tbuckley/cabot-search huggingface dataset:
Phase II study of SHR-1701 combined with famitinib in the treatment of advanced pancreatic cancer or biliary tract cancer.
Authors: Jing Xie, Zhiqiang Meng, Lianyu Chen, Yongqiang Hua, Huajun Li
Journal: Journal of Clinical Oncology (2022)

568 Background: Pancreatic cancer (PC) and biliary tract cancer (BTC) are highly malignant cancers with limited treatment (tx) options. SHR-1701 is a novel bifunctional anti-PD-L1/TGF-βRII agent. Famitinib is a multitargeted tyrosine kinase inhibitor (TKI). Many studies have proved the mutually enhanced effect of anti-angiogenesis and ICI therapy in multiple tumours. Herein, we reported the safety and efficacy of SHR-1701 in combination with famitinib in advanced PC and BTC patients (pts) who have failed previous standard tx. Methods: This is an ongoing single-site, exploratory phase II study. PC or BTC pts who have failed ≥1 prior therapy would be enrolled into PC or BTC cohort, and received SHR-1701 plus famitinib until disease progression or unacceptable toxicity. SHR1701 would be intravenously given at a fixed dose of 30mg/kg q3w. Famitinib was initially given at a dose of 20mg/d. Dose reduction of famitinib to 15mg was allowed if it was intolerable. The primary endpoint was objective response rate (ORR) as per RECIST v1.1. Simon’s two-stage minimax design was used in this trial. For each cohort, if ≥2 responses are observed among 15 patients in stage I, the study will proceed to full accrual. Results: Up to 15 Sep 2021, 15 pts and 9 pts were enrolled in PC and BTC cohorts respectively. The baseline data are shown in the table. Of 15 evaluable pts in PC cohort, one had complete response, one had partial response (PR), 6 pts had stable disease (SD). The ORR and DCR were 13% and 53%, respectively. The first stage of PC cohort had a sufficient response rate to meet full enrollment. Among 8 evaluable pts in BTC cohort, one had PR (tumor shrinkage &gt; 80%), 4 had SD. The ORR and DCR were 13% and 63%, respectively. 22 pts (92%) experienced treatment-related adverse events (TRAEs). The most frequently reported TRAEs (any grade) were proteinuria (58%), hypertension (42%), and blood urine present (42%). The incidence of Grade 3 TRAEs was 33%, among which the most common ones were hypertension (8%), and bilirubin conjugated increased (8%). No grade 4/5 TRAEs were reported. Conclusions: SHR-1701 plus famitinib showed encouraging activity with manageable safety in pts with advanced PC or BTC. Enrollment is ongoing and updated data will be presented. Clinical trial information: ChiCTR2000037927.[Table: see text]
THE THIRD ATLANTIC CITY SESSION.
Journal: JAMA (1907)

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
Fine-tuned long-acting interleukin-2 superkine potentiates durable immune responses in mice and non-human primate
Authors: Rosemina Merchant, Carole Galligan, Manjunatha Ankathatti Munegowda, L Bruce Pearce, Peter Lloyd, Paul Smith, Fahar Merchant, Minh D To
Journal: Journal for ImmunoTherapy of Cancer (2022)

Background Recombinant human interleukin-2 (rhIL-2, aldesleukin) is Food and Drug Administration approved for the treatment of metastatic melanoma and renal cell carcinoma and has achieved durable response in a subset of patients. However, its utility as an immunotherapeutic drug is limited by undesirable activation of immune suppressive regulatory T cells (Tregs) and a short half-life requiring frequent high dose administration, leading to unacceptable toxicities. We have engineered MDNA11, a long-acting IL-2 superkine, to overcome these limitations by (1) modifying receptor selectivity in favor of anti-cancer immune cells to increase therapeutic efficacy and (2) fusion to human albumin to extend the pharmacokinetic (PK) profile, circumventing the need for frequent dosing. Methods MDNA11 was evaluated using in vitro and in vivo studies including: binding analyses to measure receptor affinity, IL-2 pathway signaling, PK studies in mice, and efficacy studies in syngeneic tumor models as single agent and in combination with immune checkpoint inhibitors. Finally, the safety and pharmacodynamic profile of MDNA11 was assessed in non-human primate (NHP). Results Binding studies with MDNA11 demonstrated increased affinity for IL-2Rβ (CD122) and no binding to IL-2Rα (CD25). As a result, MDNA11 exhibits reduced/limited Treg stimulation while triggering an enhanced activation of natural killer and naïve CD8 T cells compared with rhIL-2. When administered to animals with pre-established tumors, MDNA11 controlled tumor growth in a monotherapy setting and in combination with anti-PD1 or anti-CTLA4 to induce durable tumor clearance with a once weekly dosing regimen. In a NHP model, MDNA11 was well tolerated while triggering durable and potent immune responses including expansion of lymphocytes without significant effect on Tregs and eosinophils, the latter been linked to an increased risk of vascular leak syndrome. Conclusion MDNA11 is a next generation long-acting IL-2 immunotherapeutic with a highly favorable pharmacodynamic profile that translates to a strong therapeutic efficacy in preclinical tumor models and a strong and durable immune response in NHP.
Radiology
Authors: Ronald G. Evens
Journal: JAMA (1995)

Mammography continues to be an important and controversial topic in diagnostic imaging. Last year's Contempo issue reported on the debate on whether women younger than 50 years should undergo screening—a debate that continues in 1995. A recent report<sup>1</sup>finds that radiologists' interpretation of mammograms can differ, sometimes substantially. That radiologists' opinions differ and interpretive skills vary is not unexpected, but when this is reported about a procedure that is recommended for screening of all women older than 50 years and younger women who are at risk, it becomes newsworthy and of interest to the public, as well as the profession. On a positive note, this same report focuses attention on the need to improve the professional aspect of mammography screening, certainly at least as important as improving the technical performance of the procedure that has received the most attention during the past few years. It is an important challenge
Effects of synthetic progestin on nitric oxide bioactivity and cytokines in hypertensive or overweight postmenopausal women Kwang K. Koh, Dong K. Jin, Jeong Y. Ahn, Seon K. Lee, Seong H. Yang, Gi S. Park, Ji W. Son, In S. Choi, Eak K. Shin. Cardiology, Inchon, South Korea, Radiology, Inchon, South Korea
Journal: Journal of the American College of Cardiology (2001)
Annales Paediatrici, Basel
Journal: JAMA (1964)

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
Immunisation of adults against diphtheria.
Authors: Henry Elliott, Brian Campbell, Imogen Morgan
Journal: BMJ (1978)

mg four times a day, and then to 160 mg four times a day.His ECG initially showed widespread T-wave inversion, but this abnor- mality was most marked two days later, with gross T-wave inversion in most leads (figure).Serial enzyme studies failed to confirm myocardial damage.... ..~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~...... ~~Ṽ4 ~~~~~V ECG of patient with subarachnoid haemorrhage showing T-wave inversion.Thus this patient was already taking a beta-blocker, in a dose comparable to 240 mg propranolol, but despite a further increase in dosage and apparently clinically adequate beta- blockade (resting pulse rate about 60 beats/ min) he proceeded to develop grossly abnormal ECG appearances, of a severity which we have not previously observed in association with subarachnoid haemorrhage.
An integrated framework for identifying clinical-laboratory indicators for novel pandemics: COVID-19 and MIS-C
Authors: Adam D. Nahari, Mary Beth F. Son, Jane W. Newburger, Ben Y. Reis
Journal: npj Digital Medicine (2022)

During the critical early stages of an emerging pandemic, limited availability of pathogen-specific testing can severely inhibit individualized risk screening and pandemic tracking. Standard clinical laboratory tests offer a widely available complementary data source for first-line risk screening and pandemic surveillance. Here, we propose an integrated framework for developing clinical-laboratory indicators for novel pandemics that combines population-level and individual-level analyses. We apply this framework to 7,520,834 clinical laboratory tests recorded over five years and find clinical-lab-test combinations that are strongly associated with SARS-CoV-2 PCR test results and Multisystem Inflammatory Syndrome in Children (MIS-C) diagnoses: Interleukin-related tests (e.g. IL4, IL10) were most strongly associated with SARS-CoV-2 infection and MIS-C, while other more widely available tests (ferritin, D-dimer, fibrinogen, alanine transaminase, and C-reactive protein) also had strong associations. When novel pandemics emerge, this framework can be used to identify specific combinations of clinical laboratory tests for public health tracking and first-line individualized risk screening.
Delayed puberty
Authors: Philip Lyn, Kent Hospital, G Keith
Journal: BMJ (1985)

Morris mentions several precipitating causes of infective endocarditis culled from the studies by Bayliss et al' 2 (25 May, p 1532).I would like to draw attention to an important and often forgotten route of introduction of sepsis in patients at risk in hospitals- from intravenous drip or venepuncture sites. 3Recently, we saw two children aged 11 and 12 who presented with relapse of their rheumatic fever with flitting arthralgia, pericardial rubs, and fever.These symptoms subsided on aspirin and bed rest but a week later a high swinging fever was noted, with changing heart murmurs and evidence of heart failure in one case.One of the blood cultures subsequently grew a penicillin resistant Staphylococcus aureus.The child died despite high dose intravenous penicillin, cefuroxime, and cloxacillin.In the second case no pathogens were grown despite repeated blood cultures, but the fever was later controlled with cefuroxime, cloxacillin, and gentamycin.The most likely site of entry of the organism was through the drip site, where both children had developed mild cellulitis, and neither had received any antibiotics.Poorly cleaned venepuncture sites for routine blood investigations were another possible site of entry.Routine setting up of drips in casualty is a common practice and is often far from being an aseptic procedure.Those who practise this must realise that it is not without risk, especially to patients with valvular heart disease.We believe that care with cleaning the drip site with iodine, introduction of the intravenous cannula by an aseptic technique, and regular change of drip sites before cellulitis sets in are the best ways of preventing infective endocarditis in patients at risk.
Malignant pleural mesothelioma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up☆
Authors: S. Popat, P. Baas, C. Faivre-Finn, N. Girard, A.G. Nicholson, A.K. Nowak, I. Opitz, A. Scherpereel, M. Reck
Journal: Annals of Oncology (2021)
Gender and age differences in induced atrial fibrillation Hiroshi Tada, Christian Sticherling, Steven P. Chough, Robert L. Baker, Kristina Wasmer, Radmira Greenstein, Chi-wo Chan, Hakan Oral, Frank Pelosi, Jr., Bradley P. Knight, S. Adam Strickberger, Fred Morady. University of Michigan Medical Center, Ann Arbor, MI
Journal: Journal of the American College of Cardiology (2001)
EPIDEMIOLOGY OF CANCER OF THE CERVIX
Journal: JAMA (1960)

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
Utilization of next generation sequencing (NGS) in stage IV gastrointestinal (GI) cancer patients (pts) and efficacy of electronic reminder notification (ERN) in improving utilization of NGS in the private practice community-based setting.
Authors: Kapil Foster, Carina Cedeno, Stephanie Marks, Percy Yeung, Ellen A. Ronnen
Journal: Journal of Clinical Oncology (2022)

73 Background: NGS testing allows for identification of genetic mutations/alterations that can be important in determining treatment options for advanced cancer pts. The National Comprehensive Cancer Network (NCCN) includes NGS testing as part of standard of care for many tumor types including stage IV pancreatic cancer, colon cancer, and rectal cancer and all other GI solid tumor types. Previous reports have described the utilization of NGS in clinical practice at academic centers. To our knowledge this is the first report in the private practice setting. Methods: For the historical portion, we established baseline data to quantify NGS testing frequency in stage IV GI tumor pts in our community based oncology practice by performing a retrospective chart review. In the prospective portion, the intervention of an ERN was used to alert treating physicians if NGS had not been done. Primary endpoint is the percent (%) of pts with NGS sent compared to historical control. Secondary endpoint is the % of pts with targeted therapy options made available to them. Results: In a private practice multi-office setting, 200 charts of pts with stage IV GI cancer using Flatiron’s OncoEMR software were reviewed for the retrospective cohort between July 1 to December 31, 2020. Of the 200, 44.5% (89 pts) had colon cancer, 17.5% (35 pts) had pancreatic cancer, 15% (30 pts) had rectal cancer, and 23% (46 pts) had other types of GI cancer. Of these, 87 (43.5%) pts had NGS testing; of which 41 of 89 (46.0%) are colon pts, 13 of 35 (37.1%) are pancreatic pts and 16 of 30 (53.3%) are rectal pts. For the prospective portion, between July 1 and August 15, 2021 each physician’s schedule was evaluated and an ERN was sent shortly before each Stage IV GI pt was to be seen. A total of 114 pts were reviewed, and 92 (79%) had NGS sent. Of these, 47 pts of 54 (87%) are colon pts, 12 of 15 (80%) are pancreatic pts, 16 of 21(76%) are rectal pts, and 17 of 24 (70%) are pts with other GI cancer. 2% of pts with NGS testing had a potentially actionable mutation identified. Conclusions: NGS testing is standard of care for pts with stage IV GI cancer that wish to pursue therapy. ERN was minimally helpful in increasing NGS testing. This may be in part due to the effect of the practice's emphasis on NGS testing, which increased its baseline prospective testing rate. Increased use of a team based approach in the office would be a key element to increasing compliance with the current workflow as well as use of pathways which embed the NGS testing into the treatment plan. A more robust EMR would also be vital in increasing NGS testing rates by the use of automatic reminders or order sets. Better support of the physician and use of multiple touch points is necessary until full automation is utilized for NGS testing.
Correction: Pure trigeminal motor neuropathy
Authors: R Gray, J Menage, D Cook, J Harcourt
Journal: BMJ (1988)

of the six cases ofeye injuries caused by elasticated straps Case Age Circumstances in which injury Visual acuity No (years) Sex occurred Clinical findings Management (months after injury) 1 11 M Fastening strap on trailer tent Hyphaema Bed rest 6/6 (1) 2 41 M Strapping load across lorry Corneal perforation Suturing of cornea 6/18 (3) 3 39 M Pulling strap on windsurfer Iris tear, hyphaema, vitreous haemorrhage, Bed rest, ocular hypotensives 6/18 (3) secondary glaucoma 4 63 M Fastening strap over car roof rack Hyphaema, post-traumatic cataract Bed rest, delayed surgery for cataract and 6/9 (3 months after surgery) implantation of intraocular lens 5 50 M Fastening strap over car roof rack Iris tear, retinal detachment Vitrectomy and injection of silicone oil 6/60 (8) 6 31 M Fastening strap over car roof rack Hyphaema, retinal tear Bed rest, cryotherapy to retinal tear 6/9 (1))leads would prevent accidental release.Only one hook would need to be so modified provided instructions were given to secure the gated hook first.Manufacturers should be encouraged to enclose safety warnings with elasticated straps, and the public needs to know about their potential risk.We thank the consultant staff of this hospital for permission to report on these patients.
THE OLD TIME COUNTRY DOCTOR
Journal: JAMA (1925)

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
Questions and Answers
Journal: JAMA (1985)

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
Enhancing the HSV-1-mediated antitumor immune response by suppressing Bach1
Authors: Chaohu Pan, Qiaomei Cai, Xiaorong Li, Lili Li, Liping Yang, Yu Chen, Junxiao Liu, Wancheng Liu, Meiling Gao, Tianqi Sui, Xiaoyang Wang, Huiming Fan, Jiayin Ruan, Yueyue Shi, Saihua Chen, Lucy S. Cheng, Jiayong Liu, Heng Yang, Genhong Cheng
Journal: Cellular and Molecular Immunology (2022)
Incomplete Financial Disclosure in a Viewpoint
Authors: Michael Barry, Karina Davidson, Carol Mangione
Journal: JAMA (2021)

encouraging, any shift in the USPSTF's assessment of the balance of benefits and harms requires additional evidence.In addition to the need for reliable methods to assess the increased risk of stroke associated with asymptomatic carotid artery stenosis, we require trial data of treatment outcomes comparing surgical interventions plus medical therapy with medical therapy alone in this asymptomatic population.The USPSTF agrees that future research on asymptomatic carotid artery stenosis should focus on these areas and looks forward to reviewing new evidence in future reviews.