tbuckley/cabot-search huggingface dataset:
Abstract 14830: Cellular Iron Transport Protein, Transferrin Receptor 1 Plays an Important Role in the Pathophysiology of Chronic Kidney Disease
Authors: Makiko Oboshi, Yoshiro Naito, Hisashi Sawada, Toshihiro Iwasaku, Yoshitaka Okuhara, Daisuke Morisawa, Akiyo Eguchi, Koichi Nishimura, Yuko Soyama, Shinichi Hirotani, Toshiaki Mano, Masaharu Ishihara, Takeshi Tsujino, Tohru Masuyama
Journal: Circulation (2015)

Background: Cellular iron transport protein, transferrin receptor 1 (TfR1) is required for the uptake of transferrin-bound iron into the cells. Several reports have shown that iron accumulation is associated with the pathophysiology of chronic kidney disease (CKD); however, the role of TfR1 in the pathophysiology of CKD remains unknown. Herein, we investigate TfR1 in the experimental models of CKD. Methods and Results: CKD was induced by 5/6 nephrectomy in Sprague-Dawley rats. CKD rats showed proteinuria and tubular dilatation. Of note, TfR1 expression is increased in the remnant kidney along with increased iron accumulation, as compared with controls. To investigate the functional importance of TfR1 in the pathophysiology of CKD, we subjected to 5/6 nephrectomy in TfR1 hetero knockout mice. At 8weeks after 5/6 nephrectomy, systolic blood pressure was similar in TfR1 hetero knockout mice and wild-type (WT) littermates. In contrast, urinary albumin excretion, serum BUN, and creatinine levels were increased to a lesser extent in TfR1 hetero knockout mice compared with WT littermates. In addition, renal fibrosis was observed in the remnant kidney in WT mice, while the extent was attenuated in TfR1 hetero knockout mice. Consistent with these findings, increased renal gene expression of collagen type I and collagen type III were attenuated in TfR1 hetero knockout mice compared with WT littermates. Conclusions: These results indicate that TfR1 plays a role in the pathophysiology of CKD. Understanding the role of TfR1 in the pathophysiology of CKD may lead to a novel therapeutic approach for CKD.
SAT0184 ASSOCIATION OF SERUM AND URINE LEVELS OF TWEAK, MCP-1 AND NGAL WITH DISEASE ACTIVITY IN SYSTEMIC LUPUS ERYTHEMATOSUS
Authors: Safak Mirioglu, Suzan Çinar, Halil Yazici, Ahmet Gül, Lale Ocal, Murat Inanc, Bahar Artim-Esen
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> TWEAK, MCP-1 and NGAL, mediators in pathogenesis of systemic lupus erythematosus (SLE), are proinflammatory cytokines/chemokines that are thought as potential biomarkers reflecting disease activity (1). <h3>Objectives:</h3> In this study, we aimed to investigate the association of serum (s) and urine (u) levels of TWEAK, MCP-1 and NGAL with disease activity in both renal and non-renal SLE. <h3>Methods:</h3> Thirty active patients with SLE (15 renal and 15 non-renal) were recruited. Thirty-one inactive patients with SLE (16 renal and 15 non-renal), 14 patients with ANCA-associated vasculitis (AAV) all of whom had active renal involvement and 20 healthy volunteers were selected as control groups. Serum and urine levels of TWEAK, MCP-1 and NGAL were tested using ELISA. <h3>Results:</h3> Sixty-one SLE patients, 51 (83.6%) of whom were female, with a median disease duration of 83 (23.5-135) months and a median age of 35 (27-47.5) were included in the study. Serum and urine levels of TWEAK and NGAL were significantly higher in the active SLE group compared with the inactive SLE (n=31) group (sTWEAK: p=0.005; uTWEAK: p=0.026; sNGAL: p&lt;0.001; uNGAL: p=0.002); whilst no significant differences regarding serum and urine MCP-1 levels were observed (p=0.189 and p=0.106). uTWEAK (p=0.237), sMCP-1 (p=0.141), uMCP-1 (p=0.206), sNGAL (p=0.419) and uNGAL (p=0.443) levels did not differ between patients with active LN and non-renal active SLE; yet levels of sTWEAK were higher in patients with active LN (p=0.006). There were no differences between active LN and renal active AAV. Levels of all biomarkers were correlated with SLEDAI (sTWEAK: p=0.001; uTWEAK: p=0.006; sMCP-1: p=0.049; uMCP-1: p=0.014; sNGAL: p&lt;0.001; uNGAL: p=0.002). Conclusion: sTWEAK, uTWEAK, sNGAL and uNGAL are significant biomarkers showing disease activity in SLE. However, our results implicate that these biomarkers may not be specific for SLE, and can be elevated in patients with active renal involvement of AAV. sTWEAK may be of use for discriminating active nephritis from non-renal active disease in SLE. Further studies are awaited to confirm these results (This study was funded by Istanbul University with the project number TTU-2017-24738 and Turkish Society for Rheumatology). <h3>Reference</h3> [1] Mok CC. Biomarkers for lupus nephritis: a critical appraisal. J Biomed Biotechnol. 2010;2010:638413. <h3>Disclosure of Interests:</h3> None declared
Sicca: an important manifestation of damage in systemic sclerosis (SSc) and SSc-overlap syndromes. Response to ‘Do the salivary glands of patients with systemic sclerosis show ultrasonographic modifications suggestive of Sjögren's syndrome?’ by Coudrec <i>et al</i>
Authors: Mandana Nikpour
Journal: Annals of the Rheumatic Diseases (2019)

We thank Dr Couderc et al for reporting this interesting study of ultrasonographic changes in salivary glands of patients with systemic sclerosis (SSc).1 Their findings of a high frequency of xerostomia and xerophthalmia, together with morphological echostructure modifications of the major salivary …
PF715 THE IMPACT OF CRIZANLIZUMAB ON VOC‐RELATED MEDICAL FACILITY VISITS
Authors: M. Bailey, M. Thompson, S. Brown
Journal: HemaSphere (2019)

Background: A major cause of morbidity among patients with sickle cell disease (SCD) is the intense, recurrent, unpredictable attacks, known as vaso‐occlusive crises (VOCs), which are responsible for &gt;90% of hospital admissions in SCD. An important goal of pharmacological therapy is to prevent the occurrence of these painful episodes, and in turn, reduce the clinical and economic burden of the disease. In December 2018, the United States Food and Drug Administration granted crizanlizumab (SEG101) Breakthrough Therapy designation for the prevention of VOCs in patients with SCD. This designation was granted based on positive results from the Phase II SUSTAIN trial, in which 5 mg/kg crizanlizumab was associated with a 45.3% reduction in the median annual rate of VOCs leading to healthcare visits compared with placebo. Aims: The aim of the current analysis was to investigate the impact of crizanlizumab on VOC‐related medical facility visits. Methods: sing data from the SUSTAIN trial, analyses were conducted to determine the cumulative number of VOC events across all patients, medical facility visits and by medical facility type in the 5 mg/kg crizanlizumab and placebo arms. The total cumulative number of patient days in the study was considered in determining the event rate per year, which was calculated as follows: “[Total cumulative number of VOCs across all patients]/[Total number of days observed across all patients]” ∗ 365 Incidence rate ratios (IRR) were derived using a Poisson regression model. Maximum likelihood parameter estimates were generated with standard errors to produce confidence intervals and p‐values. Effect modification over time by group was assessed by maximum likelihood. Results: The analyses showed a reduction in the overall rate of VOC events requiring a medical facility visit in the 5 mg/kg crizanlizumab group compared with the placebo group. Further examination of the impact of crizanlizumab on specific sites of care demonstrated a reduction in visits to outpatient care sites, largely driven by reduced visits to emergency care units and SCD crisis centers (Table 1). A trend to reduced inpatient admissions was also observed. Summary/Conclusion: Payers aim to reimburse treatments for SCD that reduce both the clinical and economic burden of the disease. In the SUSTAIN trial, patients treated with 5 mg/kg crizanlizumab experienced a 45.3% reduction in the median annual rate of VOCs leading to healthcare visits compared with those receiving placebo. The current analysis demonstrates that this reduction in VOCs leading to a healthcare visit was seen in most medical facility visits, largely driven by reduced visits to emergency care units and specialized SCD crisis centers. These findings suggest that patients treated with crizanlizumab will experience a substantial reduction in health care resource utilization and associated costs. image
Definition and treatment of arrhythmogenic cardiomyopathy: an updated expert panel report
Authors: Perry M. Elliott, Aris Anastasakis, Angeliki Asimaki, Cristina Basso, Barbara Bauce, Matthew A. Brooke, Hugh Calkins, Domenico Corrado, Firat Duru, Kathleen J. Green, Daniel P. Judge, David Kelsell, Pier D. Lambiase, William J. McKenna, Kalliopi Pilichou, Alexandros Protonotarios, Jeffrey E. Saffitz, Petros Syrris, Hari Tandri, Anneline Te Riele, Gaetano Thiene, Adalena Tsatsopoulou, J. Peter van Tintelen
Journal: European Journal of Heart Failure (2019)
Recessive mosaicism in <i>ABCA12</i> causes blaschkoid congenital ichthyosiform erythroderma
Authors: F.S. Leersum, M.M.B. Seyger, T.E.J. Theunissen, E.M.H.F. Bongers, P.M. Steijlen, M. Geel
Journal: British Journal of Dermatology (2019)

We report the unique case of a 3‐year‐old girl who presented with linear erythematosquamous lesions following the lines of Blaschko, suggestive of genetic mosaicism in the skin. Single‐candidate gene analyses were performed on DNA from blood, excluding Conradi–Hünermann–Happle syndrome, erythrokeratodermia variabilis and a mosaic presentation of pityriasis rubra pilaris. With whole‐exome sequencing (WES) on DNA from the patient's blood, a heterozygous missense mutation in exon 25 of the ABCA12 gene was detected. By manually scrutinizing the WES data, another low‐percentage pathogenic frameshift mutation was found in the adjacent exon 26 of the same gene. This frameshift mutation was confirmed with Sanger sequencing in DNA isolated from a lesional skin biopsy. A subsequent cloning experiment was performed to prove that the patient is compound heterozygous for both mutations in the affected skin, explaining the blaschkoid ichthyosiform erythrodermic phenotype. The patient's phenotype was elucidated by the combination of a germline mutation and an acquired postzygotic mutation in ABCA12, resulting in the diagnosis of a mosaic manifestation of autosomal recessive congenital ichthyosis. Postzygotic compound allelic loss in autosomal recessive disorders is extremely rare and will not appear as the typical phenotype of the known germline mutation‐associated disease. This is the first report of a proven biallelic mosaic presentation of an autosomal recessive genodermatosis, and we propose the term 'recessive mosaicism' for this kind of manifestation. What's already know about this topic? Specific mutations in the ABCA12 lipid transporter are known to cause different phenotypes like harlequin ichthyosis, congenital ichthyosiform erythroderma and lamellar ichthyosis. In mosaicism, two or more cell populations that are genetically different arise postzygotically in the developing embryo. In the skin, mosaicism can present itself in different patterns of affected skin, often caused by a dominant genetic mutation. What does this study add? We report a unique patient with blaschkoid congenital ichthyosiform erythroderma due to biallelic mutations, one inherited germline missense mutation and the other a postzygotic frameshift mutation in the ABCA12 gene. This study describes the diagnostic approach and applied research that can be used if one encounters a similar diagnostic dilemma with manifestations suspected for genetic mosaicism. We propose the term 'recessive mosaicism' for this kind of mosaic presentation of an autosomal recessive genodermatosis.
PF814 KNOWLEDGE, ATTITUDES AND PRACTICES ON BLOOD TRANSFUSION OF MEDICAL RESIDENTS IN A TERTIARY HOSPITAL: A QUESTIONNAIRE‐BASED STUDY
Authors: R.S. Miranda, T. Dumagay
Journal: HemaSphere (2019)

Background: Blood transfusion remains to be one of the most common procedures performed in hospitals. It is an extremely efficient and perhaps life‐saving procedure which is very much an essential part in the management of hematologic and non‐hematologic cases. The knowledge of doctors on blood transfusion has a substantial influence on the rational utilization of blood products. Aims: We aim to assess the knowledge, attitudes and practices on transfusion of internal medicine (IM) residents at the Philippine General Hospital, using the BEST‐TEST, a validated questionnaire on transfusion medicine (TM). Methods: This is a descriptive cross‐sectional study design, which included all 63 internal medicine residents undergoing training at the Philippine General Hospital for the year 2016. General data on demographics were collected, after which the participants were asked to answer the BEST‐TEST validated questionnaire on transfusion medicine Results: A total of 63 internal medicine residents with a mean age 27.9 ± 1.6 ranging from 25 to 33 years old and majority (61.9%) were between 28 to 30 years old were included in this study. Gender distribution is almost even (50.8% males). In terms of number of hours of training on transfusion medicine in medical school, a third had 4+ hours and a little more than half (50.8%) had 3+ hours. Majority (58.7%) of the internal medicine residents appraised their knowledge of transfusion medicine as intermediate, and almost all (98.4%) rated it as beginner to intermediate. BEST‐TEST mean scores were 39.1%, 40.0%, and 41.0% for the first, second, and third year residents, respectively. There is no significant correlation between test scores of the residents and number of hours of training in transfusion medicine in medical school (p = 0.694) and in residency (p = 0.927). On the other hand, there is a significant correlation between the quality (perceived helpfulness) of residency training on transfusion medicine and test scores with the scores increasing as the year level increases. Summary/Conclusion: Indeed, the results of this study has shown inadeqacy in the knowledge on transfusion medicine among internal medicine residents. Therefore, further training on transfusion medicine, maybe in the form of lecture series and seminars, may help strengthen the knowledge of the residents.
Potentially Curable Pancreatic Adenocarcinoma: ASCO Clinical Practice Guideline Update
Authors: Alok A. Khorana, Shannon E. McKernin, Jordan Berlin, Theodore S. Hong, Anirban Maitra, Cassadie Moravek, Matthew Mumber, Richard Schulick, Herbert J. Zeh, Matthew H.G. Katz
Journal: Journal of Clinical Oncology (2019)

The purpose of this guideline update is to incorporate recently reported practice-changing evidence into ASCO's recommendations on potentially curable pancreatic adenocarcinoma.ASCO convened an Expert Panel to evaluate data from PRODIGE 24/CCTG PA.6, a phase III, multicenter, randomized clinical trial of postoperative leucovorin calcium, fluorouracil, irinotecan hydrochloride, and oxaliplatin (FOLFIRINOX) versus gemcitabine alone, presented at the 2018 ASCO Annual Meeting. In addition, PubMed was searched for additional papers that may influence the existing recommendations.The Expert Panel only updated Recommendation 4.1 as a result of the practice-changing data. Recommendation 4.1 states that all patients with resected pancreatic adenocarcinoma who did not receive preoperative therapy should be offered 6 months of adjuvant chemotherapy in the absence of medical or surgical contraindications. The modified combination regimen of 5-fluorouracil, oxaliplatin, and irinotecan (mFOLFIRINOX; oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, irinotecan 150 mg/m2 D1, and 5-fluorouracil 2.4 g/m2 over 46 hours every 14 days for 12 cycles) is now preferred in the absence of concerns for toxicity or tolerance; alternatively, doublet therapy with gemcitabine and capecitabine or monotherapy with gemcitabine alone or fluorouracil plus folinic acid alone can be offered.Additional information can be found at www.asco.org/gastrointestinal-cancer-guidelines.
Diffuse intrinsic pontine gliomas (DIPG) in adolescents can have differing presentations but similar outcomes compared to those of middle childhood.
Authors: Katherine E. Warren, Elad Jacoby, Jason R. Fangusaro
Journal: Journal of Clinical Oncology (2013)

2101 Background: DIPG are invasive, treatment-resistant, brainstem tumors that generally affect children in middle childhood. The triad of cranial neuropathies, long tract signs, and ataxia are characteristic presenting signs; most patients have a short history of symptoms. Median survival is less than one year, but young children (&lt;3 years) and adults with DIPG may have a better prognosis. Other positive clinical prognostic factors include longer duration of symptoms and absence of cranial neuropathies. We assessed the presentation and outcome of adolescents with DIPG. Methods: Patients were enrolled on an IRB-approved protocol. Clinical data for patients age&gt;10 years and &lt;20 years with a diagnosis of DIPG who were evaluated and treated at the authors’ institutions were reviewed. Results: A total of 46 patients were identified. M:F was 0.77:1. Median age at diagnosis was 13 (range 10-20) yrs. Frequent presenting symptoms included headache (39 %), dizziness (25%), diplopia (27%) and cranial neuropathies (27%). Two were diagnosed as incidental findings. The interval between onset of symptoms and diagnosis ranged from 2 days-5 years, and only 9 of 41 patients (22%) reported symptom duration of less than 2 weeks. The majority (39/42) received radiation therapy, with or without adjuvant chemotherapy. Of patients for whom data is available, 8/22 (36%) did not improve or worsened during radiation therapy and 17 of 27 (63%) remained on steroids at the end of radiation. Two patients are alive with stable disease and 1 is actively receiving initial treatment. Of the patients with progressive disease for whom data is available (n=32), median time to progression was 8 mo (range 2 mo-2.5 yrs). Conclusions: Presenting symptoms of DIPG in adolescents commonly include headache, dizziness and diplopia for several weeks-months. Although the vast majority are treated with radiation therapy, clinical benefit was not observed in a significant number of patients. Overall outcome is similar to those patients diagnosed in middle childhood rather than the adult population.
Predictive utility of high-sensitivity troponin-T for new-onset heart failure is higher in women than in men
Authors: N. Navin Suthahar, L. M. G. Meems, D. J. Van Veldhuisen, J. E. Walter, R. T. Gansevoort, P. Van der Harst, J. E. Kootstra-Ros, C. Mueller, S. J. L. Bakker, R. A. De Boer
Journal: European Journal of Heart Failure (2019)
AB0475 BELIMUMAB: EXPERIENCE IN CLINICAL PRACTICE SETTINGS AT A RHEUMATOLOGY DEPARTMENT IN A TERTIARY HOSPITAL
Authors: Carolina Merino Argumánez, Olga Rusinovich, Consuelo Ramos Giráldez, María Espinosa, Hilda Godoy, Carmen Barbadillo Mateos, Jose Campos Esteban, Mercedes Jiménez Palop, Jesus Sanz, Luis Fernando Villa Alcázar, Carlos Isasi Zaragoza, Monica Fernandez Castro, José Luis Andréu Sánchez
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Belimumab is a human IgG1l monoclonal antibody directed against BAFF, a B lymphocyte survival factor. It is indicated as adjuvant treatment in adult patients with active systemic lupus erythematosus (SLE), with positive autoantibodies and with a high degree of activity of the disease despite standard treatment. <h3>Objectives:</h3> This study aims to describe a sample of patients diagnosed with SLE who received treatment with belimumab in a tertiary hospital. <h3>Methods:</h3> Retrospective longitudinal unicentric observational study. Clinical records of all patients diagnosed with SLE who had received treatment with belimumab were reviewed. Demographic characteristics, clinical manifestations and reason for belimumab indicaton were collected. <h3>Results:</h3> The twelve patients included in the sample were women. Median age was 48.5 years (31-70). The most frequent reason for indication of belimumab was uncontrolled arthritis. The average time of treatment with belimumab in the total sample was 27.5 (+/- 26.24) months, with a median of 12 months (4-78). Mean treatment time (cases in which belimumab was discontinued excluded) was 31.25 (+/- 26.98) months with a median of 25 (5-78). The average dose reduction of prednisone after initiation of treatment with belimumab (in patients in which it was considered effective) was 5 mg per day (+/- 5). It should be noted that of the 14 cases, treatment was only discontinued in 4 patients, 2 of which were withdrawn due to ineffectiveness. There were 2 adverse events that required drug withdrawal: neutropenia and urothelial carcinoma. (Table). <h3>Conclusion:</h3> BLM is a well tolerated drug and effective in clinical practice. Adverse effects leading to drug withdrawal are infrequent. <h3>Disclosure of Interests:</h3> Carolina Merino Argumánez: None declared, Olga Rusinovich: None declared, Consuelo Ramos Giráldez Speakers bureau: Sanofi, María Espinosa: None declared, Hilda Godoy: None declared, Carmen Barbadillo Mateos: None declared, Jose Campos Esteban: None declared, Mercedes Jiménez Palop: None declared, Jesus Sanz: None declared, Luis Fernando Villa Alcázar: None declared, Carlos Isasi Zaragoza : None declared, Monica Fernandez Castro: None declared, José Luis Andréu Sánchez: None declared
Fullerene(C60)-immunoconjugates: Interaction of customized water-soluble C60 derivatives with the murine anti-gp240 melanoma antibody
Authors: Jared M. Ashcroft, Dmitry A. Tsyboulski, Sergey Bachilo, R. Bruce Weisman, John W. Marks, Michael G. Rosenblum, Lon J. Wilson
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

3085 

We are striving to develop fullerene immunotherapy (FIT) using C60 and shortened carbon nanotube nanoparticles as scaffolds and containment vessels for chemotherapeutics and radionuclides.1,2 First experiments have focused on the preparation and characterization of C60-immunoconjugates derived from a murine anti-gp240 melanoma antibody(ZME-018) and the two water-soluble C60 derivatives shown below, where only the C60-SPDP derivative can form covalent bonds with the antibody. Studies have demonstrated that immunoconjugates composed of ZME-018 and various toxins are rapidly internalized into human melanoma cells in culture.3 Moreover, these conjugates effectively locate into melanoma xenographs after systemic administration and demonstrate impressive cytotoxic effects against established tumors in orthotopic models. A single-drug chemotherapeutic agent such as the recently reported C60-paclitaxel conjugate1 might be employed for FIT, but the real advantage of FIT over other immunotherapies is the potential for attachment of multiple (and possibly different) drugs to the C60 scaffold in order to create targeted, single-dosed “drug cocktails”. Results from the formation of the two C60 immunoconjugates mirrored one another, with the concentration of C60 in the C60-SPDP-(ZME-018) conjugate being 6 μM for a (C60:antibody) ratio of 35:1 compared with 15 μM in the C60-Ser-(ZME-018) conjugate for a (C60:antibody) ratio of 100:1. This result suggests that covalent bond formation between C60 derivatives and antibodies may not be a requirement for the development of FIT. 1Zakharian, T. Y.; et al. J. Am. Chem. Soc. 2005, 127, 12508-12509. 2Mackeyev, Y. A.; et al. J. Phys. Chem. B 2005, 109, 5482-5484. 3Kirkwood, J. M.; et al. J. Clin. Oncol. 1987, 8, 1247-1255.



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