tbuckley/cabot-search huggingface dataset:
Association of <i>OPRM1</i>, <i>MIR23B,</i> and <i>MIR107</i> genetic variability with acute and chronic pain after postoperative tramadol treatment in breast cancer.
Authors: Nikola Besic, Katja Goricar, Zala Vidic, Branka Strazisar, Vita Dolzan
Journal: Journal of Clinical Oncology (2021)

e24052 Background: Tramadol is an opioid analgesic often used for pain management after axillary lymph node dissection in breast cancer. It exerts its analgesic activity through activation of the G protein-coupled µ-opioid receptor, encoded by the OPRM1 gene. Genetic factors that may modify activity or expression of OPRM1 could thus affect the efficacy of tramadol treatment. This study investigated the association of genetic variability of OPRM1 and genes coding for miRNAs regulating OPRM1 expression with pain management in breast cancer patients treated with tramadol after surgery. Methods: The study included 113 breast cancer patients treated with either 75 or 37.5 mg of tramadol for pain relief after breast cancer surgery within the randomized clinical trial KCT 04/2015-DORETAonko/si at Institute of Oncology Ljubljana. All patients were genotyped for OPRM1 rs1799971 and rs677830, MIR23B rs1011784 and MIR107 rs2296616 using competitive allele-specific PCR. The association of genetic factors with acute and chronic pain was evaluated using logistic regression, Fisher’s exact test and Mann-Whitney test. Results: The investigated OPRM1 related genetic factors were not associated with acute pain measured using VAS scale within four weeks after surgery, even after adjustment for tramadol dose (all P &gt; 0.05). One year after surgery, 21 (21.1%) patients experienced chronic pain and 25 (25.3%) experienced neuropathic pain. In carriers of two polymorphic MIR107 rs2296616 alleles, chronic pain was significantly more common compared to carriers of two wild-type alleles (35.3% compared to 0% of patients, P = 0.004). Carriers of at least one polymorphic MIR23B rs1011784 allele experienced more neuropathic pain compared to carriers of two wild-type alleles after adjustment for tramadol dose (OR = 2.85, 95% CI = 1.07-7.59, P = 0.036). Conclusions: Genetic variability of miRNAs that could affect OPRM1 expression may be associated with chronic pain in breast cancer patients treated with postoperative tramadol.
Combining stem cells in myocardial infarction: The road to superior repair?
Authors: Hanne Beliën, Lize Evens, Marc Hendrikx, Virginie Bito, Annelies Bronckaers
Journal: Medicinal Research Reviews (2021)

Abstract Myocardial infarction irreversibly destroys millions of cardiomyocytes in the ventricle, making it the leading cause of heart failure worldwide. Over the past two decades, many progenitor and stem cell types were proposed as the ideal candidate to regenerate the heart after injury. The potential of stem cell therapy has been investigated thoroughly in animal and human studies, aiming at cardiac repair by true tissue replacement, by immune modulation, or by the secretion of paracrine factors that stimulate endogenous repair processes. Despite some successful results in animal models, the outcome from clinical trials remains overall disappointing, largely due to the limited stem cell survival and retention after transplantation. Extensive interest was developed regarding the combinational use of stem cells and various priming strategies to improve the efficacy of regenerative cell therapy. In this review, we provide a critical discussion of the different stem cell types investigated in preclinical and clinical studies in the field of cardiac repair. Moreover, we give an update on the potential of stem cell combinations as well as preconditioning and explore the future promises of these novel regenerative strategies.
Surveillance strategies using routine microbiology for antimicrobial resistance in low- and middle-income countries
Authors: Cherry Lim, Elizabeth A. Ashley, Raph L. Hamers, Paul Turner, Thomas Kesteman, Samuel Akech, Alejandra Corso, Mayfong Mayxay, Iruka N. Okeke, Direk Limmathurotsakul, H. Rogier van Doorn
Journal: Clinical Microbiology and Infection (2021)

BackgroundRoutine microbiology results are a valuable source of antimicrobial resistance (AMR) surveillance data in low- and middle-income countries (LMICs) as well as in high-income countries. Different approaches and strategies are used to generate AMR surveillance data.ObjectivesWe aimed to review strategies for AMR surveillance using routine microbiology results in LMICs and to highlight areas that need support to generate high-quality AMR data.SourcesWe searched PubMed for papers that used routine microbiology to describe the epidemiology of AMR and drug-resistant infections in LMICs. We also included papers that, from our perspective, were critical in highlighting the biases and challenges or employed specific strategies to overcome these in reporting AMR surveillance in LMICs.ContentTopics covered included strategies of identifying AMR cases (including case-finding based on isolates from routine diagnostic specimens and case-based surveillance of clinical syndromes), of collecting data (including cohort, point-prevalence survey, and case–control), of sampling AMR cases (including lot quality assurance surveys), and of processing and analysing data for AMR surveillance in LMICs.ImplicationsThe various AMR surveillance strategies warrant a thorough understanding of their limitations and potential biases to ensure maximum utilization and interpretation of local routine microbiology data across time and space. For instance, surveillance using case-finding based on results from clinical diagnostic specimens is relatively easy to implement and sustain in LMIC settings, but the estimates of incidence and proportion of AMR is at risk of biases due to underuse of microbiology. Case-based surveillance of clinical syndromes generates informative statistics that can be translated to clinical practices but needs financial and technical support as well as locally tailored trainings to sustain. Innovative AMR surveillance strategies that can easily be implemented and sustained with minimal costs will be useful for improving AMR data availability and quality in LMICs.
Obesity and Mortality Among Patients Diagnosed With COVID-19
Authors: Andrew N. Bamji
Journal: Annals of Internal Medicine (2021)

LettersJune 2021Obesity and Mortality Among Patients Diagnosed With COVID-19FREEAndrew N. Bamji, MBAndrew N. Bamji, MBRye, United KingdomSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L21-0062 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR: I read Tartof and colleagues' article (1) with interest. It would be valuable to investigate the role of leptin as an underlying reason for the apparent susceptibility of obese patients to COVID-19. Leptin is produced by fat cells with a role in appetite suppression; the greater the number or larger the size of the fat cells, the more leptin they will produce. In addition, leptin resistance will probably induce a feedback loop that further increases leptin levels.Leptin acts as a proinflammatory substance; hence, it will potentiate a cytokine storm. Are leptin levels substantially elevated in obese patients with COVID-19? I would not be surprised if so.Reference1. Tartof SY, Qian L, Hong V, et al. Obesity and mortality among patients diagnosed with COVID-19: results from an integrated health care organization. Ann Intern Med. 2020;173:773-81. [PMID: 32783686] doi:10.7326/M20-3742 LinkGoogle Scholar Comments 0 Comments Sign In to Submit A Comment Author, Article, and Disclosure InformationAuthors: Andrew N. Bamji, MBAffiliations: Rye, United KingdomDisclosures: The author has reported no disclosures of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L21-0062. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoObesity and Mortality Among Patients Diagnosed With COVID-19: Results From an Integrated Health Care Organization Sara Y. Tartof , Lei Qian , Vennis Hong , Rong Wei , Ron F. Nadjafi , Heidi Fischer , Zhuoxin Li , Sally F. Shaw , Susan L. Caparosa , Claudia L. Nau , Tanmai Saxena , Gunter K. Rieg , Bradley K. Ackerson , Adam L. Sharp , Jacek Skarbinski , Tej K. Naik , and Sameer B. Murali Obesity and Mortality Among Patients Diagnosed With COVID-19 Anastasios Kollias , Konstantinos G. Kyriakoulis , Konstantinos Syrigos Obesity and Mortality Among Patients Diagnosed With COVID-19 Johannes Burtscher , Grégoire P. Millet , Martin Burtscher Obesity and Mortality Among Patients Diagnosed With COVID-19 Sara Y. Tartof , Sameer B. Murali , Debbie E. Malden Metrics June 2021Volume 174, Issue 6 Page: 887 ePublished: 15 June 2021 Issue Published: June 2021 Copyright & PermissionsCopyright © 2021 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
The Place of Philosophy in Bioethics Today
Authors: Jennifer Blumenthal-Barby, Sean Aas, Dan Brudney, Jessica Flanigan, S. Matthew Liao, Alex London, Wayne Sumner, Julian Savulescu
Journal: The American Journal of Bioethics (2021)

In some views, philosophy's glory days in bioethics are over. While philosophers were especially important in the early days of the field, so the argument goes, the majority of the work in bioethics today involves the "simple" application of existing philosophical principles or concepts, as well as empirical work in bioethics. Here, we address this view head on and ask: What is the role of philosophy in bioethics today? This paper has three specific aims: (1) to respond to skeptics and make the case that philosophy and philosophers still have a very important and meaningful role to play in contemporary bioethics, (2) to discuss some of the current challenges to the meaningful integration of philosophy and bioethics, and (3) to make suggestions for what needs to happen in order for the two fields to stay richly connected. We outline how bioethics center directors, funders, and philosopher bioethicists can help.
Implementation of electronic patient-reported outcomes for symptom monitoring in a large multi-site community oncology practice.
Authors: Debra A. Patt, Lalan S. Wilfong, Kathryn Elizabeth Hudson, Amila Patel, Holly Books, Lance Ortega, Ben Pearson, Rhonda Boren, Shrutika Patil, Kristin Olson-Celli, Ethan M. Basch
Journal: Journal of Clinical Oncology (2021)

12103 Background: Among patients receiving chemotherapy, symptomatic adverse event monitoring with electronic patient-reported outcomes (ePRO) is associated with improved clinical outcomes, satisfaction, and compliance with therapy. Standard approaches for ePRO implementation are not established warranting evaluation in community cancer practices. Objective: Evaluate implementation of ePRO symptom monitoring across a large multi-site community oncology practice network. Methods: Patients initiating a new systemic therapy at one of 210 practice sites in the Texas Oncology Practice were invited to use in the Navigating Cancer ePRO platform, with rolling implementation from July-December 2020. Participating patients received a weekly prompt by text message or email (patient choice) to self-report common symptoms and well-being via web or smartphone. Severe self-reported symptoms triggered a real-time notification alert to nursing triage to address the symptom. Enrollment and compliance were systematically tracked weekly with evaluation of barriers and facilitators to adoption and sustainability. Results: 4375 patients planning systemic treatment enrolled and participated, with baseline characteristics are shown in Table 1. 73% (1841/2522) of enrolled patients with follow up completed at least one ePRO assessment, and among these individuals, 65% (8762/25061) of all available weekly ePRO assessments were completed. Over a 10-week period, compliance with weekly symptom reporting declined from 72% to 52%. Patients on oral therapy had higher compliance rates overall. Barriers currently being addressed include lack of a second reminder text/email prompt, inconsistent discussion of reported ePROs by clinicians at visits, and COVID-related changes in workflow. Facilitators included patient and staff engagement on the importance of PROs for symptom management. Conclusions: ePROs can be effectively implemented in community oncology practice. Utilization of ePROs is high, but diminishes over time without attention to barriers. Ongoing work to address barriers and optimize compliance are underway.[Table: see text]
A phase I study of SHR7390 plus camrelizumab in advanced/metastatic colorectal cancer.
Authors: Xiao-li Wei, Yang Zhang, Hongyun Zhao, Zhiqiang Wang, Yu-Hong Li, Feng Wang, Fenghua Wang, Wenfeng Fang, Ming-ming He, Huiyan Luo, Miaozhen Qiu, Ben-Yan Zou, Jie Xie, Chunlei Jin, Rui-hua Xu
Journal: Journal of Clinical Oncology (2021)

e15553 Background: PD-1 antibody monotherapy has shown durable response in colorectal cancer (CRC) patients (pts) with microsatellite instability (MSI) high status, who account for only 10–15% of all CRC pts. Preclinical studies revealed that inhibition of MAPK pathway with MEK inhibitors can increase T-cell infiltration into tumors and therefore might enhance the antitumor activity of immune checkpoint inhibitor. Thus, this study was conducted to evaluate the safety and antitumor activity of SHR7390, a MEK1/2 inhibitor, plus camrelizumab (anti-PD-1) in pts with CRC. Methods: In this single-arm, open-label, phase I study, pts with treatment-refractory advanced or metastatic CRC were enrolled to receive SHR7390 in an accelerated titration scheme at doses of 0.125, 0.25, and 0.5 mg orally qd, plus camrelizumab at a fixed dose of 200 mg IV q2w. Eligible pts were given a single dose of SHR7390, observed for 7–10 days, and then treated continuously with SHR7390 and camrelizumab in 28-day treatment cycles until disease progression, intolerable toxicities, or withdrawal of consent. A recommended dose for expansion was determined based on the safety and tolerability of the dose escalation stage. The primary endpoints were dose limiting toxicity (DLT) and maximum tolerated dose (MTD). This study is registered with ClinicalTrials.gov, number NCT03182673. Results: At data cutoff on May 30, 2020, 22 pts were enrolled. The median follow-up duration was 6 months. Seven pts had received ≥3 lines of prior treatment. MSI status were available in 21 pts (MSS/MSI-L, n = 18; MSI-H, n = 3). There were two pts each in the SHR7390 0.125 and 0.25 mg cohorts, and 0.5 mg cohort was expanded to 18 pts. One DLT (grade 3 rash) was reported in a pt in the 0.5 mg cohort and the MTD was not reached. Grade 3–4 treatment-related adverse events (TRAEs) were rash (n = 4), increased lipase, oedema peripheral, face oedema, and anemia (n = 1 each). One pt reported a grade 5 TRAE (increased intracranial pressure). Five pts (23%) achieved partial response (0.125 and 0.25 mg cohorts, n = 1 each; 0.5 mg cohort, n =3), including one out of three pts with MSS/MSI-L &amp; BRAF mutant tumors (response lasting 13 months), one out of 15 pts with MSS/MSI-L &amp; BRAF wild type tumors (response lasting 8 months), and all three pts with MSI-H tumors (responses lasting 31, 11, and 10 months, respectively). Three pts with MSS/MSI-L achieved stable disease, and the overall disease control rate reached 36%. Conclusions: SHR7390 plus camrelizumab showed a tolerable safety profile. Preliminary clinical activity was reported regardless of BRAF and MSI status, and future studies are warranted to further evaluate these results. Clinical trial information: NCT03182673.
Relative risk of hepatotoxicity associated with cyclin-dependent kinase inhibitors (CDK4/6i): A systematic review and meta-analysis of phase 3 randomized controlled trials.
Authors: Nusrat Jahan, Sariya Wongsaengsak, Shabnam Rehman, Nimesh Adhikari, Lukman Aderoju Tijani, Arrvind Raghunath
Journal: Journal of Clinical Oncology (2021)

e13037 Background: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) such as palbociclib, abemaciclib, and ribociclib have changed the landscape of management of estrogen receptor-positive and HER2-negative breast cancer in recent years. We conducted a systematic review and meta-analysis of phase 3 randomized controlled trials (RCTs) to determine the relative risk of hepatic dysfunction associated with the use of CDK4/6i. Methods: We conducted a systematic search using PRISMA guidelines in PubMed, EMBASE, American Society of Clinical Oncology (ASCO) and San Antonio Breast Cancer Symposium meeting abstracts from inception through Jan 30, 2021. Phase 3 RCTs using CDK4/6i in the intervention arm and reporting the number of events for elevation of liver enzymes were included in the analysis. The Cochran-Mantel-Haenszel method and random effects model were used to calculate the pooled risk ratio (RR) with 95% confidence interval (CI). Heterogeneity was tested by Cochran’s Q test and I 2 value. Results: Nine phase 3 RCTs — MONALEESA-2, MONALEESA-3, MONALEESA-7, MONARCH 2, MONARCH 3, MONARCH plus, monarchE, PALOMA-2, and PALOMA-3 — randomizing 5,809 patients in the CDK4/6i arms and 4,638 patients in the control arms were included in the analysis. The CDK4/6i arms used CDK4/6i such as palbociclib, abemaciclib, or ribociclib in combination with one of the standard-of-care endocrine therapies such as letrozole, anastrozole, tamoxifen, or fulvestrant. The control arms received placebo along with respective endocrine therapies. The incidence of any grade alanine aminotransferase (ALT) elevation was 13.1% in the CDK4/6i arm and 5.4% in the control arm, pooled RR: 2.18, 95% CI: 1.74-2.72, P &lt; 0.00001, I 2 = 45%. The incidence of any grade aspartate aminotransferase (AST) elevation was 12.5% in the CDK4/6i arm and 5.3% in the control arm, pooled RR: 2.00, 95% CI: 1.57-2.54, P &lt; 0.00001, I 2 = 57%. The incidence of grade 3/4 ALT elevation was 4.1% in the CDK4/6i arm and 0.8% in the control arm, pooled RR: 4.43, 95% CI: 3.08-6.37, P &lt; 0.00001, I 2 = 0%. The incidence of grade 3/4 AST elevation was 2.9% in the CDK4/6i arm and 0.9% in the control arm, pooled RR: 2.70, 95% CI: 1.75-4.19, P &lt; 0.00001, I 2 = 29%. No fatal case of hepatotoxicity has been reported. Conclusions: Cyclin-dependent kinase 4/6 inhibitors are associated with significant risk of any grade and grade 3/4 hepatic enzymes elevation. Regular monitoring of liver function is a key to early detection and initiation of appropriate management.
Mimicry of an acute pseudocyst by a gastrointestinal duplication cyst in a 14-year-old boy
Authors: Thomas Billiet, Ann Elewaut, François d’Heygere, Gert de Hertogh, Raymond Aerts, Chris Verslype, Wim Laleman
Journal: Endoscopy (2021)

A 14-year-old boy was urgently admitted to the hospital because of acute abdominal pain, vomiting, abdominal tenderness, and elevated lipase levels of up to 2000 U/L. An initial basic work-up did not show anything to suggest a conventional etiology. The diagnosis of pancreatitis was put forward, which was confirmed by an abdominal computed tomography (CT) scan. Remarkably, the scan additionally revealed a demarcated flaccid peripancreatic fluid collection anterior to the pancreas, with free surrounding intra-abdominal fluid ([Fig. 1]). At that time, it was assumed that a pre-existing acute pseudocyst had ruptured spontaneously and was causative of the clinical presentation. A further work-up by means of magnetic resonance imaging (MRI) 6 days after admission, and 3 days after the previously mentioned CT scan, strangely enough exhibited a fully re-established tense bilobular encapsulated fluid collection (length 8.3 cm, width 4.1 cm) ([Fig. 2]), instead of the previously described flaccid collection. Recurrence of the initial acute pseudocyst was suspected.
Nursing’s pivotal role in global climate action
Authors: Patricia Butterfield, Jeanne Leffers, Maribel Díaz Vásquez
Journal: BMJ (2021)

Nurses moved early and eagerly to advocate action to resist climate change and are well positioned to achieve much more. <b>Patricia Butterfield</b>, <b>Jeanne Leffers</b>, and <b>Maribel Díaz Vásquez</b> urge nurses to act boldly within and across professional boundaries
A DL-4- and TNFα-based culture system to generate high numbers of nonmodified or genetically modified immunotherapeutic human T-lymphoid progenitors
Authors: Ranjita Devi Moirangthem, Kuiying Ma, Sabrina Lizot, Anne Cordesse, Juliette Olivré, Corinne de Chappedelaine, Akshay Joshi, Agata Cieslak, John Tchen, Nicolas Cagnard, Vahid Asnafi, Antonio Rausell, Laura Simons, Julien Zuber, Tom Taghon, Frank J. T. Staal, Françoise Pflumio, Emmanuelle Six, Marina Cavazzana, Chantal Lagresle-Peyrou, Tayebeh Soheili, Isabelle André
Journal: Cellular and Molecular Immunology (2021)

Abstract Several obstacles to the production, expansion and genetic modification of immunotherapeutic T cells in vitro have restricted the widespread use of T-cell immunotherapy. In the context of HSCT, delayed naïve T-cell recovery contributes to poor outcomes. A novel approach to overcome the major limitations of both T-cell immunotherapy and HSCT would be to transplant human T-lymphoid progenitors (HTLPs), allowing reconstitution of a fully functional naïve T-cell pool in the patient thymus. However, it is challenging to produce HTLPs in the high numbers required to meet clinical needs. Here, we found that adding tumor necrosis factor alpha (TNFα) to a DL-4-based culture system led to the generation of a large number of nonmodified or genetically modified HTLPs possessing highly efficient in vitro and in vivo T-cell potential from either CB HSPCs or mPB HSPCs through accelerated T-cell differentiation and enhanced HTLP cell cycling and survival. This study provides a clinically suitable cell culture platform to generate high numbers of clinically potent nonmodified or genetically modified HTLPs for accelerating immune recovery after HSCT and for T-cell-based immunotherapy (including CAR T-cell therapy).