tbuckley/cabot-search huggingface dataset:
High immunoscore as a predictor of outcome in patients who underwent chemoimmuno-therapy in locally advanced rectal cancer: A post-hoc analysis of the correlation between immunoscore and pCR in the Averectal study.
Authors: Ali Shamseddine, Ibrahim Moustafa Khalifeh, Charbel Elias, Rim Turfa, Joseph Gergi Kattan, Deborah Mukherji, Sally Naji Temraz, Kholoud Alqasem, Rula Amarin, Tala Alawabdeh, Samer Deeba, Issa Mohamad, Faiez Daoud, Mahmoud Al Masri, Ali Dabous, Ahmad Hushki, Omar Jaber, Maya Charafeddine, Lama Farhat, Ayman Tawil
Journal: Journal of Clinical Oncology (2022)

184 Background: The immunoscore (IS), a prognostic score, was first validated in early colon cancer reflecting the immune response against the tumor. It showed potential in its ability to downstage patients with pathologic complete response (pCR) who would potentially benefit from organ-sparing therapies in locally advanced rectal cancer (LARC). We first presented our initial outcome with 37.8% pCR in patients with LARC treated with short course radiation therapy (SCRT) followed by 6 cycles of mFOLFOX plus Avelumab followed by total mesorectal excision (TME) in the ESMO 23rd World Congress on Gastrointestinal Cancer 2021 Conference (presentation # SO-30). Here we are reporting the post-hoc analysis of the correlation between pCR and pre-treatment biopsy IS to further establish the IS as a prognostic score in patients with LARC. Methods: In this Phase II study, 44 patients were accrued from three centers, of whom 40 completed radiotherapy followed by chemoimmunotherapy then TME. 39 patients with available tissue samples, containing tumor cells and its margins, were collected at baseline. CD3 and CD8 cells were counted, and the IS is then derived from the mean density percentiles of CD3 and CD8 positive T cells infiltrating the tumor and in the invasive margin of the tumor. Cutoff for a high IS was established at 62%. We then compared the tumor regression grade (TRG) with the means of IS, using the student t-test. Results: 15 patients with pCR had a mean IS of 68 +/- 22 SD as opposed to a mean IS of 52 +/- 22 SD in 24 patients without pCR (p = 0.036). Conclusions: High IS correlates with TRG as pCR and successfully predicted clinical outcome in LARC patients who underwent chemoimmuno-therapy. It is a promising potential prognostic tool in stratifying patients who would benefit from specific modalities to augment pCR and subsequent organ preservation strategy. Clinical trial information: NCT03503630.
Emerging stronger from the China crisis
Authors: None The Lancet
Journal: The Lancet (2003)

Since the outbreak of severe acute respiratory syndrome (SARS) was first reported last month, public-health authorities worldwide have been concerned that data from China, where the disease apparently originated last November, are slow to emerge and may well be inaccurate. An April 9 report confirmed that WHO finally had extensive data from Guangdong Province. But only as of April 12 were WHO officials able to investigate the situation in Beijing, where serious problems in reporting and systematic tracing of contacts have existed.
Adenosine stress echocardiography in detection of viable myocardium in postinfarcted regions Ana D. Djordjevic-Dikic, II, Miodrag C. Ostojic, Branko D. Beleslin, Ivana Nedeljkovic, Jelena Stepanovic, Sinisa Stojkovic, Milan Nedeljkovic, Jovica Saponjski. Institute for Cardiovascular Diseases, Belgrade, Yugoslavia
Journal: Journal of the American College of Cardiology (2001)
Ciprofloxacin plus gemcitabine-based chemotherapy in patients with metastatic pancreatic ductal adenocarcinoma: A pilot study of microbiome manipulation.
Authors: Seng Wee Cheo, Jonathan WJ Lee, Robert John Walsh, Raghav Sundar, Joan RE Choo, Gloria Chan, Wei-Peng Yong, Wee Yang Meah, Chiea Chuen Khor, Cheng Ean Chee
Journal: Journal of Clinical Oncology (2022)

570 Background: Gemcitabine-based chemotherapy is an approved therapy for treatment-naïve metastatic pancreatic ductal adenocarcinoma (PDAC). Inherent resistance to gemcitabine inevitably leads to cancer progression and shorter survival. It has been demonstrated that bacteria are a component of the PDAC tumor microenvironment and may play a critical role in mediating resistance to chemotherapy. Hence, the coadministration of an antibiotic to chemotherapy may potentiate antitumour drug responses. We conducted a pilot study to assess the efficacy and safety of ciprofloxacin plus gemcitabine-based chemotherapy in patients with treatment naïve metastatic PDAC. We also aimed to study gut microbiome changes during treatment with ciprofloxacin. Methods: This was a single arm study conducted at the National University Cancer Institute, Singapore. Patients (pts) with histologically confirmed metastatic PDAC were treated with nab-paclitaxel (125 mg/m 2 ) and gemcitabine (1000 mg/m 2 ) on days 1, 8, and 15 every 4 weeks, in combination with oral ciprofloxacin 500 mg twice daily. Treatment was continued until disease progression or intolerable toxicity. DNA extraction, 16S rRNA amplification and sequencing for bacteria were performed on pre- and post-treatment stool samples. Primary endpoint of this study was response rate and safety of the treatment combination. Secondary endpoints included progression free survival (PFS), overall survival (OS) and microbiome changes after treatment with ciprofloxacin. Results: From Mar 2019 – Feb 2021, 8 pts were recruited. Median age was 71 years old. Best response was stable disease in 5 (62.5%) pts and 3 pts had progressive disease (PD). Median PFS and OS were 4.3 and 15.4 months, respectively. 2 pts developed grade 4 neutropenia and 1 pt had grade 3 febrile neutropenia. Rash was common with 50% of pts developed grade 1/2 rash. No additional toxicities from ciprofloxacin were observed. Preliminary stool analysis showed significant differences in individual bacterial strains across all timepoints in the PD vs. SD groups. There was also an increased abundance in gammaproteobacteria resistant to ciprofloxacin treatment in pts with PD. Conclusions: Gemcitabine-based chemotherapy plus ciprofloxacin demonstrated clinical activity and acceptable safety profile in PDAC. Our study also highlighted that gut microbiome may play a critical role in mediating resistance to chemotherapy. Clinical trial information: NCT04523987.
Atezolizumab plus bevacizumab in Child-Pugh B advanced hepatocellular carcinoma patients.
Authors: Hyeyeong Kim, Jaekyung Cheon, Yeongjung Ha, Han Sang Kim, Chang Gon Kim, Ilhwan Kim, Chan Kim, Sang-hoon Jung, Hong Jae Chon
Journal: Journal of Clinical Oncology (2022)

397 Background: Atezolizumab plus bevacizumab (Ate/Bev) demonstrated promising efficacy and safety in patients with advanced hepatocellular carcinoma (aHCC) in the phase III IMbrave 150 trial. However, despite the high unmet need in Child-Pugh B patients, this subgroup of patients was not included in this study. Therefore, we aimed to investigate the efficacy and safety of Ate/Bev in Child-Pugh B HCC patients. Methods: This multicenter retrospective study included 27 HCC patients classified as Child-Pugh B who received Ate/Bev at four cancer referral centers between May 2020 and August 2021. Comparative analyses were performed with an independent cohort of Child-Pugh A patients from the same registry (n=130). Results: All patients received Ate/Bev as first-line systemic treatment for aHCC. The objective response rates of patients in Child-Pugh groups B and A were 14.8% and 32.3%, and the disease control rates were 55.5% and 76.1%, respectively. The median progression-free survival (PFS) and overall survival (OS) were 3.0 months (95% CI, 1.6-4.3) and 6.0 months (95% CI, 4.9-7.0) in Child-Pugh B patients, while the median PFS was 6.0 months (95% CI, 4.6-13.4) and the median OS was not-reached (95% CI not available) in Child-Pugh A group. Compared to Child-Pugh A group, grade 3-4 adverse events (AEs) were more common in the Child-Pugh B group (48.1% vs 17.7%, p=0.001), with the most frequent grade 3-4 AEs being thrombocytopenia (11.1%) and AST elevation (11.1%). The rate of treatment discontinuation due to AEs was higher in the Child-Pugh B group (14.8% vs 3.1%, p=0.030), and the reasons for discontinuation were gastrointestinal (GI) bleeding (n=2), GI perforation (n=1) and interstitial pneumonitis (n=1). Conclusions: In the Child-Pugh B subgroup of patients with aHCC, Ate/Bev treatment showed modest clinical activity. However, due to the increased frequency of serious AEs, careful evaluation of treatment response and AE management is required in this subgroup patients. [Table: see text]
Association of angiotensin-converting enzyme and angiotensin II type 1 receptor gene polymorphisms with risk of acute myocardial infarction in a low coronary risk population. Final results of the GEMIG study George Andrikopoulos, Dimitri Richter, Edward W. A. Needham, Mihalis Zairis, Elias Karambinos, Dimitris Manolatos, Konstantinos Paravolidakis, Paraskevi Vogiatzi, Stefanos Foussas, Evaggelos Papasteriadis, Christodoulos Stefanadis, John Gialafos, Raj Mattu, Pavlos Toutouzas. Hippokration …
Journal: Journal of the American College of Cardiology (2001)
Progress, Problems, and Prospects in the Intensive Care of Extremely Preterm Infants
Authors: Mikael Norman
Journal: JAMA (2022)

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
NEW ONSET ATRIAL FIBRILLATION AFTER AORTIC VALVE REPLACEMENT: A COMPARISON OF TRANSFEMORAL TRANSAPICAL, TRANSAORTIC AND SURGICAL APPROACHES
Authors: Tanyanan Tanawuttiwat, Brian O'Neill, Conrad Macon, Thomas Lucero, Orawee Chinthakanan, Alan Heldman, Mauricio Cohen, William O'Neill, Donald Williams, Robert Myerburg
Journal: Journal of the American College of Cardiology (2013)
Diphtheria as a Model
Authors: Harry F. Dowling
Journal: JAMA (1973)

Although the investigations of Pasteur and Koch opened a new world to the scientists of their day, in the beginning they contributed nothing to the therapy of disease. The first clear-cut demonstration that the science of bacteriology could lead to the cure of disease came when Behring announced, in 1890, that the serum of animals immunized with diphtheria toxin protected other animals against infection with the diphtheria bacillus.<sup>1</sup>A year later clinicians began to use this antiserum to check the course of diphtheria in patients.<sup>2(p261)</sup>Research on diphtheria took a second practical step forward when Behring showed in 1913 that the toxin could be used to immunize humans against the disease.<sup>3</sup> Thus, the pattern was laid down for others to follow: Find a toxin for each bacterium being investigated, use it to immunize animals and humans against the disease, and obtain an antiserum from animals that will
Crosslinked Protein Delivery Strategy with Precise Activity Regulation Properties for Cancer Therapy and Gene Editing
Authors: Ning Liu, Lianghan Zhu, Honghao Sun, Zhanwei Zhou, Jingwen Dong, Minjie Sun
Journal: Advanced Healthcare Materials (2022)

Abstract Protein drugs hold tremendous promise for therapeutic applications due to their direct and superior pharmacological effects. However, protein drugs can be degraded in blood stream and unable to cross many physical barriers to exert therapeutic effect. Degradable synthetic crosslinking is a versatile strategy to enhance the stability of the nanoparticle in a complex physiological medium and is helpful to get through physical barriers. Herein, crosslinked polypeptide (PABP) composed of poly‐amino acids including cystine, tyrosine, lysine, ketal bridge, and polyethylene glycol (PEG) is modularly explored and synthesized for protein delivery. Notably, plasma membrane V‐ATPase is the particular pathway which induces the macropinocytosis of the inner peptide analogous core (PAB/protein) after the outer PEG shell disassociation at tumor intercellular sites. In addition, PABP/protein achieves proteins’ activity shielding in systemic circulation and recovery in tumor cytoplasm precisely. In application, PABP/RNase‐A shows satisfying tumor accumulation and antineoplastic efficacy. More importantly, PABP/Cas9 + small guide RNA displays obvious gene editing efficiency. The crosslinked protein delivery strategy not only makes the accurate protein transport and activity regulation possible but also is promising in paving the way for clinical translation of protein drugs.
The Public Service.
Journal: JAMA (1899)

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
The Annual Dinner: Correction
Journal: BMJ (1926)

Trz T amss answered for a time.At last no tuibe could bs introduced and Dr. Merrin had to enlarge the fistula by a knife, until it took a 24 size.There was no trouble thenl for another few months, when leakage occurre(d from the side of the tuibe.Pads of various shapes have been tried-round, oval, squiare, hollowe(d out in the centre, bulged at the place wlhere the leakage seems to occur- but all to no purpose.The leakage is not conistant; it always ceases when the patient lies down, and sometimes he may be
Методи ендоскопічного гемостазу при кровотечах із верхніх відділів шлунково-кишкового тракту
Authors: Yu.M. Stepanov, O.O. Krylovа, S.I. Feshchenko
Journal: GASTROENTEROLOGY (2014)

В огляді літератури наведені характеристики різних методів ендоскопічного гемостазу. Висвітлено принципи вибору методу ендоскопічного гемостазу залежно від джерела й характеру кровотечі.
Common Ancestry-Specific Ion Channel Variants Predispose to Drug-Induced Arrhythmias
Authors: Yuko Wada, Tao Yang, Christian M. Shaffer, Laura L. Daniel, Andrew M. Glazer, Giovanni E. Davogustto, Brandon D. Lowery, Eric H. Farber-Eger, Quinn S. Wells, Dan M. Roden
Journal: Circulation (2022)

Multiple reports associate the cardiac sodium channel gene (SCN5A) variants S1103Y and R1193Q with type 3 congenital long QT syndrome and drug-induced long QT syndrome. These variants are too common in ancestral populations to be highly arrhythmogenic at baseline, however: S1103Y allele frequency is 8.1% in African Americans and R1193Q 6.1% in East Asians. R1193Q is known to increase late sodium current (INa-L) in cardiomyocytes derived from induced pluripotent stem cells but the role of these variants in modulating repolarization remains poorly understood.We determined the effect of S1103Y on QT intervals among African-American participants in a large electronic health record. Using cardiomyocytes derived from induced pluripotent stem cells carrying naturally occurring or genome-edited variants, we studied action potential durations (APDs) at baseline and after challenge with the repolarizing potassium current (IKr) blocker dofetilide and INa-L and IKr at baseline.In 1479 African-American participants with no confounding medications or diagnoses of heart disease, QT intervals in S1103Y carriers was no different from that in noncarriers. Baseline APD was no different in cells expressing the Y allele (SY, YY cells) compared with isogenic cells with the reference allele (SS cells). However, INa-L was increased in SY and YY cells and the INa-L blocker GS967 shortened APD in SY/YY but not SS cells (P<0.001). IKr was increased almost 2-fold in SY/YY cells compared with SS cells (tail current: 0.66±0.1 versus 1.2±0.1 pA/pF; P<0.001). Dofetilide challenge prolonged APD at much lower concentrations in SY (4.1 nmol/L [interquartile range, 1.5-9.3]; n=11) and YY (4.2 nmol/L [1.7-5.0]; n=5) than in SS cells (249 nmol/L [22.3-2905]; n=14; P<0.001 and P<0.01, respectively) and elicited afterdepolarizations in 8/16 SY/YY cells but only in 1/14 SS cells. R1193Q cells similarly displayed no difference in baseline APD but increased IKr and increased dofetilide sensitivity.These common ancestry-specific variants do not affect baseline repolarization, despite generating increased INa-L. We propose that increased IKr serves to maintain normal repolarization but increases the risk of manifest QT prolongation with IKr block in variant carriers. Our findings emphasize the need for inclusion of diverse populations in the study of adverse drug reactions.
Varlitinib in combination with gemcitabine and cisplatin for treatment-naïve advanced biliary tract cancer.
Authors: Do-Youn Oh, Wei-Peng Yong, Li-Tzong Chen, Ji-Won Kim, Jin Hyun Park, Kenneth Hsu, Bertil Lindmark, Nicola McIntyre, Barbara Collins, Carl Firth
Journal: Journal of Clinical Oncology (2022)

439 Background: Standard first-line treatment for advanced biliary tract cancer (BTC) with gemcitabine plus cisplatin confers only modest benefits (objective response rate [ORR], 26%; Valle et al. N Engl J Med 2010;362:1273-1281) and patient prognosis is poor. Therefore, new first-line strategies are urgently required. Human epidermal growth factor receptor (HER) tyrosine kinases are commonly overexpressed in BTC. Varlitinib is a reversible small molecule pan-HER inhibitor. Methods: This was a multicentre, phase 1B/2 study in patients with advanced BTC who had not received prior systemic therapy. Using a modified 3+3+3 escalation design in phase 1B, patients received oral varlitinib twice daily (BID) every day (starting dose 200 mg BID) plus gemcitabine/cisplatin on Days 1 and 8 in a 3-week cycle. The primary objective was to determine the maximum tolerated dose (MTD) and safety profile of varlitinib in combination with gemcitabine plus cisplatin. Patients were evaluable for MTD if they had varlitinib treatment compliance of ≥80% and received 2 doses of chemotherapy in Cycle 1, or if they experienced a dose-limiting toxicity (DLT) in Cycle 1. Preliminary efficacy was a secondary objective. Results: Overall, 23 patients were enrolled in Korea (3 sites), Singapore (1 site), and Taiwan (1 site). Patient characteristics at baseline: male, 52%; median (range) age, 66 (47-82) years; ECOG PS, 0 (43%)/ 1 (57%); primary tumor site, intrahepatic bile duct (43%)/ extrahepatic bile duct (22%)/ gallbladder (22%)/ ampulla of Vater (13%). In total, 11 and 12 patients were included in the varlitinib 200 mg and 300 mg cohorts, of whom 9 and 7 were evaluable for MTD, respectively. DLTs were observed in 2 patients in the 200 mg cohort. Prior to study termination, the 300 mg dose was being assessed with 1 patient experiencing a DLT. In the overall population (n = 23), 36% of patients in the 200 mg cohort and 67% in the 300 mg cohort had at least one grade ≥3 treatment-related adverse event. Grade ≥3 treatment-related investigations abnormalities and blood and lymphatic system disorders were reported in 27% and 18% of patients in the 200 mg cohort, and 25% and 25% of those in the 300 mg cohort, respectively. Among all 23 patients, 8 had a partial response and 12 had stable disease for ≥12 weeks, giving an ORR of 35% and a disease control rate of 87%. The median (Q1-Q3) duration of objective response was 4.0 (2.8-11.0) months. At the time of analysis, 17 patients had progression events and 6 were censored. The median (Q1-Q3) progression-free survival was 6.8 (5.1-10.7) months. Conclusions: Varlitinib combined with gemcitabine plus cisplatin was well tolerated and associated with preliminary anti-tumor activity in patients with treatment-naïve advanced BTC. Clinical trial information: NCT02992340.
Quality and Safety in Healthcare, Part XCIII
Authors: Jay A. Harolds
Journal: Clinical Nuclear Medicine (2022)

Design for Six Sigma (DFSS) is used to design new outputs such as manufactured products or to design new processes. The steps in DFSS are define, measure, analyze, design, and verify. Many sophisticated statistical tools are often used. There are advantages and disadvantages of both Lean and Six Sigma, and often a blending of the 2 methodologies are used in the Lean Six Sigma methodology.
Diabetic retinopathy after two years of intensified insulin treatment. Follow-up of the Kroc Collaborative Study. The Kroc Collaborative Study Group
Journal: JAMA (1988)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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) 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