tbuckley/cabot-search huggingface dataset:
AB0201 Capillaroscopic examination in arthritis psoriatica
Authors: Z Tarján, É Koó, I Ujfalussy
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> The capillaroscopic examination gives a possibility to find a correlation between the groups of ilnesses and the change of microcirculation based on a non-invasive method. In the publications are mentioned very seldom that decrease of the capillary loops' length and diameter, the twisting of venous side and the decrease of capillaries' density are the fundamental variables in the case of capillaroscopic examination of Arthritis Psoriatica's (AP) patients. <h3>Objectives</h3> The study was made on 34 verified AP's patients (20 male, 14 female) selected by the basis of the ARA's criterias in the authors Department of AP Outpatient. Dysqualifying criteria were the metabolic diseases, the cardiovascular diseases and smoking. <h3>Methods</h3> The period of psoriasis and arthritis was studied, and the capillary was classified on the basis of morphological criterias (hairpin-shaped, spiral, and bushy appearance) their lengthened and extended forms (arterial and venous side, the length of apical region), the density of capillaries, tearness and continousness of flow. Leitz's microscope was used for examination (35x magnification, max. 100x). The nailfold was lightened with cold light, further the paraffin oil was used to the surface. <h3>Results</h3> It was found that the period of dermatological symptoms are proportional to the number of spiral form of capillaries (r = 0.371, p &lt; 0.05). The length and width of capillaries were independent from the dermatological and arthritic symptoms (NS = p 0.05). In the case of lengthened frame, the number of bushy forms were less than the others. Then the number of the capillaries loops were decreased (p &lt; 0.05). <h3>Conclusion</h3> It is accepted in general, that the decrease of the capillaries's numbers as well as the morphological changes -as a typical form of the AP's patients -are in correlation significantly with the period of psoriasis. Disagrees with others previous publications, the authors did not find significant difference in the size of capillary loops comparing to the normal control.
Comparison of immune activity profiles of microsatellite instable colon tumors to microsatellite stable tumors having high ColoType CMS1-score.
Authors: Steven Allen Buechler
Journal: Journal of Clinical Oncology (2021)

26 Background: Microsatellite instable (MSI) metastatic colorectal cancer (CRC) tumors have been found to be responsive to immune checkpoint inhibitors. Most MSI tumors are in consensus molecular subtype CMS1. Here, in a search for microsatellite stable (MSS) samples that may respond to checkpoint inhibitors, we used the ColoType CMS1-score to identify microsatellite stable (MSS) CRC tumors that have immune activity profiles similar to MSI tumors. Methods: This study was performed in Affymetrix cohort (n = 1,888) of primary CRC tumor samples assayed with hgu133plus2 Affymetrix microarrays. Degrees of infiltration of populations of immune cells were assessed with MCPcounter. Gene Set Enrichment Analysis (GSEA) using the Hallmark gene sets was used to compare biological features between subsets of samples. An 18-gene genomic score (PembroSig) of Ayers, et al, was used to predict response to Pembrolizumab. ColoType 40-gene signature identifies the CMS of a CRC tumor using values of continuous scores, one score for each of CMS1-4. CMS1+ denotes the samples with CMS1-score sufficiently high to predict it is in CMS1. A genomic score was used to predict MSI status for all samples in Affymetrix cohort; MSI predictions using said score had 97% agreement with clinically determined MSI status for 749 Affymetrix cohort samples. Results: The MSI score predicted 240 MSI samples in Affymetrix cohort, and 211 MSS samples in CMS1+ (CMS1+/MSS). The union of MSI and CMS1+/MSS compared to other samples exhibited elevated infiltration of cytotoxic lymphocytes (p &lt; 0.0001) and CD8 T-cells (p &lt; 0.0001), activity of interferon-gamma (p = 0.006) and interferon-alpha signaling (p = 0.012), inflammatory response (p = 0.012), and elevated PembroSig score (p &lt; 0.0001). CMS1+/MSS compared to MSI showed no significance difference in any of these measures. None of the immune regulatory genes PD-1, PD-L1, PD-L2, CTLA4, LAG3, and IDO1 were differentially expressed between CMS1+/MSS and MSI. Of note, the only Hallmark gene sets enriched in MSI compared to CMS1+/MSS were DNA repair (p = 0.002) and MYC targets V1 (p = 0.009) and V2 (p = 0.013). We further analyzed the biological differences between MSI samples in CMS1+ (CMS1+/MSI, n = 190) and MSI samples not in CMS1+ (CMS1-/MSI, n = 50). We found that CMS1+/MSI compared to CMS1-/MSI exhibited elevated cytotoxic lymphocyte infiltration (p &lt; 0.0001), interferon-gamma activity (p = 0.027), and PembroSig score (p &lt; 0.0001), highlighting the relationship between immune activity and CMS1-score. Conclusions: ColoType CMS1-score identified MSS samples in Affymetrix cohort (11%) with similar immune activity as MSI samples (13%) and equivalently high values of a genomic score predictive of Pembrolizumab response.
A novel endoscopic purse-string suture technique, “loop 9”, for gastrointestinal defect closure: a pilot study
Authors: Haruhiro Inoue, Mayo Tanabe, Yuto Shimamura, Enrique Rodriguez de Santiago, Yusuke Fujiyoshi, Akiko Toshimori, Mary Raina Angeli Abad, Yohei Nishikawa, Kosuke Nashida, Kazuya Sumi, Haruo Ikeda, Manabu Onimaru, Naoyuki Uragami
Journal: Endoscopy (2021)

BACKGROUND : This study aimed to assess the feasibility and efficacy of the novel loop 9 method of gastrointestinal (GI) defect closure. METHODS : 20 patients underwent a GI procedure that required defect closure. Loop 9 can be delivered through a single instrument channel (3.2 mm) and released at the defect site. After it has been anchored by two clips positioned on opposite sides of the defect edge, the loop 9 is tightened by pulling the end of the suture intraluminally using biopsy forceps. Additional clips are placed to achieve complete closure. The primary outcome was complete closure rate. The secondary outcomes were closure time, sustained closure rate, and adverse events. RESULTS : Complete closure was achieved in 100 % of cases. The mean size of the mucosal defects was 17.5 mm (range 10-55 mm). The median closure time was 14 minutes. The sustained closure rate was 90 %. No adverse events were noted. CONCLUSIONS : The loop 9 technique is feasible and effective in achieving complete and sustained closure of therapeutic endoscopy-related GI defects.
Interventions for Tobacco Cessation in Adults, Including Pregnant Persons
Authors: Carrie D. Patnode, Jillian T. Henderson, Erin L. Coppola, Joy Melnikow, Shauna Durbin, Rachel G. Thomas
Journal: JAMA (2021)

<h3>Importance</h3> It has been estimated that in 2018 nearly 20% of adults in the US were currently using a tobacco product. <h3>Objective</h3> To systematically review the effectiveness and safety of pharmacotherapy, behavioral interventions, and electronic cigarettes for tobacco cessation among adults, including pregnant persons, to inform the US Preventive Services Task Force. <h3>Data Sources</h3> PubMed, PsycInfo, Database of Abstracts of Reviews of Effects, Cochrane Database of Systematic Reviews, Centre for Reviews and Dissemination of Health Technology Assessment; surveillance through September 25, 2020. <h3>Study Selection</h3> Systematic reviews of tobacco cessation interventions and randomized clinical trials that evaluated the effects of electronic cigarettes (e-cigarettes) or pharmacotherapy among pregnant persons. <h3>Data Extraction and Synthesis</h3> Independent critical appraisal and data abstraction; qualitative synthesis and random-effects meta-analyses. <h3>Main Outcomes and Measures</h3> Health outcomes, tobacco cessation at 6 months or more, and adverse events. <h3>Results</h3> Sixty-seven reviews addressing pharmacotherapy and behavioral interventions were included as well as 9 trials (N = 3942) addressing e-cigarettes for smoking cessation and 7 trials (N = 2285) of nicotine replacement therapy (NRT) use in pregnancy. Combined pharmacotherapy and behavioral interventions (pooled risk ratio [RR], 1.83 [95% CI, 1.68-1.98]), NRT (RR, 1.55 [95% CI, 1.49-1.61]), bupropion (RR, 1.64 [95% CI, 1.52-1.77]), varenicline (RR, 2.24 [95% CI, 2.06-2.43]), and behavioral interventions such as advice from clinicians (RR, 1.76 [95% CI, 1.58-1.96]) were all associated with increased quit rates compared with minimal support or placebo at 6 months or longer. None of the drugs were associated with serious adverse events. Five trials (n = 3117) reported inconsistent findings on the effectiveness of electronic cigarettes on smoking cessation at 6 to 12 months among smokers when compared with placebo or NRT, and none suggested higher rates of serious adverse events. Among pregnant persons, behavioral interventions were associated with greater smoking cessation during late pregnancy (RR, 1.35 [95% CI, 1.23-1.48]), compared with no intervention. Rates of validated cessation among pregnant women allocated to NRT compared with placebo were not significantly different (pooled RR, 1.11 [95% CI, 0.79-1.56], n = 2033). <h3>Conclusions and Relevance</h3> There is strong evidence that a range of pharmacologic and behavioral interventions, both individually and in combination, are effective in increasing smoking cessation in nonpregnant adults. In pregnancy, behavioral interventions are effective for smoking cessation, but data are limited on the use of pharmacotherapy for smoking cessation. Data on the effectiveness and safety of electronic cigarettes for smoking cessation among adults are also limited and results are inconsistent.
The Case | Acute kidney injury associated with chronic myelomonocytic leukemia
Authors: Inna Mohamadou, David Buob, Marion Rabant, Jérémy Pichon, Stéphane Gaudry, Yosu Luque, Eric Rondeau, Isabelle Brocheriou, Cédric Rafat
Journal: Kidney International (2021)
Heterosexism, homonegativity, and the sociopolitical dangers of orthodox models of prejudice reduction
Authors: Darren Langdridge
Journal: Behavioral and Brain Sciences (2012)

Abstract Criticism of orthodox models of prejudice reduction is particularly relevant for lesbians, gay men, and bisexuals, particularly when considering stage models of coming-out. If social change is to be effected regarding endemic homonegativity and heterosexism, then it is argued that a radical rethink is needed to the understandable but misinformed desire to get us to like each other more.
The use of elevated circulating hepatocyte growth factor (HGF) level as a potential prognostic biomarker in locally advanced pancreatic cancer.
Authors: Hannah Johnson Roberts, Jennifer Yon-Li Wo, Beow Y. Yeap, Christine A. Ulysse, Janet E. Murphy, Colin D. Weekes, David P. Ryan, Jeffrey William Clark, Cristina R. Ferrone, Keith D. Lillemoe, Motaz Qadan, Carlos Fernandez-del Castillo, Rakesh K. Jain, Theodore S. Hong, Gabriel Dan Duda
Journal: Journal of Clinical Oncology (2021)

429 Background: The hepatocyte growth factor (HGF)/c-MET pathway has pleiotropic functions in tumor progression including invasion and cancer cell survival. The potential use of circulating plasma HGF as a prognostic biomarker is not known. Methods: This was an analysis of plasma HGF in patients enrolled in a single arm phase II study (NCT01821729) of patients with previously untreated locally advanced pancreatic ductal adenocarcinoma (PDAC) treated with FOLFIRINOX and losartan followed by chemoradiotherapy before resection was attempted (Murphy JE et al., 2019). Eligible patients from the trial included those who had undergone baseline research labs including HGF. Circulating HGF was measured in the plasma on day 1 of treatment using ELISA, and the median value was used to define high vs low levels for the purpose of analysis. The association of elevated HGF with overall survival (OS) was analyzed by univariable and multivariable Cox regression, adjusting for tumor size (≤ versus &gt; 40 mm) and serum CA19-9 (≤ versus &gt; 37 U/mL). Results: There were 46 eligible patients with a median follow up of 31 months. The median age was 63 (range 42-78) and 52% were female (24/46). Median tumor size was 41.4 mm (range 18–68 mm). There were 41/46 patients (89.1%) with elevated baseline CA19-9. Median baseline HGF was 1,250.55 pg/mL (range 650.9–6,459.1). Median OS was 38.4 months for patients with baseline HGF at or below the median, and 19.3 months for those with elevated HGF. On univariate analysis, elevated HGF was associated with poorer OS (HR 2.28, 95% CI 1.06–4.87, p = 0.03). On multivariate analysis, after controlling for tumor size and baseline CA19-9, elevated plasma HGF remained significantly associated with poorer OS (HR 2.58, 95% CI 1.16–5.70, p = 0.02). Conclusions: In conclusion, elevated baseline circulating plasma HGF is an independent biomarker of poorer OS in patients with locally advanced PDAC treated with neoadjuvant therapy. Further randomized studies are needed to define the negative predictive biomarker value for high plasma HGF and identify the optimal HGF range as well as determine applicability to other stages of disease. These results support the continued investigation of plasma HGF in ongoing clinical trials with PDAC patients.
Results of biomarker analysis from phase II trial of nivolumab in refractory biliary tract cancer.
Authors: Elaine Tan, Dae Won Kim, Junmin Zhou, Michael J. Schell, Vincent Chung, Olatunji B. Alese, Richard D. Kim
Journal: Journal of Clinical Oncology (2021)

338 Background: Our previous phase II study demonstrated that nivolumab provides modest but durable clinical efficacy in patients (pts) with refractory biliary tract cancer (BTC), suggesting the significant clinical benefit of nivolumab in selected pts and identification of potential predictive biomarkers. Here, we report outcomes from the biomarker analysis. Methods: Pre-treatment tumor samples were obtained and assessed for immunohistochemistry (IHC) with PD-1 and PDL-1 antibodies, mRNA sequencing (RNAseq), and whole exome sequencing (WES). Clinical efficacy was correlated with the molecular analysis. Prior cisplatin exposure was reviewed to evaluate the impact of cisplatin on the tumor mutational burden (TMB) and clinical outcome. Results: Among 46 pts who had tumor response evaluation, 31 pts received cisplatin prior to nivolumab, and 15 were cisplatin-naive. Pre-treatment tumor samples were assessed for IHC (n = 42), RNAseq (n = 11), and WES (n = 11) based on tissue availability. There was no statistically significant correlation between prior cisplatin exposure and clinical outcome. Among 42 available tumor samples, 18 (43%) expressed PD-L1 positivity ( &gt; 1%), which was associated with a statistically significant prolonged progression free survival (PFS). Median PFS was 10.4 months for PD-L1 positive vs 2.4 months for PD-L1 negative (HR 0.23, 95% CI 0.10-0.51; P &lt; 0.001), while there was no statistically significant correlation between PD-1 expressing tumor infiltrating lymphocytes and clinical outcome. There was also no statistically significant difference in TMB of cisplatin-exposed (n = 8) vs. cisplatin-naïve tumor samples (n = 3) (9162, SD = 150 vs. 8898, SD = 806, p = 0.62). In comparing the group with prolonged disease control of at least 16 weeks (n = 4) to those with rapid disease progression (n = 7) who had mRNA sequencing performed, levels of AC005609.1, FAT3, TMEM151A, ADARB2, FAM153A were all significantly upregulated (p &lt; 0.01), while levels of CLCA1, MUC2, IGHV3-43, SWORA6, and CRISP3 were all significantly downregulated (p &lt; 0.01). Conclusions: Prior cisplatin exposure did not lead to statistically significant differences in clinical outcome or TMB in advanced BTC pts treated with nivolumab. However, PD-L1 expression &gt; 1% correlated with improved PFS, and variations in level of certain mRNA sequences were noted when comparing pts who had rapid disease progression vs. prolonged disease control with nivolumab. This suggests that BTC pts with positive PD-L1 expression and a particular mRNA profile may have a favorable response to nivolumab. Further studies are needed to confirm these findings. Clinical trial information: NCT02829918.
The Purchase of Medical Care Through Fixed Periodic Payment.
Journal: JAMA (1933)

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Immunotherapeutic strategies targeting B cell maturation antigen in multiple myeloma
Authors: Yi Fang, Jian Hou
Journal: Military Medical Research (2021)

Abstract Multiple myeloma (MM) is the second most common hematologic malignancy, and is characterized by the clonal expansion of malignant plasma cells. Despite the recent improvement in patient outcome due to the use of novel therapeutic agents and stem cell transplantation, all patients eventually relapse due to clone evolution. B cell maturation antigen (BCMA) is highly expressed in and specific for MM cells, and has been implicated in the pathogenesis as well as treatment development for MM. In this review, we will summarize representative anti-BCMA immune therapeutic strategies, including BCMA-targeted vaccines, anti-BCMA antibodies and BCMA-targeted CAR cells. Combination of different immunotherapeutic strategies of targeting BCMA, multi-target immune therapeutic strategies, and adding immune modulatory agents to normalize anti-MM immune system in minimal residual disease (MRD) negative patients, will also be discussed.
Association of Serum Mannose With Acute Respiratory Distress Syndrome Risk and Survival
Authors: Yongyue Wei, Hui Huang, Ruyang Zhang, Zhaozhong Zhu, Ying Zhu, Lijuan Lin, Xuesi Dong, Liangmin Wei, Xin Chen, Zhonghua Liu, Yang Zhao, Li Su, Feng Chen, David C. Christiani
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Acute respiratory distress syndrome (ARDS) confers high mortality risk among critically ill patients. Identification of biomarkers associated with ARDS risk may guide clinical diagnosis and prognosis. <h3>Objective</h3> To systematically evaluate the association of blood metabolites with ARDS risk and survival. <h3>Design, Setting, and Participants</h3> In this cohort study, data from the Molecular Epidemiology of ARDS (MEARDS) study, a prospective cohort of 403 patients with ARDS and 1227 non-ARDS controls, were analyzed. Patients were recruited in intensive care units (ICUs) at Massachusetts General Hospital and Beth Israel Deaconess Medical Center, both in Boston, Massachusetts, from January 1, 1998, to December 31, 2014. Data analysis was performed from December 9, 2018, to January 4, 2019. <h3>Main Outcomes and Measures</h3> Participants were followed up daily for ARDS development defined by Berlin criteria, requiring fulfillment of chest radiograph and oxygenation criteria on the same calendar day during invasive ventilatory assistance. A 2-stage study design was used to explore novel metabolites associated with ARDS risk and survival. <h3>Results</h3> Of the 1630 participants from MEARDS who were admitted to the ICU , 403 (24.7%) were diagnosed with ARDS (mean [SD] age, 63.0 [17.0] years; 251 [62.3%] male) and 1227 (75.3%) were at-risk but did not have ARDS (mean [SD] age, 62.3 [16.9] years; 753 [61.4%] male). Mendelian randomization suggested that genetically regulated serum mannose was associated with ARDS risk (odds ratio [OR], 0.64; 95% CI, 0.53-0.78;<i>P</i> = 7.46 × 10<sup>−6</sup>) in the discovery stage. In the functional validation stage incorporating 83 participants with ARDS and matched at-risk participants in the control group from the ICU, the protective association of mannose with ARDS risk was validated (OR, 0.67; 95% CI, 0.46-0.97;<i>P</i> = .03). Furthermore, serum mannose was associated with 28-day (OR, 0.25; 95% CI, 0.11-0.56;<i>P</i> = 6.95 × 10<sup>−4</sup>) and 60-day (OR, 0.36; 95% CI, 0.19-0.71;<i>P</i> = 3.12 × 10<sup>−3</sup>) mortality and 28-day (hazard ratio, 0.49; 95% CI, 0.32-0.74;<i>P</i> = 6.41 × 10<sup>−4</sup>) and 60-day (hazard ratio, 0.55; 95% CI, 0.37-0.80;<i>P</i> = 2.11 × 10<sup>−3</sup>) survival. <h3>Conclusions and Relevance</h3> In this study, genetically regulated serum mannose appeared to be associated with ARDS risk and outcome, and increased serum mannose at admission was associated with reduced ARDS risk and better survival. These findings could inform prevention and clinical intervention in ARDS cases, which have increased with the expansion of the coronavirus disease 2019 pandemic.
SAT0014 Treatment of psoriatic arthritis and psoriasis vulgaris with the tumour necrosis factor blocker infiximab
Authors: EE Cauza, MS Spak, KC Cauza, UH Hanusch-Enserer, AD Dunky, EW Wagner
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Tumour necrosis factor a (TNF a), a proinflammatory cytokine, is considered to be one of the important mediators in the pathogenesis of psoriasis and psoriatic arthritis (PsA) and may therefore be a useful target for specific immunotherapy. Treatment of rheumatoid arthritis with TNF inhibitors has proven to be extremely effective, so the aim of our study was to evaluate the efficacy and safety of multiple infusions with a humanised anti-tumour necrosis factor a monoclonal antibody (infliximab) in PsA and Psoriasis. <h3>Objectives</h3> <h3>Methods</h3> Over a period of 22 weeks, nine consecutive patients (5 men, 4 women, mean age 57.3 years, mean duration of PsA/Psoriasis 17.2/18.1 years) who had both active psoriasis and PsA and fulfilled diagnostic criteria were included in this study. Treatment resistant patients with active disease received infusions of 3 mg/kg infliximab (at week 0, 2, 6 14, and 22). The primary endpoints included the changes from baseline to week 22 in the swollen and tender joint count and the improvements of the psoriasis activity (Pasi). <h3>Results</h3> The treatment was well tolerated, only one mild side effect was noted. Significant improvements were observed after 2 weeks in the decrease of swollen and tender joint count, which fell from a median of 5.3 and 17.88 at study entry to a median of 1.44 and 9.77 by week 2 (p = 0.02/p = 0.002) and maintained up to week 22. Over the treatment period of twenty two weeks the mean Pasi changed statistically significant from 19.04 to 4.39 (p = 0.002). The improvements of the main parameters are summarised in Table 1. <h3>Conclusion</h3> Multiple infusions of infliximab were effective and well tolerated in patients with active psoriasis and PsA. The results provide a good evidence that specific cytokine blockade can be effective in inflammatory disease and offers patients with PsA and psoriasis a new direction of treatment.