tbuckley/cabot-search huggingface dataset:
Differential effects of gefitinib and cetuximab on EGFR mutant non-small cell lung cancers (NSCLC)
Authors: Toru Mukohara, Jeffrey A. Engelman, Neal Lindeman, Balazs Halmos, Bruce E. Johnson, Pasi A. Jänne
Journal: Cancer Research (2005)

2165  Somatic mutations in the tyrosine kinase (TK) domain of the epidermal growth factor receptor (EGFR) have recently been found to closely correlate with tumor responses to the EGFR-TK inhibitor, gefitinib (‘Iressa’), in patients with NSCLC. However, little is known about the efficacy of the EGFR directed antibody, cetuximab, in EGFR mutant NSCLCs. We examined the effects of gefitinib (3.3 nM to 10 μM) and cetuximab (33 ng/ml to 100 μg/ml) on in vitro cell growth by MTS assay in NSCLC cell lines with different EGFR genotypes: wild type (EGFRWT; A549, H441, and H1666); exon 21 L858R missense mutant (EGFRL858R; H3255); and exon 19 deletion mutant (EGFRdel; DFCILU-011). In the H1666 EGFRWT cell line, both gefitinib and cetuximab caused partial growth inhibition (47% and 43% growth inhibition using 1 μM and 10 μg/ml, respectively). In contrast, both H441 and A549 were resistant to both agents. Both gefitinib and cetuximab led to only partial inhibition of EGFR phosphorylation in H1666. Treatment with either 1 μM gefitinib or 10 μg/ml cetuximab induced apoptosis in H1666 (gefitinib:9.3+/− 1.0 %; cetuximab:11.2 +/− 2.5 %) but not in H441 cells. However, both cell lines harboring the EGFR mutations were very sensitive to gefitinib (IC50 for H3255 and DFCILU-011, 63 and 20 nM, respectively) and resistant to cetuximab (IC50 > 100 μg/ml). Consistent with these observations, 1 μM gefitinib led to significantly greater increase in apoptosis than 10 μg/ml cetuximab (H3255: gefitinib: 23.6 +/− 9.2 %, cetuximab 3.7 +/− 1.1 %; DFCILU-011: gefitinib 11 +/− 1.5%, cetuximab 0 +/− 0.9%). Gefitinib treatment also led to complete inhibition of EGFR phosphorylation while cetuximab had minimal effects on EGFR phosphorylation. To further evaluate the differences between wildtype and mutant EGFRs, we examined the effects of these agents in NIH-3T3 cells stably expressing EGFR that was either wild type or contained the L858R or exon 19 deletion mutations. In NIH-3T3/EGFRWT cells, both gefitinib and cetuximab led only to partial blockade of phophorylation of EGFR. However in NIH-3T3/EGFRL858R and NIH-3T3/EGFRdel cells gefitinib completely abrogated phosphorylation of EGFR at 0.1 μM but cetuximab led to only partial inhibition even at 100 μg/ml. We also sequenced EGFR from 3 NSCLC patients who received treatment with both cetuximab and gefitinib. Two patients who initially had stable disease with single agent cetuximab but subsequently developed disease progression achieved partial responses when treated with gefitinib. The third patient had a complete response to gefitinib but subsequently progressed, and was then treated with cetuximab with disease progression. All three patients had somatic mutations (exon 19 deletions) in EGFR.These findings suggest that gefitinib and cetuximab have differential effects on EGFR mutant NSCLCs and that patients with EGFR TK mutations should be treated with EGFR TKIs.
Bioactive extracellular matrix scaffolds engineered with proangiogenic proteoglycan mimetics and loaded with endothelial progenitor cells promote neovascularization and diabetic wound healing
Authors: Siqi He, Tanaya Walimbe, Hongyuan Chen, Kewa Gao, Priyadarsini Kumar, Yifan Wei, Dake Hao, Ruiwu Liu, Diana L. Farmer, Kit S. Lam, Jianda Zhou, Alyssa Panitch, Aijun Wang
Journal: Bioactive Materials (2021)

Diabetic ischemic wound treatment remains a critical clinical challenge. Neovascularization plays a significant role in wound healing during all stages of the tissue repair process. Strategies that enhance angiogenesis and neovascularization and improve ischemic pathology may promote the healing of poor wounds, particularly diabetic wounds in highly ischemic conditions. We previously identified a cyclic peptide LXW7 that specifically binds to integrin αvβ3 on endothelial progenitor cells (EPCs) and endothelial cells (ECs), activates vascular endothelial growth factor (VEGF) receptors, and promotes EC growth and maturation. In this study, we designed and synthesized a multi-functional pro-angiogenic molecule by grafting LXW7 and collagen-binding peptides (SILY) to a dermatan sulfate (DS) glycosaminoglycan backbone, named LXW7-DS-SILY, and further employed this multi-functional molecule to functionalize collagen-based extracellular matrix (ECM) scaffolds. We confirmed that LXW7-DS-SILY modification significantly promoted EPC attachment and growth on the ECM scaffolds
Screening for Chlamydia and Gonorrhea
Authors: Jill Jin
Journal: JAMA (2021)

US Preventive Services Task Force; Karina W. Davidson, PhD, MASc; Michael J. Barry, MD; Carol M. Mangione, MD, MSPH; Michael Cabana, MD, MA, MPH; Aaron B. Caughey, MD, PhD; Esa M. Davis, MD, MPH; Katrina E. Donahue, MD, MPH; Chyke A. Doubeni, MD, MPH; Alex H. Krist, MD, MPH; Martha Kubik, PhD, RN; Li Li, MD, PhD, MPH; Gbenga Ogedegbe, MD, MPH; Lori Pbert, PhD; Michael Silverstein, MD, MPH; Melissa A. Simon, MD, MPH; James Stevermer, MD, MSPH; Chien-Wen Tseng, MD, MPH, MSEE; John B. Wong, MD
The future looks bleak for the junior doctors
Authors: Michael Gardiner, Stephanie D’Costa
Journal: BMJ (2021)

As doctors recruited early to help with the first wave of the covid-19 pandemic, we share the concerns raised by Nabavi and Munro about morale among junior doctors.1 Emergency measures and prioritisation of clinical duties over teaching and training were indisputably needed at the time, as we faced an unprecedented crisis. But we are now also providing routine care—elective …
Whole-body PET tracking of a d-dodecapeptide and its radiotheranostic potential for PD-L1 overexpressing tumors
Authors: Kuan Hu, Wenyu Wu, Lin Xie, Hao Geng, Yiding Zhang, Masayuki Hanyu, Lulu Zhang, Yinghuan Liu, Kotaro Nagatsu, Hisashi Suzuki, Jialin Guo, Yundong Wu, Zigang Li, Feng Wang, Mingrong Zhang
Journal: Acta Pharmaceutica Sinica B (2021)

Peptides that are composed of dextrorotary (d)-amino acids have gained increasing attention as a potential therapeutic class. However, our understanding of the in vivo fate of d-peptides is limited. This highlights the need for whole-body, quantitative tracking of d-peptides to better understand how they interact with the living body. Here, we used mouse models to track the movement of a programmed death-ligand 1 (PD-L1)-targeting d-dodecapeptide antagonist (DPA) using positron emission tomography (PET). More specifically, we profiled the metabolic routes of [64Cu]DPA and investigated the tumor engagement of [64Cu/68Ga]DPA in mouse models. Our results revealed that intact [64Cu/68Ga]DPA was primarily eliminated by the kidneys and had a notable accumulation in tumors. Moreover, a single dose of [64Cu]DPA effectively delayed tumor growth and improved the survival of mice. Collectively, these results not only deepen our knowledge of the in vivo fate of d-peptides, but also underscore the utility of d-peptides as radiopharmaceuticals.
Therapeutic Drug Monitoring vs Standard Therapy During Infliximab Induction in Patients With Chronic Immune-Mediated Inflammatory Diseases—Reply
Authors: Silje Watterdal Syversen, Nils Bolstad, Espen A. Haavardsholm
Journal: JAMA (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Toll-like receptor 4–mediated enteric glia loss is critical for the development of necrotizing enterocolitis
Authors: Mark L. Kovler, Andres J. Gonzalez Salazar, William B. Fulton, Peng Lu, Yukihiro Yamaguchi, Qinjie Zhou, Maame Sampah, Asuka Ishiyama, Thomas Prindle, Sanxia Wang, Hongpeng Jia, Peter Wipf, Chhinder P. Sodhi, David J. Hackam
Journal: Science Translational Medicine (2021)

TLR4-induced enteric glia loss leads to experimental NEC through BDNF loss, which can be treated with by compound J11.
Fertility preservation in young breast cancer patients: A population-based study.
Authors: Diana Nguyen, Ghader Jamjoum, Ari N. Meguerditchian
Journal: Journal of Clinical Oncology (2021)

90 Background: Treatment-related infertility is an important cause of distress in young women with breast cancer (YWBC) that is preventable by fertility preservation (FP) prior to initiating therapy. This study assesses FP service use by YWBC in Quebec (Canada). Methods: Administrative claims for women ≤ 40 diagnosed between 01-04-2012 and 31-03-2018 were identified using Quebec’s universal health services database (RAMQ). Access to and use of FP services were ascertained by identifying claims for a visit with an obstetrician/gynecologist (OB/GYN) ≤ 90 days of diagnosis, followed by claims for ovarian stimulation, ovule harvesting or artificial insemination. Patient, disease and treatment-related predictors were estimated using logistic regression. Results: 1 616 YWBC were treated. Mean age was 36 (SD 4.1), 72.1% had a CCI = 0, 84.5% were urban residents, and 72.2% experienced some form of socioeconomical disadvantages. Stage distribution was: 0.93%, 68.8, and 30.3% for stages 0, 1-2, and 3 respectively. 53.0% had a mastectomy, 40.8% received chemotherapy (CT), 70.7% received radiotherapy, 20.9% initiated anti-estrogen therapy. 387 YWBC consulted an OB/GYN within 90 days of diagnosis and 155 subsequently received FP services. Predictors associated with FP use included: decreased age (OR= 0.82, 95CI = 0.79-0.86), type of surgery (OR = 0.46, CI = 0.22-0.97), social isolation (OR =1.39, 95CI = 0.99-1.96) and receipt of chemotherapy (OR = 1.74, 95CI = 1.10-2.76). Conclusions: Only 23.9% of eligible YWBC in Quebec accessed FP specialists. Of these, 40.1% chose to move forward with FP. These findings raise important questions on how to optimize access to FP expertise. [Table: see text]
Barriers to patient-centered oncology care: Pilot study of home infusion of anticancer immunotherapy.
Authors: David Michael Gill, Wendy Burr, Mckenzie Bell, Alisa Thomas, Jenny Simmonds, Megan Mullalley, Libby Petersen, Zoya Sandhu, Sarah Kator, Melissa Banner, Terence Duane Rhodes, Ramya Thota, Derrick S. Haslem
Journal: Journal of Clinical Oncology (2021)

36 Background: ASCO published a position statement regarding home infusion of anticancer therapy in June 2020. This statement recommends independent research to evaluate the safety and effectiveness of home infusions. Intermountain Healthcare (IM) incorporated this statement into its oncology care with an IRB-approved, prospective single-arm pilot study to determine the safety and feasibility of home administration of checkpoint inhibitor (CPI) immunotherapy with synchronous telemedicine visits. Methods: Patients with cancer receiving treatment at Intermountain Medical Center and Intermountain Cancer Center St. George were screened for enrollment into an IRB-approved, non-randomized pilot study of 20 patients. Eligibility criteria required patients to receive a CPI for an FDA-approved indication, live in Washington County or Salt Lake County, Utah, and have commercial payer coverage of CPI home infusion. Eligible patients were required to receive 2 doses of CPI at an infusion center, and patients who experienced an infusion reaction were excluded from receiving home infusion. Home infusion nurses are trained in oncology, CPIs, and home infusion reaction protocol. During synchronous video visits, infusion nurses are trained to perform the hands-on portions of the physical exam. A financial analysis estimated cost to IM and commercial payers for routine and home CPI infusions. Results: 622 patients were screened, of which 104 were receiving a CPI. 64 patients lived in an eligible county and 19 patients had commercial payer coverage. Of patients on CPIs, 8.7% (9/104) met all eligibility criteria accounting for 1.4% (9/622) of all patients with cancer screened (Table). Financial analysis estimated $829 cost (excluding drug cost) to IM for standard infusion reimbursement compared to $599 for in-home CPI infusions, accounting for savings of $230 per infusion. Majority of cost savings are from elimination of infusion center facilities fee ($495). Analysis includes $269 for home infusion nurse wages. Subsequent analysis for commercial payer SelectHealth estimates $270 reimbursement savings for the payer. Conclusions: Home immunotherapy infusions are estimated to be cost effective for both IM and commercial payers. However, lack of drug coverage and the rural demographics of Utahns with cancer are barriers to home CPI infusions. The pilot study was discontinued per infeasibility stopping criteria.[Table: see text]
Steps towards digital tools for personalised physical activity promotion
Authors: David E Conroy, Gary G Bennett, Constantino M Lagoa, Kathleen Y Wolin
Journal: British Journal of Sports Medicine (2021)

Digital health has grown from a collection of provocative ideas into a multibillion-dollar industry in just over a decade in part because of the promise of this technology for improving physical activity monitoring and promotion strategies. Systematic reviews and meta-analyses of evidence for this technology are beginning to accumulate.1 2 In this commentary, we offer some important considerations as the field moves towards creating personalised strategies for promoting physical activity.

First, apps and wearable trackers are often portrayed as tools for promoting physical activity, but, by themselves, they are not treatments. They are simply vehicles for delivering the psychologically active ingredients of behaviour change, akin to the capsule that encloses pharmacologically active agents in medication. Physicians do not prescribe medication based on the delivery vehicle alone; they consider the mechanism of dysfunction to target, active ingredients in the drug and dosing to inform treatments. It is inappropriate to conclude that digital tools promote positive changes in activity; poorly designed interventions deployed via digital modes are no more than a digital placebo—they lack a defined target or active ingredient but are delivered in a shiny new capsule.

Second, between-group differences in treatment and control groups are …
P14.56 Pattern of care of Brain Tumor patients in the last months of life: analysis of a cohort of 3045 patients in the Lazio region in the last 10 years
Authors: A Pace, V Belleudi, L Pinarelli, V Villani, F Poggi, D Benincasa, M Davoli
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND The final days of life of Brain Tumor patients (BT) present special challenges and often palliative care approach is underutilyzed. Several studies reported that BT patients in the last months of life receive frequent hospital readmissions and ER accesses as result of bad quality of End of Life care. Early integration of pallative care has been demonstrated to improve quality of care in advanced stage of disease and quality of death in cancer patients. With the aim to evaluate pattern of treatment and the rate of hospital readmission in the last months of life, we retrospectively analyzed a consecutive serie of BT patients discharged after a diagnosis of BT. MATERIAL AND METHODS Data regarding hospital readmission and treatment received in the last two months of life were collected from the Lazio Region Healthcare database. Adult patients discharged with diagnosis ICD-9 191.* between 1/1/2010 until 31/12/2019, were included in this study. RESULTS 6672 patients were identified and 3045 who have died before 31/12/2019 were included (median age 67 y;M1700). In the last two month of life 42.6% received hospital reamission (4.6% intensive care unit) and 37.9% had ER accesses. 24.5% received chemotherapy and 12.1% radiotherapy. In the last 30 days 33% were readmitted in hospital and 24.2% were admitted in ER. 11.7% were treated with chemotherapy and 6% with radiotherapy. CONCLUSION Strategies to improve quality of care at the end of life and to decrease re-hospitalization and futile treatments are becoming increasingly important to improve quality of death and to reduce costs of Healthcare System.
Accuracy of teledermatology for nonpigmented neoplasms
Authors: Erin M. Warshaw, Frank A. Lederle, Joseph P. Grill, Amy A. Gravely, Ann K. Bangerter, Lawrence A. Fortier, Kimberly A. Bohjanen, Karen Chen, Peter K. Lee, Harold S. Rabinovitz, Robert H. Johr, Valda N. Kaye, Sacharitha Bowers, Rachel Wenner, Sharone K. Askari, Deborah A. Kedrowski, David B. Nelson
Journal: Journal of the American Academy of Dermatology (2009)
Maintenance with daratumumab or observation following treatment with bortezomib, thalidomide, and dexamethasone with or without daratumumab and autologous stem-cell transplant in patients with newly diagnosed multiple myeloma (CASSIOPEIA): an open-label, randomised, phase 3 trial
Authors: Philippe Moreau, Cyrille Hulin, Aurore Perrot, Bertrand Arnulf, Karim Belhadj, Lotfi Benboubker, Marie C Béné, Sonja Zweegman, Hélène Caillon, Denis Caillot, Jill Corre, Michel Delforge, Thomas Dejoie, Chantal Doyen, Thierry Facon, Cécile Sonntag, Jean Fontan, Mohamad Mohty, Kon-Siong Jie, Lionel Karlin, Frédérique Kuhnowski, Jérôme Lambert, Xavier Leleu, Margaret Macro, Frédérique Orsini-Piocelle, Murielle Roussel, Anne-Marie Stoppa, Niels W C J van de Donk, Soraya Wuillème, Annemiek Broijl, Cyrille Touzeau, Mourad Tiab, Jean-Pierre Marolleau, Nathalie Meuleman, Marie-Christiane Vekemans, Matthijs Westerman, Saskia K Klein, Mark-David Levin, Fritz Offner, Martine Escoffre-Barbe, Jean-Richard Eveillard, Réda Garidi, Tahamtan Ahmadi, Maria Krevvata, Ke Zhang, Carla de Boer, Sanjay Vara, Tobias Kampfenkel, Veronique Vanquickelberghe, Jessica Vermeulen, Hervé Avet-Loiseau, Pieter Sonneveld
Journal: The Lancet Oncology (2021)
Outbreak of SARS-CoV-2 B.1.617.2 (Delta) Variant Infections Among Incarcerated Persons in a Federal Prison — Texas, July–August 2021
Authors: Liesl M. Hagan, David W. McCormick, Christine Lee, Sadia Sleweon, Lavinia Nicolae, Thomas Dixon, Robert Banta, Isaac Ogle, Cristen Young, Charles Dusseau, Shawn Salmonson, Charles Ogden, Eric Godwin, TeCora Ballom, Tara Ross, Hannah Browne, Jennifer L. Harcourt, Azaibi Tamin, Natalie J. Thornburg, Hannah L. Kirking, Phillip P. Salvatore, Jacqueline E. Tate
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

Incarcerated populations have experienced disproportionately higher rates of COVID-19-related illness and death compared with the general U.S. population, due in part to congregate living environments that can facilitate rapid transmission of SARS-CoV-2, the virus that causes COVID-19, and the high prevalence of underlying medical conditions associated with severe COVID-19 (1,2). The SARS-CoV-2 B.1.617.2 (Delta) variant has caused outbreaks among vaccinated and unvaccinated persons in congregate settings and large public gatherings (3,4). During July 2021, a COVID-19 outbreak involving the Delta variant was identified in a federal prison in Texas, infecting 172 of 233 (74%) incarcerated persons in two housing units. The Federal Bureau of Prisons (BOP) partnered with CDC to investigate. CDC analyzed data on infection status, symptom onset date, hospitalizations, and deaths among incarcerated persons. The attack rate was higher among unvaccinated versus fully vaccinated persons (39 of 42, 93% versus 129 of 185, 70%; p = 0.002).† Four persons were hospitalized, three of whom were unvaccinated, and one person died, who was unvaccinated. Among a subset of 70 persons consenting to an embedded serial swabbing protocol, the median interval between symptom onset and last positive reverse transcription-polymerase chain reaction (RT-PCR) test result in fully vaccinated versus unvaccinated persons was similar (9 versus 11 days, p = 0.37). One or more specimens were culture-positive from five of 12 (42%) unvaccinated and 14 of 37 (38%) fully vaccinated persons for whom viral culture was attempted. In settings where physical distancing is challenging, including correctional and detention facilities, vaccination and implementation of multicomponent prevention strategies (e.g., testing, medical isolation, quarantine, and masking) are critical to limiting SARS-CoV-2 transmission (5).
COVID-19 Critical Illness: A Data-Driven Review
Authors: Jennifer C. Ginestra, Oscar J.L. Mitchell, George L. Anesi, Jason D. Christie
Journal: Annual Review of Medicine (2021)

The coronavirus disease 2019 (COVID-19) pandemic has posed unprecedented challenges in critical care medicine, including extreme demand for intensive care unit (ICU) resources and rapidly evolving understanding of a novel disease. Up to one-third of hospitalized patients with COVID-19 experience critical illness. The most common form of organ failure in COVID-19 critical illness is acute hypoxemic respiratory failure, which clinically presents as acute respiratory distress syndrome (ARDS) in three-quarters of ICU patients. Noninvasive respiratory support modalities are being used with increasing frequency given their potential to reduce the need for intubation. Determining optimal patient selection for and timing of intubation remains a challenge. Management of mechanically ventilated patients with COVID-19 largely mirrors that of non-COVID-19 ARDS. Organ failure is common and portends a poor prognosis. Mortality rates have improved over the course of the pandemic, likely owing to increasing disease familiarity, data-driven pharmacologics, and improved adherence to evidence-based critical care.
Man charged after assaulting staff at GP surgery
Authors: Gareth Iacobucci
Journal: BMJ (2021)

GP leaders have expressed their shock and anger after staff working in a surgery in Manchester were attacked by a patient.

Greater Manchester Police1 reported that a 59 year old man was arrested and subsequently charged after four members of staff were injured at the Florence House Medical Practice on 17 September. Two of the victims were taken to hospital with head injuries.

Olumuiwa Oduntan, of Openshaw, was charged with one count of a section 47 assault, one count of malicious communications, and one count of affray. Oduntan appeared at Manchester Magistrates Court on 20 September 2021, and …