bluuebunny/crossref_metadata_2025 huggingface dataset:
Populism as Parody: The Visual Self-Presentation of Jair Bolsonaro on Instagram
Authors: Mendonça Ricardo F. , Caetano Renato Duarte
Published: November 2020

This study analyzes the visual self-representation of current Brazilian President Jair Bolsonaro, who is considered to be one of the exponents of the recent rise of rightwing neopopulism. Despite the growing body of literature analyzing contemporary populism, little has been said about the deployment of images in the construction of public meanings relevant to popular understandings of populist leaders. This research draws from the social media analysis of Casullo to investigate how the images posted on Bolsonaro’s Instagram account show him (1) as a mirror of the people, (2) someone extraordinary, and (3) quick to appropriate symbols of power. Referencing the work of Butler, we document how the visual self-representation of Bolsonaro is marked by eccentricity and unsophistication, which makes his demeanor, body, and appropriation of institutional power function as a series of parodies. His performance hyperbolizes the transgressive aspect of populism, producing a vertiginous and pleasurable ambiguity toward the figure of the leader. In emptying the presidency from its extraordinary dimension, the parody paradoxically does something extraordinary by reestablishing the distance that it seeks to eliminate. His eccentric rejection of basic social standards, over-the-top masculinity, and impromptu use of everyday objects as props work to construct an image that he is just an ordinary man, extraordinarily occupying the presidency.
Reversible Encephalopathy Due to Venous Hypertension From Arteriovenous Hemodialysis Graft
Authors: Mazzola Maria Antonietta , Ramineni Anil , Burns Joseph D. , Lerner David P.
Published: November 2020

Venous congestive encephalopathy is a rare complication in patients with arteriovenous hemodialysis grafts. It commonly manifests as encephalopathy of fluctuating severity, often with seizures. Because these patients typically have multiple significant chronic health problems, venous hypertension’s contribution to the patient’s cognitive decline can easily be overlooked. This nonspecific presentation can make diagnosis challenging, therefore delaying treatment. We describe a case of progressive, fluctuating encephalopathy with seizures due to cerebral venous congestion caused by arterial shunting from an upper limb arteriovenous (AV) fistula to the proximal venous system, that was initially unrecognized, yet ultimately reversed by elimination of the source of venous hypertension.
Collagen Growth Pattern in Human Articular Cartilage of the Knee
Authors: Jørgensen Adam E.M. , Schjerling Peter , Krogsgaard Michael R. , Petersen Michael M. , Olsen Jesper , Kjær Michael , Heinemeier Katja M.
Published: November 2020

Objective

During skeletal growth, the articular cartilage expands to maintain its cover of bones in joints, however, it is unclear when and how cartilage grows. We aim to determine the expanding growth pattern and timing across the tibia plateau in human knees.

Design

Six human tibia plateaus (2 healthy, 2 with osteoarthritis, and 2 with posttraumatic osteoarthritis) were used for full-depth cartilage sampling systematically across the joint surface at 12 medial and 4 lateral sites. Methodologically, we took advantage of the performed nuclear bomb tests in the years 1955 to 1963, which increased the atmospheric 14C that was incorporated into human tissues. Cartilage was treated enzymatically to extract collagen, analyzed for 14C content, and year at formation was determined from historical atmospheric 14C concentrations.

Results

By age-determination, each tibia condyle had central points of formation surrounded by later-formed cartilage toward the periphery. Furthermore, the tibia plateaus contained collagen with 14C levels corresponding to mean donor age of 11.7 years (±3.8 SD). Finally, the medial condyle had lower 14C levels corresponding to formation 1 year later than the lateral condyle ( P = 0.009).

Conclusions

Human cartilage on the tibia plateau contains collagen that has experienced little if any turnover since school-age. The cartilage formation develops from 2 condyle centers and radially outward with the medial condyle finishing slightly later than the lateral condyle. This suggests a childhood programmed cartilage formation with a very limited adulthood collagen turnover.
Fluctuations of driving pressure during mechanical ventilation indicates elevated central venous pressure and poor outcomes
Authors: Mao Jia‐Yu , Li Dong‐Kai , Ding Xin , Zhang Hong‐Min , Long Yun , Wang Xiao‐Ting , Liu Da‐Wei
Published: November 2020

Inappropriate mechanical ventilation may induce hemodynamic alterations through cardiopulmonary interactions. The aim of this study was to explore the relationship between airway pressure and central venous pressure during the first 72 h of mechanical ventilation and its relevance to patient outcomes. We conducted a retrospective study of the Department of Critical Care Medicine of Peking Union Medical College Hospital and a secondary analysis of the MIMIC‐III clinical database. The relationship between the ranges of driving pressure and central venous pressure during the first 72 h and their associations with prognosis were investigated. Data from 2790 patients were analyzed. Wide range of driving airway pressure (odds ratio, 1.0681; 95% CI, 1.0415–1.0953; p < 0.0001) were independently associated with mortality, ventilator‐free time, intensive care unit and hospital length of stay. Furthermore, wide range of driving pressure and elevated central venous pressure exhibited a close correlation. The area under receiver operating characteristic demonstrated that range of driving pressure and central venous pressure were measured at 0.689 (95% CI, 0.670–0.707) and 0.681 (95% CI, 0.662–0.699), respectively. Patients with high ranges of driving pressure and elevated central venous pressure had worse outcomes. Post hoc tests showed significant differences in 28‐day survival rates (log‐rank (Mantel–Cox), 184.7; p < 0.001). In conclusion, during the first 72 h of mechanical ventilation, patients with hypoxia with fluctuating driving airway pressure have elevated central venous pressure and worse outcomes.
Hemodynamic effects of fluoxetine in pulmonary arterial hypertension: an open label pilot study
Authors: Sodimu Adetoun , Bartolome Sonja , Igenoza Oluwatosin P. , Chin Kelly M.
Published: November 2020

In order to evaluate the therapeutic potential of fluoxetine in pulmonary arterial hypertension, 13 patients with pulmonary arterial hypertension underwent catheterization before and after 12 (N = 5) or 24 (N = 8) weeks fluoxetine therapy. No change was seen in the primary endpoint of pulmonary vascular resistance, other hemodynamic values, or any secondary endpoints.
Brainstem lesions are associated with sleep apnea in multiple sclerosis
Authors: Levit Elle , Bouley Andrew , Baber Ursela , Djonlagic Ina , Sloane Jacob A
Published: November 2020

Background

Studies linking MRI findings in MS patients with obstructive sleep apnea severity are limited.

Objective

We conducted a retrospective study to assess MRI abnormalities associated with obstructive sleep apnea (OSA) in patients with multiple sclerosis (MS).

Methods

We performed retrospective chart review of 65 patients with multiple sclerosis who had undergone polysomnography (PSG) for fatigue as well as brain MRI. We measured the number of lesions in the brainstem and calculated the standardized third ventricular width (sTVW) as a measure of brain atrophy, and subsequently performed correlation analyses of the apnea-hypopnea index (AHI) with brainstem lesion location, sTVW, and Expanded Disability Status Scale (EDSS).

Results

MS Patients with OSA were significantly older and had a higher body mass index (BMI) and higher AHI measures than patients without OSA. After adjustment for covariates, significant associations were found between AHI and lesion burden in the midbrain (p < 0.01) and pons (p = 0.05), but not medulla.

Conclusions

Midbrain and pontine lesions burden correlated with AHI, suggesting MS lesion location could contribute to development of OSA.
Analysis of the coracoid morphology with multiplanar 2D CT and its effects on the graft size in the Latarjet procedure
Authors: Sarı Abdulkadir , Sasani Hadi , Çetin Mehmet Ümit , Günaydin Burak , Kilinç Seyran , Yildirim Ilker , Dinçel Yaşar Mahsut
Published: November 2020

Purpose:

In this study, we aimed to reveal the individual differences regarding the size of the coracoid and their effects on the classical and modified Latarjet procedures.

Methods:

Computed tomography images of 120 patients (mean age: 41.18 ± 12.01 years) without shoulder complaints or shoulder instability were evaluated retrospectively. The glenoid width, the surgical graft length, and the coracoid total length, width, and thickness were measured using the multiplanar reconstruction method on the Sectra Picture Archiving and Communications System (PACS) system. Age, gender, side, the dominant hand, and the height of the patients were recorded and the correlations between them were investigated. On the created hypothetical model, the current size of the coracoid was evaluated to determine what size of glenoid defects it could repair by employing the classical and the modified Latarjet techniques.

Results:

There was no significant difference between the right-hand-dominant group and the left-hand-dominant group in terms of coracoid measurement results ( p > 0.05). Again, there was no statistically significant difference between the right and the left side regarding the coracoid size ( p > 0.05). A positive correlation could be detected only between age and the coracoid width and thickness ( p < 0.05). A positive correlation was also found between the glenoid width and the coracoid width and thickness in both shoulders ( p < 0.001). Coracoid thickness could fill in the defects that amounted to 40% of the glenoid width, while the coracoid width could fill in for the defects that were 50% of the glenoid width in both genders.

Conclusion:

Our study showed that hand dominance and side were not effective on the coracoid dimensions. In addition, it has been shown that the coracoid dimensions did not have a significant effect in the choice of Latarjet technique in terms of defect repair and that repair rates of up to 40% could be achieved in glenoid defects with both techniques.
Intramedullary hemostasis further reduces postoperative anemia in patients over 70 years old undergoing total hip arthroplasty
Authors: Tang Kaying , Wu Yahong , Mu Yuan , Li Ruidong , Nie Mao , Yin Liangjun
Published: November 2020

Purpose:

Postoperative anemia has been a threat to total hip arthroplasty patients. We introduced a novel medullary cavity hemostasis (MCH) technique and combined it with tranexamic acid (TXA) to prevent postoperative anemia in elder patients. This trial was conducted to evaluate the effectiveness and safety of this technique.

Methods:

In this retrospective consecutive study, each group has 88 patients who were all over 70 years old. In the control group, patients were given TXA. In the experimental group, the MCH technique and same TXA application were used.

Results:

The average of total blood loss, drainage volume, and hidden blood loss were significantly less in the experimental group. The postoperative hemoglobin (Hb) level was significantly higher in the experimental group (100.6 g/dL) than it is in the control group (81.4 g/dL). None of the patient has shown signs of prosthesis subsidence, periprosthetical osteolysis, or stem loosening during follow-ups in the average follow-up time of 3 years.

Conclusion:

We discovered that application of TXA alone is not sufficient to prevent postoperative moderate anemia in patients over 70 years old. Combination of TXA and MCH is an effective and safe way to alleviate the severity of postoperative anemia.
Patient Satisfaction With Medical Services Provided at Unani Medicine Hospital, Bengaluru: A Cross-Sectional Study
Authors: Ahmad Ejaz , Itrat Malik
Published: November 2020

In medical care, patient satisfaction is a key indicator of the quality of care. Many studies have agreed on the fact that measuring patient satisfaction is a useful tool for determining the effectiveness of health care delivery and the quality of medical care provided. Hence, present study was aimed to determine the level of patient’s satisfaction with the quality of medical care services rendered in a teaching hospital of Unani medicine. A hospital-based cross-sectional study was conducted at the National Institute of Unani Medicine Hospital, Bengaluru, from April 2019 to October 2019 on 500 patients sampled from various service delivery points of the health facility. Data were gathered through exit interviews of patients after obtaining their written informed consent. A predesigned and pretested questionnaire on patient satisfaction patient satisfaction questionnaire (PSQ-18) was used as a study tool. The overall mean patient satisfaction score was 4.82 ± 0.23. Mean satisfaction was highest in the interpersonal manner (4.94) and communication (4.94), followed by time spent with the doctor (4.91), technical quality (4.87), financial aspect (4.87), accessibility and convenience (4.65), and least in general satisfaction (4.54). No sociodemographic variables were found to correlate significantly with satisfaction score ( P > .05). In clinical variables, treatment effectiveness was found to be significantly associated with the satisfaction score ( P = .002). The study found that overall patients were highly satisfied with the medical services provided by the health facility. Furthermore, the study finds that treatment effectiveness has a more significant effect on patients’ satisfaction compared with other factors.
Disseminating a patient-centered education bundle to reduce missed doses of pharmacologic venous thromboembolism (VTE) prophylaxis to a community hospital
Authors: Owodunni Oluwafemi P , Lau Brandyn D , Shaffer Dauryne L , McQuigg Danielle , Samuel Deborah , Kantsiper Mindy , Harris James E , Hobson Deborah B , Kraus Peggy S , Webster Kristen LW , Holzmueller Christine G , Kia Mujan Varasteh , Streiff Michael B , Haut Elliott R
Published: November 2020

Background

Venous thromboembolism (VTE) is a leading cause of preventable harm in hospitalized patients. However, many doses of prescribed pharmacologic VTE prophylaxis are frequently missed. We investigated the effect of a patient-centered education bundle on missed doses of VTE prophylaxis in a community hospital.

Methods

We performed a pre-post analysis examining missed doses of VTE prophylaxis in a community hospital. A real-time alert from the electronic health record system facilitated the delivery of a patient education bundle intervention. We included all patient visits on a single floor where at least 1 dose of VTE prophylaxis was prescribed during pre- (January 1, 2018, - November 31, 2018) and post- (January 1 - June 31, 2019) intervention periods. Outcomes included any missed dose (primary) and reasons for missed doses (refusal, other [secondary]) and were compared between both periods.

Results

1,614 patient visits were included. The proportion of any missed dose significantly decreased (13.8% vs. 8.2% [OR, 0.56; 95% CI, 0.48, 0.64]) between the pre-post intervention periods. Patient refusal was the most frequent reason for missed doses. In the post-intervention period, patient refusal significantly decreased from 8.8% to 5.0% (OR, 0.54; 95% CI, 0.46, 0.64). Similarly, other reasons for missed doses significantly decreased from 5.0% to 3.2% (OR, 0.62; 95% CI, 0.51, 0.77).

Conclusions

A real-time alert-triggered patient-centered education bundle developed and tested in an academic hospital, significantly reduced missed doses of prescribed pharmacologic VTE prophylaxis when disseminated to a community hospital.
Plasmablasts derive from CD23– activated B cells after the extinction of IL-4/STAT6 signaling and IRF4 induction
Authors: Pignarre Amandine , Chatonnet Fabrice , Caron Gersende , Haas Marion , Desmots Fabienne , Fest Thierry
Published: November 2020

The terminal differentiation of B cells into antibody-secreting cells (ASCs) is a critical component of adaptive immune responses. However, it is a very sensitive process, and dysfunctions lead to a variety of lymphoproliferative neoplasias including germinal center–derived lymphomas. To better characterize the late genomic events that drive the ASC differentiation of human primary naive B cells, we used our in vitro differentiation system and a combination of RNA sequencing and Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC sequencing). We discovered 2 mechanisms that drive human terminal B-cell differentiation. First, after an initial response to interleukin-4 (IL-4), cells that were committed to an ASC fate downregulated the CD23 marker and IL-4 signaling, whereas cells that maintained IL-4 signaling did not differentiate. Second, human CD23– cells also increased IRF4 protein to levels required for ASC differentiation, but they did that independently of the ubiquitin-mediated degradation process previously described in mice. Finally, we showed that CD23– cells carried the imprint of their previous activated B-cell status, were precursors of plasmablasts, and had a phenotype similar to that of in vivo preplasmablasts. Altogether, our results provide an unprecedented genomic characterization of the fate decision between activated B cells and plasmablasts, which provides new insights into the pathological mechanisms that drive lymphoma biology.
Integrative genomic analysis of pediatric T-cell lymphoblastic lymphoma reveals candidates of clinical significance
Authors: Khanam Tasneem , Sandmann Sarah , Seggewiss Jochen , Ruether Charlotte , Zimmermann Martin , Norvil Allison B. , Bartenhagen Christoph , Randau Gerrit , Mueller Stephanie , Herbrueggen Heidi , Hoffmann Per , Herms Stefan , Wei Lanying , Woeste Marius , Wuensch Christian , Gowher Humaira , Oschlies Ilske , Klapper Wolfram , Woessmann Wilhelm , Dugas Martin , Burkhardt Birgit
Published: November 2020

T-cell lymphoblastic lymphoma (T-LBL) is a heterogeneous malignancy of lymphoblasts committed to T-cell lineage. The dismal outcomes (15%-30%) after T-LBL relapse warrant establishing risk-based treatment. To our knowledge, this study presents the first comprehensive, systematic, integrated, genome-wide analysis including relapsed cases that identifies molecular markers of prognostic relevance for T-LBL. NOTCH1 was identified as the putative driver for T-LBL. An activated NOTCH/PI3K-AKT signaling axis and alterations in cell cycle regulators constitute the core oncogenic program for T-LBL. Mutated KMT2D was identified as a prognostic marker. The cumulative incidence of relapse was 47% ± 17% in patients with KMT2D mutations, compared with 14% ± 3% in wild-type KMT2D. Structural analysis of the mutated domains of KMT2D revealed a plausible impact on structure and functional consequences. These findings provide new insights into the pathogenesis of T-LBL, including high translational potential. The ongoing LBL 2018 trial (www.clinicaltrials.gov #NCT04043494) allows for prospective validation and subsequent fine tuning of the stratification criteria for T-LBL risk groups to improve survival of pediatric patients.
Rurioctocog alfa pegol PK-guided prophylaxis in hemophilia A: results from the phase 3 PROPEL study
Authors: Klamroth Robert , Windyga Jerzy , Radulescu Vlad , Collins Peter W. , Stasyshyn Oleksandra , Ibrahim Hishamshah Mohd , Engl Werner , Tangada Srilatha D. , Savage William , Ewenstein Bruce
Published: November 2020

Rurioctocog alfa pegol prophylaxis targeting factor VIII (FVIII) troughs ≥1% has shown to be efficacious with an acceptable safety profile in people with hemophilia A (PwHA). The PROPEL trial compared safety and efficacy of 2 target FVIII troughs in PwHA aged 12 to 65 years, with severe disease, annualized bleeding rate ≥2, and previous FVIII treatment. PwHA were randomized to 12 months’ pharmacokinetic (PK)-guided rurioctocog alfa pegol prophylaxis targeting FVIII troughs of 1% to 3% (reference arm) or 8% to 12% (elevated arm); first 6 months was treatment-adjustment period. The primary endpoint was absence of bleeds during the second 6 months, analyzed using multiple imputations (full analysis set [FAS]). In the 1% to 3% and 8% to 12% arms, respectively, point estimates (95% confidence interval) of proportions of PwHA with zero total bleeds were 42% (29% to 55%) and 62% (49% to 75%) in FAS (N = 115; P = .055) and 40% (27% to 55%) and 67% (52% to 81%) in per-protocol analysis set (N = 95; P = .015). Dosing frequency and consumption varied in each arm. Adverse events (AEs) occurred in 70/115 (60.9%) PwHA; serious AEs in 7/115 (6%) PwHA, including 1 treatment-related in 8% to 12% arm (transient anti–FVIII inhibitor). There were no deaths, serious thrombotic events, or AE-related discontinuations. PK-guided prophylaxis was achievable and efficacious in both arms. No new safety signals were observed in the 8% to 12% arm. These results demonstrate elevated FVIII troughs can increase the proportion of PwHA with zero bleeds and emphasize the importance of personalized treatment. This trial was registered at www.clinicaltrials.gov as #NCT02585960.
Chemotherapy or allogeneic transplantation in high-risk Philadelphia chromosome–negative adult lymphoblastic leukemia
Authors: Ribera Josep-Maria , Morgades Mireia , Ciudad Juana , Montesinos Pau , Esteve Jordi , Genescà Eulàlia , Barba Pere , Ribera Jordi , García-Cadenas Irene , Moreno María José , Martínez-Carballeira Daniel , Torrent Anna , Martínez-Sánchez Pilar , Monsalvo Silvia , Gil Cristina , Tormo Mar , Artola María Teresa , Cervera Marta , González-Campos José , Rodríguez Carlos , Bermúdez Arancha , Novo Andrés , Soria Beatriz , Coll Rosa , Amigo María-Luz , López-Martínez Aurelio , Fernández-Martín Rosa , Serrano Josefina , Mercadal Santiago , Cladera Antònia , Giménez-Conca Alberto , Peñarrubia María-Jesús , Abella Eugènia , Vall-llovera Ferran , Hernández-Rivas Jesús-María , Garcia-Guiñon Antoni , Bergua Juan-Miguel , de Rueda Beatriz , Sánchez-Sánchez María-José , Serrano Alfons , Calbacho María , Alonso Natalia , Méndez-Sánchez Jose-Ángel , García-Boyero Raimundo , Olivares Matxalen , Barrena Susana , Zamora Lurdes , Granada Isabel , Lhermitte Ludovic , Feliu Evarist , Orfao Alberto
Published: November 2020

The need for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in adults with Philadelphia chromosome–negative (Ph−) acute lymphoblastic leukemia (ALL) with high-risk (HR) features and adequate measurable residual disease (MRD) clearance remains unclear. The aim of the ALL-HR-11 trial was to evaluate the outcomes of HR Ph− adult ALL patients following chemotherapy or allo-HSCT administered based on end-induction and consolidation MRD levels. Patients aged 15 to 60 years with HR-ALL in complete response (CR) and MRD levels (centrally assessed by 8-color flow cytometry) <0.1% after induction and <0.01% after early consolidation were assigned to receive delayed consolidation and maintenance therapy up to 2 years in CR. The remaining patients were allocated to allo-HSCT. CR was attained in 315/348 patients (91%), with MRD <0.1% after induction in 220/289 patients (76%). By intention-to-treat, 218 patients were assigned to chemotherapy and 106 to allo-HSCT. The 5-year (±95% confidence interval) cumulative incidence of relapse (CIR), overall survival (OS), and event-free survival probabilities for the whole series were 43% ± 7%, 49% ± 7%, and 40% ± 6%, respectively, with CIR and OS rates of 45% ± 8% and 59% ± 9% for patients assigned to chemotherapy and of 40% ± 12% and 38% ± 11% for those assigned to allo-HSCT, respectively. Our results show that avoiding allo-HSCT does not hamper the outcomes of HR Ph− adult ALL patients up to 60 years with adequate MRD response after induction and consolidation. Better postremission alternative therapies are especially needed for patients with poor MRD clearance. This trial was registered at www.clinicaltrials.gov as # NCT01540812.
Real-world experience with caplacizumab in the management of acute TTP
Authors: Dutt Tina , Shaw Rebecca J. , Stubbs Matthew , Yong Jun , Bailiff Benjamin , Cranfield Tanya , Crowley Maeve P. , Desborough Michael , Eyre Toby A. , Gooding Richard , Grainger John , Hanley John , Haughton Joanna , Hermans Joannes , Hill Quentin , Humphrey Louise , Lowe Gillian , Lyall Hamish , Mohsin Muhammad , Nicolson Phillip L. R. , Priddee Nicole , Rampotas Alexandros , Rayment Rachel , Rhodes Susan , Taylor Alice , Thomas William , Tomkins Oliver , Van Veen Joost J. , Lane Steven , Toh Cheng-Hock , Scully Marie
Published: November 2020

The cornerstone of life-saving therapy in immune-mediated thrombotic thrombocytopenic purpura (iTTP) has been plasma exchange (PEX) combined with immunomodulatory strategies. Caplacizumab, a novel anti–von Willebrand factor nanobody trialed in 2 multicenter randomized controlled trials (RCTs) leading to European Union and US Food and Drug Administration approval, has been available in the United Kingdom (UK) through a patient access scheme. Data were collected retrospectively from 2018 to 2020 for 85 patients (4 children) receiving caplacizumab from 22 UK hospitals. Patient characteristics and outcomes in the real-world clinical setting were compared with caplacizumab trial end points and historical outcomes in the precaplacizumab era. Eighty-four of 85 patients received steroid and rituximab alongside PEX; 26% required intubation. Median time to platelet count normalization (3 days), duration of PEX (7 days), and hospital stay (12 days) were comparable with RCT data. Median duration of PEX and time from PEX initiation to platelet count normalization were favorable compared with historical outcomes (P < .05). Thrombotic thrombocytopenic purpura (TTP) recurred in 5 of 85 patients; all had persistent ADAMTS13 activity < 5 IU/dL. Of 31 adverse events in 26 patients, 17 of 31 (55%) were bleeding episodes, and 5 of 31 (16%) were thrombotic events (2 unrelated to caplacizumab); mortality was 6% (5/85), with no deaths attributed to caplacizumab. In 4 of 5 deaths, caplacizumab was introduced >48 hours after PEX initiation (3-21 days). This real-world evidence represents the first and largest series of TTP patients, including pediatric patients, receiving caplacizumab outside of clinical trials. Representative of true clinical practice, the findings provide valuable information for clinicians treating TTP globally.
ER-associated degradation preserves hematopoietic stem cell quiescence and self-renewal by restricting mTOR activity
Authors: Liu Lu , Inoki Ayaka , Fan Kelly , Mao Fengbiao , Shi Guojun , Jin Xi , Zhao Meiling , Ney Gina , Jones Morgan , Sun Shengyi , Dou Yali , Inoki Ken , Qi Ling , Li Qing
Published: November 2020

Hematopoietic stem cells (HSC) self-renew to sustain stem cell pools and differentiate to generate all types of blood cells. HSCs remain in quiescence to sustain their long-term self-renewal potential. It remains unclear whether protein quality control is required for stem cells in quiescence when RNA content, protein synthesis, and metabolic activities are profoundly reduced. Here, we report that protein quality control via endoplasmic reticulum-associated degradation (ERAD) governs the function of quiescent HSCs. The Sel1L/Hrd1 ERAD genes are enriched in the quiescent and inactive HSCs, and conditional knockout of Sel1L in hematopoietic tissues drives HSCs to hyperproliferation, which leads to complete loss of HSC self-renewal and HSC depletion. Mechanistically, ERAD deficiency via Sel1L knockout leads to activation of mammalian target of rapamycin (mTOR) signaling. Furthermore, we identify Ras homolog enriched in brain (Rheb), an activator of mTOR, as a novel protein substrate of Sel1L/Hrd1 ERAD, which accumulates upon Sel1L deletion and HSC activation. Importantly, inhibition of mTOR, or Rheb, rescues HSC defects in Sel1L knockout mice. Protein quality control via ERAD is, therefore, a critical checkpoint that governs HSC quiescence and self-renewal by Rheb-mediated restriction of mTOR activity.
Bone marrow dendritic cell aggregates associate with systemic immune dysregulation in chronic myelomonocytic leukemia
Authors: Mangaonkar Abhishek A. , Reichard Kaaren K. , Binder Moritz , Coltro Giacomo , Lasho Terra L. , Carr Ryan M. , Chiu April , Negron Vivian , Hefazi Mehrdad , Anagnostou Theodora , Timm Michael M. , Hiebert James W. , Villasboas Jose C. , Gonsalves Wilson I. , Gangat Naseema , Shah Mithun , Alkhateeb Hassan B. , Al-Kali Aref , Elliott Michelle A. , Begna Kebede H. , Wolanskyj-Spinner Alexandra P. , Litzow Mark R. , Hogan William J. , Ansell Stephen M. , Pardanani Animesh , Tefferi Ayalew , Patnaik Mrinal M.
Published: November 2020

Key Points

Systemic immune microenvironment signatures in CMML indicate an altered T- and natural killer cell balance. CMML bone marrow dendritic cell aggregates associate with disease progression and systemic regulatory T-cell phenotypic switch.
Management of tracheo-oesophageal fistula in adults
Authors: Kim Hyun S. , Khemasuwan Danai , Diaz-Mendoza Javier , Mehta Atul C.
Published: November 2020

Tracheo-oesophageal fistula (TOF) is a pathological connection between the trachea and the oesophagus that is associated with various underlying conditions including malignancies, infections, inhalation injuries and traumatic damage. As the condition spans multiple organ systems with varying aetiologies and acuities, TOF poses unique diagnostic and management challenges to pulmonologists, gastroenterologists and thoracic surgeons alike. Although stents have been a cornerstone in the management of TOF, there exists a large gap in our understanding of their efficacy and precise methodology, making stenting procedure both art and science. TOFs relating to underlying oesophageal or tracheal malignancies require advanced understanding of the airway and digestive tract anatomy, dimensions of the fistula, stent characteristics and types, and the interplay between the oesophageal stent and the airway stent if dual stenting procedure is elected. In this review article, we review the most up-to-date data on risk factors, clinical manifestations, diagnostic approaches, management methods and prognosis. Consequently, this article serves to evaluate current therapeutic strategies and the future directions in the areas of 3D-printed stents, over-the-scope clipping systems, tissue matrices and atrial septal closure devices.
Health-related quality of life of patients with idiopathic pulmonary fibrosis: a systematic review and meta-analysis
Authors: Cox Ingrid A. , Borchers Arriagada Nicolas , de Graaff Barbara , Corte Tamera J. , Glaspole Ian , Lartey Stella , Walters E. Haydn , Palmer Andrew J.
Published: November 2020

Idiopathic pulmonary fibrosis (IPF) is one of the most common forms of interstitial lung disease presenting in persons 50 years and older. Through a comprehensive review of available studies, we aimed to assess health-related quality of life (HRQoL) of people living with IPF and the instruments used in this assessment.

Searches were conducted up to May, 2020. Quality appraisal and data extraction were performed using pre-designed forms. Narrative synthesis approach was used to report results of the systematic review and a random effects model was used for the meta-analysis. A leave-one-out sensitivity analysis was performed, and a trim and fill method was used to assess publication bias.

The review included 134 studies. The most used instruments to measure HRQoL were St George's Respiratory Questionnaire (SGRQ), Short Form 36 (SF36) and EuroQoL (EQ5D). Standardised mean scores (95% confidence interval) for these instruments were as follows: SGRQ total score: 44.72 (42.21–47.22); SF36 physical component score (PCS): 37.00 (34.74–39.26) SF36 mental component score (MCS): 50.18 (48.41–51.95); King's Brief Interstitial Lung Disease questionnaire total score: 58.38 (55.26–61.51); and EQ5D utility: 0.73 (0.68–0.79). Analysis of standardised means for both SGRQ and SF36 demonstrated worse scores in physical health domains as compared to mental health domains.

This systematic review confirms that IPF negatively affected HRQoL, mostly impacting the physical health domains. This study also demonstrated that a diverse number of instruments are used to evaluate HRQoL. In view of this diversity, a standardised approach to measurement of HRQoL for IPF is important to ensure that comparisons made are reliable.
Different stability of miRNAs and endogenous control genes in archival specimens of papillary thyroid carcinoma
Authors: Pamedytyte Daina , Leipute Enrika , Zilaitiene Birute , Sarauskas Valdas , Dauksiene Dalia , Dauksa Albertas , Zvirbliene Aurelija
Published: November 2020

Background

The most popular miRNA quantitation technique is RQ-PCR with relative gene expression method that requires an endogenous control (EC) gene for data normalization. However, there are insufficient data and selection criteria on the most suitable ECs for miRNA expression studies in many cancer types including papillary thyroid carcinoma (PTC). Therefore, in this study we evaluated the impact of chosen EC and archival formalin-fixed, paraffin-embedded (FFPE) PTC tissue age on estimated target miRNA expression.

Methods

RQ-PCR was used to determine expression levels of five miRNAs (miR-146b, miR-222, miR-21, miR-221 and miR-181b) and three different endogenous controls (RNU48, let-7a, miR-16), which were used to normalize the data. In total, 400 FFPE PTC tissues were analyzed that have been stored from 1 to 15 years.

Results

The stability of commonly used ECs RNU48 and let-7a significantly differs from the stability of target miRNA in archival FFPE PTC tissues. Moreover, these differences have a great impact on miRNA expression results when FFPE tissue samples have been stored for a different period of time.

Conclusions

It is important to select an ECs not only stable in the tissue of interest but also with similar stability to target miRNA, especially when working with samples of different age.
Placental growth factor for the prognosis of women with preeclampsia (fullPIERS model extension): context matters
Authors:   for the fullPIERS Group, Ukah U. Vivian , Payne Beth A. , Hutcheon Jennifer A. , Chappell Lucy C. , Seed Paul T. , Conti-Ramsden Frances Inez , Ansermino J. Mark , Magee Laura A. , von Dadelszen Peter
Published: November 2020

Background

The fullPIERS risk prediction model was developed to identify which women admitted with confirmed diagnosis of preeclampsia are at highest risk of developing serious maternal complications. The model discriminates well between women who develop (vs. those who do not) adverse maternal outcomes. It has been externally validated in several populations. We assessed whether placental growth factor (PlGF), a biomarker associated with preeclampsia risk, adds incremental value to the fullPIERS model.

Methods

Using a cohort of women admitted into tertiary hospitals in well-resourced settings (the USA and Canada), between May 2010 to February 2012, we evaluated the incremental value of PlGF added to fullPIERS for prediction of adverse maternal outcomes within 48 h after admission with confirmed preeclampsia. The discriminatory performance of PlGF and the fullPIERS model were assessed in this cohort using the area under the receiver’s operating characteristic curve (AUROC) while the extended model (fullPIERS +PlGF) was assessed based on net reclassification index (NRI) and integrated discrimination improvement (IDI) performances.

Results

In a cohort of 541 women delivered shortly (< 1 week) after presentation, 8.1% experienced an adverse maternal outcome within 48 h of admission. Prediction of adverse maternal outcomes was not improved by addition of PlGF to fullPIERS (NRI: -8.7, IDI − 0.06). Discriminatory performance (AUROC) was 0.67 [95%CI: 0.59–0.75] for fullPIERS only and 0.67 [95%CI: 0.58–0.76]) for fullPIERS extended with PlGF, a performance worse than previously documented in fullPIERS external validation studies (AUROC > 0.75).

Conclusions

While fullPIERS model performance may have been affected by differences in healthcare context between this study cohort and the model development and validation cohorts, future studies are required to confirm whether PlGF adds incremental benefit to the fullPIERS model for prediction of adverse maternal outcomes in preeclampsia in settings where expectant management is practiced.
Range of abduction in patients with Legg-Calvé-Perthes disease – a nationwide register-based cohort study
Authors: El-Harbiti Ahmad , Hailer Yasmin D.
Published: November 2020

Background

Range of abduction often decreases during Legg-Calvé-Perthes Disease (LCPD) disease. However, a good range of abduction is required during the course of LCPD, especially when containment surgery should be performed. This study aimed to investigate how many patients registered in the Swedish Pediatric Orthopedic Quality register (SPOQ) with LCPD had reduced range of abduction at diagnosis in relation to sex or age at diagnosis or severity of disease (lateral pillar class at the time at diagnosis), if physiotherapy (PT) was prescribed and has a beneficial impact in maintaining (or increasing) abduction and if the range of abduction at diagnosis before fragmentation stage is predictive for the lateral pillar classification at fragmentation stage.

Methods

The national Swedish Pediatric Orthopedic Quality Register (SPOQ), established in 2015, is used to identify patients with LCPD. The patients are registered at three time points: at diagnosis, at potential surgery and 2 years after diagnosis. Range of abduction and information on PT are required to register at all registration sessions. One hundred ninety-nine hips from 192 children were registered in the SPOQ.

Results

Of all hips, the mean range of abduction at diagnosis was 39 degrees (range 0 to 90). One hundred twenty-six patients (63%) either received instructions for PT or were referred to a physiotherapist; two patients were treated additionally with an abduction brace. There was a trend that patients who received PT, compared to patients without PT, either maintained or increased their range of abduction at the 2-year follow-up. Older age at diagnosis correlated with decreased range of abduction at the 2-year follow-up (Estimate [Est]: − 3.1, 95% confidence interval [CI]: − 4.4 to − 1.7). The degree of abduction at diagnosis before fragmentation stage correlated with the lateral pillar group at the fragmentation stage (Est: -5.3, 95% CI: − 10.0 to − 1.1).

Conclusion

In all, 63% of the children with LCPD in SPOQ received either written instructions or were referred to PT or both. PT seems to have a favorable impact for maintaining the range of abduction in children with LCPD. Children with a lower range of abduction at diagnosis (before the fragmentation stage) developed a higher degree of lateral pillar involvement as measured by the lateral pillar classification.
A prospective study of the muscle strength and reaction time of the quadriceps, hamstring, and gastrocnemius muscles in patients with plantar fasciitis
Authors: Lee Jin Hyuck , Jung Hae Woon , Jang Woo Young
Published: November 2020

Background

Muscle weakness is an important etiological factor in plantar fasciitis (PF), but available data on the role of the quadriceps, hamstring, and gastrocnemius (GCM) muscles are limited. The aim of this study was to compare the strength and reaction time of the quadriceps, hamstring, and GCM muscles and foot pressure between patients with PF and normal controls.

Methods

A total of 21 PF patients and 21 normal controls were enrolled. Muscle strength was measured by the peak torque per body weight (Nmkg− 1 × 100). Muscle reaction time was evaluated by the acceleration time (AT, milliseconds). Foot pressure and posture were assessed by pedobarography [valgus/varus index (VV index), %].

Results

The strength of the quadriceps was significantly lower in the affected ankles of the PF group than in the control group (p = 0.005). The AT of the quadriceps and hamstring muscles was significantly increased in the affected ankles of the PF group than in the control group (quadriceps: p = 0.012, hamstring: p = 0.001), while the AT of the GCM muscle was significantly decreased (p = 0.009) and significantly correlated negatively with quadriceps muscle strength (r = −.598, p = 0.004) and AT (r = −.472, p = 0.031). Forefoot (p = 0.001) and hindfoot (p = 0.000) pressure were significantly greater, with the VV index showing hindfoot valgus, in the affected ankles in the PF group compared to the control group (p = 0.039).

Conclusions

This study demonstrated weakness and delayed reaction time of the quadriceps and hamstring muscles, with a rapid reaction time of the GCM muscle, in patients with PF.

Clinical relevance

Clinicians and therapists should assess the function of the quadriceps and hamstring muscles when planning the management of PF patients without muscle tightness.
Risk of invasive breast cancer in relatives of patients with breast carcinoma in situ: a prospective cohort study
Authors: Mukama Trasias , Fallah Mahdi , Brenner Hermann , Xu Xing , Sundquist Kristina , Sundquist Jan , Kharazmi Elham
Published: November 2020

Background

Wide implementation of mammography screening has resulted in increased numbers of women diagnosed with breast carcinoma in situ. We aimed to determine the risk of invasive breast cancer in relatives of patients with breast carcinoma in situ in comparison to the risk in relatives of patients with invasive breast cancer.

Methods

We analyzed the occurrence of cancer in a nationwide cohort including all 5,099,172 Swedish women born after 1931 with at least one known first-degree relative. This was a record linkage study of Swedish family cancer datasets, including cancer registry data collected from January 1, 1958, to December 31, 2015. We calculated standardized incidence ratios (SIRs) and 10-year cumulative risk of breast cancer diagnosis for women with a family history of in situ and invasive breast cancer.

Results

Having one first-degree relative with breast carcinoma in situ was associated with 50% increased risk of invasive breast cancer (SIR = 1.5, 95% CI 1.4–1.7) when compared to those who had no family history of invasive breast cancer or breast carcinoma in situ in either first- or second-degree relatives. Similarly, having one first-degree relative with invasive breast cancer was associated with 70% (1.7, 1.7–1.8) increased risk. The 10-year cumulative risk for women at age 50 with a relative with breast carcinoma in situ was 3.5% (2.9–3.9%) and was not significantly different from 3.7% (3.6–3.8%) risk for 50-year-old women with a relative with invasive breast cancer (95% confidence intervals overlapped).

Conclusions

The risk of invasive breast cancer for women with a family history of breast carcinoma in situ was comparable to that for women with a family history of invasive breast cancer. Therefore, family history of breast carcinoma in situ should not be overlooked in recommendations for breast cancer prevention for women with a family history of breast cancer.
Polyamines and related signaling pathways in cancer
Authors: Li Jiajing , Meng Yan , Wu Xiaolin , Sun Yuxin
Published: November 2020

Polyamines are aliphatic compounds with more than two amino groups that play various important roles in human cells. In cancer, polyamine metabolism dysfunction often occurs, and regulatory mechanisms of polyamine. This review summarizes the existing research on the metabolism and transport of polyamines to study the association of oncogenes and related signaling pathways with polyamines in tumor cells. Drugs that regulate enzymes have been developed for cancer treatment, and in the future, more attention should be paid to treatment strategies that simultaneously modulate polyamine metabolism and carcinogenic signaling pathways. In addition, the polyamine pathway is a potential target for cancer chemoprevention. As an irreversible suicide inhibitor of the ornithine decarboxylase (a vital enzyme of polyamine synthesis), Difluoro-methylornithine had been shown to have the chemoprevention effect on cancer. Therefore, we summarized and analyzed the chemoprophylaxis effect of the difluoromethylornithine in this systematic review.
Association of ambient air pollution with cardiovascular disease risks in people with type 2 diabetes: a Bayesian spatial survival analysis
Authors: Su Pei-Fang , Sie Fei-Ci , Yang Chun-Ting , Mau Yu-Lin , Kuo Shihchen , Ou Huang-Tz
Published: November 2020

Background

Evidence is limited on excess risks of cardiovascular diseases (CVDs) associated with ambient air pollution in diabetic populations. Survival analyses without considering the spatial structure and possible spatial correlations in health and environmental data may affect the precision of estimation of adverse environmental pollution effects. We assessed the association between air pollution and CVDs in type 2 diabetes through a Bayesian spatial survival approach.

Methods

Taiwan’s national-level health claims and air pollution databases were utilized. Fine individual-level latitude and longitude were used to determine pollution exposure. The exponential spatial correlation between air pollution and CVDs was analyzed in our Bayesian model compared to traditional Weibull and Cox models.

Results

There were 2072 diabetic patients included in analyses. PM2.5 and SO2 were significant CVD risk factors in our Bayesian model, but such associations were attenuated or underestimated in traditional models; adjusted hazard ratio (HR) and 95% credible interval (CrI) or confidence interval (CI) of CVDs for a 1 μg/m3 increase in the monthly PM2.5 concentration for our model, the Weibull and Cox models was 1.040 (1.004–1.073), 0.994 (0.984–1.004), and 0.994 (0.984–1.004), respectively. With a 1 ppb increase in the monthly SO2 concentration, adjusted HR (95% CrI or CI) was 1.886 (1.642–2.113), 1.092 (1.022–1.168), and 1.091 (1.021–1.166) for these models, respectively.

Conclusions

Against traditional non-spatial analyses, our Bayesian spatial survival model enhances the assessment precision for environmental research with spatial survival data to reveal significant adverse cardiovascular effects of air pollution among vulnerable diabetic patients.

Graphical abstract