tbuckley/cabot-search huggingface dataset:
Loss of α-gal during primate evolution enhanced antibody-effector function and resistance to bacterial sepsis
Authors: Sumnima Singh, Jessica A. Thompson, Bahtiyar Yilmaz, Hai Li, Sebastian Weis, Daniel Sobral, Mauro Truglio, Frederico Aires da Silva, Sandra Aguiar, Ana Rita Carlos, Sofia Rebelo, Silvia Cardoso, Erida Gjini, Gabriel Nuñez, Miguel P. Soares
Journal: Cell Host & Microbe (2021)
HP0009 Audit of a rheumatology nurse specialist (rns) shoulder injection clinic
Authors: WD Pointer, PL Williams
Journal: Annals of the Rheumatic Diseases (2001)

<h3></h3> In order to shorten waiting times for referrals for shoulder pain, we have set up a dedicated clinic, run by a RNS trained in assessment and management of shoulder problems, including injection of corticosteroid, to which all consecutive new patients, who were thought likely from the letter of referral to benefit from an injection were allocated. Diagnosis was discussed and confirmed with the Rheumatologist. The results of the first 56 patients (23 male) to attend have been audited. Diagnosis was as follows: Adhesive Capsulitis 21, Supraspinatus Tendonitis 11, Rotator Cuff Lesion 7, Non-specific shoulder pain 5, Occupation related shoulder pain 3, Bicipital Tendonitis 3, Thoracic outlet compression 1, Acromioclavicular joint pain 1, Posture related shoulder pain 1, Fibromyalgia 1, Referred pain from hepatic secondaries 1, Secondary deposit 1. In 18 patients (32%) the clinic and GP diagnoses were the same. In 16 (28.6%) they differed and in 22 (37.5%) the GP letter indicated painful shoulder but no specific diagnosis. Of these patients 36 (64%) were treated with injection. The remaining 20 (36%) were not injected for the following reasons: Symptoms resolved 12, Patient declined 3, Inappropriate 4, Reason not recorded 1. Of the 56 patients audited, 49 were available for review by telephone at a minimum of 3 months after initial visit. The results of this interview showed that 17 had complete resolution of symptoms, 21 had more than 50% improvement, 1 less than 50% improvement, 5 said their symptoms were unchanged and 5 stated their symptoms were worse. <h3>Conclusion</h3> A RNS shoulder injection clinic works well but the range of possible diagnoses requires close collaboration with the Rheumatologist.
Perspectives and Advances in the Understanding of Tuberculosis
Authors: Rachel L. Kinsella, Dennis X. Zhu, Gregory A. Harrison, Anne E. Mayer Bridwell, Jerome Prusa, Sthefany M. Chavez, Christina L. Stallings
Journal: Annual Review of Pathology Mechanisms of Disease (2021)

Mycobacterium tuberculosis ( Mtb), the causative agent of tuberculosis (TB), remains a leading cause of death due to infection in humans. To more effectively combat this pandemic, many aspects of TB control must be developed, including better point of care diagnostics, shorter and safer drug regimens, and a protective vaccine. To address all these areas of need, better understanding of the pathogen, host responses, and clinical manifestations of the disease is required. Recently, the application of cutting-edge technologies to the study of Mtb pathogenesis has resulted in significant advances in basic biology, vaccine development, and antibiotic discovery. This leaves us in an exciting era of Mtb research in which our understanding of this deadly infection is improving at a faster rate than ever, and renews hope in our fight to end TB. In this review, we reflect on what is known regarding Mtb pathogenesis, highlighting recent breakthroughs that will provide leverage for the next leaps forward in the field.
124I-PET/CT–Guided Diagnosis and Personalized Treatment of Metastatic Papillary Thyroid Cancer to the Pancreas
Authors: Bernadette Z. Y. Wong, Graeme Dickie, Peter Garcia, Dominique Scott, David A. Pattison
Journal: Clinical Nuclear Medicine (2021)

Abstract Metastasis to the pancreas from differentiated thyroid carcinoma is rare. A new pancreatic lesion was identified on surveillance imaging of a man with metastatic papillary thyroid carcinoma 7 years after initial diagnosis. Imaging with 124 I-PET/CT was performed to noninvasively confirm metastatic thyroid cancer and provide prospective dosimetry to guide selection of a safe and effective administered activity of 131 I. This case demonstrates the emerging role of 124 I-PET/CT as a useful diagnostic scan, pretherapy scan, and dosimetric tool to deliver personalized therapy for patients with metastatic thyroid cancer.
Diabetic Ketoacidosis at the Time of Diagnosis of Type 1 Diabetes in Children
Authors: Meranda Nakhla, David Cuthbertson, Dorothy J. Becker, Daniéle Pacaud, Johnny Ludvigsson, Mikael Knip, Laurent Legault
Journal: JAMA Pediatrics (2021)

This cohort study assesses the risk of diabetic ketoacidosis at the diagnosis of type 1 diabetes among children who participated in the Trial to Reduce Insulin-Dependent Diabetes Mellitus in the Genetically at Risk (TRIGR).
Effect of treatment disparities on survival in disadvantaged black and white patients with stage IV colorectal cancer (CRC).
Authors: Douglas S Swords, Hop Sanderson Tran Cao, Brian K. Bednarski, Jean-Nicolas Vauthey, George J. Chang, Y. Nancy You
Journal: Journal of Clinical Oncology (2021)

13 Background: Non-Hispanic Black patients (NHBs) and low socioeconomic status (SES) non-Hispanic White patients (NHWs) have worse cancer outcomes. In most cancers, the relative importance of treatment disparities vs. other pathways are undefined. We estimated the proportion of overall survival (OS) disparities mediated by treatment disparities in NHBs and NHWs with stage IV CRC. Methods: We queried the National Cancer Database for NHBs and NHBs (aged 18-80) diagnosed with stage IV CRC in 2010-16. Zip code SES was defined as low (quartile 1 income and education), high (quartile 4 income and education), and middle. Exclusions were missing SES, chemotherapy contraindications/refusal, unknown treatment, and &lt; 60 days follow-up. From available variables, we examined 3 plausible treatment mediators of OS: chemotherapy, metastatectomy, and treatment at &gt; 1 CoC facility. Primary tumor resection was not analyzed to avoid immortal time bias. We used inverse odds ratio weighting (IORW) to estimate the proportion mediated ( PM) while adjusting for sex, age, cancer history, comorbidities, year, tumor location, grade, LVI, CEA, and KRAS status. Results: Among 70,773 patients, the rate of low SES was 3.6-fold higher among NHBs than NHWs. There were graded associations between higher SES and rates of each mediator (Cuzick trend tests, all p ⩽ 0.01). Furthermore, low and middle SES NHB and NHWs all had significantly lower rates of each mediator than high SES NHWs (Table, part A). 5-yr OS ranged from 14.5% in low SES NHBs to 21.9% in high SES NHWs. Low and middle SES NHWs and all NHBs had shorter adjusted OS than high SES NHWs (Table, part B). PMs were higher for low and middle SES NHBs vs. NHWs (27-28% vs. 19-22%). PMs were largest for metastasectomy (9.9-16.1%) and smallest for chemotherapy (5.0-7.9%). Conclusions: Treatment disparities mediate at least 20-30% of OS disparities in NHBs and NHWs with stage IV CRC. These estimates may represent the lower bound of true PMs since many aspects of treatment quality were unmeasured. These findings imply that policies addressing treatment disparities are projected to partially close survival gaps. [Table: see text]
THU0149 Temporo-mandibular damage in psoriatic arthritis
Authors: VV Badokin, VM Grinin, VA Nasonova
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Psoriatic arthritis (PA) is a chronic progressing spinal and articular disease associated with psoriasis resulting in development of erosive arthritis, ankylosing of joints and intraarticular osteolysis. It is included into seronegative arthritides and has clinical-radiological peculiarities common for this group of diseases. <h3>Objectives</h3> To find out the prevalence and character of temporo-mandibular damage (TMD) during PA and determine the correlation of such damage with other manifestations of this disease. <h3>Methods</h3> 76 PA pts were examined. Median age of pts was 36.7 ± 5.6 years and median disease duration 3.4 ± 0.8 years. Radiological stage of damage (except TMD) in 42.1% of pts was II according Steinbrocker and in 39.5% – III. All pts had clinical examination of TMD with detailing of volume of mobility, possible dislocation of articular disk, determining of mandibular deviation during mouth opening, cephalometric studies. TMD radiography by method of Schuller and Parma, orthopantomorphography, stratal magnetic-resonance computer tomography. <h3>Results</h3> TMD in PA debut was found in 25 (32.9%) of pts and occupied the 6th place by frequency among other articular damages. In 60% of cases arthralgia was noticed. In some cases there were stable arthralgias and speedy decrease of articular mobility of this localization. More often we found bilateral damage as compared with unilateral. There were cases of isolated TMD in PA debut. In the developed stage of the disease almost all pts (67 out of 76, or 88.1%) demonstrated painfulness during palpation of periarticular muscles. Limitation of mandibular excursion of III and IV stage was found in 18 pts. TMD deviations were noticed prevalently in unilateral damage of them. No occlusion pathology or deformation of face skeleton was found. According to TMD radiography, aside from osteoporosis and narrowing of articular space, 27 pts demonstrated erosion of joints surfaces and in 6 cases osteolysis of the head of the mandible. In the majority of cases the stage of TMD correlated to radiological PA stage as a whole. <h3>Conclusion</h3> TMD is a frequent PA clinical manifestation. The frequency and character of such damage are closely related with the activity of inflammatory processes, arthritis prevalence and stage of its development.
Neoadjuvant Chemoradiotherapy Combined with Atezolizumab for Resectable Esophageal Adenocarcinoma: A Single-arm Phase II Feasibility Trial (PERFECT)
Authors: Tom van den Ende, Nicolien C. de Clercq, Mark I. van Berge Henegouwen, Suzanne S. Gisbertz, E.D. Geijsen, R.H.A. Verhoeven, Sybren L. Meijer, Sandor Schokker, M.P.G. Dings, Jacques J.G.H.M. Bergman, Nadia Haj Mohammad, Jelle P. Ruurda, Richard van Hillegersberg, Stella Mook, Max Nieuwdorp, Tanja D. de Gruijl, Tanya T.D. Soeratram, Bauke Ylstra, Nicole C.T. van Grieken, Maarten F. Bijlsma, Maarten C.C.M. Hulshof, H.W.M. van Laarhoven
Journal: Clinical Cancer Research (2021)

The CROSS trial established neoadjuvant chemoradiotherapy (nCRT) for patients with resectable esophageal adenocarcinoma (rEAC). In the PERFECT trial, we investigated the feasibility and efficacy of nCRT combined with programmed-death ligand-1 (PD-L1) inhibition for rEAC.Patients with rEAC received nCRT according to the CROSS regimen combined with five cycles of atezolizumab (1,200 mg). The primary endpoint was the feasibility of administering five cycles of atezolizumab in ≥75% patients. A propensity score-matched nCRT cohort was used to compare pathologic response, overall survival, and progression-free survival. Exploratory biomarker analysis was performed on repeated tumor biopsies.We enrolled 40 patients of whom 85% received all cycles of atezolizumab. Immune-related adverse events of any grade were observed in 6 patients. In total, 83% proceeded to surgery. Reasons for not undergoing surgery were progression (n = 4), patient choice (n = 2), and death (n = 1). The pathologic complete response rate was 25% (10/40). No statistically significant difference in response or survival was found between the PERFECT and the nCRT cohort. Baseline expression of an established IFNγ signature was higher in responders compared with nonresponders (P = 0.043). On-treatment nonresponders showed either a high number of cytotoxic lymphocytes (CTL) with a transcriptional signature consistent with expression of immune checkpoints, or a low number of CTLs.Combining nCRT with atezolizumab is feasible in patients with rEAC. On the basis of our exploratory biomarker study, future studies are necessary to elucidate the potential of neoadjuvant immunotherapy in patient subgroups.See related commentary by Catenacci, p. 3269.
Characteristics and growth rate of lung metastases in patients with primary gastrointestinal malignancies: A retrospective cohort analysis.
Authors: Shohei Burns, Maya Vella, Alan Paciorek, Li Zhang, Chloe Evelyn Atreya, Eric Andrew Collisson, Mary Uan-Sian Feng, Robin Kate Kelley, Margaret A. Tempero, Katherine Van Loon, Andrew H. Ko
Journal: Journal of Clinical Oncology (2021)

442 Background: There are no formal guidelines for the management of GI cancer pts with lung-exclusive or lung-predominant metastases (LM), which generally take a more indolent course than metastatic disease occurring at other anatomic sites. We performed a retrospective analysis at a high-volume tertiary care center to evaluate host and tumor characteristics of this pt population, describe treatment approaches, and model patterns and rates of growth. Methods: Eligible pts were identified through Cancer Center registry data, provider recall, and electronic record review. Criteria included LM occurring either synchronously (SLM) or metachronously (MLM) w/primary cancer diagnosis; nodal, but not visceral or peritoneal, mets allowed. Data re: demographics, tumor characteristics, and rx modalities were collected. We reviewed all eligible CT +/- PET scan reports to gather data on #, location, and size of pulm mets, with all images subsequently reviewed by an independent radiologist. Up to 5 pulm mets were tracked through each pt’s clinical course. Growth rate was estimated using a linear mixed model analysis considering patients as the random. Results: Forty pts were identified between 9/2009 - 12/2019 (23 F/17 M; 28 white/7 Asian/5 other/multi; median age 62 y.o.; n = 15 w/tobacco hx). Tumor types: pancreatic (n = 18), colorectal (n = 12), hepatobiliary (n = 7), other (n = 3). SLM vs MLM:13/27; intact vs resected primary = 16/24. Median time from orig cancer dx to onset of MLM = 16 mos (range, 1 to 60 mos). No. of pulm mets at 1st appearance: 1 (n = 7); 2-5 (n = 17); 6-10 (n = 16). Median size of largest pulm met at 1st appearance = 6 mm (range, 0-39 mm); avg growth rate of largest pulm met = 0.18 mm/month (95% CI, 0.08-0.27). Avg growth rate of up to 5 largest lesions (sum) = 0.35 mm/month (95% CI, 0.07-0.64). Median f/u time prior to rx initiation for MLM = 172 days (range, 25-1547 days); 18 pts developed additional mets during their observation period. Rx modalities for LM: surg (n = 6), radiation (n = 18), systemic rx (n = 32). Addn details specific to cancer type, progression patterns, and pt outcomes will be presented at the meeting. Conclusions: The natural hx of LM varies across the spectrum of GI malignancies. Further larger-scale efforts to define patterns of growth of LM for different GI cancers, informed by size, #, and clinical/molecular features, are needed to guide appropriate timing and selection of rx as well as surveillance strategies.
Out of the Blue Acute May-Thurner Syndrome
Authors: Siddharth Agarwal
Journal: Clinical Cardiology and Cardiovascular Interventions (2021)

May-Thurner syndrome (MTS) is defined as extrinsic ilio-femoral venous compression by the aorto-iliac arterial system against vertebral bodies and has been associated with many abnormalities involving the arterial system as well as bony structures around the ilio-caval region. We present an unusual case of a patient who came with phlegmasia cerulea dolens in the setting of acute onset MTS after chiropractic vertebral manipulation and was treated with a multimodal interventional approach, combining pharmaco-mechanical catheter directed thrombectomy along with venoplasty with stenting and subsequent post-procedure anticoagulation and antiplatelet prophylaxis.
SAT0067 Serum cartilage oligomeric matrix protein (comp) as a prognostic marker in knee osteoarthritis
Authors: V Vilim, M Olejarova, S Machacek, J Gatterova, K Pavelka
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Three previously published studies aimed to relate rediographic disease progression in OA to baseline serum COMP levels (1–3). In two studies, the authors found no correlation between baseline serum COMP levels and subsequent progression of knee osteoarthritis (OA).<sup>1,2</sup> In the study of hip OA, however, the authors found significant correlation between baseline serum COMP levels and yearly mean narrowing of joint space width.<sup>3</sup> <h3>Objectives</h3> To evaluate serum COMP level measured at baseline with a new sandwich ELISA as a predictor of disease progression of knee OA. <h3>Methods</h3> Patients with established OA (n = 54) represented placebo-taking group from finished and now opened 3-years long double-blind drug trial. Standing anthero-posterior radiographs of both knees were taken at the beginning and at the end of the study and used to measure joint space width at the medial compartment. COMP was quantified by newly developed sandwich ELISA with monoclonal antibodies 16-F12 and 17-C10. <h3>Results</h3> The increased serum COMP level at baseline correlated with 3-years change of joint space width (expressed as the sum of joint space narrowing in both knees) (linear regression, r = 0.315, p &lt; 0.05). <h3>Conclusion</h3> We were able to relate serum COMP levels measured at baseline with the new assay to the radiographic progression of knee OA and extend the findings of Conrozier <i>et al</i>.<sup>3</sup> from hip also to knee OA. At present, serum COMP level cannot be used to prognosticate OA course in individual patients due to high variability and overlap of values but it may help in sorting out groups of patients which are at risk of more aggresive development. <h3>References</h3> Sharif M, <i>et al</i>. Br J Rheumatol. 1995;34:306–10 Petersson IF, <i>et al</i>. Br J Rheumatol. 1998;37:46–50 Conrozier T, <i>et al</i>. Ann Rheum Dis. 1998;57:527–32
Loss of tRNA-modifying enzyme Elp3 activates a p53-dependent antitumor checkpoint in hematopoiesis
Authors: Adeline Rosu, Najla El Hachem, Francesca Rapino, Kevin Rouault-Pierre, Joseph Jorssen, Joan Somja, Eve Ramery, Marc Thiry, Laurent Nguyen, Maarten Jacquemyn, Dirk Daelemans, Christopher M. Adams, Dominique Bonnet, Alain Chariot, Pierre Close, Fabrice Bureau, Christophe J. Desmet
Journal: The Journal of Experimental Medicine (2021)

The hematopoietic system is highly sensitive to perturbations in the translational machinery, of which an emerging level of regulation lies in the epitranscriptomic modification of transfer RNAs (tRNAs). Here, we interrogate the role of tRNA anticodon modifications in hematopoiesis by using mouse models of conditional inactivation of Elp3, the catalytic subunit of Elongator that modifies wobble uridine in specific tRNAs. Loss of Elp3 causes bone marrow failure by inducing death in committing progenitors and compromises the grafting activity of hematopoietic stem cells. Mechanistically, Elp3 deficiency activates a p53-dependent checkpoint in what resembles a misguided amino acid deprivation response that is accompanied by Atf4 overactivation and increased protein synthesis. While deletion of p53 rescues hematopoiesis, loss of Elp3 prompts the development of p53-mutated leukemia/lymphoma, and inactivation of p53 and Elongator cooperatively promotes tumorigenesis. Specific tRNA-modifying enzymes thus condition differentiation and antitumor fate decisions in hematopoietic stem cells and progenitors.
Abstract 11831: Measures of Aortic Stiffness, Central Blood Pressure and Pulsatile Arterial Load Predict Thoracic Aortic Aneurysm Growth: Results From a Prospective Cohort Study With Sex-Specific Analyses
Authors: Kevin E Boczar, Munir Boodhwani, Luc Beauchesne, Carole Dennie, Kwan L Chan, Thais Coutinho
Journal: Circulation (2018)

Background: Thoracic aortic aneurysm (TAA) is a disease associated with high morbidity and mortality. However, useful strategies for risk assessment and medical management are lacking. Further, wom...
Prospective, multicenter study of apatinib combine with TACE in treating intermediate to advanced stage HCC patients: A real-world study from China.
Authors: Hailiang Li, Hongtao Hu, Guangshao Cao, Gang Wu, Pengxu Ding, Zhen Li, Qiuliang Wei, Huanzhang Niu, Zukuan Chang, Jun Yin
Journal: Journal of Clinical Oncology (2021)

282 Background: Combination of transcatheter arterial chemoembolization (TACE) with apatinib are emerging as an effective treatment for patients with intermediate to advanced stage HCC. However, the data of HCC treated by apatinib in the real-world setting are not reported. In this real-world study, we aimed to explore the efficacy and safety of HCC pts which underwent TACE combine with apatinib. Methods: This was a prospective, multicenter observational study in a real-world setting and this study was approved by our Ethics Committee. Pts aged ≥18 years with well diagnosed intermediate or advanced stage HCC were included. The pts received apatinib plus TACE treatment as the first-line therapy. TACE treatment was performed on demand, the dose of apatinib was selected by the investigator. The primary endpoint was progression-free survival (PFS). The secondary endpoints were overall survival rate (OS), objective response rate (ORR), disease control rate (DCR) and safety profile. All of the objective response was assessed by independent central review per mRECIST criteria. Results: From Jun 2019 to Feb 2020, a total of 98 well diagnosed HCC pts with age from 31 to 86 were enrolled in this study. As of August 2020, the median follow-up was 9.5 months. The mPFS of 98 pts was 7 months. The ORR, DCR and 6 months OS rate was 35.7%, 76.5% and 82.6%, respectively.The PFS was 7.5 months in intermediate stage and 6.4 months in advanced stage. The ORR was 46.3% in intermediate stage (41 cases) and 28% in advanced stage (57 cases) HCC. And the 6 months OS rate was 90.2% in intermediate stage and 77.1% in advanced stage HCC. Overall, 17 (17.3%) pts had grade≥3 treatment-related AEs. All of the safety adverse effects can be tolerated or reduced after symptomatic treatment and no unexpected adverse events were observed. Conclusions: In this real-world study, apatinib showed a favorable efficacy and safety profile in pts with intermediate and advanced stage cancer. Apatinib combination TACE therapy might lead to better survival benefit in first-line treatment for HCC pts. Clinical trial information: ChiCTR1900024030.