tbuckley/cabot-search huggingface dataset:
FRI0156 Cytokine responses to streptococcus sanguis in patients with behcet’s disease
Authors: G Mumcu, T Ergun, N Aritan, E Eksioglu-Demiralp, H Direskeneli
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Atypical streptococcal infections (Streptoccocus Sanguis, Salivarius) are implicated in the pathogenesis of Behcet’s Disease (BD), a systemic vasculitis of unknown aetiology. <h3>Objectives</h3> This study aimed to investigate in mononuclear cell culture supernatants, <i>in vitro</i> cytokine responses to S. Sanguis in patients with BD compared to psoriasis (PS) and healthy controls (HC). <h3>Methods</h3> Twelve patients with BD (4F/8M, mean age: 33.6 years), 7 with PS (4F/3M, mean age: 38.2 years) and 10 HC (7F/3M, mean age: 27.5 years) were included in the study. IL-4, IL-10, and IFN-γ responses were measured in peripheral blood mononuclear cell culture supernatants by ELISA after 48 h stimulations with S. Sanguis (10 μg/ml) and PHA (20 μg/ml). Positive responses were defined as above mean+2SD of unstimulated samples from HC. <h3>Results</h3> Positive IL-10 responses to S. Sanguis were observed in 5/12 patients with BD (mean: 94 pg/ml), 2/7 with PS (76 pg/ml), and 3/10 with HC (57 pg/ml). IFN-γ responses were prominent both after S. Sanguis (BD: 4/12 positive, 31 pg/ml; PS: 1/7 positive, 19 pg/ml; HC: 1/10 positive,19 pg/ml) and PHA (BD: 4/12 positive, 493 pg/ml; PS: 1/7 positive, 47 pg/ml; HC: 0/10 positive, 10 pg/ml). No IL-4 responses were observed in any group against both antigens. <h3>Conclusion</h3> Although Th1 type cytokine responses are generally accepted to be dominant in BD, in addition to IFN-γ, a prominent IL-10 response against S. Sanguis is observed in this study. These results suggest that a more complex cytokine profile is present in BD against microbial antigens.
Effects of Lifestyle Intervention of Maternal Gestational Diabetes Mellitus on Offspring Growth Pattern Before Two Years of Age
Authors: Jing Li, Jinnan Liu, Cuiping Zhang, Gongshu Liu, Junhong Leng, Leishen Wang, Weiqin Li, Zhijie Yu, Gang Hu, Juliana C.N. Chan, Xilin Yang
Journal: Diabetes Care (2021)

Our group conducted a population-based randomized controlled trial (RCT) in Tianjin, China, which tested the effectiveness of intensive care (IC) versus usual care (UC) on adverse pregnancy outcomes among women with gestational diabetes mellitus (GDM), and found that with IC of GDM during pregnancy a 98-g birth weight reduction and a 34% risk reduction in macrosomia were achieved (1). We further followed offspring born to women enrolled in the RCT from 1 month to 2 years after delivery to test whether IC of GDM during pregnancy modified early-life growth of offspring born to Chinese women with GDM.

The study settings, population, and design have been previously described (1). Briefly, a total of 19,847 pregnant women were screened for GDM with a glucose challenge test between the 24th and 28th weeks of pregnancy, and 2,921 women with a glucose challenge test level ≥7.8 mmol/L underwent the standard oral glucose tolerance test. Of them, 1,440 women with GDM were identified based on the International Association of Diabetes and Pregnancy Study Group (IADPSG) criteria (2) and 706 eligible women were randomized to either IC or UC group and completed the trial. The UC included one group diabetes education session at diagnosis of GDM, while the IC included additional two individualized diabetes education sessions at the …
First-line nivolumab plus ipilimumab combined with two cycles of chemotherapy in patients with non-small-cell lung cancer (CheckMate 9LA): an international, randomised, open-label, phase 3 trial
Authors: Luis Paz-Ares, Tudor-Eliade Ciuleanu, Manuel Cobo, Michael Schenker, Bogdan Zurawski, Juliana Menezes, Eduardo Richardet, Jaafar Bennouna, Enriqueta Felip, Oscar Juan-Vidal, Aurelia Alexandru, Hiroshi Sakai, Alejo Lingua, Pamela Salman, Pierre-Jean Souquet, Pedro De Marchi, Claudio Martin, Maurice Pérol, Arnaud Scherpereel, Shun Lu, Thomas John, David P Carbone, Stephanie Meadows-Shropshire, Shruti Agrawal, Abderrahim Oukessou, Jinchun Yan, Martin Reck
Journal: The Lancet Oncology (2021)
Antimicrobial therapy for otitis media with effusion ('secretory' otitis media)
Authors: E. I. Cantekin
Journal: JAMA (1991)

<h3>Objective.</h3> —To determine the effectiveness of antimicrobial treatment for otitis media with effusion ("secretory" otitis media) in children. <h3>Data Source.</h3> —We report the reexamination of a previously published study by Mandel et al that evaluated the efficacy of a 2-week course of antimicrobials (amoxicillin trihydrate) with and without a 4-week course of an oral decongestant-antihistamine combination in a double-blind, placebo-controlled, randomized trial involving 518 infants and children with otitis media with effusion. <h3>Data Synthesis.</h3> —At 4 weeks, amoxicillin efficacy as determined by a tympanometric criterion (<i>P</i>=.121) or by a measure of improvement in hearing (<i>P</i>=.311) was insignificant. Only by otoscopic judgment, which is shown to contain a systematic bias as used in this clinical trial, could an argument be made for a marginal efficacy of amoxicillin at the 4-week end point. Logistic regression analyses of the combined effects of treatment and prognostic factors showed no significant differences between placebo- and antibiotic-treated groups for unilateral effusions and for bilateral effusions. When subjects with unilateral and bilateral effusions were combined, the estimated efficacy of antibiotic treatment was 12.3% by otoscopy (<i>P</i>=.014) and 4.8% by tympanometry (<i>P</i>=.171). We also demonstrate the sensitivity of outcome to diagnostic measures used and provide statistical evidence questioning the validity of otoscopic observations in this study. Six weeks after the termination of amoxicillin therapy, the recurrence of effusion was two to six times higher in the amoxicillin-treated children than in those treated with placebo (<i>P</i>=.001), and resolution of effusion was not significantly different among antibiotic and placebo groups (13.6% and 11.3%, respectively;<i>P</i>=.477). <h3>Conclusions.</h3> —Amoxicillin with and without decongestant-antihistamine combination is not effective for the treatment of persistent asymptomatic middle-ear effusions in infants and children. (<i>JAMA</i>. 1991;266:3309-3317)
PARP inhibitor Olaparib overcomes Sorafenib resistance through reshaping the pluripotent transcriptome in hepatocellular carcinoma
Authors: Xiao-Dong Yang, Fan-En Kong, Ling Qi, Jia-Xin Lin, Qian Yan, Jane Ho Chun Loong, Shao-Yan Xi, Yue Zhao, Yan Zhang, Yun-Fei Yuan, Ning-Fang Ma, Stephanie Ma, Xin-Yuan Guan, Ming Liu
Journal: Molecular Cancer (2021)

Abstract Hepatocellular carcinoma (HCC) is one of the most common human malignancies worldwide with very poor prognosis. Resistance to targeted therapeutic drugs such as sorafenib remains one of the major challenges in clinical treatment. In the present study, PARP1 was found to be highly expressed in human embryonic stem cells, but progressively decreased upon specified hepatic differentiation. Reactivation of PARP1 expression was also detected in HCC residual tumors after sorafenib treatment in xenograft mouse model, indicating the potential important roles of PARP1 in stem cell pluripotency and HCC sorafenib treatment resistance. Overexpression of PARP1 was frequently observed in HCC patients, and closely associated with poor clinical outcome. Treatment of Sorafenib induced activation of DNA damage repair signaling, which is highly active and essential for maintenance of stem cell pluripotency in HCC residual tumors. PARP inhibitor Olaparib extensively suppressed the DNA damage repair signaling, and significantly inhibited the global pluripotent transcriptional network. The repression of key pluripotent transcriptional factors and DNA damage repair signaling by Olaparib was mainly through CHD1L-mediated condensation of the chromatin structure at their promotor regions. The global reshaping of the pluripotent transcriptome by Olaparib might reinforce Sorafenib in eliminating HCC residual tumors and enhance therapeutic efficiency.
Risk of Covid-19 Illness Among EMS Providers Following Cardiopulmonary Resuscitation and Aerosol Generating Procedures
Authors: A. D. Brown, L. Schwarcz, C. R. Counts, L. M. Barnard, B. Y. Yang, J. M. Emert, A. J. Latimer, C. Drucker, J. Blackwood, P. J. Kudenchuk, M. R. Sayre, T. D. Rea
Journal: Circulation (2020)
AB0909 TREATMENT WITH DENOSUMAB IN GLUCOCORTICOSTEROID-INDUCED OSTEOPOROSIS IN PATIENTS WITH RHEUMATOID ARTHRITIS
Authors: M. Osipyan, M. Efraimidou, S. Bazeyan, A. Antikyan, V. Vardanyan, K. Ginosyan
Journal: Annals of the Rheumatic Diseases (2020)

Background: Glucocorticosteroids (GCS) are widely used in the treatment of rheumatoid arthritis (RA) as bridge-therapy. Though, according to last recommendations for the treatment of RA GCS should be considered in short-term and different dose regimens and routes of administration and should be tapered as rapidly as clinically feasible. But in some cases, patients received GCS for a long period in low doses (&lt;7.5 mg/day prednisone equivalent). It is well known, that long-term GCS use is associated with osteoporosis and increased risk of fracture, even at low daily doses. On the other hand, RA itself leads to the changes in the biomechanical properties of bones through the increased production of pro-inflammatory cytokines. Furthermore, immobilization due to pain from inflamed joints and impairment of physical activity are in response for osteoporosis formation. In addition, patients with RA are often co-prescribed a proton pump inhibitor, which have a reported effect on occurrence of osteoporosis. Taking into consideration all mentioned above patients with RA, receiving GCS therapy reveal high risk for osteoporosis and fracture formation and require corresponding treatment. Objectives: The aim of this study is to evaluate the effect of 12 months treatment with denosumab (bone-modifying agent) in patients with RA, continuing to receive GCS. Methods: 50 female patients with RA (mean age 54 ± 6.3 years) were enrolled in this study. Duration of RA was 10.5 ± 3.2 years. All patients received prednisone 15,3± 10,25 mg/day with gradually escalation of dose for ≥ 12 months. As DMARD therapy patients received methotrexate dose in average 15-20mg/week (75%), leflunomide 20 mg/day (25%). Bone mineral density (BMD) is measured in all patients by Dual-energy X-ray absorptiometry (DEXA) at baseline and 12 months after treatment with denosumab. All patients received denosumab 60 mg subcutaneously once every 6 months. Results: The measurement of BMD at baseline revealed the following results: T-score in lumbar spine was -1,95 ± 1,36 and in total hip -1,64± 0,94 with high major osteoporotic fracture risk. All patients completed the study. The BMD after 12 months significantly increased both in lumbar spine +4,2 % (p&lt;0,001) and in total hip +2,1% (p&lt;0,001). Conclusion: Denosumab should be considered as a drug of choice in RA patients, continuing to receive GCS. Further large investigations are needed to assess the BMD after discontinuation of denosumab and evaluate fracture risk in this population of patient. References: [1]J.Compston. Glucocorticoid-induced osteoporosis: an update. Endocrine. 2018; 61(1): 7–16. doi: 10.1007/s12020-018-1588-2 [2]A.Giovanni, S.Kenneth. Glucocorticoid-induced osteoporosis update. Current Opinion in Rheumatology: 2019;31(4): 388-393. doi: 10.1097/BOR.0000000000000608 Disclosure of Interests: None declared
An enhanced care package to improve asthma management in Malawian children: a randomised controlled trial
Authors: Sarah Rylance, Beatrice Chinoko, Bright Mnesa, Chris Jewell, Jonathan Grigg, Kevin Mortimer
Journal: Thorax (2021)

Background Shortages of clinical staff make chronic asthma care challenging in low-income countries. We evaluated an outpatient asthma care package for children, including task-shifting of asthma management roles. Methods We conducted a non-blinded individually randomised controlled trial at a tertiary-level government hospital in Blantyre, Malawi. Children aged 6–15 years diagnosed with asthma were recruited from outpatient clinic, stratified by Childhood Asthma Control Test (cACT) score and allocated 1:1 from a concealed file, accessed during electronic questionnaire completion. The intervention, delivered by non-physicians, comprised clinical assessment, optimisation of inhaled treatment, individualised asthma education. The control group received standard care from outpatient physicians. Primary outcome for intention-to-treat analysis was change in cACT score at 3 months. Secondary outcomes included asthma exacerbations requiring emergency healthcare and school absence. Findings Between September 2018 and December 2019, 120 children (59 intervention; 61 control) were recruited; 65.8% males, with mean (SD) age 9.8 (2.8) years, mean (SD) baseline cACT 20.3 (2.6). At 3 months, intervention children (n=56) had a greater mean (SD) change in cACT score from baseline (2.7 (2.8) vs 0.6 (2.8)) compared with standard care participants (n=59); a difference of 2.1 points (95% CI: 1.1 to 3.1, p&lt;0.001). Fewer intervention children attended emergency healthcare (7.3% vs 25.4%, p=0.02) and missed school (20.0% vs 62.7%, p&lt;0.001) compared with standard care children. Interpretation The intervention resulted in decreased asthma symptoms and exacerbations. Wider scale-up could present substantial benefits for asthmatic patients in resource-limited settings. Trial registration number PACTR201807211617031.
Abstract 2142: Diagnostic and Prognostic Value of Augmented ST-Segment Elevation at Exercise Testing in Patients with Brugada Syndrome
Authors: Hisaki Makimoto, Eiichiro Nakagawa, Hiroshi Takaki, Kenichiro Yamagata, Hiro Kawata, Hideo Okamura, Takashi Noda, Kazuhiro Satomi, Kazuhiro Suyama, Takashi Kurita, Naohiko Aihara, Shiro Kamakura, Wataru Shimizu
Journal: Circulation (2008)

Background : It has been reported that ST-segment elevation was augmented at early recovery phase or at peak exercise during exercise testing in some patients with Brugada syndrome (BrS), but its diagnostic and prognostic value has not fully been clarified. Methods : Treadmill exercise testing (TMT) was conducted in 93 patients (pts) with BrS (22 documented VF, 31 syncope alone, and 40 asymptomatic; 91 males, 46±14 years) and 22 healthy control subjects (20 males, 48±14 years, 11 with incomplete right bundle branch block (RBBB) and 4 with complete RBBB). Results : The augmentation of ST-segment elevation ≥0.05mV in V1-V3 leads compared with that before exercise was observed at early recovery phase (1– 4 minutes at recovery phase) in 32 BrS pts (34%, Group1), at peak exercise in 8 BrS pts (9%, Group 2), but not in either the remaining 53 BrS pts (57%, Group 3) or 22 control subjects. There were no significant differences among the 3 BrS groups in the baseline clinical (age, gender, family history of sudden death, SCN5A mutation), electrocardiographic (PR, QRS duration, QTc interval and ST amplitude), and electrophysiologic (AH, HV interval, and VF induction) variables except for the positive ratio of signal averaged ECG (87%, 48%, 63%; P= 0.001). No significant difference was observed in the proportion of previous cardiac events (VF/syncope/asymptomatic; 6/12/14, 0/3/5, 16/16/21, respectively for Group 1, 2, and 3). During 76.0, 74.8, and 52.0 months follow-up, VF occurred in 12/32 (38%) pts of Group1, 0/8 (0 %) pts of Group2, and 10/53 (19%) pts of Group3. Augmentation of ST-segment elevation at early recovery phase was a significant and an independent predictor for subsequent VF occurrence (12/32 (38%) in Group1 vs. 10/61 (16%) in Group2 and 3; hazard ratio [HR]= 1.68; P=0.014), especially in 31 pts with a history of syncope alone (6/12 (50%) in Group1 vs. 1/19 (5%) in Group2 and 3; HR=3.44; P=0.004). Conclusions : Our data suggest that augmentation of ST-segment elevation at early recovery phase during exercise testing can be a predictor of poor prognosis in patients with Brugada syndrome, especially in those with a history of syncope alone.
Endothelial cell metabolic memory causes cardiovascular dysfunction in diabetes
Authors: Yufeng Yao, Qixue Song, Changqing Hu, Xingwen Da, Yubing Yu, Zuhan He, Chengqi Xu, Qiuyun Chen, Qing K Wang
Journal: Cardiovascular Research (2021)

The aim of this study was to identify the molecular mechanism for hyperglycaemia-induced metabolic memory in endothelial cells (ECs), and to show its critical importance to development of cardiovascular dysfunction in diabetes.
Are overwhelmed health systems an inevitable consequence of covid-19? Experiences from China, Thailand, and New York State
Authors: Viroj Tangcharoensathien, Mary T Bassett, Qingyue Meng, Anne Mills
Journal: BMJ (2021)

<h3>Background:</h3> Clinical guidelines aim to improve the safety and quality of patient care by providing clinicians with graded recommendations based on evidence of best practice. <h3>Objective:</h3> To evaluate the effects of the introduction of clinical guidelines for allied health professionals, and to estimate the effectiveness of the guideline dissemination and implementation strategies used. <h3>Methods:</h3> A comprehensive search of six electronic databases to June 2006 and the Cochrane Effective Practice and Organisation of Care database was conducted. Randomised controlled trials, controlled clinical trials, controlled before and after studies and interrupted time series studies were included if the intervention was aimed at implementing guidelines in the allied health professions. Articles were screened for eligibility and their methodological quality was assessed; data were extracted independently by two reviewers. <h3>Results:</h3> Fourteen studies met the inclusion criteria. The methodological quality varied greatly, with the proportion of quality criteria met ranging from 0 to 6 out of seven. In most studies, the effects reported for patient and process outcomes were small and in favour of the intervention group. Of the 14 included studies, 10 focused on educational interventions. Six of the 14 studies used a single intervention strategy and seven used a multi-faceted implementation strategy. One study compared both single and multi-faceted strategies. Multi-faceted interventions were no more effective than single intervention strategies and effects of the same strategy varied across trials. <h3>Conclusions:</h3> There is no evidence to support a set guideline implementation strategy for allied health professionals. When implementing clinical guidelines it is important to first identify specific barriers to change using theoretical frameworks of behaviour change and then develop strategies that deal with these barriers. When measuring the effectiveness of these strategies, professionals should consider the use of both patient and process outcomes and choose outcomes that reflect their aims.
Utilization of Surgical Manpower in a Prepaid Group Practice
Authors: Edward F.X. Hughes, Eugene M. Lewit, Richard N. Watkins, Richard Handschin
Journal: New England Journal of Medicine (1974)

Abstract To study the utilization of surgeons in a prepaid group setting, the operative work loads, of seven general surgeons comprising the general surgical staff of a prepaid group practice of 158,000 enrollees were determined. The median weekly work load, 9.9 hernia equivalents per week, was over three times that of a previously studied population of 19 general surgeons in fee-for-service community practice (3.1 hernia equivalents) and approximated a previously elaborated consensus standard of a full weekly surgical work load (10 hernia equivalents). The median complexity of inpatient, ambulatory and all operations was 1.14, 0.16, and 1.00 hernia equivalents, respectively. Evidence suggested that the most complex operations were handled by the most highly trained surgeons; 23.8 per cent of operations were performed on an ambulatory basis. The results suggest that the prepaid group practice under study is able to utilize efficiently both general surgeons and the resources devoted to general surgery. (N Engl J Med 291:759–763, 1974)
AB0067 Vascular endothelial growth factor (vegf) and its receptors in rheumatoid arthritis and osteoarthritis
Authors: B Fink, A Böttcher, B Schwarloh, M Fuerst, N Hansen-Algenstaedt, W Rüther, P Algenstaedt
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Rheumatoid arthritis (RA) is characterised by synovial proliferation. Tissue proliferation in general is known to be dependent on sufficient oxygen and nutrition supply. Therefore angiogenesis, the process of new vessel formation, is considered to play a crucial role not only for tumour growth but also in rheumatoid arthritis. The angiogenetic process is regulated by several cytocines. Most important factor is the Vascular Endothelial Growth Factor (VEGF) and its cognate receptors KDR and FLT-1, known to be regulated by hypoxia as well as inflammatory cytocines. On the other hand RA is a chronic inflammatory process. <h3>Objectives</h3> The aim of this study was to investigate whether the angiogentic process in RA is a local versus a systemic effect. <h3>Methods</h3> Synovial tissue was taken during total knee replacement from 20 patients with RA and 20 patients with osteoarthritis (OA). Expression of VEGF, KDR and FLT-1 mRNA was analysed quantitatively using real-time PCR (Light-Cycler). Moreover in these patients plasma level of VEGF was examined using ELISA. <h3>Results</h3> VEGF and FLT-1 were detected in the synovial tissue of all RA- and OA-patients. The levels were significantly higher in patients with RA compared to OA. KDR was established in 60% of RA and 25% of OA. Plasma level of VEGF was increased in 100% of the RA-patients and in 60% of the OA-patients. <h3>Conclusion</h3> VEGF and its cognate receptors are significantly higher expressed in synovial tissue of patients with rheumatoid arthritis. Increased expression levels in patients with osteoarthritis might be due to reactive inflammatory synovitis. Therefore antiangiogenitic therapy might be useful not only in rheumatoid arthritis but also in reactive inflammatory arthritis. Significantly increased VEGF-plasma-levels in patients with rheumatoid arthritis may explain the benefit of a systemic, versus a local anti-angiogentic therapy.