tbuckley/cabot-search huggingface dataset:
Response to: ‘Correspondence on ‘Risk of venous thromboembolism in knee, hip and hand osteoarthritis: a general population-based cohort study’’ by Lin et al
Authors: Chao Zeng, Zidan Yang, Guanghua Lei, Yuqing Zhang
Journal: Annals of the Rheumatic Diseases (2021)

Lin et al 1 raised three points with regard to residual confounding to affect our findings. Below we provide point-by-point replies to the three comments.

First, we agree that immobilisation duration is a strong risk factor for postoperative venous thromboembolism (VTE). The aim of our study was to examine the relation of incident osteoarthritis (OA) to the risk of VTE (ie, the total effect) and to assess to what extent the effect of incident OA on the risk of VTE is through its effect on knee/hip replacement (ie, …
MCL-1 dependency as a novel vulnerability for aggressive B cell lymphomas
Authors: Michelle Y. Wang, Tao Li, Yuan Ren, Bijal D. Shah, Tint Lwin, Jing Gao, Kenneth H. Shain, Wei Zhang, Xiaohong Zhao, Jianguo Tao
Journal: Blood Cancer Journal (2021)

Dear Editor,Mantle cell lymphoma (MCL) and diffuse large B cell lymphoma (DLBCL) are aggressive hematologic malignancies characterized by the accumulation of lymphoid cells defective in cell apoptosis biology and function 1 .The anti-apoptotic B cell lymphoma 2 (BCL-2) family proteins are pivotal regulators of the mitochondrial apoptotic pathway and genetic aberrations in these genes are associated with lymphomagenesis and chemotherapeutic resistance.These anti-apoptotic proteins, most notably BCL-2 and myeloid cell leukemia 1 (MCL-1), promote the survival of lymphoma cells by counteracting the activity of pro-apoptotic proteins such as BCL-2-like protein 11 (BCL2L11, also known as BIM) 2-4 .Pharmacological targeting of BCL-2 is highly effective in certain B cell lymphomas, but de novo and acquired resistance to BCL-2 inhibitor monotherapy often develop, especially in aggressive B cell lymphomas.Moreover, the other major anti-apoptotic BCL-2 family proteins, BCL-XL and MCL-1, are demonstrated to be the main determinants of resistance to venetoclax 5 .Additionally, MCL-1 is recurrently highly expressed in various kinds of non-Hodgkin's B cell lymphomas 6 .Collectively, these data support the hypothesis that MCL-1 plays a central role in B cell lymphoma progression and drug resistance.Pharmacologically targeting MCL-1, therefore, represents an attractive strategy to combat these lymphomas.To this end, there is a great need to develop and apply selective small-molecule MCL-1 inhibitors as part of a first-line
Response to: ‘Correspondence on ‘Systemic sclerosis and the COVID-19 pandemic: World Scleroderma Foundation preliminary advice for patient management’’ by Snarskaya and Vasileva
Authors: Cosimo Bruni, Marco Matucci-Cerinic
Journal: Annals of the Rheumatic Diseases (2021)

We read with great interest the response from Snarskaya and Vasileva.1 A second wave of SARS-CoV-2 infection is now a global reality2: since the publication of the World Scleroderma Foundation preliminary advice on the management on systemic sclerosis (SSc) patients during the first COVID-19 pandemic,3 growing evidence has accumulated on COVID-19 affected SSc patients.4 Up to 22 June, at the end of the first wave, 25 cases of SSc-COVID-19 were published in the literature, most of them undergoing immunosuppressant treatment with corticosteroids (CCS), conventional synthetic disease modifying antirheumatic drugs (csDMARDs) (methotrexate or mycophenolate mofetil) or biological DMARD (bDMARDs) (rituximab or tocilizumab) and with a variable outcome.4 This heterogeneity was a limitation in understanding the possible influence of ongoing immunosuppression and the effect of administered treatments. A recent meta-analysis, including 62 studies with more than 300 000 patients with autoimmune diseases, concluded that bDMARD monotherapy was a protective factor for COVID-19-related hospitalisation and death, in particular with antitumour necrosis factor alpha, while the use of CCS, conventional-synthetic DMARDS (csDMARD) and csDMARDs/bDMARD combination exposed the patients to a higher risk.5 A focused analysis on SSc population has described more SSc-COVID-19 cases: 1/64 patients in Crisafulli et al ,6 1/168 patients in Bellan et al 7 and 2/526 patients in Del Papa et al ,8 with one of them, previously …
New regimens and directions in the management of newly diagnosed multiple myeloma
Authors: Susan Bal, Smith Giri, Kelly N. Godby, Luciano J. Costa
Journal: American Journal of Hematology (2021)

The introduction of novel agents over the last decade has rapidly expanded the therapeutic landscape of multiple myeloma (MM) for both transplant-eligible and transplant-ineligible patients. The assessment of minimal residual disease (MRD) by next-generation flow cytometry or next-generation sequencing is established as a powerful predictor of long-term outcomes. The use of MRD in response-adapted clinical trials may provide opportunities to identify candidates for treatment escalation and de-escalation. Agents with proven activity in the relapsed and refractory setting are being studied in the management of high-risk newly diagnosed MM (NDMM). Here, we summarize the most recent clinical trials that have led to the current paradigms in the management of NDMM. We also discuss how novel agents could be incorporated in the newly diagnosed setting and potential clinical trial designs that could leverage MRD information with the goal of treatment optimization.
Serum Galectin-3 and Subsequent Risk of Coronary Heart Disease in Subjects With Childhood-Onset Type 1 Diabetes: A Cohort Study
Authors: Maryam Saeed, German Tapia, Inger Ariansen, Lars C. Stene, Ingebjørg Seljeflot, Grethe S. Tell, Torild Skrivarhaug, Geir Joner
Journal: Diabetes Care (2021)

OBJECTIVE To study whether serum galectin-3 and other biomarkers of inflammation predict coronary heart disease (CHD) in subjects with long-standing childhood-onset type 1 diabetes. RESEARCH DESIGN AND METHODS A population-based nationwide cohort of 299 subjects with type 1 diabetes diagnosed in Norway at &amp;lt;15 years of age during 1973–1982 was examined in 2002–2003 at a mean age of 33 years (range 21–44), with mean diabetes duration of 24 years (range 19–30). Subjects were followed through 31 December 2017 for their first CHD event registered by a hospitalization or cause of death using nationwide registries. Stored serum samples were available for 296 subjects and analyzed for interleukin-6 (IL-6), IL-6 receptor, IL-18, hs-CRP, matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1 (TIMP-1), galectin-3, and high-sensitivity troponin T. Adjusted hazard ratios (aHRs) for CHD per SD increase in biomarker were estimated using Cox regression. RESULTS Of 295 subjects, 40 (13.6%) had a documented CHD event during a mean follow-up of 14.4 years (range 0.5–16). IL-6 (aHR 1.32 [95% CI 1.07–1.63]), galectin-3 (aHR 1.44 [95% CI 1.09–1.80]), and TIMP-1 (aHR 1.37 [95% CI 1.04–1.81]) were significant predictors of CHD after adjustment for conventional risk factors. CONCLUSIONS Galectin-3 was significantly associated with future CHD in subjects with type 1 diabetes, and if the results are replicated in larger studies, it may aid in prediction together with conventional risk factors for CHD.
Gut microbiota composition reflects disease severity and dysfunctional immune responses in patients with COVID-19
Authors: Yun Kit Yeoh, Tao Zuo, Grace Chung-Yan Lui, Fen Zhang, Qin Liu, Amy YL Li, Arthur CK Chung, Chun Pan Cheung, Eugene YK Tso, Kitty SC Fung, Veronica Chan, Lowell Ling, Gavin Joynt, David Shu-Cheong Hui, Kai Ming Chow, Susanna So Shan Ng, Timothy Chun-Man Li, Rita WY Ng, Terry CF Yip, Grace Lai-Hung Wong, Francis KL Chan, Chun Kwok Wong, Paul KS Chan, Siew C Ng
Journal: Gut (2021)

Although COVID-19 is primarily a respiratory illness, there is mounting evidence suggesting that the GI tract is involved in this disease. We investigated whether the gut microbiome is linked to disease severity in patients with COVID-19, and whether perturbations in microbiome composition, if any, resolve with clearance of the SARS-CoV-2 virus.In this two-hospital cohort study, we obtained blood, stool and patient records from 100 patients with laboratory-confirmed SARS-CoV-2 infection. Serial stool samples were collected from 27 of the 100 patients up to 30 days after clearance of SARS-CoV-2. Gut microbiome compositions were characterised by shotgun sequencing total DNA extracted from stools. Concentrations of inflammatory cytokines and blood markers were measured from plasma.Gut microbiome composition was significantly altered in patients with COVID-19 compared with non-COVID-19 individuals irrespective of whether patients had received medication (p<0.01). Several gut commensals with known immunomodulatory potential such as Faecalibacterium prausnitzii, Eubacterium rectale and bifidobacteria were underrepresented in patients and remained low in samples collected up to 30 days after disease resolution. Moreover, this perturbed composition exhibited stratification with disease severity concordant with elevated concentrations of inflammatory cytokines and blood markers such as C reactive protein, lactate dehydrogenase, aspartate aminotransferase and gamma-glutamyl transferase.Associations between gut microbiota composition, levels of cytokines and inflammatory markers in patients with COVID-19 suggest that the gut microbiome is involved in the magnitude of COVID-19 severity possibly via modulating host immune responses. Furthermore, the gut microbiota dysbiosis after disease resolution could contribute to persistent symptoms, highlighting a need to understand how gut microorganisms are involved in inflammation and COVID-19.
Covid-19: Arthritis drugs improve survival in intensive care patients, shows study
Authors: Jacqui Wise
Journal: BMJ (2021)

Covid-19: Arthritis drugs improve survival in intensive care patients, shows study Jacqui WiseTwo rheumatoid arthritis drugs will now be used to treat the patients with severe covid-19 in intensive care, after new findings have shown that they significantly improve survival and cut the time spent in hospital by a week to 10 days.Results from the REMAP-CAP trial showed that the interleukin 6 receptor antagonists tocilizumab and sarilumab reduced mortality from 35.8% to 27.3% compared with standard care-an absolute reduction of 8.5% and a relative reduction in mortality of 24%. 1 The benefit was seen when the drugs were given within 24 hours of patients entering intensive care and were in addition to a corticosteroid, such as dexamethasone.
Carbamylated HDL and Mortality Outcomes in Type 2 Diabetes
Authors: David T.W. Lui, Ching-Lung Cheung, Alan C.H. Lee, Ying Wong, Sammy W.M. Shiu, Kathryn C.B. Tan
Journal: Diabetes Care (2021)

Carbamylation is part of the aging process and causes adverse changes in the structure and function of proteins. Lipoproteins are subjected to carbamylation. We investigated the usefulness of carbamylated HDL as a prognostic indicator of survival in patients with type 2 diabetes and the association with mortality outcomes.Baseline plasma carbamylated HDL was measured by ELISA in a cohort of 1,517 patients with type 2 diabetes. The primary outcome was all-cause mortality, and the secondary outcomes were cause-specific deaths, including cardiovascular, renal, infection, and cancer related.Over a median follow-up of 14 years, 292 patients died, and the mortality rate was 14.5 per 1,000 person-years. Plasma carbamylated HDL level was higher in those with a fatal outcome (46.1 ± 17.8 µg/mL vs. 32.9 ± 10.7; P < 0.01). Patients in the third (hazard ratio [HR] 2.11; 95% CI 1.40-3.17; P < 0.001) and fourth quartiles (HR 6.55; 95% CI 4.67-9.77; P < 0.001) of carbamylated HDL had increased mortality risk. After adjustment for conventional risk factors, elevated carbamylated HDL was independently associated with all-cause mortality (HR 1.39; 95% CI 1.28-1.52; P < 0.001) as well as with all the cause-specific mortalities. Adding plasma carbamylated HDL level improved the power of the multivariable models for predicting all-cause mortality, with significant increments in C index (from 0.78 to 0.80; P < 0.001), net reclassification index, and integrated discrimination improvement.Carbamylation of HDL renders HDL dysfunctional, and carbamylated HDL is independently associated with mortality outcomes in patients with type 2 diabetes.
Covid-19: Health secretary vows to reduce bureaucracy faced by vaccination volunteers
Authors: Abi Rimmer
Journal: BMJ (2021)

Doctors volunteering to give the covid-19 vaccine should not have to undertake unnecessary training, such as on preventing terrorism, the health secretary has said.

Retired doctors who have volunteered to help with the vaccine roll out through NHS Professionals have been asked to complete 18 training modules which include preventing radicalisation and fire safety. One retired GP said on Twitter that she had given up trying to sign up to volunteer after spending seven hours reading about things she already knew. “I just wanted to help,” she said.1

Speaking on the Today programme on 4 January, Matt Hancock said that he would remove some of the requirements, including preventing radicalisation training. “At the moment the NHS has all the …
Small-caliber plastic stent for endoscopic ultrasound-guided drainage of a non-dilated pancreatic duct
Authors: Dosuke Iwadate, Yousuke Nakai, Tsuyoshi Hamada, Takao Itoi, Kazuhiko Koike
Journal: Endoscopy (2021)

Endoscopic ultrasound (EUS)-guided pancreatic drainage is increasingly utilized in cases where endoscopic retrograde cholangiopancreatography (ERCP) is not possible [1] [2] [3]. EUS-guided pancreatic drainage for a non-dilated pancreatic duct (PD) not only poses technical challenges but also increases the risk of procedure-related pancreatitis as well as stent-induced ductal injury. A small-caliber stent might be suitable for a non-dilated PD to prevent ductal injury and upstream main duct obstruction, but there has been no report on a dedicated 5-Fr EUS-guided pancreatic drainage stent. Herein we present a newly designed 5-Fr plastic stent for EUS-guided pancreatic drainage (Through & Pass Type IT; Gadelius Medical, Tokyo, Japan) ([Fig. 1]), which is a thinner type of a previously reported stent [4].
Transpancreatic biliary sphincterotomy versus double guidewire in difficult biliary cannulation: a randomized controlled trial
Authors: Leena Kylänpää, Vilja Koskensalo, Arto Saarela, Per Ejstrud, Marianne Udd, Outi Lindström, Mia Rainio, Andrea Tenca, Jorma Halttunen, Gunnar Qvigstad, Urban Arnelo, Niklas Fagerström, Truls Hauge, Lars Aabakken, Juha Grönroos
Journal: Endoscopy (2021)

Abstract Background Difficult biliary cannulation in endoscopic retrograde cholangiopancreatography (ERCP) increases the risk of post-ERCP pancreatitis (PEP). The purpose of this prospective, randomized, multicenter study was to compare two advanced rescue methods, transpancreatic biliary sphincterotomy (TPBS) and a double-guidewire (DGW) technique, in difficult common bile duct (CBD) cannulation. Methods Patients with native papilla and planned CBD cannulation were recruited at eight Scandinavian hospitals. An experienced endoscopist attempted CBD cannulation with wire-guided cannulation. If the procedure fulfilled the definition of difficult cannulation and a guidewire entered the pancreatic duct, randomization to either TPBS or to DGW was performed. If the randomized method failed, any method available was performed. The primary end point was the frequency of PEP and the secondary end points included successful cannulation with the randomized method. Results In total, 1190 patients were recruited and 203 (17.1 %) were randomized according to the study protocol (TPBS 104 and DGW 99). PEP developed in 14/104 patients (13.5 %) in the TPBS group and 16/99 patients (16.2 %) in the DGW group (P = 0.69). No difference existed in PEP severity between the groups. The rate of successful deep biliary cannulation was significantly higher with TPBS (84.6 % [88/104]) than with DGW (69.7 % [69/99]; P = 0.01). Conclusions In difficult biliary cannulation, there was no difference in PEP rate between TPBS and DGW techniques. TPBS is a good alternative in cases of difficult cannulation when the guidewire is in the pancreatic duct.
MO01.11 The Relative Survival Impact of Thorough Staging and Appropriate Treatment in Non-Small-Cell Lung Cancer (NSCLC)
Authors: M. Taylor, M. Smeltzer, M. Ray, N. Faris, C. Fehnel, O. Akinbobola, B. Jackson, C. Foust, L. McHugh, R.S. Signore, R. Fox, J. Wright, R. Optican, K. Tonkin, E.T. Robbins, R. Osarogiagbon
Journal: Journal of Thoracic Oncology (2021)
The importance of anosmia, ageusia and age in community presentation of symptomatic and asymptomatic SARS-CoV-2 infection in Louisiana, USA; a cross-sectional prevalence study
Authors: Amy K. Feehan, Daniel Fort, Cruz Velasco, Jeffrey H. Burton, Julia Garcia-Diaz, Eboni G. Price-Haywood, Eric Sapp, Dawn Pevey, Leonardo Seoane
Journal: Clinical Microbiology and Infection (2021)

ObjectiveWhile many seroprevalence studies of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been performed, few are demographically representative. This investigation focused on defining the nature and frequency of symptomatic and asymptomatic SARS-CoV-2 infection in a representative, cross-sectional sample of communities in Louisiana, USA.MethodsA sample of 4778 adults from New Orleans and Baton Rouge, Louisiana were given a survey of symptoms and co-morbidities, nasopharyngeal swab to test for active infection (PCR), and blood draw to test for past infection (IgG). Odds ratios, cluster analysis, quantification of virus and antibody, and linear modelling were used to understand whether certain symptoms were associated with a positive test, how symptoms grouped together, whether virus or antibody varied by symptom status, and whether being symptomatic was different across the age span.ResultsReported anosmia/ageusia was strongly associated with a positive test; 40.6% (93/229) tested positive versus 4.8% (218/4549) positivity in those who did not report anosmia/ageusia (OR 13.6, 95% CI 10.1–18.3). Of the people who tested positive, 47.3% (147/311) were completely asymptomatic. Symptom presentation clustered into three groups; low/no symptoms (0.4 ± 0.9, mean ± SD), highly symptomatic (7.5 ± 1.9) or moderately symptomatic (4.0 ± 1.5). Quantity of virus was lower in the asymptomatic versus symptomatic group (cycle number 23.3 ± 8.3 versus 17.3 ± 9.0; p < 0.001). Modelling the probability of symptoms showed changes with age; the highest probability of reporting symptoms was 64.6% (95% CI 50.4–76.5) at age 29 years, which decreased to a probability of 49.3% (95% CI 36.6–62.0) at age 60 years and only 25.1% (95% CI 5.0–68.1) at age 80 years.ConclusionAnosmia/ageusia can be used to differentiate SARS-CoV-2 infection from other illnesses, and, given the high ratio of asymptomatic individuals, contact tracing should include those without symptoms. Regular testing in congregant settings of those over age 60 years may help mitigate asymptomatic spread.
Overcoming the barriers to dissemination and implementation of quality measures for gastrointestinal endoscopy: European Society of Gastrointestinal Endoscopy (ESGE) and United European Gastroenterology (UEG) position statement
Authors: Raf Bisschops, Matthew D. Rutter, Miguel Areia, Cristiano Spada, Dirk Domagk, Michel F. Kaminski, Andrew Veitch, Wafaa Khannoussi, Ian M. Gralnek, Cesare Hassan, Helmut Messmann, Thierry Ponchon, Paul Fockens, Alex Dignass, Mario Dinis-Ribeiro
Journal: Endoscopy (2021)

Abstract The European Society of Gastrointestinal Endoscopy (ESGE) has developed performance measures and established a framework for quality assessment for gastrointestinal endoscopy in Europe. Most national societies actively undertake initiatives to implement and explicitly endorse these quality indicators. Given this, ESGE proposes that, at a national level, strong leadership should exist to disseminate and implement quality parameters. Thus, understanding the potential barriers that may vary locally is of paramount importance. ESGE suggests that each national society should prioritize quality and standards of care in gastrointestinal endoscopy in their activities and should survey/understand which measures are a local priority to their members and make measuring quality intrinsic to daily endoscopy practice.
Mast Cells Promote Nonalcoholic Fatty Liver Disease Phenotypes and Microvesicular Steatosis in Mice Fed a Western Diet
Authors: Lindsey Kennedy, Vik Meadows, Amelia Sybenga, Jennifer Demieville, Lixian Chen, Laura Hargrove, Burcin Ekser, Wasim Dar, Ludovica Ceci, Debjyoti Kundu, Konstantina Kyritsi, Linh Pham, Tianhao Zhou, Shannon Glaser, Fanyin Meng, Gianfranco Alpini, Heather Francis
Journal: Hepatology (2021)

Background and Aims Nonalcoholic fatty liver disease (NAFLD) is simple steatosis but can develop into nonalcoholic steatohepatitis (NASH), characterized by liver inflammation, fibrosis, and microvesicular steatosis. Mast cells (MCs) infiltrate the liver during cholestasis and promote ductular reaction (DR), biliary senescence, and liver fibrosis. We aimed to determine the effects of MC depletion during NAFLD/NASH. Approach and Results Wild‐type (WT) and KitW‐sh (MC‐deficient) mice were fed a control diet (CD) or a Western diet (WD) for 16 weeks; select WT and KitW‐sh WD mice received tail vein injections of MCs 2 times per week for 2 weeks prior to sacrifice. Human samples were collected from normal, NAFLD, or NASH mice. Cholangiocytes from WT WD mice and human NASH have increased insulin‐like growth factor 1 expression that promotes MC migration/activation. Enhanced MC presence was noted in WT WD mice and human NASH, along with increased DR. WT WD mice had significantly increased steatosis, DR/biliary senescence, inflammation, liver fibrosis, and angiogenesis compared to WT CD mice, which was significantly reduced in KitW‐sh WD mice. Loss of MCs prominently reduced microvesicular steatosis in zone 1 hepatocytes. MC injection promoted WD‐induced biliary and liver damage and specifically up‐regulated microvesicular steatosis in zone 1 hepatocytes. Aldehyde dehydrogenase 1 family, member A3 (ALDH1A3) expression is reduced in WT WD mice and human NASH but increased in KitW‐sh WD mice. MicroRNA 144‐3 prime (miR‐144‐3p) expression was increased in WT WD mice and human NASH but reduced in KitW‐sh WD mice and was found to target ALDH1A3. Conclusions MCs promote WD‐induced biliary and liver damage and may promote microvesicular steatosis development during NAFLD progression to NASH through miR‐144‐3p/ALDH1A3 signaling. Inhibition of MC activation may be a therapeutic option for NAFLD/NASH treatment.