tbuckley/cabot-search huggingface dataset:
AB0109 Cardiac abnormalities in system scleroderma
Authors: R Yatsyshyn, YE Neyko, YU Delva
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> During last decade the morbidity rates in system scleroderma (SSc) have been increased. The bridge-head of aggression in SSc is huge, since there are actually no organs without connective tissue in the human organism. It also determines a high frequency of different visceral complications in SSc. The cardiac lesions in SSc are frequent visceral manifestation of illness, very often resulting in fatal consequences. In this context we attempted to analyse the main forms of cardiac pathology in SSc. <h3>Objectives</h3> We examined 52 patients (pts) with SSc. Among them women were predominant (38/52, 73%). The age of patients and duration of disease varied from 29 to 48 and from 2 to 9 years, the average age of patients and average duration of disease constituted 36.2 ± 1.1 and 4.6 ± 0.4 years respectively. The patients with moderate activity of pathological process (degree I and II) were absolute majority (46/52 pts, 88.4%). Visceral implications were diagnosed in 42/52 pts (80.7%), among them cardiac lesions – in 41/52 pts (78.8%). <h3>Methods</h3> Electrocardiography (ECG), echocardiography (EchoCG). <h3>Results</h3> ECG abnormalities were detected in 41/52 pts (78.8%). Cardiac arrhythmia was determined in 32/52 pts (61.5%). Its most frequent form was extrasystole (18/52 pts, 34.6%): ventricular (9/52 pts, 17.3%), atrial (6/52 pts, 11.5%), atrioventricular (3/52 pts, 5.8%), single (8/52 pts, 15.4%) and group (10/52 pts, 19.2%) extrasystole. Violations of conductivity were also frequent: atrial – in 18/52 pts (34.6%), ventricular – in 16/52 pts (11.5%), right bundle-branch block – in 6/52 pts (11.5%). These abnormalities correlated with duration of disease, but did not depend on activity of SSc. Among 41 patients with ECG abnormalities the decrease of voltage was detected, possibly due to expanded cardiosclerosis. EchoCG was conducted to determine myocardial contractility. In 27/52 pts (51.9%) was diagnosed LVEF reduction on 5%, in 11/52 pts (21.2%) – on 7–8%, in 3/52 pts (5.8%) – on 10% and more. The mitral valve diseases and pericardial implications were detected in 8/52 pts (15.4%) and 11/52 pts (21.2%) respectively. Among all these patients the phenomena of myocardial dystrophy and hypoxia, violation of conductivity, excitability and cardiac output were detected that resulted in chronic heart failure. In many cases the heart failure was latent, resulting in late diagnosis and treatment. <h3>Conclusion</h3> Carditis was diagnosed among more than three fourth of patients with SSc. The main reason of its development seems to be system sclerosis. <h3>References</h3> Guseva NG. System scleroderma and Nenoaiiay neeaðiaaðiey and pseudosclerodermic syndromes. Moscow: Medicine, 1993: 269 Jimenez SA, Hitraya E, Varga J. Pathogenesis of scleroderma. Collagen. Rheum Dis Clin North Am. 1996;22(4):647–74
Development of a cure model for the estimation of long-term outcomes in patients with microsatellite instability(MSI)-high metastatic colorectal cancer (mCRC) receiving immune-checkpoint inhibitors (ICIs).
Authors: Filippo Pietrantonio, Gabriele Infante, Sara Lonardi, Francesca Corti, Rossana Intini, Massimiliano Salati, Elisabetta Fenocchio, Carmen Belli, Chiara Cremolini, Giovanni Fucà, Alessandra Anna Prete, Virginia Quarà, Paolo Manca, Andrea Spallanzani, Federica Morano, Maria Di Bartolomeo, Giuseppe Curigliano, Filippo G. De Braud, Vittorina Zagonel, Rosalba Miceli
Journal: Journal of Clinical Oncology (2021)

87 Background: Anti-PD-(L)1-based therapy yielded unprecedented efficacy in patients with MSI-high mCRC. A relevant proportion of subjects may achieve long-term disease control when receiving ICIs, particularly anti-PD-1 plus anti-CTLA-4 combo. However, some patients still experience treatment refractoriness or short-term clinical benefit. Methods: We analyzed data of 163 patients with MSI-high mCRC treated with anti-PD-1 +/- anti-CTLA-4 agents. The endpoint was progression-free survival (PFS); multivariable analyses were performed using a cure model (Othus et al, CCR 2012), which allows to test which factors, including ICI type, could identify patients achieving long-term disease control. To account for biases consistent with non-random ICI assignment, we estimated a propensity score (covariates: ECOG PS, age, sex, primary tumor location, its resection, adjuvant treatment, synchronous presentation of mets, mucinous histotype, RAS/BRAF status, n. prior treatment lines, previous chemo, n. metastatic sites, presence of peritoneal, lung, liver, bone, brain, nodal mets), and then in the cure model we applied an inverse-probability-of-treatment-weight (IPTW) based on propensity score. A beforehand variable selection was operated using a random survival forest (RSF) model (RSF covariates: all the propensity score covariates plus ICI line and ICI type, platelets count (PLT), NLR, LDH), where we introduced a weight system in order to adjust variable selection net of ICI type. Results: RFS selected 5 variables: ICI type, ECOG PS, NLR, PLT and N. prior lines, the combination of which allowed to estimate the cure probability: the higher the probability the greater the chance of achieving long-term disease control. The Table shows the odds ratio estimates, defining the chance of being “cured” according to the values of the selected variables. ICI type was significantly associated with long-term disease control: patients treated with anti CTLA-4-combo achieved the highest chance of being cured, 3.41 times greater than the chance of patients treated with anti PD-1 mono. The median cure probability was as higher as 70.1% (IQR: 51.9-81.0%) with CTLA-4-combo vs 34.8% (IQR: 18.4-51.9%) with anti-PD-1 mono; the probability within treatment groups was varying according to ECOG PS, NLR, PLT and n. prior lines. Conclusions: Based on 5 variables including the ICI treatment type, a nomogram was built in order to estimate the cure probability in patients with MSI-high mCRC and potentially assist clinicians in their clinical practice. [Table: see text]
Reported Adverse Drug Reactions Associated With the Use of Hydroxychloroquine and Chloroquine During the COVID-19 Pandemic
Authors: Justine Perez, Matthieu Roustit, Marion Lepelley, Bruno Revol, Jean-Luc Cracowski, Charles Khouri
Journal: Annals of Internal Medicine (2021)

Background: A few weeks after the beginning of the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), uncontrolled trials and in vitro studies suggested that chloroquine and hydroxychloroquine may have efficacy in treating coronavirus disease 2019 (COVID-19) (1).Although very preliminary, the results of these studies received extraordinary media coverage and several high-profile figures, including some health regulatory authorities, endorsed the use of chloroquine and hydroxychloroquine to treat COVID-19.This led to a huge demand for and substantial use of these drugs; the Centers for Disease Control and Prevention identified an 80-fold increase in new prescriptions for hydroxychloroquine, particularly by nondermatologists and nonrheumatologists, between March 2019 and March 2020 (2).However, major clinical trials have concluded that hydroxychloroquine and chloroquine are unlikely to be effective in treating or preventing COVID-19, leading the U.S. Food and Drug Administration (FDA) to suspend its emergency use authorization for these drugs on 15 June 2020 (3).Nevertheless, little is known about the impact of this massive use of chloroquine and hydroxychloroquine on the number and nature of induced adverse drug reactions (ADRs).Objective: To use the FDA Adverse Event Reporting System (FAERS) database to quantify the change in number Figure 1.Cumulative (top) and weekly (bottom) ADR reports associated with chloroquine and hydroxychloroquine and related noteworthy events from January to September 2018, 2019, and 2020.
Severe respiratory failure in COVID19 patients was associated with higher transaminases values during the disease outbreak
Authors: M. Tacelli, B. Magro, L. Pasulo, M. De Giorgio, F. Leonardi, M. Grazia Lucà, G. Gaffuri, M. Triolo, G. Mangia, D. Nobile, M. Rizzi, F. Di Marco, R. Cosentini, A. Gianatti, S. Fagiuoli
Journal: Hepatology (2020)

Background: Sars-Cov-2 pneumonia is a pandemic disease with high morbidity and mortality In literature transaminases were frequently found abnormal but their role has not been clarified, particularly in patients with liver disease (LD)  Aim of this retrospective study is to explore the role of transaminases on short-term prognosis of hospitalized COVID-19 patients Methods: patients admitted in hospital for respiratory failure due to Sars-Cov-2 were consecutively recruited Primary endpoint: evaluate role of transaminases on disease progression (DP)  Secondary endpoints: find possible risk factors for (1) mortality and (2) composite outcome consisting of DP or death Results: 135 patients included Median age was 68 years (IQR 58-74), 33 3% (n=45) were female AST/ ALT at admission and after 7 days were abnormal in about two/thirds of cases CPAP patients had transaminases more frequently abnormal (p=0 01) Transaminases alterations were predictive of DP at univariate analysis In multivariate analysis CRP at day 7 was predictor of DP (OR 3 08 and 1 08) while cardiopathy and ventilation type at admission were significantly associated with death (OR 9 95 and 11 5)  Conclusion: This study individuates possible prognostic factors in Sars-Cov-2 pneumonia Transaminases values do not predict DP or death, even if more severe patients have a higher prevalence of transaminases elevation CRP at day 7 is a predictor of DP, while cardiopathy and type of ventilation at admission are predictive factors of short-term mortality
Clinical Outcomes with Multikinase Inhibitors after Progression on First-Line Atezolizumab plus Bevacizumab in Patients with Advanced Hepatocellular Carcinoma: A Multinational Multicenter Retrospective Study
Authors: Changhoon Yoo, Jwa Hoon Kim, Min-Hee Ryu, Sook Ryun Park, Danbi Lee, Kang Mo Kim, Ju Hyun Shim, Young-Suk Lim, Han Chu Lee, Joycelyn Lee, David Tai, Stephen Lam Chan, Baek-Yeol Ryoo
Journal: Liver Cancer (2021)

Atezolizumab-bevacizumab is the new standard of care for first-line treatment of advanced hepatocellular carcinoma (HCC). However, the optimal sequence of therapy after disease progression on atezolizumab-bevacizumab is unclear.This multinational, multicenter, and retrospective study assessed clinical outcomes of patients with advanced HCC who received subsequent systemic therapy after progression on atezolizumab-bevacizumab between July 2016 and April 2019.Among 71 patients treated with atezolizumab-bevacizumab, a total of 49 patients who received subsequent systemic therapy were included in this analysis; the median age was 60 years (range, 37-80) and 73.5% were male. All patients were classified as Child-Pugh A and Barcelona-Clinic Liver Cancer stage C. Multikinase inhibitors (MKIs), including sorafenib (n = 29), lenvatinib (n = 19), and cabozantinib (n = 1), were used as second-line therapy for all patients. The objective response rate and disease control rate were 6.1 and 63.3%, respectively, in all patients. With a median follow-up duration of 11.0 months, median progression-free survival (PFS) and overall survival (OS) were 3.4 months (95% confidence interval [CI] 1.8-4.9) and 14.7 months (95% CI 8.1-21.2) in all patients. Median PFS with lenvatinib was significantly longer than that with sorafenib (6.1 vs. 2.5 months; p = 0.004), although there was no significant difference in median OS (16.6 vs. 11.2 months; p = 0.347). Treatment-related adverse events (TRAEs) of any grade and grade 3 occurred in 42 (85.7) and 8 (16.3%) of patients. Common TRAEs included hand-foot syndrome (n = 26, 53.1%), fatigue (n = 14, 28.6%), hypertension (n = 14, 28.6%), and diarrhea (n = 12, 24.5%).Second-line treatment with MKIs, mostly sorafenib and lenvatinib, showed comparable efficacy and manageable toxicities in patients with advanced HCC after disease progression on atezolizumab-bevacizumab.
Zwitterionic self-assembled nanoparticles as carriers for Plasmodium targeting in malaria oral treatment
Authors: Arnau Biosca, Pol Cabanach, Muthanna Abdulkarim, Mark Gumbleton, Cristian Gómez-Canela, Miriam Ramírez, Inés Bouzón-Arnáiz, Yunuen Avalos-Padilla, Salvador Borros, Xavier Fernàndez-Busquets
Journal: Journal of Controlled Release (2021)

The current decline in antimalarial drug efficacy due to the evolution of resistant Plasmodium strains calls for new strategies capable of improving the bioavailability of antimalarials, especially of those whose lipophilic character imparts them a low solubility in biological fluids. Here we have designed, synthesized and characterized amphiphilic zwitterionic block copolymers forming nanoparticles capable of penetrating the intestinal epithelium that can be used for oral administration. Poly(butyl methacrylate-co-morpholinoethyl sulfobetaine methacrylate) (PBMA-MESBMA)-based nanoparticles exhibited a specific targeting to Plasmodium falciparum-infected vs. parasite-free red blood cells (74.8%/0.8% respectively), which was maintained upon encapsulation of the lipophilic antimalarial drug curcumin (82.6%/0.3%). The in vitro efficacy of curcumin upon encapsulation was maintained relative to the free compound, with an IC50 around 5 μM. In vivo assays indicated a significantly increased curcumin concentration in the blood of mice one hour after being orally fed PBMA-MESBMA-curcumin in comparison to the administration of free drug (18.7 vs. 2.1 ng/ml, respectively). At longer times, however, plasma curcumin concentration equaled between free and encapsulated drug, which was reflected in similar in vivo antimalarial activities in Plasmodium yoelii yoelii-infected mice. Microscopic analysis in blood samples of fluorescently labeled PBMA-MESBMA revealed the presence of the polymer inside P. yoelii yoelii-parasitized erythrocytes one hour after oral administration to infected animals.
Abstract 9362: Senescence Marker Protein 30 has a Cardio-protective Role in Doxorubicin-induced Cardiac Dysfunction
Authors: Makiko Miyata, Satoshi Suzuki, Tomofumi Misaka, Yasuchika Takeishi
Journal: Circulation (2013)

Background: Senescence marker protein 30 (SMP30), which was originally identified as an aging marker protein, is assumed to act as a novel anti-aging factor in the liver, lungs and brain. Anthracyclines are the drugs most closely related to acute and late cardiac toxicity. One of the mechanisms responsible for doxorubicin (DOX) cardiotoxicity is the formation of reactive oxygen species (ROS) which can harm membrane lipids and other cellular components, leading to cardiomyocyte apoptosis and death. We hypothesized that SMP30 has cardio-protective function due to its anti-aging and anti-oxidant effects on doxorubicin (DOX)-induced cardiac dysfunction. Methods and Results: SMP30 knockout (SMP30 KO) mice, SMP30 transgenic (SMP30 TG) mice with cardiac-specific overexpression of SMP30 gene and wild-type (WT) littermate mice were given intra-peritoneal injections of DOX (20 mg/kg) or saline. Seven days after DOX injection, echocardiography revealed that left ventricular ejection fraction was more severely reduced in the DOX-treated SMP30 KO mice than in the DOX-treated WT mice, but was preserved in the DOX-treated SMP30 TG mice. Generation of ROS and oxidative DNA damage in the myocardium were greater in the DOX-treated SMP30 KO mice than in the DOX-treated WT mice, but much less in the SMP30 TG mice. The number of deoxynucleotidyl transferase-mediated dUTP nick end-labeling positive cardiomyocytes was higher in the DOX-treated SMP30 KO mice and lower in the DOX-treated SMP30 TG mice compared to that in the DOX-treated WT mice. Caspase-3 activity was higher in the DOX-treated SMP30 KO mice and lower in the DOX-treated SMP30 TG mice compared with the DOX-treated WT mice. The ratio of Bax to Bcl-2 was higher in the DOX-treated SMP30 KO mice and lower in the DOX-treated SMP30 TG mice than in the DOX-treated WT mice. Phosphorylation activity of SAPK/JNK was increased in the DOX-treated SMP30 KO mice and was decreased in the DOX-treated SMP30 TG mice compared with the DOX-treated WT mice. Conclusions: SMP30 has a cardio-protective role by anti-oxidative and anti-apoptotic effects in DOX-induced cardiotoxicity, and can be a new therapeutic target to prevent DOX-induced heart failure.
Intranasal temperature-sensitive hydrogels of cannabidiol inclusion complex for the treatment of post-traumatic stress disorder
Authors: Lulu Pang, Siqing Zhu, Jinqiu Ma, Lin Zhu, Yijing Liu, Ge Ou, Ruiteng Li, Yaxin Wang, Yi Liang, Xu Jin, Lina Du, Yiguang Jin
Journal: Acta Pharmaceutica Sinica B (2021)

Post-traumatic stress disorder (PTSD) is a psychiatric disease that seriously affects brain function. Currently, selective serotonin reuptake inhibitors (SSRIs) are used to treat PTSD clinically but have decreased efficiency and increased side effects. In this study, nasal cannabidiol inclusion complex temperature-sensitive hydrogels (CBD TSGs) were prepared and evaluated to treat PTSD. Mice model of PTSD was established with conditional fear box. CBD TSGs could significantly improve the spontaneous behavior, exploratory spirit and alleviate tension in open field box, relieve anxiety and tension in elevated plus maze, and reduce the freezing time. Hematoxylin and eosin and c-FOS immunohistochemistry slides showed that the main injured brain areas in PTSD were the prefrontal cortex, amygdala, and hippocampus CA1. CBD TSGs could reduce the level of tumor necrosis factor-α caused by PTSD. Western blot analysis showed that CBD TSGs increased the expression of the 5-HT1A receptor. Intranasal administration of CBD TSGs was more efficient and had more obvious brain targeting effects than oral administration, as evidenced by the pharmacokinetics and brain tissue distribution of CBD TSGs. Overall, nasal CBD TSGs are safe and effective and have controlled release. There are a novel promising option for the clinical treatment of PTSD.
Molecular markers of type 2 airway inflammation are similar between eosinophilic severe asthma and eosinophilic chronic obstructive pulmonary disease
Authors: Michael Fricker, Vanessa M. McDonald, Natasha A. Winter, Katherine J. Baines, Peter A. B. Wark, Jodie L. Simpson, Peter G. Gibson
Journal: Allergy (2021)

Airway and systemic eosinophilia are important treatable traits in both severe asthma and COPD. The molecular basis of eosinophilia in COPD is poorly understood but could involve type 2 cytokines (IL5, IL13) and prostaglandin D2 (PGD2 ).This study included non-obstructive airways disease (OAD) controls (n = 19), a COPD cohort (n = 96) and a severe asthma cohort (n = 84). Demographics, exacerbation history, disease impact (SGRQ) and spirometry were assessed. Participants were categorized as eosinophilic using either sputum eosinophil proportion (≥3%) or blood eosinophil count (≥300/μL). Sputum type 2 inflammatory measures included PGD2 by ELISA and gene expression (qPCR) of IL5, IL13 and the haematopoietic PGD2 synthase (HPGDS).Type 2 markers did not differ across groups except HPGDS mRNA which was highest in non-OAD controls and lowest in COPD. IL5 and IL13 mRNA and PGD2 levels were significantly increased in eosinophilic vs non-eosinophilic severe asthma but did not differ between eosinophilic COPD and eosinophilic severe asthma or non-eosinophilic COPD. HPGDS expression was higher in eosinophilic severe asthma compared with eosinophilic COPD. Results were similar using sputum or blood eosinophil cut-offs. Sputum IL5 and IL13 were highly intercorrelated in severe asthma (r = 0.907, p < 0.001) and COPD (r = 0.824, p < 0.001), were moderately correlated with sputum eosinophils in severe asthma (IL5 r = 0.440, p < 0.001; IL13 r = 0.428, p < 0.001) and were weakly correlated in COPD (IL5 r = 0.245, p < 0.05; IL13 r = 0.317, p < 0.05).Molecular markers of type 2 airway inflammation do not differ between eosinophilic asthma and eosinophilic COPD; however, the relationship between eosinophilia and type 2 airway markers appears weaker in COPD than in severe asthma.
Low energy amplitude modulated radiofrequency electromagnetic fields to show antitumor effect in combination with standard treatment or as monotherapy in patients with advanced hepatocellular carcinoma.
Authors: Yone De Camargo Setogute, Frederico Costa, Micelange Carvalho Sousa, Pablo Diego Lima, Luciana Carvalho, Elizabeth Santos, Brenda Pires Gumz, Fernanda Azevedo, Jorge Sabbaga, Tiago Biachi De Castria, Denis Leonardo Fontes Jardim, Daniela Freitas, Natally Horvat, Regis Franca, Leonardo Testagrossa, Tatiana Zanesco, Antonio Francisco Iemma, Jack Tuszynski
Journal: Journal of Clinical Oncology (2021)

332 Background: Exposure to amplitude-modulated radiofrequency electromagnetic fields (EMF) in immortalized hepatocellular carcinoma (HCC) cell cultures and xenograft models demonstrated anti-tumor effect. Patients with advanced HCC exposed to systemic EMF showed objective response with potential survival benefit. Methods: An open-label, single center, prospective clinical protocol was performed in advanced HCC patients as an initial, second or third treatment modality. Systemic exposure to EMF modulated at patient-specific frequencies was applied as an add-on strategy (combination) to systemic conventional treatment or as a single therapeutic modality. A spoon-shaped antenna placed in the oral cavity delivered EMF over 90 minutes with monthly repetitions until death or consent of withdrawal. The primary objective was overall survival (OS) in comparison with historical control group of 45 advanced patients HCC from the same institution. Retrospective radiological review was conducted by two independent radiologists for objective response (OR) using RECIST1.1 criterion. Results: From March 2018 to April 2020, 55 advanced HCC patients were submitted to 373 EMF exposures. 87% were male, median age of 67, 84% were BLCL-C, 16% were Child-Pugh B, 29% had extra-hepatic metastasis, 55% had failed previous treatment and 71% had documented radiological progression. 31(56%) patients received EMF in combination with systemic therapy (25 sorafenib, 3 lenvatinib, 3 nivolumab). 24 patients received EMF as single treatment modality. The median OS for the entire patient cohort was 11.5 months. The median OS for combination treatment was 12.0 month and the median OS for single modality was 11.3 months. The median OS for the historical control was 5.3 month. The median OS from the entire cohort and the historical control were significant different (p = 0.0026) but the median OS from combination and single modality were not (p = 0.3434). Radiological images were available from 38(69%) patients. There were 6/38 (16%) documented objective responses (1 CR and 5 PR) and 30/38 (79%) patients experienced disease control. 4/21 (19%) OR were in patients using TKIs + EMF and 2/17 (12%) OR were in patients using EMF alone. Conclusions: EMF showed objective anti-tumor effect in combination with TKI or as single modality in advanced HCC patients. EMF showed improvement in overall survival in comparison with the historical control group supporting future development as a novel systemic treatment modality in advanced HCC patients. Clinical trial information: NCT 01686412.
Treatment of Helicobacter pylori infection Reply
Authors: O M P JOLOBE, S K LAM
Journal: Gut (1998)

Editor,—Apart from validating the reversibility of the pathogenic processes mediated by Helicobacter pylori in the causation of duodenal ulcer, the study by Lam et al ( Gut 1997; 41 :43–8) also served as a reminder that, even in H pylori associated ulcer disease, other mechanisms have a reversible aetiopathogenic role, exemplified by the spontaneous remission documented through the use of placebo. There is …