bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abnormal MRI signal intensity of the triangular fibrocartilage complex in asymptomatic wrists
Authors: Wang Zhixin , Chen Shanlin , Liu Bo , Qian Zhanhua , Zhu Jin , Wang Qianqian 
Published: December 2022

We investigated abnormal MRI findings of the triangular fibrocartilage complex in 154 asymptomatic volunteers (21–79 years). Except prevalence, we focused on the morphological features of abnormal signals in relation to age. The majority of full-thickness tears were located in the articular disc (63 participants). The incidence of disc perforation with characteristics of ulnar impaction syndrome increased significantly with age. Asymptomatic full-thickness tears of the ulnar attachment were found in ten participants (seven over 60 years old). The proximal and distal laminae of the ulnar attachment could not be differentiated in 36 participants. In conclusion, MRI is of limited value for the elderly in diagnosing triangular fibrocartilage disorders. For young subjects, MRI is still valuable, especially in diagnosing ulnar detachment, although the ability to distinguish between proximal and distal laminae remains questionable. Disc perforations in volunteers mimicked ulnar impaction syndrome, therefore age, clinical signs and other factors should also be considered in clinical diagnosis. Level of evidence: III
Clinical significance of acute exacerbation in interstitial lung disease with antineutrophil cytoplasmic antibody: an indicator of poor prognosis
Authors: Wu Tingting , Zhang Yun , Cen Zekai , Ying Yanan , Sun Chao , Lv Chengna , Ding Qunli 
Published: December 2022

Background: The association between interstitial lung disease (ILD) and antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV) has been increasingly recognized in recent years. The clinical features and prognostic differences between AAV-associated ILD and isolated ANCA-positive idiopathic interstitial pneumonias (IIPs) remain unclear. The purpose of this study was to determine the clinical significance and prognosis of ANCA-positive ILD to further guide clinical management. Methods: This study retrospectively reviewed the data of 379 ILD patients with available ANCA results and ultimately analysed 49 ANCA-positive patients. AAV diagnosis was based on the 2012 revised Chapel Hill Consensus Conference (CHCC) criteria, and 33 of 49 patients were diagnosed with microscopic polyangiitis (MPA). The baseline clinical information and laboratory parameters were collected and analysed at each patient’s initial diagnosis. Results: Among 49 ANCA-positive ILD patients, the high-resolution computed tomography (HRCT) pattern was mainly usual interstitial pneumonia (UIP) (59.18%), followed by nonspecific interstitial pneumonia (NSIP) (26.53%). The C-reactive protein (CRP) level (43.89± 40.61 versus 18.74± 20.05, p = 0.028) and erythrocyte sedimentation rate (ESR) (71.97± 42.73 versus 40.69± 28.46, p = 0.011) were significantly higher in the MPA-ILD group than in the ANCA-IIP group. Haemoglobin (113.09 ± 24.47 versus 132.19± 13.34, p = 0.006) and albumin (32.95± 5.84 versus 36.52± 3.94, p = 0.032) levels were significantly lower. Survival was shorter among MPA-ILD patients than among ANCA-IIP patients [hazard ratio (HR) 3.38, 95% confidence interval (CI) 1.32–8.67, p = 0.040]. In the multivariable Cox analysis, a diagnosis of MPA (HR 3.91, 95% CI 1.07–14.08, p = 0.038) and acute exacerbation (AE) of ILD (HR 9.43, 95% CI 2.89–30.30, p < 0.001) were significantly independently associated with shorter survival in ANCA-positive ILD patients, and the NSIP pattern (HR 0.07, 95% CI 0.01–0.41, p = 0.003) was independently associated with prolonged survival. Conclusion: ANCA-ILD patients mostly have myeloperoxidase (MPO)-ANCA positivity and an MPA diagnosis. Survival was shorter among MPA-ILD patients than among ANCA-IIP patients. Respiratory failure and AE were associated with poorer prognosis. Early antifibrotic treatment may be a reasonable treatment option in fibrotic ILD patients with ANCA positivity.
Clinical Outcomes of the Lateral Trabecular Metal Total Ankle Replacement at a 5-Year Minimum Follow-up
Authors: Kim Jaeyoung , Gagne Oliver J. , Rajan Lavan , Caolo Kristin , Sofka Carolyn , Ellis Scott J. , Demetracopoulos Constantine A. , Deland Jonathan T. 
Published: December 2022

Background The Trabecular Metal (Zimmer Biomet, Warsaw, IN) total ankle arthroplasty (TAA) system uses a lateral approach with a fibular osteotomy to gain access to the tibiotalar joint and a sagittally curved tibial component. This is the first TAA system to laterally approach the ankle, and few studies have explored outcomes associated with this implant. This study aimed to report the 5-year clinical and radiographic outcomes as well as the survivorship of the implant. Methods Over a 3-year period, 2 fellowship-trained foot and ankle surgeons used this implant system to treat 38 end-stage arthritic ankles. Reoperation and revision data were collected from all patients (100%) as part of the local prospective database. Patients completed the Foot and Ankle Outcome Score (FAOS) questionnaire preoperatively and at each annual follow-up visit; scores for a minimum of 5 years were available for 28 (73.7%) patients. A radiographic analysis compared postoperative coronal and sagittal alignment in weightbearing radiographs at a minimum of 5 years with that at 3 months postoperatively, as well as cyst or lucency formation, which was available for 21 patients (55.3%). Results At 5 years, there were 3 revisions (7.9%) and 9 reoperations (23.7%). Reoperations included 4 fibular hardware removal and 5 medial gutter debridement procedures. The FAOS significantly improved for all domains (P < .05). Implant positioning did not significantly change between 3 months and 5 years postoperatively. Conclusion Our 5-year results in this small series using this unique prosthesis showed good overall survivorship (92.1%) and a reoperation rate of 23.7%, along with clinically significant improvement in patient-reported outcomes. Levels of Evidence: Level IV: Retrospective case series
Experimental investigation of blast mitigation of pre-fractal obstacles
Authors: Isaac Obed Samuelraj , Alshammari Omar Ghareeb , Clarke Samuel David , Rigby Samuel Edward 
Published: December 2022

Obstacles arranged into a pre-fractal shape (Sierpinski carpet) were tested for their blast attenuation abilities using 250 g PE4 at three different scaled distances ( Z = 1.87, 2.24, 2.99 m/kg1/3). Three pre-fractal iterations were tested, as well as free-field tests for comparative purposes. Reductions in peak overpressure up to 26% and peak specific impulse up to 19% were observed, attributed to a mechanism known as ‘trapping’. This mechanism is characterised by a reduction in the ability of a blast wave to advect downstream, with corresponding increases in pressure observed within the bounds of the pre-fractal obstacle. Attenuation magnitudes and areas of reduced pressure and impulse were found to be drastically different with each pre-fractal iteration, with a transition from shadowing to wave trapping as the obstacles more closely resembled true fractals. A linear dependence on a newly-defined obstruction factor ( OF) was found for arrival time, overpressure and impulse at the sensor locations, suggesting that the attenuation of a pre-fractal obstacle is inherently determinable. The results indicate that the mechanism of blast mitigation of pre-fractal obstacles is fundamentally different from singular or arrays of regular obstacles, and could be exploited further to develop novel protective structures with enhanced blast attenuation.
A case of tumor-induced osteomalacia masked by acute kidney injury
Authors: Kanduri Swetha Rani , Kovvuru Karthik , Wickman Terrance J , Velez Juan Carlos Q 
Published: December 2022

Introduction: Hypophosphatemia in patients with tumor-induced osteomalacia (TIO) is due to abnormal excess production of fibroblast growth factor 23 (FGF-23) causing urinary phosphate wasting. However, in patients with coexisting acute kidney injury (AKI), hypophosphatemia may not be apparent as AKI reduces filtration and excretion of phosphate. Case report: We describe a case of 36-year-old woman who presented with right-sided abdominal pain. Initial laboratory testing revealed non oliguric AKI with creatinine (Cr) of 2.0 mg/dL (baseline 1.2 mg/dL), low phosphate (1.8 mg/dL), and normal parathyroid (PTH) levels. Hypophosphatemia in the setting of AKI and normal PTH raised suspicion for renal phosphate wasting disorder independent of PTH, triggering an order for FGF-23 level. Further into hospital stay, the AKI worsened (Cr rose to 7.2 mg/dL) and phosphate levels increased to 6.7 mg/dL casting doubt on the initial suspicion. However, FGF-23 level resulted at 12,715 RU/mL, strongly suggesting TIO. Random liver biopsy was obtained as part of TIO work up due to liver ultrasound findings of hepatomegaly, diffuse parenchymal heterogenicity mimicking steatosis and potential ill-defined mass. Liver specimen showed tumor cells positive for CD56 and Ki-67, indicating high-grade metastatic neuro endocrine tumor which was the likely source of FGF-23. Patient rapidly deteriorated and opted for comfort measures. Conclusion: TIO typically manifests with overt hypophosphatemia. This case highlights the fact that decreased glomerular filtration rate may mask the degree of urinary phosphate wasting resulting in normal to high serum phosphate level. This warrants high index of suspicion to diagnose an underlying phosphate wasting disorder in the setting of normal to high serum phosphate levels and reduced kidney function.
Arthroscopic Removal of the Polyethylene Glenoid Component After Total Shoulder Arthroplasty: A Systematic Review
Authors: Ozdag Yagiz , Baylor Jessica , Hayes Daniel , Grandizio Louis C 
Published: December 2022

Purpose To identify prior studies of arthroscopic glenoid component removal after total shoulder arthroplasty (TSA) and understand indications, techniques and patient outcomes. Methods A search of the English language literature on arthroscopic removal of the glenoid component (ARGC) after TSA published between 2005 and 2021 was performed from MEDLINE and EMBASE databases. Articles with ARGC after TSA were identified and we recorded article characteristics as well as patient demographics and outcomes contained within the studies. Results A total of six publications (two case reports and four retrospective case series) detailing the outcome of ARGC performed on twenty-five shoulders were identified. The average time from index procedure to glenoid removal was 117 months and mean age at time of ARGC was 75 years. Although patient reported outcomes measures (PROMs) varied in type and reporting style, all articles reported improvements in PROMs. Twenty patients in this systematic review were evaluated for post-operative complications and the complication rate was found to be 15% (n = 3). There were 2 cases (18%) of superior migration of the humeral head relative to the glenoid and no reported cases of anterior or posterior humeral head subluxation. Two of 25 patients (8%) underwent subsequent open revision procedures. Conclusions The limited number of publications in this systematic review demonstrates that ARGC after TSA can result in improvements in both pain and PROMs. This less-invasive arthroscopic technique may be an alternative to open revision for lower demand patients; however, future prospective, comparative studies are necessary to better define indications.
Cloned antibodies from patients with HIT provide new clues to HIT pathogenesis
Authors: Zhu Wen , Zheng Yongwei , Yu Mei , Wu Yaling , Wei Jianhui , Zhou Lu , Fu Guoping , Schneider Nicholas , Jones Curtis , Irani Mehraboon , Padmanabhan Anand , Aster Richard , Wang Demin , Wen Renren 
Published: December 2022

AbstractHeparin-induced thrombocytopenia (HIT) is a serious adverse drug reaction characterized by antibodies that recognize platelet factor 4/heparin complexes (PF4/H) and activate platelets to create a prothrombotic state. Although a high percentage of heparin-treated patients produce antibodies to PF4/H, only a subset also makes antibodies that are platelet activating (PA). A close correlation between PA antibodies and the likelihood of experiencing HIT has been demonstrated in clinical studies, but how PA (presumptively pathogenic) and nonactivating (NA) (presumptively benign) antibodies differ from each other at the molecular level is unknown. To address this issue, we cloned 7 PA and 47 NA PF4/H-binding antibodies from 6 patients with HIT and characterized their structural and functional properties. Findings showed that PA clones differed significantly from NA clones in possessing 1 of 2 heavy chain complementarity-determining region 3 (HCDR3) motifs, RX1-2R/KX1-2R/H (RKH) and YYYYY (Y5), in an unusually long complementarity-determining region 3 (≥20 residues). Mutagenic studies showed that modification of either motif in PA clones reduced or abolished their PA activity and that appropriate amino acid substitutions in HCDR3 of NA clones can cause them to become PA. Repertoire sequencing showed that the frequency of peripheral blood IgG+ B cells possessing RKH or Y5 was significantly higher in patients with HIT than in patients without HIT given heparin, indicating expansion of B cells possessing RKH or Y5 in HIT. These findings imply that antibodies possessing RKH or Y5 are relevant to HIT pathogenesis and suggest new approaches to diagnosis and treatment of this condition.
RUNX1 isoform disequilibrium promotes the development of trisomy 21–associated myeloid leukemia
Authors: Gialesaki Sofia , Bräuer-Hartmann Daniela , Issa Hasan , Bhayadia Raj , Alejo-Valle Oriol , Verboon Lonneke , Schmell Anna-Lena , Laszig Stephanie , Regényi Enikő , Schuschel Konstantin , Labuhn Maurice , Ng Michelle , Winkler Robert , Ihling Christian , Sinz Andrea , Glaß Markus , Hüttelmaier Stefan , Matzk Sören , Schmid Lena , Strüwe Farina Josepha , Kadel Sofie-Katrin , Reinhardt Dirk , Yaspo Marie-Laure , Heckl Dirk , Klusmann Jan-Henning 
Published: December 2022

Abstract
Gain of chromosome 21 (Hsa21) is among the most frequent aneuploidies in leukemia. However, it remains unclear how partial or complete amplifications of Hsa21 promote leukemogenesis and why children with Down syndrome (DS) (ie, trisomy 21) are particularly at risk of leukemia development. Here, we propose that RUNX1 isoform disequilibrium with RUNX1A bias is key to DS-associated myeloid leukemia (ML-DS). Starting with Hsa21-focused CRISPR–CRISPR-associated protein 9 screens, we uncovered a strong and specific RUNX1 dependency in ML-DS cells. Expression of the RUNX1A isoform is elevated in patients with ML-DS, and mechanistic studies using murine ML-DS models and patient-derived xenografts revealed that excess RUNX1A synergizes with the pathognomonic Gata1s mutation during leukemogenesis by displacing RUNX1C from its endogenous binding sites and inducing oncogenic programs in complex with the MYC cofactor MAX. These effects were reversed by restoring the RUNX1A:RUNX1C equilibrium in patient-derived xenografts in vitro and in vivo. Moreover, pharmacological interference with MYC:MAX dimerization using MYCi361 exerted strong antileukemic effects. Thus, our study highlights the importance of alternative splicing in leukemogenesis, even on a background of aneuploidy, and paves the way for the development of specific and targeted therapies for ML-DS, as well as for other leukemias with Hsa21 aneuploidy or RUNX1 isoform disequilibrium.
Contribution of mutant HSC clones to immature and mature cells in MDS and CMML, and variations with AZA therapy
Authors: Schnegg-Kaufmann Annatina S. , Thoms Julie A. I. , Bhuyan Golam Sarower , Hampton Henry R. , Vaughan Lachlin , Rutherford Kayleigh , Kakadia Purvi M. , Lee Hui Mei , Johansson Emma M. V. , Failes Timothy W. , Arndt Greg M. , Koval Jason , Lindeman Robert , Warburton Pauline , Rodriguez-Meira Alba , Mead Adam J. , Unnikrishnan Ashwin , Davidson Sarah , Polizzotto Mark N. , Hertzberg Mark , Papaemmanuil Elli , Bohlander Stefan K. , Faridani Omid R. , Jolly Christopher J. , Zanini Fabio , Pimanda John E. 
Published: December 2022

Abstract
Myelodysplastic neoplasms (MDSs) and chronic myelomonocytic leukemia (CMML) are clonal disorders driven by progressively acquired somatic mutations in hematopoietic stem cells (HSCs). Hypomethylating agents (HMAs) can modify the clinical course of MDS and CMML. Clinical improvement does not require eradication of mutated cells and may be related to improved differentiation capacity of mutated HSCs. However, in patients with established disease it is unclear whether (1) HSCs with multiple mutations progress through differentiation with comparable frequency to their less mutated counterparts or (2) improvements in peripheral blood counts following HMA therapy are driven by residual wild-type HSCs or by clones with particular combinations of mutations. To address these questions, the somatic mutations of individual stem cells, progenitors (common myeloid progenitors, granulocyte monocyte progenitors, and megakaryocyte erythroid progenitors), and matched circulating hematopoietic cells (monocytes, neutrophils, and naïve B cells) in MDS and CMML were characterized via high-throughput single-cell genotyping, followed by bulk analysis in immature and mature cells before and after AZA treatment. The mutational burden was similar throughout differentiation, with even the most mutated stem and progenitor clones maintaining their capacity to differentiate to mature cell types in vivo. Increased contributions from productive mutant progenitors appear to underlie improved hematopoiesis in MDS following HMA therapy.
Knowledge to date on secondary malignancy following hematopoietic cell transplantation for sickle cell disease
Authors: Fitzhugh Courtney D. 
Published: December 2022

Abstract
Allogeneic hematopoietic cell transplantation, gene therapy, and gene editing offer a potential cure for sickle cell disease (SCD). Unfortunately, myelodysplastic syndrome and acute myeloid leukemia development have been higher than expected after graft rejection following nonmyeloablative conditioning and lentivirus-based gene therapy employing myeloablative busulfan for SCD. Somatic mutations discovered in 2 of 76 patients who rejected their grafts were identified at baseline at much lower levels. While a whole-genome sequencing analysis reported no difference between patients with SCD and controls, a study including whole-exome sequencing revealed a higher prevalence of clonal hematopoiesis in individuals with SCD compared with controls. Genetic risk factors for myeloid malignancy development after curative therapy for SCD are currently being explored. Once discovered, decisions could be made about whether gene therapy may be feasible vs allogeneic hematopoietic cell transplant, which results in full donor chimerism. In the meantime, care should be taken to perform a benefit/risk assessment to help patients identify the best curative approach for them. Long-term follow-up is necessary to monitor for myeloid malignancies and other adverse effects of curative therapies for SCD.
Thrombocytopenia in pregnancy
Authors: Pishko Allyson M. , Marshall Ariela L. 
Published: December 2022

Abstract
Hematologists are often consulted for thrombocytopenia in pregnancy, especially when there is a concern for a non-pregnancy-specific etiology or an insufficient platelet count for the hemostatic challenges of delivery. The severity of thrombocytopenia and trimester of onset can help guide the differential diagnosis. Hematologists need to be aware of the typical signs of preeclampsia with severe features and other hypertensive disorders of pregnancy to help distinguish these conditions, which typically resolve with delivery, from other thrombotic microangiopathies (TMAs) (eg, thrombotic thrombocytopenic purpura or complement-mediated TMA). Patients with chronic thrombocytopenic conditions, such as immune thrombocytopenia, should receive counseling on the safety and efficacy of various medications during pregnancy. The management of pregnant patients with chronic immune thrombocytopenia who are refractory to first-line treatments is an area that warrants further research. This review uses a case-based approach to discuss recent updates in diagnosing and managing thrombocytopenia in pregnancy.
Expanding the platelet inventory to mitigate the impact of severe shortages
Authors: Stubbs James R. , Shaz Beth H. , Vassallo Ralph R. , Roback John D. 
Published: December 2022

AbstractThe platelet collection and distribution system, based on volunteer nonremunerated donors, apheresis platelet collections, and primarily 1-directional distribution of platelets for up to 5-day room temperature storage at hospitals, typically performs well and provides therapeutic support for hundreds of thousands of patients annually. However, direct and indirect effects of the coronavirus disease 2019 pandemic, particularly during the Omicron wave, produced dramatic systemic failures and severe shortages. We propose 4 initiatives to reinforce the existing platelet pipeline and buffer the platelet supply against future unexpected disruptions.
Gene therapy for hemophilia
Authors: Nathwani Amit C. 
Published: December 2022

Abstract
The cloning of the factor VIII (FVIII) and factor IX (FIX) genes in the 1980s has led to a succession of clinical advances starting with the advent of molecular diagnostic for hemophilia, followed by the development of recombinant clotting factor replacement therapy. Now gene therapy beckons on the back of decades of research that has brought us to the final stages of the approval of 2 products in Europe and United States, thus heralding a new era in the treatment of the hemophilias. Valoctocogene roxaparvovec, the first gene therapy for treatment of hemophilia A, has been granted conditional marketing authorization in Europe. Another approach (etranacogene dezaparvovec, AMT-061) for hemophilia B is also under review by regulators. There are several other gene therapy approaches in earlier stages of development. These approaches entail a one-off infusion of a genetically modified adeno-associated virus (AAV) engineered to deliver either the FVIII or FIX gene to the liver, leading to the continuous endogenous synthesis and secretion of the missing coagulation factor into the circulation by the hepatocytes, thus preventing or reducing bleeding episodes. Ongoing observations show sustained clinical benefit of gene therapy for &gt;5 years following a single administration of an AAV vector without long-lasting or late toxicities. An asymptomatic, self-limiting, immune-mediated rise in alanine aminotransferase is commonly observed within the first 12 months after gene transfer that has the potential to eliminate the transduced hepatocytes in the absence of treatment with immunosuppressive agents such as corticosteroids. The current state of this exciting and rapidly evolving field, as well as the challenges that need to be overcome for the widespread adaptation of this new treatment paradigm, is the subject of this review.