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.

The Human Phenotype Ontology in 2021.

The Human Phenotype Ontology (HPO, https://hpo.jax.org) was launched in 2008 to provide a comprehensive logical standard to describe and computationally analyze phenotypic abnormalities found in human disease. The HPO is now a worldwide standard for phenotype exchange. The HPO has grown steadily since its inception due to considerable contributions from clinical experts and researchers from a diverse range of disciplines. Here, we present recent major extensions of the HPO for neurology, nephrology, immunology, pulmonology, newborn screening, and other areas. For example, the seizure subontology now reflects the International League Against Epilepsy (ILAE) guidelines and these enhancements have already shown clinical validity. We present new efforts to harmonize computational definitions of phenotypic abnormalities across the HPO and multiple phenotype ontologies used for animal models of disease. These efforts will benefit software such as Exomiser by improving the accuracy and scope of cross-species phenotype matching. The computational modeling strategy used by the HPO to define disease entities and phenotypic features and distinguish between them is explained in detail.We also report on recent efforts to translate the HPO into indigenous languages. Finally, we summarize recent advances in the use of HPO in electronic health record systems.

Expansion of the Human Phenotype Ontology (HPO) knowledge base and resources.

The Human Phenotype Ontology (HPO)-a standardized vocabulary of phenotypic abnormalities associated with 7000+ diseases-is used by thousands of researchers, clinicians, informaticians and electronic health record systems around the world. Its detailed descriptions of clinical abnormalities and computable disease definitions have made HPO the de facto standard for deep phenotyping in the field of rare disease. The HPO's interoperability with other ontologies has enabled it to be used to improve diagnostic accuracy by incorporating model organism data. It also plays a key role in the popular Exomiser tool, which identifies potential disease-causing variants from whole-exome or whole-genome sequencing data. Since the HPO was first introduced in 2008, its users have become both more numerous and more diverse. To meet these emerging needs, the project has added new content, language translations, mappings and computational tooling, as well as integrations with external community data. The HPO continues to collaborate with clinical adopters to improve specific areas of the ontology and extend standardized disease descriptions. The newly redesigned HPO website (www.human-phenotype-ontology.org) simplifies browsing terms and exploring clinical features, diseases, and human genes.

The Human Phenotype Ontology in 2017.

Deep phenotyping has been defined as the precise and comprehensive analysis of phenotypic abnormalities in which the individual components of the phenotype are observed and described. The three components of the Human Phenotype Ontology (HPO; www.human-phenotype-ontology.org) project are the phenotype vocabulary, disease-phenotype annotations and the algorithms that operate on these. These components are being used for computational deep phenotyping and precision medicine as well as integration of clinical data into translational research. The HPO is being increasingly adopted as a standard for phenotypic abnormalities by diverse groups such as international rare disease organizations, registries, clinical labs, biomedical resources, and clinical software tools and will thereby contribute toward nascent efforts at global data exchange for identifying disease etiologies. This update article reviews the progress of the HPO project since the debut Nucleic Acids Research database article in 2014, including specific areas of expansion such as common (complex) disease, new algorithms for phenotype driven genomic discovery and diagnostics, integration of cross-species mapping efforts with the Mammalian Phenotype Ontology, an improved quality control pipeline, and the addition of patient-friendly terminology.

Impact of a Patient-Facing Enhanced Genomic Results Report to Improve Understanding, Engagement, and Communication.

"The objective of this study was to" test the effectiveness of an enhanced genomic report on patient-centered outcome domains including communication, engagement and satisfaction. "Study design utilized" a prospective, randomized, mixed-methods desctiptive study of a whole genome sequencing results report, GenomeCOMPASS™, that was accessed by providers through the electronic health record and by patients through the associated patient portal. "The study was set in" an integrated healthcare delivery system in central Pennsylvania. "Eighty-four" parents of 46 children with undiagnosed Intellectual Disability, Autism Spectrum Disorder and/or multiple congenital anomalies who had participated in a previous study offering whole genome sequencing for their affected child were invited to enroll. Fifty-two parents enrolled. Following a traditional genetics results informing visit, the study coordinator stratified families by diagnostic result and uninformative result and then randomized families within each group to an intervention arm to receive the GenomeCOMPASS™ report or to the usual care arm to receive a summary letter from the medical geneticist. A letter inviting enrollment included a baseline survey, which once returned, constituted enrollment. Surveys were administered at 3 months post-genetics visit. At 6 months, the usual care arm crossed over to receive the intervention and were administered an additional survey at 3 months. Qualitative interviews were conducted following survey completion to augment the survey data regarding the patient centered outcomes of interest. Patient reported outcomes including communication, engagement, empowerment and satisfaction. In the intervention arm, GenomeCOMPASS™ reports were released to 14 families (N = 28 parents) and of those 21 (75%) returned 3 month surveys. In the usual care arm, 12 families (N = 24 parents) received usual care summary letters and of those 20 (83%) returned 3 month surveys. At crossover, GenomeCOMPASS™ reports were released to 20 individuals and 15 (75%) returned 3 month surveys. Qualitative interviews were conducted with 5 individuals. Use of the GenomeCOMPASS™ report was reported by this small group of parents to improve communication with providers and non-health professionals such as educators and therapists and led to increased engagement and high satisfaction. Providers and others involved in the children's care also endorsed the report's effectiveness. Reports that addressed negative findings, i.e. uninformative results, were not found to be useful. Although the number of users was small, this study supports that customizable template reports may provide a useful and durable source of information that can support and enhance the information provided by genetics professionals in traditional face-to-face encounters. TRIAL REGISTRATION: Clinicaltrials.gov (Record 2013-0594).

Meta-analysis of open and endovascular repair of popliteal artery aneurysms.

OBJECTIVE: Endovascular popliteal artery aneurysm repair (EPAR) is increasingly used over open surgical repair (OPAR). The purpose of this study was to analyze the available literature on their comparative outcomes. METHODS: The PubMed and Embase databases were searched to identify studies comparing OPAR and EPAR. Studies with only one treatment and fewer than five patients were excluded. Demographics and outcomes were collected. Bias risk was assessed using a modified version of the Newcastle-Ottawa Scale. Results were computed from random-effects meta-analyses using the DerSimonian-Laird algorithm. RESULTS: A total of 14 studies were identified encompassing 4880 popliteal artery aneurysm repairs (OPAR, 3915; EPAR, 1210) during the last decade. OPAR patients were younger (standard mean difference, -0.798 [-0.798 to -1.108]; P < .001) and more likely to have worse tibial runoff (odds ratio [OR], 1.949 (1.15-3.31); P = .013) than EPAR patients. OPAR had higher odds of wound complications (OR, 5.182 [2.191-12.256]; P < .001) and lower odds of thrombotic complications (OR, 0.362 [0.155-0.848]; P < .001). OPAR had longer length of stay (standardized mean difference, 2.158 [1.225-3.090]; P < .001) and fewer reinterventions (OR, 0.275 [0.166-0.454]; P < .001). Primary patency was better for OPAR at 1 year and 3 years (relative risk, 0.607 [P = .01] and 0.580 [P = .006], respectively). There was no difference in secondary patency at 1 year and 3 years (0.770 [P = .458] and 0.642 [P = .073], respectively). CONCLUSIONS: EPAR has a lower wound complication rate and shorter length of hospital stay compared with OPAR. This comes at the cost of inferior primary patency but not secondary patency out to 3 years. Studies reporting long-term outcomes are lacking and necessary.

Enhancing genomic laboratory reports: A qualitative analysis of provider review.

This study reports on the responses of physicians who reviewed provider and patient versions of a genomic laboratory report designed to communicate results of whole genome sequencing. Semi-structured interviews addressed concept communication, elements, and format of example genome reports. Analysis of the coded transcripts resulted in recognition of three constructs around communication of genome sequencing results: (1) Providers agreed that whole genomic sequencing results are complex and they welcomed a report that provided supportive interpretation information to accompany sequencing results; (2) Providers strongly endorsed a report that included active clinical guidance, such as reference to practice guidelines, if available; and (3) Providers valued the genomic report as a resource that would serve as the basis to facilitate communication of genome sequencing results with their patients and families. Providers valued both versions of the report, though they affirmed the need for a provider-oriented report. Critical elements of the report included clear language to explain the result, as well as consolidated yet comprehensive prognostic information with clear guidance over time for the clinical care of the patient. Most importantly, it appears a report with this design has the potential not only to return results but also serves as a communication tool to help providers and patients discuss and coordinate care over time.

Enhancing genomic laboratory reports from the patients' view: A qualitative analysis.

The purpose of this study was to develop a family genomic laboratory report designed to communicate genome sequencing results to parents of children who were participating in a whole genome sequencing clinical research study. Semi-structured interviews were conducted with parents of children who participated in a whole genome sequencing clinical research study to address the elements, language and format of a sample family-directed genome laboratory report. The qualitative interviews were followed by two focus groups aimed at evaluating example presentations of information about prognosis and next steps related to the whole genome sequencing result. Three themes emerged from the qualitative data: (i) Parents described a continual search for valid information and resources regarding their child's condition, a need that prior reports did not meet for parents; (ii) Parents believed that the Family Report would help facilitate communication with physicians and family members; and (iii) Parents identified specific items they appreciated in a genomics Family Report: simplicity of language, logical flow, visual appeal, information on what to expect in the future and recommended next steps. Parents affirmed their desire for a family genomic results report designed for their use and reference. They articulated the need for clear, easy to understand language that provided information with temporal detail and specific recommendations regarding relevant findings consistent with that available to clinicians.

The attitudes of psychiatric hospital staff toward hospitalization and treatment of patients with borderline personality disorder.

BACKGROUND: Negative attitudes towards patients with borderline personality disorder (BPD) may affect their treatment. We aimed to identify attitudes toward patients with BPD. METHODS: Clinicians in four psychiatric hospitals in Israel (n = 710; psychiatrists, psychologists, social workers and nurses) were approached and completed questionnaires on attitudes toward these patients. RESULTS: Nurses and psychiatrists reported encountering a higher number of patients with BPD during the last month, and exhibited more negative attitudes and less empathy toward these patients than the other two professions. The whole sample evaluated the decision to hospitalize such a patient as less justified than the decision to hospitalize a patient with Major Depressive Disorder. Negative attitudes were positively correlated with caring for greater numbers of patients with BPD in the past month and in the past 12 months. Nurses expressed the highest interest in studying short-term methods for treating patients with BPD and a lower percentage of psychiatrists expressed an interest in improving their professional skills in treating these patients. CONCLUSIONS: The findings show that nurses and psychiatrists differ from the other professions in their experience and attitudes toward patients with BPD. We conclude that nurses and psychiatrists may be the target of future studies on their attitudes toward provocative behavioral patterns (e.g., suicide attempts) characterizing these patients. We also recommend implementing workshops for improving staff attitudes toward patients with BPD.

Intrusive trauma recollections is associated with impairment of interference inhibition and psychomotor speed in PTSD.

BACKGROUND: Intrusive cognitions that enter consciousness involuntarily are prominent symptoms of posttraumatic stress disorder (PTSD). The present study aimed to identify neuropsychological mechanisms involved. METHOD: Fifty PTSD outpatients and 50 healthy controls were tested using Finger Tapping, Simple and Choice Reaction Times and Stroop Tasks, to measure motor, psychomotor speed, response selection, and interference inhibition ability respectively. RESULTS: PTSD patients performed poorly in all tests, presumably owing to their generalized slowness of information processing and motor reaction. Psychomotor speed was a predictor of slowness and high error rate during the Stroop. Impaired inhibition, as measured by the interference index of the Stroop task, explained 9.7% of the predicated variance in frequency of re-experiencing PTSD symptoms and 23.5% of the predicated variance in augmentation of the interference response time. CONCLUSION: Impaired interference control may be related to internal (re-experiencing) and external (sensory) stimuli that leads to cognitive deficits in PTSD patients.

Cutting balloon septotomy for repair of right common iliac artery aneurysm in the setting of type B aortic dissection.

We report a case of using cutting balloon septotomy for a 5-cm right common iliac artery aneurysm repair in a patient with a chronic type B aortic dissection after open repair 10 years before. This technique uses intravenous ultrasound to facilitate deployment of a cutting balloon to shear through the dissection flap, allowing for optimization of the landing zone for endovascular repair of a right common iliac artery aneurysm. Various methods are available for performing septotomy, and the use of a cutting balloon is one that helps with stent placement and position.

Inferior vena cava reconstruction to alleviate back pain.

We present the case of a 38-year-old man with end-stage renal disease receiving hemodialysis via a left femoral loop graft who developed debilitating back pain. During a maintenance fistulogram, we found a completely occluded inferior vena cava and engorged lumbar veins. The patient underwent inferior vena cava reconstruction with stenting, which resulted in complete resolution of the engorged lumbar veins on venography and a significant reduction in his back pain. Engorgement of the lumbar veins can cause significant pain, and treatment of the underlying pathology can alleviate these symptoms.

On-chip Rayleigh imaging and spectroscopy of carbon nanotubes.

We report a novel on-chip Rayleigh imaging technique using wide-field laser illumination to measure optical scattering from individual single-walled carbon nanotubes (SWNTs) on a solid substrate with high spatial and spectral resolution. This method in conjunction with calibrated AFM measurements accurately measures the resonance energies and diameters for a large number of SWNTs in parallel. We apply this technique for fast mapping of key SWNT parameters, including the electronic-types and chiral indices for individual SWNTs, position and frequency of chirality-changing events, and intertube interactions in both bundled and distant SWNTs.

[Periodic breathing Cheyne-Stokes type, predict excessively reduced exercise tolerance in patients with chronic heart failure].

INTRODUCTION: Periodic breathing (PB) is evident during exercise in some patients with chronic heart failure (CHF) and is accompanied by hyperventilation. AIM: To determine whether the presence of PB predicts excessive reduced exercise capacity in patients with severe CHF relative to patient with CHF of similar severity but with no PB. METHODS: Sixty-one CHF patients underwent cardiopulmonary exercise from 2009 to 2011 as part of their evaluation for cardiac transplantation. From this data, we selected patients in which the term "periodic breathing" appeared in their report. Matching patients with CHF without PB were identified from the same pool. RESULTS: Fifteen CHF patients with PB and 18 patients with CHF with similar ejection fraction but without PB (control) were identified from the pool of 61 patients. The PB group had a lower peak oxygen uptake related to body weight (VO2/ kg] and anaerobic threshold [AT) than the control group, by 30 +/- 11 and 39 +/- 4%, respectively (p < 0.05). The ventilatory equivalent for CO2 production (VE/VCO2) at the AT was higher and the end tidal pressure of CO2 (PETCO2) was lower in the control group as compared with the PB group (p < 0.05]. VE/ VCO2 at the AT was inversely correlated with peak VO2/kg [r = -0.45, p < 0.05]. DISCUSSION: PB in patients with severe CHF is associated with excessively reduced exercise capacity. Increased ventilatory requirement may enhance dyspnea and may add to exercise limitation in these patients. CONCLUSION: Periodic breathing reflects the severity of CHF and is associated with excessively reduced exercise tolerance in patients with CHF.

Lidocaine Ineffectiveness Suggests New Psychopharmacology Drug Target.

Objectives: The mechanism of many neuropsychiatric disorders remains unknown, but the ineffectiveness of the sodium channel blocker lidocaine has been suggested to be a biomarker for Attention Deficit Hyperactivity Disorder (ADHD) and a severe form of Premenstrual Syndrome (PMS) that is considered psychiatric. We conducted single-arm double-blind clinical trials to test whether lidocaine ineffectiveness can be used as a biomarker to identify people with these conditions and provide a clue as to the molecular mechanism and potential psychopharmacological intervention. Experimental Design: We developed a noninvasive taste test for lidocaine ineffectiveness, validated by comparing lidocaine injections to pain testing in 12 subjects, and assessed it in individuals with ADHD and PMS. Principal Observations: Lidocaine ineffectiveness had a strong association in women with ADHD + PMS in a sample of 53 subjects and controls (p < 0.001). Conclusions: These results suggest the possibility of the biological understanding of the combination of ADHD and PMS that is characteristic of the psychiatric disorder Premenstrual Dysphoric Disorder (PMDD). These results and comparison to family pedigrees of a neuromuscular channelopathy with overlapping symptoms suggest the possibility that the clinical phenotype in PMDD is produced by sensory overstimulation, and amenable to molecular understanding and treatment.

Transcriptome changes in stages of non-alcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the United States and globally. The currently understood model of pathogenesis consists of a 'multiple hit' hypothesis in which environmental and genetic factors contribute to hepatic inflammation and injury. AIM: To examine the genetic expression of NAFLD and non-alcoholic steatohepatitis (NASH) tissue samples to identify common pathways that contribute to NAFLD and NASH pathogenesis. METHODS: We employed the Search Tag Analyze Resource for Gene Expression Omnibus platform to search the The National Center for Biotechnology Information Gene Expression Omnibus to elucidate NAFLD and NASH pathology. For NAFLD, we conducted meta-analysis of data from 58 NAFLD liver biopsies and 60 healthy liver biopsies; for NASH, we analyzed 187 NASH liver biopsies and 154 healthy liver biopsies. RESULTS: Our results from the NAFLD analysis reinforce the role of altered metabolism, inflammation, and cell survival in pathogenesis and support recently described contributors to disease activity, such as altered androgen and long non-coding RNA activity. The top upstream regulator was found to be sterol regulatory element binding transcription factor 1 (SREBF1), a transcription factor involved in lipid homeostasis. Downstream of SREBF1, we observed upregulation in CXCL10, HMGCR, HMGCS1, fatty acid binding protein 5, paternally expressed imprinted gene 10, and downregulation of sex hormone-binding globulin and insulin-like growth factor 1. These molecular changes reflect low-grade inflammation secondary to accumulation of fatty acids in the liver. Our results from the NASH analysis emphasized the role of cholesterol in pathogenesis. Top canonical pathways, disease networks, and disease functions were related to cholesterol synthesis, lipid metabolism, adipogenesis, and metabolic disease. Top upstream regulators included pro-inflammatory cytokines tumor necrosis factor and IL1B, PDGF BB, and beta-estradiol. Inhibition of beta-estradiol was shown to be related to derangement of several cellular downstream processes including metabolism, extracellular matrix deposition, and tumor suppression. Lastly, we found riciribine (an AKT inhibitor) and ZSTK-474 (a PI3K inhibitor) as potential drugs that targeted the differential gene expression in our dataset. CONCLUSION: In this study we describe several molecular processes that may correlate with NAFLD disease and progression. We also identified ricirbine and ZSTK-474 as potential therapy.