tbuckley/cabot-search huggingface dataset:
MRI‐Based Iron Phenotyping and Patient Selection for Next‐Generation Sequencing of Non–Homeostatic Iron Regulator Hemochromatosis Genes
Authors: André Viveiros, Benedikt Schaefer, Marlene Panzer, Benjamin Henninger, Michaela Plaikner, Christian Kremser, André Franke, Sören Franzenburg, Marc P. Hoeppner, Reinhard Stauder, Andreas Janecke, Herbert Tilg, Heinz Zoller
Journal: Hepatology (2021)

Background and Aims High serum ferritin is frequent among patients with chronic liver disease and commonly associated with hepatic iron overload. Genetic causes of high liver iron include homozygosity for the p.Cys282Tyr variant in homeostatic iron regulator ( HFE ) and rare variants in non‐HFE genes. The aims of the present study were to describe the landscape and frequency of mutations in hemochromatosis genes and determine whether patient selection by noninvasive hepatic iron quantification using MRI improves the diagnostic yield of next‐generation sequencing (NGS) in patients with hyperferritinemia. Approach and Results A cohort of 410 unselected liver clinic patients with high serum ferritin (defined as ≥200 μg/L for women and ≥300 μg/L for men) was investigated by HFE genotyping and abdominal MRI R2*. Forty‐one (10%) patients were homozygous for the p.Cys282Tyr variant in HFE . Of the remaining 369 patients, 256 (69%) had high transferrin saturation (TSAT; ≥45%) and 199 (53%) had confirmed hepatic iron overload (liver R2* ≥70 s −1 ). NGS of hemochromatosis genes was carried out in 180 patients with hepatic iron overload, and likely pathogenic variants were identified in 68 of 180 (38%) patients, mainly in HFE (79%), ceruloplasmin (25%), and transferrin receptor 2 (19%). Low spleen iron (R2* &lt;50 s −1 ), but not TSAT, was significantly associated with the presence of mutations. In 167 patients (93%), no monogenic cause of hepatic iron overload could be identified. Conclusions In patients without homozygosity for p.Cys282Tyr, coincident pathogenic variants in HFE and non‐HFE genes could explain hyperferritinemia with hepatic iron overload in a subset of patients. Unlike HFE hemochromatosis, this type of polygenic hepatic iron overload presents with variable TSAT. High ferritin in blood is an indicator of the iron storage disease, hemochromatosis. A simple genetic test establishes this diagnosis in the majority of patients affected. MRI of the abdomen can guide further genetic testing.
Abstract 15332: Impact of Coronary Lesion Characteristics Assessed by Multidetector Coronary Computed Tomography on Periprocedural Myocardial Necrosis for Chronic Total Occlusion: Multicenter Registry Study
Authors: Eisuke Usui, Takayuki Niida, Makoto Araki, Junji Matsuda, Yoshihisa Kanaji, Tadashi Murai, Tetsumin Lee, Shigeki Kimura, Taishi Yonetsu, Tsunekazu Kakuta
Journal: Circulation (2015)

Background: Periprocedural myocardial infarction (PMI) has been shown to be associated with worse prognosis of patients who underwent percutaneous coronary intervention (PCI). Specific characteristics of culprit lesions detected on multidetector computed tomography (MDCT) have not been fully elucidated as predictors of PMI in patients with chronic total occlusion (CTO) lesions. We investigated to determine whether predictive MDCT characteristics exist for PMI associated with CTO PCI. Methods: 79 stable angina patients with 80 CTO lesions who underwent pre-PCI MDCT and CTO PCI at three institutions between Dec 2011 and May 2015 were included. Lesions were divided into 2 groups based on the presence (PMI group, n=20; 25%) or absence (non-PMI group, n=60; 75%) of post-PCI peak cardiac troponin (cTn) elevation of more than institutional URLx20. Clinical characteristics, procedural variables, and MDCT findings were compared between these two groups. Uni- and multivariate logistic regression analysis were performed to identify the predictors of PMI. Results: There was no significant difference in clinical characteristics between both groups. PCI success was achieved in 64 (80%) patients. Fluoroscopic time and contrast use was significantly greater in PMI group. There was no significant difference in the frequency of PMI between PCI success and failure. Frequency of the use of retrograde approach was significantly higher with PMI. In MDCT analysis, lesion length was significantly longer in PMI group (median 35.6 [IQR 26.5-45.8] mm vs. 23.7 [12.8-36.4] mm, p=0.01). Napkin-ring sign (CT density &lt;130HU) was also significantly associated with PMI group (25.0% vs. 6.7%, p=0.04). Multivariate logistic regression analysis revealed that retrograde approach (odds ratio: 6.41; 95% confidence interval: 1.95 to 21.1; p&lt;0.01) was a significant predictor of PMI after controlling for confounding factors. Napkin-ring sign showed a borderline significant association with PMI (odds ratio: 4.64; 95% confidence interval: 0.98 to 22.0; p=0.05). Conclusion: PMI is not uncommon in patients undergoing elective CTO PCI regardless of procedure success or failure. MDCT before PCI may help identify patients at high risk for PMI associated with CTO PCI.
Addressing distress management challenges: Recommendations from the consensus panel of the American Psychosocial Oncology Society and the Association of Oncology Social Work
Authors: Teresa L. Deshields, Sharla Wells‐Di Gregorio, Stacy R. Flowers, Kelly E. Irwin, Ryan Nipp, Lynne Padgett, Brad Zebrack
Journal: CA A Cancer Journal for Clinicians (2021)

Abstract Distress management (DM) (screening and response) is an essential component of cancer care across the treatment trajectory. Effective DM has many benefits, including improving patients' quality of life; reducing distress, anxiety, and depression; contributing to medical cost offsets; and reducing emergency department visits and hospitalizations. Unfortunately, many distressed patients do not receive needed services. There are several multilevel barriers that represent key challenges to DM and affect its implementation. The Consolidated Framework for Implementation Research was used as an organizational structure to outline the barriers and facilitators to implementation of DM, including: 1) individual characteristics (individual patient characteristics with a focus on groups who may face unique barriers to distress screening and linkage to services), 2) intervention (unique aspects of DM intervention, including specific challenges in screening and psychosocial intervention, with recommendations for resolving these challenges), 3) processes for implementation of DM (modality and timing of screening, the challenge of triage for urgent needs, and incorporation of patient‐reported outcomes and quality measures), 4) organization—inner setting (the context of the clinic, hospital, or health care system); and 5) organization—outer setting (including reimbursement strategies and health‐care policy). Specific recommendations for evidence‐based strategies and interventions for each of the domains of the Consolidated Framework for Implementation Research are also included to address barriers and challenges.
Association of Positive Fluid Balance at Discharge After Sepsis Management With 30-Day Readmission
Authors: Michael S. Yoo, Shiyun Zhu, Yun Lu, John D. Greene, Helen L. Hammer, Colin T. Iberti, Siamack Nemazie, Martin P. Ananias, Caitlin M. McCarthy, Robert M. O’Malley, Karlyn L. Young, Karolin O. Reed, Robert A. Martinez, Kawai Cheung, Vincent X. Liu
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Although early fluid administration has been shown to lower sepsis mortality, positive fluid balance has been associated with adverse outcomes. Little is known about associations in non–intensive care unit settings, with growing concern about readmission from excess fluid accumulation in patients with sepsis. <h3>Objective</h3> To evaluate whether positive fluid balance among non–critically ill patients with sepsis was associated with increased readmission risk, including readmission for heart failure. <h3>Design, Setting, and Participants</h3> This multicenter retrospective cohort study was conducted between January 1, 2012, and December 31, 2017, among 57 032 non–critically ill adults hospitalized for sepsis at 21 hospitals across Northern California. Kaiser Permanente Northern California is an integrated health care system with a community-based population of more than 4.4 million members. Statistical analysis was performed from January 1 to December 31, 2019. <h3>Exposures</h3> Intake and output net fluid balance (I/O) measured daily and cumulatively at discharge (positive vs negative). <h3>Main Outcomes and Measures</h3> The primary outcome was 30-day readmission. The secondary outcomes were readmission stratified by category and mortality after living discharge. <h3>Results</h3> The cohort included 57 032 patients who were hospitalized for sepsis (28 779 women [50.5%]; mean [SD] age, 73.7 [15.5] years). Compared with patients with positive I/O (40 940 [71.8%]), those with negative I/O (16 092 [28.2%]) were older, with increased comorbidity, acute illness severity, preexisting heart failure or chronic kidney disease, diuretic use, and decreased fluid administration volume. During 30-day follow-up, 8719 patients (15.3%) were readmitted and 3639 patients (6.4%) died. There was no difference in readmission between patients with positive vs negative I/O (HR, 1.00; 95% CI, 0.95-1.05). No association was detected between readmission and I/O using continuous, splined, and quadratic function transformations. Positive I/O was associated with decreased heart failure–related readmission (HR, 0.80 [95% CI, 0.71-0.91]) and increased 30-day mortality (HR, 1.23 [95% CI, 1.15-1.31]). <h3>Conclusions and Relevance</h3> In this large observational study of non–critically ill patients hospitalized with sepsis, there was no association between positive fluid balance at the time of discharge and readmission. However, these findings may have been limited by variable recording and documentation of fluid intake and output; additional studies are needed to examine the association of fluid status with outcomes in patients with sepsis to reduce readmission risk.
POS0352 ALLELIC VARIANTS IN THE ABCG2 GENE CAN LEAD TO HYPERURICEMIA AND GOUT
Authors: K. Pavelcova, J. Bohata, B. Stiburkova
Journal: Annals of the Rheumatic Diseases (2021)

Background: The level of uric acid is largely determined by the functions of urate transporters, which are located in the kidney and intestine. The ABCG2 protein is the major excretor of uric acid and its dysfunction may lead to the development of hyperuricemia and gout. Objectives: The aim of our study was to detect the occurrence and frequency of allelic variants in the ABCG2 gene that can lead to impaired function of the ABCG2 protein and to the development of hyperuricemia and gout. Methods: We examined allelic variants of ABCG2 using PCR amplification and Sanger sequencing of all coding regions and exon-intron boundaries in 359 patients with primary hyperuricemia and gout. Results: We found a rare in-frame deletion p.K360del and 15 missense variants, two of which were common (p.V12M, p.Q141K) and 13 were very rare (p.M71V, p.G74D, p.M131I, p.R147W, p.T153M, p.I242T, p.R236X, p.F373C, p.T421A, p.T434M, p.S476P, p.S572R, p.D620N). The p.R236X variant leads to a premature stop codon. The p.V12M variant probably has a protective effect against gout (minor allele frequency – MAF – in our cohort = 0,025 / MAF in the European population = 0,061), while the p.Q141K variant increases the risk of gout (MAF in our cohort = 0,213 / MAF in the European population = 0,094) (1). As for the rare variants, the p.R147W, p.T153M, p.F373C, p.T434M, p.S476P and p.S572R according to functional analyzes reduce the function of the ABCG2 protein (2). Based on in silico prediction, the impact on reduced function is expected for variants p.M71V, p.G74D, p.M131I, p.R147W, p.I242T, p.F373C, p.T434M, p.S476P and p.S572R. Conclusion: Our data suggest that the common variant p.Q141K and most of the rare variants in the ABCG2 gene affect the function of the ABCG2 urate transporter and are a genetic risk factor for hyperuricemia and gout. References: [1]Stiburkova B, et al. Functional non-synonymous variants of ABCG2 and gout risk. Rheumatology (Oxford). 2017 Nov 1; 56(11):1982-1992. [2]Toyoda Y, et al. Functional characterization of clinically-relevant rare variants in ABCG2 identified in a gout and hyperuricemia cohort. Cells. 2019 Apr 18;8(4). Acknowledgements: This study was supported by the project for conceptual development of research organization 00023728 (Institute of Rheumatology) and RVO VFN64165. Disclosure of Interests: None declared
POS0155-HPR DIAPHRAGMATIC BREATHING RELAXATION TECHNIQUE TO DECREASE ANXIETY DURING JOINT INFILTRATION: A RANDOMIZED CONTROLLED TRIAL
Authors: R. Ben Aissa, S. Boussaid, H. Tbini, H. Sahli, S. Jemmali, S. Rekik, M. El Euch
Journal: Annals of the Rheumatic Diseases (2021)

Background: Joint infiltration is the injection of therapeutic substances directly into a joint. It may be a stressful experience for patients as imagined different from other usual injections. Several techniques are used to manage anxiety and pain during such a procedure. Objectives: To evaluate the effectiveness of diaphragmatic breathing relaxation on reducing anxiety and pain during joint infiltration. Methods: Patients scheduled for a joint infiltration at the rheumatology department’s daycare unit were recruited. All infiltrations were performed using steroids without anesthetic therapy except for the hip. Patients were randomized into two groups (cases=38, controls=34). Cases learned from a trained health agent diaphragmatic breathing relaxation technique to perform it immediately before and during the procedure while controls received the usual procedure. We used the Visual Analogue Scale (VAS) to assess self-estimated both anxiety (VAS-Anx) and pain (VAS-Pain) as evaluated on pre and post-joint infiltration. VAS-Pain was evaluated as expected then as experienced respectively on pre and post-infiltration. We also assessed heart rate and blood pressure on pre and post-procedure. Results: Seventy-two participants were included with a mean age of 55.48 ± 12.39 years (39-78), treated for an inflammatory rheumatic or degenerative disease (21, 51 respectively), and receiving joint infiltration for the first time among 37. Sites of infiltrations were: wrist=7, elbow=10, shoulder=17, hip=1, knee=22, epidural=6, plantar heel=9. There were no significant differences in pre-procedural VAS-Anx, VAS-pain, or physiological parameters between cases and controls. Cases had a significant decrease in VAS-Anx from pre to post-infiltration (Mean post-VAS-Anx=23.33/100, p=0,017) but not significant compared with controls (p=0.297). Patients who have performed the breathing technique had no significant decrease in VAS-Pain from pre- to post-infiltration (p=0.083) and compared with controls (p=0.662). Physiological parameters showed a significant decrease in heart rate of cases from pre to post-infiltration (p&lt;0,0001) and compared with controls (p=0,036), but no significant decrease in systolic or diastolic blood pressure from pre to post-infiltration and compared with controls. There were no correlations between all participants’ VAS-Anx/VAS-Pain and age, gender, infiltration site or history and joint pain causes. Conclusion: This study suggests that diaphragmatic breathing relaxation is an effective nonpharmacological intervention that could be used in controlling anxiety and experienced pain during joint infiltration. Disclosure of Interests: None declared
The 4DPRR Index and Mechanical Power: A Step Ahead or Four Steps Backward?
Authors: Luigi Camporota, Mattia Busana, John J. Marini, Luciano Gattinoni
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

We thank the authors for calling attention to an important recent study on examining the use of pharmacotherapy with buspirone in patients with central sleep apnea related to heart failure with reduced ejection fraction (1) in our recent statement (2).As noted, the study found important decreases in chemoreflex sensitivity to carbon dioxide without changes in sensitivity to oxygen.These findings lend support to emerging evidence that central chemoreceptors play an important role in the pathogenesis of central sleep apnea in those with heart failure and stand in contrast to the traditional view that peripheral chemoreceptors are the sole important drivers in this context (3).Although the reductions in the apnea-hypopnea index in this study were modest, this work provides a foundation for much needed novel clinical investigations in addition to clarifying relevant underlying neurobiology.
Arrhythmia Mechanism and Dynamics in a Humanized Mouse Model of Inherited Cardiomyopathy Caused by Phospholamban R14del Mutation
Authors: Nour Raad, Philip Bittihn, Marine Cacheux, Dongtak Jeong, Zeki Ilkan, Delaine Ceholski, Erik Kohlbrenner, Lu Zhang, Chen-Leng Cai, Evangelia G. Kranias, Roger J. Hajjar, Francesca Stillitano, Fadi G. Akar
Journal: Circulation (2021)

Background: Arginine (Arg) 14 deletion (R14del) in the calcium regulatory protein phospholamban (hPLN R14del ) has been identified as a disease-causing mutation in patients with an inherited cardiomyopathy. Mechanisms underlying the early arrhythmogenic phenotype that predisposes carriers of this mutation to sudden death with no apparent structural remodeling remain unclear. Methods: To address this, we performed high spatiotemporal resolution optical mapping of intact hearts from adult knock-in mice harboring the human PLN WT (wildtype [WT], n=12) or the heterozygous human PLN R14del mutation (R14del, n=12) before and after ex vivo challenge with isoproterenol and rapid pacing. Results: Adverse electrophysiological remodeling was evident in the absence of significant structural or hemodynamic changes. R14del hearts exhibited increased arrhythmia susceptibility compared with wildtype. Underlying this susceptibility was preferential right ventricular action potential prolongation that was unresponsive to β-adrenergic stimulation. A steep repolarization gradient at the left ventricular/right ventricular interface provided the substrate for interventricular activation delays and ultimately local conduction block during rapid pacing. This was followed by the initiation of macroreentrant circuits supporting the onset of ventricular tachycardia. Once sustained, these circuits evolved into high-frequency rotors, which in their majority were pinned to the right ventricle. These rotors exhibited unique spatiotemporal dynamics that promoted their increased stability in R14del compared with wildtype hearts. Conclusions: Our findings highlight the crucial role of primary electric remodeling caused by the hPLN R14del mutation. These inherently arrhythmogenic features form the substrate for adrenergic-mediated VT at early stages of PLN R14del induced cardiomyopathy.
Spatial, temporal, and demographic patterns in prevalence of smoking tobacco use and initiation among young people in 204 countries and territories, 1990–2019
Authors: Marissa B Reitsma, Luisa S Flor, Erin C Mullany, Vin Gupta, Simon I Hay, Emmanuela Gakidou
Journal: The Lancet Public Health (2021)

BackgroundUniversally, smoking cessation rates among established smokers are poor. Preventing young people from starting use of and becoming addicted to tobacco products remains a key strategy to end the tobacco epidemic. Previous country-specific studies have found that initiation of smoking tobacco use occurs predominantly among young people and have found mixed progress in reducing the prevalence of smoking tobacco use among young people. Current and comparable estimates for all countries are needed to inform targeted interventions and policies.MethodsWe modelled two indicators: prevalence of current smoking tobacco use among young adults aged 15–24 years, and the age at which current smokers aged 20–54 years in 2019 began smoking regularly. We synthesised data from 3625 nationally representative surveys on prevalence of smoking and 254 on age at initiation. We used spatiotemporal Gaussian process regression to produce estimates of the prevalence of smoking and age of initiation by sex, for 204 countries and territories for each year between 1990 and 2019.FindingsGlobally in 2019, an estimated 155 million (95% uncertainty interval 150–160) individuals aged 15–24 years were tobacco smokers, with a prevalence of 20·1% (19·4–20·8) among males and 4·95% (4·64–5·29) among females. We estimated that 82·6% (82·1–83·1) of current smokers initiated between ages 14 and 25 years, and that 18·5% (17·7–19·3) of smokers began smoking regularly by age 15 years. Although some countries have made substantial progress in reducing the prevalence of smoking tobacco use among young people, prevalence in 2019 still exceeds 20% among males aged 15–24 years in 120 countries and among females aged 15–24 years in 43 countries.InterpretationThe fact that most smokers start smoking regularly before age 20 years highlights the unique window of opportunity to target prevention efforts among young people and save millions of lives and avert health-care costs in the future. Countries can substantially improve the health of their populations by implementing and enforcing evidence-based tobacco control policies that prevent the next generation from initiating smoking.FundingBloomberg Philanthropies.
Augmenting anti-CD19 and anti-CD22 CAR T-cell function using PD-1-CD28 checkpoint fusion proteins
Authors: Franziska Blaeschke, Dana Stenger, Antonia Apfelbeck, Bruno L. Cadilha, Mohamed-Reda Benmebarek, Jasmin Mahdawi, Eva Ortner, Mareike Lepenies, Nicola Habjan, Felicitas Rataj, Semjon Willier, Theresa Kaeuferle, Robbie G. Majzner, Dirk H. Busch, Sebastian Kobold, Tobias Feuchtinger
Journal: Blood Cancer Journal (2021)