Percutaneous core needle biopsy of neuroblastoma in the pediatric population: what have we learned in the last decade.

INTRODUCTION: Historically, neuroblastoma has been diagnosed by surgical open biopsy (SB). In recent decades, core needle biopsy (CNB) has replaced surgical biopsy due to its safe and adequate method of obtaining tissue diagnosis. AIM: Our study aimed to assess the effectiveness of CNB in obtaining tissue diagnosis for neuroblastoma and evaluate its safety profile in terms of post-operative complications, in comparison to SB. METHODS: A retrospective cohort study, including all patients younger than 18 years who were diagnosed with neuroblastoma from 2012 until 2022 in a single tertiary medical center. Patients' demographics, tumor size and location, pathological results, and clinical outcomes were collected. RESULTS: 79 patients were included in our study: 35 biopsies were obtained using image-guided CNB and 44 using SB. Patients' and tumor characteristics including age, gender, tumor volume, and stage were similar in both groups. The biopsy adequacy rate in the CNB group was 91% and 3 patients in this group underwent repeated biopsy. The safety profile in the CNB group was similar to the SB group. CONCLUSIONS: CNB is a safe method and should be considered the first choice for obtaining tissue diagnosis when feasible due to its high adequacy in terms of tumor histopathological features.

Barriers to Adolescents' Adherence to Medical Advice after Metabolic Bariatric Surgery: A Statistical Analysis.

Background: Adolescent obesity has markedly increased worldwide, and metabolic bariatric surgery is an effective treatment option. A major predictor of the outcomes of this procedure is adherence to post-surgery lifestyle changes and medical recommendations. While adolescents generally have more difficulty adhering to medical advice than adults, their failure to do so could adversely affect their physical and psychological health, the cost-effectiveness of medical care, and the results of clinical trials. To our knowledge, this is the first attempt to identify the characteristics associated with the adherence of adolescents and their families to medical advice after bariatric surgery. Methods: We investigated potential variables influencing adherence to medical advice in adolescents diagnosed with severe obesity enrolled in a nutritional and behavior-oriented bariatric program-a 3-month pre-surgical outpatient intervention and a 6-month post-surgical follow-up. The program monitored weight, program attendance, diet compliance, lifestyle changes, and daily activities. All participants and parents completed a standard battery of questionnaires, provided demographic information, and participated in a semi-structured interview about their lifestyle. Results: The study group consisted of 47 adolescents: 34 girls and 13 boys, aged 13-18 years. Over time, three groups emerged with different degrees of adherence-high, low, and delayed low adherence. The analyses showed that adolescents' depression, autonomy, and independence from their family had strong, significant effects on adherence across the groups. Conclusions: Using adherence typologies, practitioners may be able to identify, predict, and tailor interventions to improve adolescent adherence to post-surgery recommendations. Parents have an important role in ensuring that adolescents undergoing metabolic bariatric surgery follow medical advice after the procedure.

Revealing the Hidden Clerkship Curriculum: A Qualitative Analysis.

BACKGROUND AND OBJECTIVES: Family medicine (FM) clerkships have learning objectives to define what students should learn by the end of their clerkship, but how do we know what larger lessons students are taking away? This study aimed to explore the FM clerkship explicit and hidden curriculum. METHODS: Students were asked to list their top five take-home points at the end of their FM clerkship at two institutions. A total of 668 written reflections were qualitatively analyzed. RESULTS: Thirteen code categories emerged: scope of practice, health care systems, role of FM in the system, traits of a family doctor, values of FM, cultural competency and social justice, challenges of FM care, evidence-based medicine, clinical skills for a student, personal impact, life skills and tips, patient centeredness, and clinical pearls. Prominent subcategories included prevention, team-based care, doctor-patient relationship, and continuity of care. CONCLUSIONS: When compared to the FM clerkship learning objectives at both institutions, four code categories emerged that were not part of the explicit objectives: traits of a family doctor, challenges in FM care, personal impact, and life skills and tips. Conversely, some nuances of the learning objective of FM in the health care system regarding decreasing cost and improving health outcomes and equity were not represented in the coded categories of student responses. These findings could potentially help FM clerkships nationally define ways to improve messaging around challenges in FM care and help the 25 x 2030 initiative to produce more family physicians in the United States.

Identifying Student Mistreatment Through Peer-Facilitated Learning Environment Sessions.

PROBLEM: Data from the Association of American Medical Colleges (AAMC) Medical School Graduation Questionnaire (GQ) show persistent high rates of medical student mistreatment, and multiple barriers to student reporting of mistreatment exist. The authors examined whether learning environment sessions (LESs) allow students opportunities to identify and describe patterns of mistreatment missed by other avenues of reporting. APPROACH: Peer-facilitated LESs were instituted in 2018-2019 at Boston University School of Medicine. The LESs were scheduled once during every third-year core clerkship block. Third- and fourth-year students trained as peer-facilitators led discussions of topics relevant to the student clinical experience using a standardized facilitator guide. Minutes, including details of reported events, were completed during the session and visible to all students participating. These minutes were sent to clerkship leadership and the medical education office for action once student grades were submitted. OUTCOMES: Summative content analysis was conducted on 44 LES minutes from sessions held in January-November 2019. Reported incidents were categorized into broad categories of negative treatment (NT), negative learning environment (NLE), and positive learning environment (PLE). Sixty-three instances of NT were identified. Of these, 37 fit within the scope of the AAMC GQ mistreatment categories. The remaining 26 instances of NT were classified into 7 novel categories of medical student mistreatment. Instances of NLE were most discussed by students and categorized into 5 subthemes. Examples of PLE were categorized into 4 subthemes, which encompassed 11 descriptors of core qualities of an ideal preceptor or educational environment. NEXT STEPS: LESs have aided in identifying and describing new patterns of mistreatment. They fulfill a unique role by allowing students to identify, analyze, and report mistreatment in a facilitated and protected space. Formal evaluations of institutional improvement in the learning environment, reduction in medical student mistreatment, and subsequent improvement in AAMC GQ data are needed.

Training Medical Students as Peer-Facilitators to Identify Medical Student Mistreatment in the Clerkship Year.

Introduction: Data from the Association of American Medical Colleges' Medical School Graduation Questionnaire show persistent trends of medical student mistreatment nationwide. To reduce the barriers and increase actionable reporting of mistreatment, we integrated peer-facilitated learning environment sessions led by a group of trained third- and fourth-year medical students in all core clinical clerkships. Methods: During the 2018-2019 academic year, third-year medical students were recruited, oriented, and trained to act as facilitators of sessions on mistreatment. The sessions occurred once every clerkship block, using a standardized session introduction and guide. After a 6-month pilot, new medical students were recruited and worked as scribe/facilitator pairs, receiving an additional 1.5-hour training midyear, which was evaluated with a postworkshop survey. Results: Thirty-eight students implemented 43 peer-facilitated sessions and completed deidentified minutes of each session, which were shared with clerkship directors and the Medical Education Office for review. Survey data from midyear facilitator training indicated that facilitators highly agreed peer-led sessions were an important avenue for students to process experiences of mistreatment (3.9 out of 4), understood barriers to reporting (3.8 out of 4) and definitions of mistreatment (3.6 out of 4), and felt confident to facilitate these sessions (3.6 out of 4). Discussion: Peer-facilitated sessions offer a method to learn more about student experiences with mistreatment in real time and create a new avenue for communication between faculty and students. Assembling a stable core team of third- and fourth-year students trained in facilitation skills ensures the sustainability and relevance of the program.

Finding Information Framework: A Tool to Teach Life-Long Learning Skills.

INTRODUCTION: In this age of rapid information expansion, medical education can no longer be taught solely by information acquisition, but rather requires information management and information mastery at both the point of learning as well as at the clinical point of care. We must teach our trainees how to ask, categorize, and answer their own questions-skills required to be a life-long learner. We developed the Finding Information Framework (FIF), a conceptual algorithm as well as web-based tool and app, to guide medical students in asking and categorizing their questions and to link them directly to the most appropriate information resource for their questions. Here we assess the functionality of the FIF following its implementation in the first-year medical school curriculum problem-based learning (PBL) course. METHODS: First-year medical students (n=126) utilized the FIF in their longitudinal problem-based learning course discussion groups and completed an anonymous survey. RESULTS: Qualitative and quantative data suggest that the FIF was easy to use (86.5%), supported the course curriculum (80%), and helped students find relevant information to answer their questions (77%) from trusted reliable resources (70%). Qualitative comments also suggest that the FIF is initially a helpful tool during the PBL course but becomes less useful over time as students become more familiar with resources. CONCLUSION: The FIF assists students in identifying trusted resources and in efficiently and effectively finding answers to questions at the point of learning. These data suggest that students are internalizing the tool's conceptual algorithm over time, reinforcing the teaching of information management and information mastery.

Parapet Along the Roof: Injury Prevention in the Context of an Ancient, But Still Relevant, Commandment.

BACKGROUND: Falling from a height accounts for 14.1% of all hospital admissions for traumatic injury. In 5% of cases, the injury is severe or critical, and in 1.5%, it is fatal. The dangers of falling have been recognized since time immemorial. Indeed, the Bible instructs us to build a parapet around the roof of our home so that, "…you may not bring the guilt of bloodshed on your house if someone falls from it" (Deuteronomy 22:8). This commandment highlights the relatively simple and practical means by which we can prevent falls. It is also one of a series of ethical laws that are presented to help us understand and obey the larger Biblical precepts of loving one's neighbor and guarding the sanctity of life. The concept teaches us that it is the responsibility of all individuals to be cognizant of others and to avoid harming people through negligence or carelessness. The aim of this article is to explain the commandment to build a parapet in the context of the risk of falling from a height and to expand on its wider implications. The present work was prompted in part by the alarming increase in fatal and near-fatal accidents in Israel in two particular populations.

Pediatric and Adolescent Surgical Breast Clinic: Preliminary Experience.

STUDY OBJECTIVE: The diagnostic and treatment tools used in breast centers are largely geared to adults, and there is little consideration of the unique characteristics of breast diseases in younger age groups. Herein we report on the preliminary experience of a specialized breast clinic for children and adolescents. DESIGN: Retrospective, observational. SETTING: Pediatric Surgical Breast Clinic of Schneider Children's Medical Center of Israel. PARTICIPANTS: Patients referred to the clinic during the first 18 months of its establishment. INTERVENTIONS AND MAIN OUTCOME MEASURES: Rate of breast masses, rate of malignancy, and types of evaluation and treatment. RESULTS: Forty-seven patients aged 0-19 years were referred. Breast masses were suspected in 23/47 (48.9%) and confirmed using ultrasound in 14/47 (29.7%; mean age, 16.4 years), followed by needle core biopsy in 7. Seven patients had multiple masses. Breast Imaging and Reporting Data System scores ranged from 3 to 4b. All cases were treated as fibroadenomas. Four patients underwent surgery because of a large mass (>5 cm; n = 3) or patient's preference to remove the lump rather than follow-up (n = 1). There were no malignancies. The median time from patient identification of the mass until seeking medical help was 5 months. CONCLUSION: Several findings distinct to this age group were highlighted: high rate of multiple masses, lack of malignancy, and high risk of delayed diagnosis. Care should be taken when using Breast Imaging and Reporting Data System categorization because it was formulated for adults and might be very limited in the adolescent population. Longer-term studies of larger cohorts are planned.

Emergencies in the Treatment of Wandering Spleen.

BACKGROUND: Wandering spleen is a rare entity that may pose a surgical emergency following torsion of the splenic vessels, mainly because of a delayed diagnosis. Complications after surgery for wandering spleen may necessitate emergency treatment. OBJECTIVES: To describe the clinical course and treatment for children who underwent emergency surgeries for wandering spleen at a tertiary pediatric medical center over a 21 year period and to indicate the pitfalls in diagnosis and treatment as reflected by our experience and in the literature. METHODS: The database of a tertiary pediatric medical center was searched retrospectively for all children who underwent emergency treatment for wandering spleen between 1996 and 2017. Data were collected from the medical files. The relevant literature was reviewed. RESULTS: Of ten patients who underwent surgery for wandering spleen during the study period, five underwent seven emergency surgeries. One patient underwent surgery immediately at initial presentation. In the other four, surgical treatment was delayed either due to misdiagnosis or for repeated imaging studies to confirm the diagnosis. Emergency laparotomy revealed an ischemic spleen in all patients; splenectomy was performed in two and the spleen was preserved in three. Four of the seven emergency operations were performed as the primary surgery and three were performed to treat complications. CONCLUSIONS: Wandering spleen should ideally be treated on an elective or semi-elective basis. Surgical delays could be partially minimized by a high index of suspicion at diagnosis and by eliminating unnecessary and time-consuming repeated imaging studies.

Essential Genes Embody Increased Mutational Robustness to Compensate for the Lack of Backup Genetic Redundancy.

Genetic robustness is a hallmark of cells, occurring through many mechanisms and at many levels. Essential genes lack the common robustness mechanism of genetic redundancy (i.e., existing alongside other genes with the same function), and thus appear at first glance to leave cells highly vulnerable to genetic or environmental perturbations. Here we explore a hypothesis that cells might protect against essential gene loss through mechanisms that occur at various cellular levels aside from the level of the gene. Using Escherichia coli and Saccharomyces cerevisiae as models, we find that essential genes are enriched over non-essential genes for properties we call "coding efficiency" and "coding robustness", denoting respectively a gene's efficiency of translation and robustness to non-synonymous mutations. The coding efficiency levels of essential genes are highly positively correlated with their evolutionary conservation levels, suggesting that this feature plays a key role in protecting conserved, evolutionarily important genes. We then extend our hypothesis into the realm of metabolic networks, showing that essential metabolic reactions are encoded by more "robust" genes than non-essential reactions, and that essential metabolites are produced by more reactions than non-essential metabolites. Taken together, these results testify that robustness at the gene-loss level and at the mutation level (and more generally, at two cellular levels that are usually treated separately) are not decoupled, but rather, that cellular vulnerability exposed due to complete gene loss is compensated by increased mutational robustness. Why some genes are backed up primarily against loss and others against mutations still remains an open question.

Correction: Overcoming Resistance of Cancer Cells to PARP-1 Inhibitors with Three Different Drug Combinations.

[This corrects the article DOI: 10.1371/journal.pone.0155711.].

Overcoming Resistance of Cancer Cells to PARP-1 Inhibitors with Three Different Drug Combinations.

Inhibitors of poly[ADP-ribose] polymerase 1 (PARPis) show promise for treatment of cancers which lack capacity for homologous recombination repair (HRR). However, new therapeutic strategies are required in order to overcome innate and acquired resistance to these drugs and thus expand the array of cancers that could benefit from them. We show that human cancer cell lines which respond poorly to ABT-888 (a PARPi), become sensitive to it when co-treated with vorinostat (a histone deacetylase inhibitor (HDACi)). Vorinostat also sensitized PARPis insensitive cancer cell lines to 6-thioguanine (6-TG)-a drug that targets PARPis sensitive cells. The sensitizing effect of vorinostat was associated with increased phosphorylation of eukaryotic initiation factor (eIF) 2α which in and of itself increases the sensitivity of cancer cells to ABT-888. Importantly, these drug combinations did not affect survival of normal fibroblasts and breast cells, and significantly increased the inhibition of xenograft tumor growth relative to each drug alone, without affecting the mice weight or their liver and kidney function. Our results show that combination of vorinostat and ABT-888 could potentially prove useful for treatment of cancer with innate resistance to PARPis due to active HRR machinery, while the combination of vorinostat and 6-TG could potentially overcome innate or acquired resistance to PARPis due to secondary or reversal BRCA mutations, to decreased PARP-1 level or to increased expression of multiple drug resistant proteins. Importantly, drugs which increase phosphorylation of eIF2α may mimic the sensitizing effect of vorinostat on cellular response to PARPis or to 6-TG, without activating all of its downstream effectors.

The One Minute Learner: Evaluation of a New Tool to Promote Discussion of Medical Student Goals and Expectations in Clinical Learning Environments.

BACKGROUND AND OBJECTIVES: The transition from pre-clerkship to clerkship curriculum in medical school presents many challenges to students. Student roles and supervising physicians' expectations vary widely. Efforts to ease this transition have included third-year orientations, skills sessions, field- specific training, and peer-to-peer communication/support. We developed a new tool, called The One Minute Learner (OML), to promote and structure discussion of student goals and expectations and empower student ownership of learning. The OML can be used quickly and easily by students and faculty to facilitate integration of medical students into the clinical setting. This paper describes the OML and reports evaluation of its effectiveness through student evaluations. METHODS: We compared student responses to two end-of-clerkship questions for the academic year before the OML was implemented to the first year of implementation. Students rated their orientation to their roles and responsibility and rated the communication of what was expected of them. RESULTS: The percentage of students rating these highly increased dramatically: for "I was oriented to my responsibilities and role," the percentage rating it highly (4--5 on a 5-point Likert scale) increased from 47% to 82%. For "Expectations of my role were communicated to me clearly" the percentage rating it highly increased from 66% to 89%. CONCLUSIONS: The OML is a new tool that can promote and structure a proactive discussion between student and teacher about goals and expectations, leading to better integration of students into the variety of clinical setting in which they rotate.

Assessing and Documenting the Cognitive Performance of Family Medicine Residents Practicing Outpatient Medicine.

BACKGROUND: Development of cognitive skills for competent medical practice is a goal of residency education. Cognitive skills must be developed for many different clinical situations. INNOVATION: We developed the Resident Cognitive Skills Documentation (CogDoc) as a method for capturing faculty members' real-time assessment of residents' cognitive performance while they precepted them in a family medicine office. The tool captures 3 dimensions of cognitive skills: medical knowledge, understanding, and its application. This article describes CogDoc development, our experience with its use, and its reliability and feasibility. METHODS: After development and pilot-testing, we introduced the CogDoc at a single training site, collecting all completed forms for 14 months to determine completion rate, competence development over time, consistency among preceptors, and resident use of the data. RESULTS: Thirty-eight faculty members completed 5021 CogDoc forms, documenting 29% of all patient visits by 33 residents. Competency was documented in all entrustable professional activities. Competence was statistically different among residents of different years of training for all 3 dimensions and progressively increased within all residency classes over time. Reliability scores were high: 0.9204 for the medical knowledge domain, 0.9405 for understanding, and 0.9414 for application. Almost every resident reported accessing the individual forms or summaries documenting their performance. CONCLUSIONS: The CogDoc approach allows for ongoing assessment and documentation of resident competence, and, when compiled over time, depicts a comprehensive assessment of residents' cognitive development and ability to make decisions in ambulatory medicine. This approach meets criteria for an acceptable tool for assessing cognitive skills.

Entrustable professional activities in family medicine.

BACKGROUND: The Accreditation Council for Graduate Medical Education Outcome Project intended to move residency education toward assessing and documenting resident competence in 6 dimensions of performance important to the practice of medicine. Although the project defined a set of general attributes of a good physician, it did not define the actual activities that a competent physician performs in practice in the given specialty. These descriptions have been called entrustable professional activities (EPAs). OBJECTIVE: We sought to develop a list of EPAs for ambulatory practice in family medicine to guide curriculum development and resident assessment. METHODS: We developed an initial list of EPAs over the course of 3 years, and we refined it further by obtaining the opinion of experts using a Delphi Process. The experts participating in this study were recruited from 2 groups of family medicine leaders: organizers and participants in the Preparing the Personal Physician for Practice initiative, and members of the Society of Teachers of Family Medicine Task Force on Competency Assessment. The experts participated in 2 rounds of anonymous, Internet-based surveys. RESULTS: A total of 22 experts participated, and 21 experts participated in both rounds of the Delphi Process. The Delphi Process reduced the number of competency areas from 91 to 76 areas, with 3 additional competency areas added in round 1. CONCLUSIONS: This list of EPAs developed through our Delphi process can be used as a starting point for family medicine residency programs interested in moving toward a competency-based approach to resident education and assessment.

Downregulation of the hemoglobin scavenger receptor in individuals with diabetes and the Hp 2-2 genotype: implications for the response to intraplaque hemorrhage and plaque vulnerability.

In individuals with diabetes mellitus (DM), the haptoglobin (Hp) genotype is a major determinant of susceptibility to myocardial infarction. We have proposed that this is because of DM and Hp genotype-dependent differences in the response to intraplaque hemorrhage. The macrophage hemoglobin scavenging receptor CD163 plays an essential role in the clearance of hemoglobin released from lysed red blood cells after intraplaque hemorrhage. We sought to test the hypothesis that expression of CD163 is DM and Hp genotype-dependent. CD163 was quantified in plaques by immunohistochemistry, on peripheral blood monocytes (PBMs) by FACS, and as soluble CD163 (sCD163) in plasma by ELISA. In DM plaques, despite an increase in macrophage infiltration, CD163 immunoreactivity was lower, resulting in a dramatic reduction in the percentage of macrophages expressing CD163 (27+/-2% versus 70+/-2%, P=0.0001). In individuals with DM as compared with individuals without DM, the percentage of PBMs expressing CD163 was reduced (3.7+/-0.6% versus 7.1+/-0.9%, P<0.002) whereas soluble plasma CD163 was increased (2.6+/-1.1 microg/mL versus 1.6+/-0.8 microg/mL, P<0.0005). Among DM individuals, the Hp 2-2 genotype was associated with a decrease in the percentage of PBMs expressing CD163 (2.3+/-0.5% versus 5.6+/-1.3%, P=0.01) and an increase in plasma soluble CD163 (3.0+/-0.2 microg/mL versus 2.3+/-0.2 microg/mL, P=0.04). Taken together, these results demonstrate an impaired hemoglobin clearance capacity in Hp 2-2 DM individuals and may provide the key insight explaining the increased incidence of myocardial infarction in this population.

Genetically determined heterogeneity in hemoglobin scavenging and susceptibility to diabetic cardiovascular disease.

A major function of haptoglobin (Hp) is to bind hemoglobin (Hb) to form a stable Hp-Hb complex and thereby prevent Hb-induced oxidative tissue damage. Clearance of the Hp-Hb complex can be mediated by the monocyte/macrophage scavenger receptor CD163. We recently demonstrated that diabetic individuals homozygous for the Hp 2 allele (Hp 2-2) were at 500% greater risk of cardiovascular disease (CVD) compared with diabetic individuals homozygous for the Hp 1 allele (Hp 1-1). No differences in risk by Hp type were seen in individuals without diabetes. To understand the relationship between the Hp polymorphism and diabetic CVD, we sought to identify differences in antioxidant and scavenging functions between the Hp types and to determine how these functions were modified in diabetes. The scavenging function of Hp was assessed using rhodamine-tagged and 125I-Hp in cell lines stably transfected with CD163 and in macrophages expressing endogenous CD163. We found that the rate of clearance of Hp 1-1-Hb by CD163 is markedly greater than that of Hp 2-2-Hb. Diabetes is associated with an increase in the nonenzymatic glycosylation of serum proteins, including Hb. The antioxidant function of Hp was assessed with glycosylated and nonglycosylated Hb. We identified a severe impairment in the ability of Hp to prevent oxidation mediated by glycosylated Hb. We propose that the specific interaction between diabetes, CVD, and Hp genotype is the result of the heightened urgency of rapidly clearing glycosylated Hb-Hp complexes from the subendothelial space before they can oxidatively modify low-density lipoprotein to atherogenic oxidized low-density lipoprotein.