tbuckley/cabot-search huggingface dataset:
Serum lipocalin-2 is a potential biomarker for the clinical diagnosis of nonalcoholic steatohepatitis
Authors: Gang Xu, Yu-Min Wang, Miao-Miao Ying, Sui-Dan Chen, Zong-Rui Li, Hong-Lei Ma, Ming-Hua Zheng, Jian Wu, Chunming Ding
Journal: Clinical and Molecular Hepatology (2021)

Background/Aims: Nonalcoholic steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver disease (NAFLD) characterized by hepatic steatosis, inflammation, hepatocellular injury, and fibrosis. We aimed to investigate the usefulness of a key biomarker, lipocalin-2 (LCN2), for the detection of NASH progression.Methods: A mouse NASH model was established using a high-fat diet and a high-sugar drinking water. Gene expression profile of the NASH model was analyzed using RNA sequencing. Moreover, 360 NAFLD patients (steatosis, 83; NASH, 277), 40 healthy individuals, and 87 patients with alcoholic fatty liver disease were recruited.Results: Inflammatory infiltration, focal necrosis in the leaflets, steatosis, and fibrosis were documented in the mouse liver. In total, 504 genes were differentially expressed in the livers of NASH mice, and showed significant functional enrichment in the inflammation-related category. Upregulated liver LCN2 was found to be significantly interactive with various interleukins and toll-like receptors. Serum LCN2 levels were significantly increased in NAFLD patients. Serum LCN2 levels were correlated with steatosis, intralobular inflammation, semiquantitative fibrosis score, and nonalcoholic fatty liver disease activity score. The area under the curve of serum LCN2 was 0.987 with a specificity of 100% and a sensitivity of 93.5% for NASH diagnosis, and 0.977 with almost the same specificity and sensitivity for steatosis.Conclusions: LCN2 might be involved in the transition from NAFL to NASH by mediating inflammation. Serum LCN2 levels might be a novel biomarker for the diagnosis of NASH.
The Effect of Exenatide Once Weekly on Carotid Atherosclerosis in Individuals With Type 2 Diabetes: An 18-Month Randomized Placebo-Controlled Study
Authors: Juraj Koska, Raymond Q. Migrino, Keith C. Chan, Kelly Cooper-Cox, Peter D. Reaven
Journal: Diabetes Care (2021)

OBJECTIVE Glucagon-like peptide 1 receptor agonists (GLP-1RAs) improved multiple proatherogenic risk factors and reduced cardiovascular events in recent clinical trials, suggesting that they may slow progression of atherosclerosis. We tested whether exenatide once weekly reduces carotid plaque progression in individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS In a double-blind, pragmatic trial, 163 participants were randomized (2:1) to exenatide (n = 109) or placebo (n = 54). Changes in carotid plaque volume and composition were measured at 9 and 18 months by multicontrast 3 Tesla MRI. Fasting and post–high-fat meal plasma glucose and lipids, and endothelial function responses, were measured at 3, 9, and 18 months. RESULTS Exenatide reduced hemoglobin A1c (HbA1c) (estimated difference vs. placebo 0.55%, P = 0.0007) and fasting and postmeal plasma glucose (19 mg/dL, P = 0.0002, and 25 mg/dL, P &amp;lt; 0.0001, respectively). Mean (SD) change in plaque volume in the exenatide group (0.3% [2%]) was not different from that in the placebo group (−2.2% [8%]) (P = 0.4). The change in plaque volume in the exenatide group was associated with changes in HbA1c (r = 0.38, P = 0.0004), body weight, and overall plasma glucose (r = 0.29, P = 0.007 both). There were no differences in changes in plaque composition, body weight, blood pressure, fasting and postmeal plasma triglycerides, and endothelial function between the groups. CONCLUSIONS Exenatide once weekly for up to 18 months improved fasting and postprandial glycemic control but did not modify change in carotid plaque volume or composition. This study raises the possibility that short-term antiatherosclerotic effects may not play a central role in the cardiovascular benefits of GLP-1RAs.
OP0128 Femoral neck fractures in osteoporotic patients
Authors: DN Stratan, M Popa, O Alexa, L Stratan
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> The aim of the study was to evaluate the role of osteoporosis in the treatment of the femoral neck fractures. <h3>Methods</h3> One hundred and twelve patients with femoral neck fractures were treated in our department in two years. The average age of the patients was 68.3 years old (47–91 years old). Fractures were classified according Garden classification and the degree of osteoporosis was appreciated for each patient using Singh system of classification. The treatment was related to the age, displacement of the fracture and degree of osteoporosis. Osteoporosis (Singh I-III) was recorded in 73 patients (65.2%). Most of the fractures of patients with osteoporosis were displaced (Garden III-IV). The undisplaced fractures were treated by internal fixation with three canulated screws in all cases regardless the degree of osteoporosis (22 patients). We avoided internal fixation in patients with osteoporosis and displaced fractures at whom the arthroplasty was the first choice of treatment: hemiarthroplasty with an Austin Moore prosthesis was the indication of choice in patients with a life expectancy less than five years (9 patients); the cemented bipolar prosthesis was preferred in patients with a non-affected acetabulum (52 patients); the cemented prosthesis was indicated in patients with a marked degree of osteoporosis (Singh I-III) or in those with a preexisting diseased acetabular cartilage affecting the ipsilateral hip (20 patients); the uncemented prosthesis was rarely used, in patients under 65 years old with a Singh index IV-VI (8 patients). <h3>Results</h3> Following this treatment very good and good results (according Merle d'Aubigne scale) were noted in 68% of cases. We have also to emphasise that in 80% of the cases treated by cemented bipolar prosthesis, the patients could return to their normal prefracture level of physical activity. <h3>Conclusion</h3> Osteoporosis must be taken into account when the operative technique for a femoral neck fracture is considered. Singh system seems to be very useful for the prognosis and management of this type of fractures. However from all the prosthesis the bipolar type seems to be the best choice in patients with osteoporosis and a fracture of the femoral neck and the cemented variant is offering the best functionality of the involved hip.
Re: Fredrick Leidberg, Petter Kollberg, Marie Allerbo, et al. Preventing Parastomal Hernia After Ileal Conduit by the Use of a Prophylactic Mesh: A Randomised Study. Eur Urol 2020;78:757–63
Authors: Deepansh Dalela, Isaac Palma-Zamora, Craig Rogers
Journal: European Urology (2021)
Phase II trial of the PARP inhibitor, niraparib, in BRCA1-Associated Protein 1 (BAP1) and other DNA damage response (DDR) pathway deficient neoplasms including cholangiocarcinoma.
Authors: Thomas J. George, David L. DeRemer, Ji-Hyun Lee, Stephen Staal, Merry Jennifer Markham, Dennie V. Jones, Peter Joel Hosein, Karen Colleen Daily, Jonathan Alexander Chatzkel, Brian Hemendra Ramnaraign, Julia Lee Close, Martina Cathryn Murphy, Carmen Joseph Allegra, Sherise C. Rogers, azka ali, Robert A. Hromas
Journal: Journal of Clinical Oncology (2021)

TPS354 Background: BRCA1-Associated Protein 1 (BAP1) is a critical regulator of the cell cycle, cellular differentiation, cell death, and DNA damage response. It also acts as a tumor suppressor. Preclinical models demonstrate significant synthetic lethality in BAP1 mutant cell lines and patient xenografts when treated with PARP inhibitors, independent of underlying BRCA status, suggesting this mutation confers a BRCA-like phenotype. BAP1 is mutated, leading to a loss of functional protein, in up to 30% of cholangiocarcinomas as well as several other solid tumors. Methods: This phase 2, open-label, single arm multicenter study aims to exploit the concept of synthetic lethality with the use of the PARP inhibitor niraparib in pts with metastatic relapsed or refractory solid tumors. Eligible pts with measurable metastatic and incurable solid tumors are assigned to one of two cohorts: Cohort A (histology-specific): tumors harboring suspected BAP1 mutations including cholangiocarcinoma, uveal melanoma, mesothelioma or clear cell renal cell carcinoma with tissue available for BAP1 mutational assessment via NGS or Cohort B (histology-agnostic): tumors with known DNA damage response (DDR) mutations (Table) confirmed by CLIA-approved NGS. Other key eligibility criteria include age ≥18 years, adequate cardiac, renal, hepatic function and Eastern Cooperative Oncology Group performance status of 0 to 1. Pts with known BRCA1 or BRCA2 mutations or prior PARPi exposure are excluded. Pts receive niraparib 200-300mg daily (depending on weight and/or platelet count) continuously. Primary endpoint is objective response rate with secondary endpoints of PFS, OS, toxicity and exploratory biomarker determinations. Radiographic response by RECIST criteria is measured every 8 weeks while on treatment. Cohort A has fully enrolled. Cohort B enrollment continues to a maximum of 47 total evaluable subjects with expansion cohorts allowable for histologic or molecular subtypes meeting pre-specified responses. NCT03207347 Clinical trial information: NCT03207347. [Table: see text]
Enoxacin Up‐Regulates MicroRNA Biogenesis and Down‐Regulates Cytotoxic CD8 T‐Cell Function in Autoimmune Cholangitis
Authors: Arata Itoh, David Adams, Wenting Huang, Yuehong Wu, Kritika Kachapati, Kyle J. Bednar, Patrick S. C. Leung, Weici Zhang, Richard A. Flavell, M. Eric Gershwin, William M. Ridgway
Journal: Hepatology (2021)

Background and Aims Primary biliary cholangitis (PBC) is a prototypical organ‐specific autoimmune disease that is mediated by autoreactive T‐cell attack and destruction of cholangiocytes. Despite the clear role of autoimmunity in PBC, immune‐directed therapies have failed to halt PBC, including biologic therapies effective in other autoimmune diseases. MicroRNA (miRNA) dysregulation is implicated in the pathogenesis (PBC). In the dominant‐negative TGF‐β receptor type II (dnTGFβRII) mouse model of PBC, autoreactive CD8 T cells play a major pathogenic role and demonstrate a striking pattern of miRNA down‐regulation. Enoxacin is a small molecule fluoroquinolone that enhances miRNA biogenesis, partly by stabilizing the interaction of transactivation response RNA‐binding protein with Argonaute (Ago) 2. Approach and Results We hypothesized that correcting aberrant T‐cell miRNA expression with enoxacin in dnTGFβRII mice could modulate autoreactive T‐cell function and prevent PBC. Here, we show that liver‐infiltrating dnTGFβRII CD8 T cells have significantly decreased levels of the miRNA biogenesis molecules prolyl 4‐hydroxylase subunit alpha 1 (P4HA1) and Ago2 along with significantly increased levels of granzyme B and perforin. Enoxacin treatment significantly up‐regulated miRNAs in dnTGFβRII CD8 T cells and effectively treated autoimmune cholangitis in dnTGFβRII mice. Enoxacin treatment directly altered T cells both ex vivo and in vitro , resulting in altered memory subset numbers, decreased proliferation, and decreased interferon‐γ production. Enoxacin significantly decreased CD8 T‐cell expression of the transcription factor, Runx3 , and significantly decreased perforin expression at both the mRNA and protein levels. Conclusions Enoxacin increases miRNA expression in dnTGFβRII CD8 T cells, reduces CD8 T‐cell pathogenicity, and effectively halted progression of autoimmune biliary disease. Targeting the miRNA pathway is a therapeutic approach to autoimmunity that corrects pathological miRNA abnormalities in autoreactive T cells.
Risk of morbidity and mortality inCOVID-19 patients with cancer
Authors: N. Alpert, B. Marcellino, J. Rapp, W. Lieberman-Cribbin, E. Taioli
Journal: Clinical Cancer Research (2020)

Introduction: Morbidity and mortality of cancer patients with COVID-19 have not been examined  The goal of thisanalysis was to compare the demographics and clinical characteristics of COVID-19 cancer patients to the rest ofCOVID-19 patients and assess whether cancer is associated with morbidity or mortality  Methods: COVID-19-positive patients with an inpatient or emergency encounter at the Mount Sinai Health Systembetween 03/01/20-05/27/20 were included in the analysis  Patients were compared across cancer status(noncancer, non-solid cancers, and solid cancers) on demographics and clinical characteristics  Multivariable logisticregressions were used to model the associations of cancer status with sepsis, acute venous thromboembolism, andmortality  Results: There were 5,516 COVID-19 positive patients included, 96 (1 7%) with non-solid cancers and 325 (5 8%)with solid cancers  Those with solid cancers were significantly older (mean: 70 9 vs  63 8 and 63 2 years) and morelikely to be non-Hispanic Black (26 5% vs  23 9% and 22 9%) than noncancer and non-solid cancers patients  Those with cancer had significantly more additional comorbid conditions (42 7% and 49 8% ≥2 comorbidities for non-solidand solid cancers, vs  30 4% for noncancer)  Platelets (mean [noncancer]: 223 8, mean [non-solid cancer]: 182 6, mean [solid cancer]: 218 3 × 10 /μL), white blood cell count (mean [noncancer]: 8 4, mean [non-solid cancer]: 6 7, mean [solid cancer]: 8 0 × 10 /μL), hemoglobin (mean [noncancer]: 13 1, mean [non-solid cancer]: 11 2, mean [solidcancer]: 12 0 g/dL), and red blood cell count (mean [non-cancer]: 4 5, mean [non-solid cancer]: 3 7, mean [solid cancer]: 4 1 × 10 /μL) were significantly lower in cancer patients, and lowest in those with non-solid cancers  Afteradjustment and compared to noncancer patients, those with cancer had significantly higher risk of acute venousthromboembolism (OR : 1 77, 95% CI: 1 01-3 09) and sepsis (OR : 1 34, 95% CI: 1 09-1 64)  There was nosignificant difference in mortality (OR : 1 02, 95% CI: 0 81-1 29)  There was no significant difference in alloutcomes for solid and non-solid cancer types  Conclusion: COVID-19 patients with cancer, particularly solid tumors, are significantly older, with morecomorbidities than those without cancer  There was no statistically significant difference in mortality for COVID-19patients with cancer, but a significantly higher risk of thromboembolism and sepsis  Further research into the effectthat cancer treatments may have in inflammatory and immune responses to COVID is warranted
The CDCP1 Signaling Hub: A Target for Cancer Detection and Therapeutic Intervention
Authors: Tashbib Khan, Thomas Kryza, Nicholas J. Lyons, Yaowu He, John D. Hooper
Journal: Cancer Research (2021)

Abstract CUB-domain containing protein 1 (CDCP1) is a type I transmembrane glycoprotein that is upregulated in malignancies of the breast, lung, colorectum, ovary, kidney, liver, pancreas, and hematopoietic system. Here, we discuss CDCP1 as an important hub for oncogenic signaling and its key roles in malignant transformation and summarize approaches focused on exploiting it for cancer diagnosis and therapy. Elevated levels of CDCP1 are associated with progressive disease and markedly poorer survival. Predominantly located on the cell surface, CDCP1 lies at the nexus of key tumorigenic and metastatic signaling cascades, including the SRC/PKCδ, PI3K/AKT, WNT, and RAS/ERK axes, the oxidative pentose phosphate pathway, and fatty acid oxidation, making important functional contributions to cancer cell survival and growth, metastasis, and treatment resistance. These findings have stimulated the development of agents that target CDCP1 for detection and treatment of a range of cancers, and results from preclinical models suggest that these approaches could be efficacious and have manageable toxicity profiles.
FRI0174 Catastrophic antiphospholipid syndrome in a patient with severe hypertension
Authors: S Rednic, L Damian, L Goga, M Petrescu, A Cristea, HD Bolosiu
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> The catastrophic antiphospholipid syndrome (CAPS) is an uncommon complication of the antiphospholipid syndrome (APS). It presents as acute multi-organ failure and more frequently involves the kidneys, lungs, gastrointestinal tract and the skin. CAPS is caused by widespread thrombosis of small and medium vessels. <h3>Objectives</h3> <h3>Methods</h3> Case report:&nbsp;We describe the case of a young female admitted with severe and accelerated hypertension. No evidence of systemic disease was observed at that time and the physical examination revealed extensive livedo reticularis. In subsequent years she also suffered several transient cerebrovascular accidents with minor neurological sequelae. The anticardiolipin antibodies (ACL) titers were usually and repeatedly extremely high. Renal angiography found normal proximal renal arteries. Renal biopsy showed ischaemic glomeruli without proliferative lesions, but with focal intimal fibrosis, thrombosis of the intrarenal vessels in the absence of vasculitis. The diagnostic of primary antiphospholipid syndrome was formulated. She was treated with antihypertensive drugs, anticoagulant and antiaggregant therapy, escalating doses of steroids, plasmapheresis. <h3>Results</h3> Clinical course: Despite of this treatment she developed progressive multiorgan failure with malignant hypertension, renal failure, central nervous system manifestation (grand mal seizures, hemiparesis, amaurosis fugax, steady deterioration of consciousness) and gastrointestinal involvement (abdominal pain due to infarction or ischaemic ulceration of the bowel). She died as a result of a combination of renal and respiratory failure. Postmortem examination revealed extensive multiorgan arterial microthrombi. <h3>Conclusion</h3> Discussion:&nbsp;The case suggests that hypertension and renal failure should be recognised as a complication of APS, the aetiology being primary intrarenal vascular disease with nephroangiosclerosis. It illustrates also how primary APS presenting with renal manifestation can result in a fatal form of CAPS. <h3>References</h3> Asherson RA. The catastrophic antiphospholipid syndrome 1998. A review of the clinical features, possible pathogenesis and treatment. Lupus 1998;7(Suppl 2):S55–62 Durand JM, Lefevre P, Kaplanski G, Casanova P, Soubeyrand J. Accelerated hypertension and nephroangiosclerosis associated with antiphospholipid syndrome. Report of two cases and review of the literature. Clin Rheumatol. 1994;13(4):635–40
Abstract 18112: Impact of Valvuloarterial Impedance on Cardiac Sympathetic Nerve Activity in Patients With Severe Aortic Stenosis
Authors: Tetsuari Onishi, Takahiro Sawada, Nobuyuki Takahashi, Yasue Tsukishiro, Akira Shimane, Yasuyo Taniguchi, Yoshinori Yasaka, Hiroya Kawai
Journal: Circulation (2017)

Background: Valvuloarterial impedance (Zva) was proposed for the estimation of global left ventricular (LV) afterload in patients with aortic stenosis (AS). Cardiac sympathetic nerve activity evalu...
Abstract 10338: Atrial Fibrillation in a Multinational Asian Heart Failure Cohort
Authors: Vera J Goh, Wan Ting Tay, Tiew Hwa K Teng, Yvonne M Chia, Jasper Tromp, Inder Anand, Carolyn S Lam
Journal: Circulation (2018)

Introduction: The clinical and echocardiographic correlates of atrial fibrillation (AF) among patients with heart failure and preserved versus reduced ejection fraction (HFpEF vs HFrEF) have not be...
Change in skeletal muscle index and its prognostic significance in conversion therapy for initially unresectable colorectal cancer.
Authors: Hiroaki Nozawa, Shigenobu Emoto, Koji Murono, Yasutaka Shuno, Soichiro Ishihara
Journal: Journal of Clinical Oncology (2021)

56 Background: Systemic chemotherapy can cause loss of skeletal muscle mass in colorectal cancer (CRC) patients in the neoadjuvant and palliative settings. However, it is largely unknown how the body composition is changed by chemotherapy rendering unresectable CRC to resectable disease or how it affects the prognosis. This study aimed at elucidating the effects of systemic chemotherapy on skeletal muscles and survival in stage IV CRC patients who underwent conversion therapy. Methods: We reviewed 98 stage IV CRC patients who received systemic chemotherapy in our hospital. According to the treatment setting, patients were divided into the ‘Conversion’, ‘Neoadjuvant chemotherapy (NAC)’, and ‘Palliation’ groups. The cross-sectional area of skeletal muscles at the third lumbar level and changes in the skeletal muscle index (SMI), defined as the area divided by height squared, during chemotherapy were compared among patient groups. The effects of these parameters on prognosis were analyzed in the Conversion group. Results: The mean SMI increased by 8.0% during chemotherapy in the Conversion group (n = 38), whereas it decreased by 6.2% in the NAC group (n = 18) and 3.7% in the Palliation group (n = 42, p &lt; 0.0001). Moreover, patients with increased SMI during chemotherapy had a better overall survival (OS) than those whose SMI decreased in the Conversion group (p = 0.021). The increase in SMI was an independent predictor of favorable OS on multivariate analysis (hazard ratio: 0.26). Conclusions: Stage IV CRC patients who underwent conversion to resection often had an increased SMI. As such an increase in SMI further conveys a survival benefit in conversion therapy, it may be important to make efforts to preserve muscle mass by meticulous approaches, such as nutritional support, muscle exercise programs, and pharmacological intervention even during chemotherapy in patients with metastatic CRC.