tbuckley/cabot-search huggingface dataset:
FRI0118 RISK OF LIVER FIBROSIS ON TRANSIENT ELASTOGRAPHY IN PATIENTS WITH RHEUMATIC DISEASE UNDER LONG-TERM METHOTREXATE TREATMENT
Authors: S. J. Choi, J. S. Lee, S. H. Nam, W. J. Seo, J. S. Oh, S. Hong, Y. G. Kim, C. K. Lee, B. Yoo
Journal: Annals of the Rheumatic Diseases (2020)

Background: Methotrexate (MTX) is a cornerstone drug for the treatment of rheumatic disease and low doses of MTX are both tolerable and safe, with monitored toxicity, assessed via the liver function test. However, there is still controversy regarding the risk of liver fibrosis with long-term use of MTX. Transient elastography is commonly used to assess and monitor fibrosis progression in patients with chronic liver disease. Objectives: The present study aims to investigate liver fibrosis using transient elastography and related factors in patients with rheumatic disease receiving long-term MTX. Methods: The present retrospective, longitudinal, cross-sectional study included patients with an autoimmune disease who are taking cumulative MTX dosed over 7 g, and who had liver fibrosis upon examination using transient elastography. Liver fibrosis was defined as liver stiffness, valued over 7.2 kPa. Logistic regression analysis was performed to identify factors associated with liver fibrosis, and receiver operating characteristics analysis was used to determine the predictive value of each factor. Results: We included 83 patients with autoimmune disease, with a median MTX cumulative dose of 11.6 (range 7.3-16.0) g. Sixty-eight patients (81.9%) had rheumatoid arthritis (RA), and 13 patients (15.7%) had Takayasu arteritis. The median MTX exposure duration was 18 (range 9-31) years. The median liver stiffness value was 4 (range 1.8-10.2) kPa. Five patients (6%) showed liver fibrosis (3 patients; RA, 2 patients; Takayasu arteritis). In the linear regression analysis, cumulative MTX dose showed a tendency towards a positive correlation with increasing liver stiffness value (r2 =0.039, p = 0.074). In the logistic regression analysis, cumulative MTX dose was associated with a higher risk of liver fibrosis (OR: 1.734, 95% CI: 1.060–2.837, p = 0.029). In addition, cumulative MTX dose had an area under the curve (AUC) of 0.813 (95% CI 0.695-0.930) and a sensitivity of 80% and specificity of 71.8% at a cut-off value of 12.7 g. Conclusion: Liver fibrosis was observed in 6% of patients with long-term MTX use and higher cumulative MTX doses increased the risk of liver fibrosis. Thus, transient elastography should be considered in patients exposed to high cumulative doses of MTX. Disclosure of Interests: None declared
A phase I study to evaluate the safety of multiantigen stimulated tumor specific cell therapy (MASCT-I) in subjects with advanced gastric cancer.
Authors: Zhaode Bu, Ziyu Jia, Ke Ji, Xin Ji, Ji Zhang, Xiaojiang Wu, Yanjun Kong, Aimin Zhu, Xiaoshuang Li, Jiafu Ji
Journal: Journal of Clinical Oncology (2021)

200 Background: Gastric cancer was the fifth cancer world wide and the third leading cause of cancer-related death. PD-1 antibody has been approved for treatment in gastric cancer patients with positive expression of PD-L1 and microsatellite instability. MASCT-I (Multi-Antigen Stimulated Cell Therapy-I Injection) is an autologous non-engineered immune cell therapy for solid tumor, it is composed of multiple-antigen peptides(15 tumor associated antigens) loaded mature dendritic cells (DCs) and in vitro DC stimulated and proliferated effector T cells, the combination of MASCT-I and PD1 antibody could have a synergistic anti-tumor effect. Methods: This is a single center, phase I trial to explore the safety and tolerance of the combination of MASCT-I and PD-1 antibody in advanced gastric cancer (NCT03393416). 15 patients with PD-L1 expression or microsatellite instability were enrolled between April 2018, and June 2019. Camrelizumab was administered once every two weeks, DC and T cells were sequential administered once a month. Therapy continued until the disease progresses. Results: Only adverse reaction below grade 2 was observed related to MASCT-I,such as fever, fatigue etc. Abnormal liver function and reactive capillary hyperplasia may be related to Camrelizumab. Among the 15 patients, the longest treatment duration was 18.9 months, and the median progression-free survival (mPFS) was 3.93 months, among which, mPFS of patients with microsatellite instability is 10.23 months, mPFS of patients expressing PD-L1 is 2.35 months, which is slightly higher than the historical data of Camrelizumab alone in the treatment of advanced gastric cancer (8 weeks for mPFS). The patient 1002 always had high content of CD8+ cells and NK cells and the positive immune response in their bodies, which may plays a role in killing the tumor cells. Conclusions: The combination of MASCT-I and Camrelizumab in the treatment of advanced gastric cancer or gastroesophageal junction cancer is a safe treatment regimen, and its efficacy deserves further study. Clinical trial information: NCT03393416.
Lesson of the month: management for aspiration of a silver nitrate pencil tip during tracheostomy care
Authors: Simon Deshayes, Romain Magnier, Frédérick Rault, Sylvain Teulier, Helen Fouquet, Emmanuel Bergot, Aurélien Justet
Journal: Thorax (2021)

We present the cases of two laryngectomised patients who were treated for granulomas of the tracheostomy orifice with a silver nitrate pencil. During tracheostomy care, the tip broke off, was aspirated and fell into the bronchial tree. Necrotising ulcerative injuries of the right bronchial tree with clear delineation were found without lesions in the subsegmental division. To prevent the risk of secondary stenosis of the small airways induced by the spread of silver nitrate, we did not irrigate with saline solution as previously reported. Antibiotherapy and endoscopic monitoring were performed. Complete healing in 4–6 weeks was found without stenosis of the bronchial tree or bleeding.
Functional monocytic myeloid-derived suppressor cells increase in blood but not airways and predict COVID-19 severity
Authors: Sara Falck-Jones, Sindhu Vangeti, Meng Yu, Ryan Falck-Jones, Alberto Cagigi, Isabella Badolati, Björn Österberg, Maximilian Julius Lautenbach, Eric Åhlberg, Ang Lin, Rico Lepzien, Inga Szurgot, Klara Lenart, Fredrika Hellgren, Holden Maecker, Jörgen Sälde, Jan Albert, Niclas Johansson, Max Bell, Karin Loré, Anna Färnert, Anna Smed-Sörensen
Journal: Journal of Clinical Investigation (2021)

The immunopathology of coronavirus disease 2019 (COVID-19) remains enigmatic, causing immunodysregulation and T cell lymphopenia. Monocytic myeloid-derived suppressor cells (M-MDSCs) are T cell suppressors that expand in inflammatory conditions, but their role in acute respiratory infections remains unclear. We studied the blood and airways of patients with COVID-19 across disease severities at multiple time points. M-MDSC frequencies were elevated in blood but not in nasopharyngeal or endotracheal aspirates of patients with COVID-19 compared with healthy controls. M-MDSCs isolated from patients with COVID-19 suppressed T cell proliferation and IFN-γ production partly via an arginase 1–dependent (Arg-1–dependent) mechanism. Furthermore, patients showed increased Arg-1 and IL-6 plasma levels. Patients with COVID-19 had fewer T cells and downregulated expression of the CD3ζ chain. Ordinal regression showed that early M-MDSC frequency predicted subsequent disease severity. In conclusion, M-MDSCs expanded in the blood of patients with COVID-19, suppressed T cells, and were strongly associated with disease severity, indicating a role for M-MDSCs in the dysregulated COVID-19 immune response.
Understanding the impact of COVID-19 on the colorectal cancer community: Barriers and opportunities for care.
Authors: Reese Garcia, Andrea Dwyer, Molly McDonnell
Journal: Journal of Clinical Oncology (2021)

29 Background: The novel coronavirus (COVID-19) has caused numerous disruptions across the cancer prevention and treatment landscape. Conservative modeling studies examining the effect of COVID-19 on cancer screening and treatment for breast and colorectal cancer (CRC) suggest that there will be 10,000 excess deaths from both cancers combined over the next decade. The goal of this analysis was to better understand the impact of COVID-19 on the CRC community, including gaps and opportunities for improving access to care and survivorship needs, and to advocate for the best possible care through policy, education and engagement of the entire cancer ecosystem. Methods: In April 2020, Fight Colorectal Cancer (Fight CRC) distributed an online survey to the colorectal cancer community. The survey was distributed through social media channels and targeted emails from April 24-May 5, 2020. Virtual focus groups were also conducted to gather rich qualitative data from cancer patients and caregivers about their experiences during the novel coronavirus pandemic. Results: In total, 222 individuals responded to the survey (survivors = 68%, caregiver = 12%, first degree family member = 8%, other = 8%), and 10 CRC survivors participated in focus groups (stage III = 30%, stage IV = 70%). Treatment disruptions and mental health were prevalent themes in both the survey and focus group. Over one-third of survey respondents indicated facing treatment disruptions (37%) and a majority (78%) of colorectal cancer patients reported feeling nervous and anxious. Another primary concern among respondents was access to care. Patients on Medicare were more likely than patients on private insurance to report having difficulties affording food and basic supplies. People living in rural areas were more likely to have greater concerns about maintaining a supportive network than those living in suburban areas. Conclusions: People with cancer face unique challenges as a result of the novel coronavirus, including treatment disruptions, increased feelings of anxiety, and financial concerns. Numerous health inequities also exist among low-income and rural patient groups. Identifying the barriers that patients face provides an opportunity to address the nuanced needs of the colorectal cancer community. Clinicians, supportive care providers, and advocacy organizations can tailor care delivery, increase access to care, and prepare patients for the future with reliable and accurate resources amidst a pandemic.
Fecal Immunochemical Testing vs Sigmoidoscopy for Cancer Screening
Authors: Anita Slomski
Journal: JAMA (2021)

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Abstract P183: 20-year Secular Trend of Cardiovascular Disease Comorbidities in the United States, 1997-2016
Authors: Dianjianyi Sun, Tao Zhou, Xiang Li, Yoriko Heianza, Xiaoyun Shang, Lu Qi
Journal: Circulation (2018)

Background: Cardiovascular disease (CVD) has been the number one cause of death and disability in the US and globally for decades, and its comorbidity complicates the management of CVD. However, little is known about the secular trend of CVD comorbidities in national representative populations in the last 20 years. Methods: Prevalence of CVD and nine major chronic comorbidities was estimated using data from 1,324,214 adults aged 18 years and older in the National Health Interview Survey (NHIS) from 1997 through 2016, with age-standardized to the U.S. population in the year 2000. Results: CVD prevalence in the US adult population significantly declined in the past twenty years (from 6.6% in 1997 to 5.9% in 2016, P trend &lt;0.01in Figure a). And such trend was shown in women and whites (P trend &lt;0.01), but not in men and blacks (P trend &gt;0.05). We ranked the nine major chronic comorbidities (high to low) in the CVD patients (Figure b.), including (1) hypertension, (2) respiratory conditions, (3) nervous system conditions, (4) digestive conditions, (5) diabetes, (6) cancer, (7) genitourinary conditions, (8) circulatory conditions, and (9) endocrine/nutritional/metabolic conditions. From 1997 to 2016, the prevalence of CVD comorbidities including hypertension (38.8% to 50.2%), digestive conditions (17.0% to 27.1%), diabetes (10.0% to 19.2%), cancer (9.4% to 12.8%), and genitourinary conditions (4.1% to 5.2%) continuingly increased (all P trend &lt;0.01), while respiratory conditions declined (35.9% to 27.6%, P trend &lt;0.01). Similar trends of CVD comorbidities were observed among subgroups stratified by gender or by race. Conclusions: CVD prevalence in the U.S. adults have declined significantly in the past two decades, but rates of CVD comorbidities including hypertension, digestive conditions, diabetes, cancer, and genitourinary conditions increased substantially.
A phase III trial of tumor-treating fields with nab-paclitaxel and gemcitabine for front-line treatment of locally-advanced pancreatic adenocarcinoma (LAPC): PANOVA-3.
Authors: Vincent J. Picozzi, Teresa Macarulla, Philip Agop Philip, Carlos Roberto Becerra, Tomislav Dragovich
Journal: Journal of Clinical Oncology (2021)

TPS448 Background: Tumor Treating Fields (TTFields) are a non-invasive, regional antimitotic treatment modality, which has been approved for the treatment of glioblastoma. TTFields at specific frequency (150-200 kHz) are delivered via transducer arrays placed on the skin in proximity to the tumor site. TTFields predominantly act by disrupting the formation of the mitotic spindle during metaphase. TTFields were effective in multiple preclinical models of pancreatic cancer. The phase 2 PANOVA study, the first trial testing TTFields in pancreatic cancer patients, demonstrated the safety and preliminary efficacy of TTFields when combined with nab-paclitaxel and gemcitabine in both metastatic and LAPC. The Phase 3 PANOVA-3 trial (NCT03377491) is designed to test the efficacy and safety of adding TTFields to nab-paclitaxel and gemcitabine combination in LAPC. Methods: Patients (N = 556) with unresectable, LAPC (per NCCN guidelines) will be enrolled in this prospective, randomized trial. Patients should have an ECOG score of 0-2 and no prior progression or treatment. Patients will be stratified based on their performance status and geographical region, and will be randomized 1:1 to TTFields plus nab-paclitaxel and gemcitabine or to nab-paclitaxel and gemcitabine alone. Chemotherapy will be administered at standard dose of nab-paclitaxel (125 mg/m 2 ) and gemcitabine (1000 mg/m2 once weekly). TTFields (150 kHz) will be delivered at least 18 hours/day until local disease progression per RECIST Criteria V1.1. Follow up will be performed q8w, including a CT scan of the chest and abdomen. Following local disease progression, patients will be followed monthly for survival. Overall survival will be the primary endpoint and progression-free survival, objective response rate, rate of resectability, quality of life and toxicity will all be secondary endpoints. Sample size was calculated using a log-rank test comparing time to event in patients treated with TTFields plus chemotherapy with control patients on chemotherapy alone. PANOVA-3 is designed to detect a hazard ratio 0.75 in overall survival. Type I error is set to 0.05 (two-sided) and power to 80%. Clinical trial information: NCT03377491.
繰り返すin stent restenosis(ISR)に対しDCA,Rotablatorを用いたstent debulkingが有効であった2症例
Authors: 白坂明広, 佐々木良雄, 内匠拓朗, 稲永桂, 松浦靖, 竹岡玲, 北口勝司, 岩瀬知行, 河合忠一
Journal: Circulation (2002)
SAT0458 THE POLYMORPHISM ON FAT MASS AND OBESITY ASSOCIATED GENE (FTO) WAS ASSOCIATED WITH LOW BONE MASS IN JAPANESE COMMUNITY DWELLING POPULATION.
Authors: K. Arima, M. Tamai, F. Nonaka, N. Iwamoto, S. Mizukami, T. Nishimura, Y. Abe, T. Origuchi, K. Aoyagi
Journal: Annals of the Rheumatic Diseases (2020)

Background: A polymorphism on FTO (OMIM 610966) was reported as a causal variant for obesity, plays a critical rule not only in amount of adipose tissue but also in function of mitochondrial thermogenesis1. Objectives: To examine the association of the genotype on a single nucleotide polymorphism on FTO with bone health. Methods: FTO rs1421085 polymorphism was genotyped in 1,601 community-dwelling Japanese participants. This cross-sectional study was nested in Nagasaki Islands Study, which is a prospective cohort in Goto City, in islands of Japan. Participants were recruited at medical check-ups for community dwelling population. Bone mass of the calcaneus was evaluated with stiffness index calculated using a quantitative ultrasound measurement. Low bone mass was defined as a stiffness index less than 80 % of the young adult mean. Sera and peripheral blood mononuclear cells were obtained. The SNP of rs1421085 was genotyped using hydrolysis probe. The chi-squared test was used to determine whether the variants were in equilibrium in that population. Trend for the median of BMI among genotypes was assessed using the Jonckheere-Terpstra test. Potential associations between FTO polymorphism and overweight and between the polymorphism and low bone mass were evaluated using logistic regression. All analyses were carried out using SPSS 23. Results: Genotype and allele frequencies for the polymorphism were in Hardy-Weinberg equilibrium (minor allele frequency 0.16, p = 0.40) in 1,601 community-dwelling persons (mean age was 68.5 years in men and 68.1 years in women). There were significant associations between the minor allele and higher median of BMI on dose dependent manner in men (p = 0.04 for trend in men and p = 0.10 for trend in women, respectively), and between the minor allele and overweight (&gt;25 in BMI, OR 1.52, 95%CI 1.07 2.14, p=0.02 in men, OR 1.48, 95%CI 1.16 1.95, p=0.01 in women). Logistic regression analysis showed a significant protective association in men with carriers of minor allele against low bone mass after an adjustment for age and BMI (OR 0.63, 95%CI 0.44 0.90, p=0.01 in men, not significant in women). Conclusion: Our study indicated significant associations of the polymorphism on FTO with BMI and bone mass among community dwelling men. The polymorphism may play a rule in a part of bone health with higher BMI and other beneficial functions. References: [1]N Engl J Med. 2015; 373: 895-907 Disclosure of Interests: None declared
The COVID-19 Economy, Unemployment Insurance, and Population Health
Authors: Elizabeth Rigby
Journal: JAMA Network Open (2021)

unemployment insurance under the CARES Act as well as the broader public impacted in numerous ways by the COVID-19 pandemic-related economic crisis.As of this writing, in the final days of the 116th Congress, policy makers have forged a smaller but still substantial relief package that would expand the needed unemployment insurance, albeit at a reduce rate, alongside other economic supports.Currently at issue and holding up final approval of the bill is the size of a direct stimulus benefit that would be sent to most low-and middle-income US individuals.These 1-time payments are beyond the scope of the study by Raifman et al, 2 but their findings combined with the broader literature tell us that these types of economic benefits should be viewed as tools that serve 2 purposes: to provide much-needed economic relief and to blunt the harm to US health associated with the COVID-19 pandemic-related economic downturn.
SAT0104 Are coagulopathies involved in nontraumatic avascular necrosis?
Authors: N Mehsen, JP Vernhes, V Guérin, P Germain, L Malterre, J Dehais, F Parrot, T Schaeverbeke
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Various conditions are considered as classical etiologies of nontraumatic avascular necrosis (AVN), such as endogenous or exogenous hypercorticism, alcoholism, barotraumatisms, systemic lupus, diabetes mellitus and hyperlipidemia. However, in many cases, none of these conditions are identified and AVN is considered to be idiopathic. <h3>Objectives</h3> To seek thrombophilic disorders in a cohort of patients with AVN. <h3>Methods</h3> All patients with AVN hospitalised in our departments during a couple of years were enrolled in this prospective study. Diagnosis of AVN was performed on X-rays and/or MRI when necessary and possible. Biological investigations included: glycemia, cortisolemia, ferritinemia, cholesterolemia, lipoproteinemia, haemoglobin electrophoresis, ANA, antiphospholipid antibodies, anti-B2GP1 antibodies, lupus anticoagulant, antiprothrombin antibodies, antithrombin, protein C, protein S, factor VIII, IX, XI, activated protein C resistance, prothrombin gene mutation, homocysteinemia and methionin load test. <h3>Results</h3> 17 patients were enrolled, 9 men and 8 women, aged 34 to 76, with various stages of AVN (from stage 1 to 4). Antithrombin III deficiency was diagnosed in a woman. Resistance to activated protein C was found in another woman. Hyperhomocysteinemia was identified in 6 patients: two women (associated with antiphospholipid antibodies in one case), and 4 men. A lupus anticoagulant was found in one man and one woman. Two other patients were found to be homozygous to methyl-tetra-hydrofolate reductase (MTHFR) mutation, condition which leads to a susceptibility to hyperhomocysteinemia. <h3>Conclusion</h3> 59% of our patients with AVN were found to have a thrombophilic disorder. We suggest that such a disorder may precipitate thrombosis when added to other risk factors. Among these thrombophilic disorders, hyperhomocysteinemia seemed to be the most frequent factor associated with AVN. If hyperhomocysteinemia is confirmed to be involved in AVN, these results should be of special interest in prevention of recurrences, as hyperhomocysteinemia can be corrected by folic acid, B6 and B12 supplementation.