus allowing it to be passed through the bore of a standard 19-gauge FNA needle to acquire tissue. METHODS: This study consisted of a retrospective review of all cases of EUS-guided through-the-needle forceps biopsy technique (TTNFB) performed for pancreatic cystic lesions at a single academic tertiary care center over a 12-month period. Technical success was defined as acquisition of adequate tissue for formal histologic analysis. Safety was assessed through the monitoring and recording of periprocedural and postprocedural adverse events. RESULTS: The technical success of EUS-guided TTNFB was 87% (13/15). EUS-guided TTNFB with histologic analysis yielded pancreatic cyst diagnoses in 11 of 15 (73%) patients, compared with 0 of 15 (0%) patients with the use of EUS-FNA and cytologic analysis (P < .001). Of the 15 cystic lesions, 8 were diagnosed as intrapapillary mucinous neoplasm based on EUS-TTNFB. CONCLUSION: This TTNFB technique has the potential to improve the diagnostic yield of EUS-FNA for pancreatic cystic neoplasms.

A dynamic interplay of enhancer elements regulates Klf4 expression in naïve pluripotency.

Transcription factor (TF)-directed enhanceosome assembly constitutes a fundamental regulatory mechanism driving spatiotemporal gene expression programs during animal development. Despite decades of study, we know little about the dynamics or order of events animating TF assembly at cis-regulatory elements in living cells and the long-range molecular "dialog" between enhancers and promoters. Here, combining genetic, genomic, and imaging approaches, we characterize a complex long-range enhancer cluster governing Krüppel-like factor 4 (Klf4) expression in naïve pluripotency. Genome editing by CRISPR/Cas9 revealed that OCT4 and SOX2 safeguard an accessible chromatin neighborhood to assist the binding of other TFs/cofactors to the enhancer. Single-molecule live-cell imaging uncovered that two naïve pluripotency TFs, STAT3 and ESRRB, interrogate chromatin in a highly dynamic manner, in which SOX2 promotes ESRRB target search and chromatin-binding dynamics through a direct protein-tethering mechanism. Together, our results support a highly dynamic yet intrinsically ordered enhanceosome assembly to maintain the finely balanced transcription program underlying naïve pluripotency.

Resetting Human Naïve Pluripotency.

The rodent naive pluripotent state is believed to represent the preimplantation inner cell mass state of the developing blastocyst and can derive self-renewing pluripotent embryonic stem cells (ESCs) in vitro. Nevertheless, human ESCs exhibit epigenetic, metabolic, and transcriptomic characteristics more akin to primed pluripotent stem cells (PSCs) derived from the postimplantation epiblast. Understanding the genetic and epigenetic mechanisms that constrain human ESCs in the primed state is crucial for the human naive pluripotent state resetting and numerous applications in regenerative medicine. In this review, we begin by defining the naive and primed states in the murine model and compare the epigenetic characteristics of those states to the human PSCs. We also examine the various reprogramming schemes to derive the human naive pluripotent state. Finally, we discuss future perspectives of studying and deriving the human naive PSCs in the context of cellular engineering and regenerative medicine.

Observational study with everolimus (Certican) in combination with low-dose cyclosporine in de novo heart transplant recipients.

BACKGROUND/METHODS: This observational study reports on immunosuppression with cyclosporine (CsA) in 38 de novo heart transplant recipients receiving everolimus compared with 14 patients receiving mycophenolate mofetil (MMF). RESULTS: Mean (+/- SD) everolimus C0 blood levels remained stable within 5 to 7 ng/ml. Mean CsA C0 blood levels were reduced by 47%, from 240 +/- 57 ng/ml at 2 weeks post-transplant to 128 +/- 38 ng/ml at Month 6 and by 58% to 101 +/- 26 ng/ml at Month 12 in the everolimus group, compared to 18% from 246 +/- 54 ng/ml at 2 weeks post-transplant to 201 +/- 48 ng/ml at Month 6 and by 35% to 160 +/- 41 ng/ml in MMF patients. Efficacy was high with a rejection rate of 23.6% (everolimus) vs 28.5% (MMF) by Month 12. Mean pre-transplant serum creatinine levels of 1.67 +/- 0.59 mg/dl decreased to 1.53 +/- 0.57 mg/dl under everolimus and increased from 1.22 +/- 0.36 to 1.99 +/- 0.75 mg/dl in the MMF group by Month 12 post-transplant. However, calculated GFR declined in both groups by Month 12 (everolimus: from 71 +/- 29 to 57 +/- 27 ml/min/1.73 m2; MMF: from 73 +/- 22 to 44 +/- 24 ml/min/1.73 m2), with stabilization after 3 to 6 months in everolimus-treated patients and after 6 to 9 months in MMF-treated patients. CONCLUSIONS: Everolimus allows marked reduction of CsA exposure without significant loss of efficacy and also provides early protection of renal function.