tbuckley/cabot-search huggingface dataset:
Apatinib plus vinorelbine versus vinorelbine for advanced triple-negative breast cancer with failed first or second-line treatment: The NAN trial.
Authors: Doudou Li, Zhonghua Tao, Biyun Wang, Leiping Wang, Jun Cao, Xichun Hu, Jian Zhang
Journal: Journal of Clinical Oncology (2021)

1075 Background: No standard treatment exists for triple negative breast cancer (TNBC) with failure of multi-line therapies. Apatinib is a small-molecule tyrosine kinase inhibitor that has promising anti-angiogenesis and antitumor activity for TNBC. We aimed to evaluate the safety and efficacy of adding apatinib to chemotherapy in patients with metastatic TNBC with failed first/second-line treatment. Methods: This randomized, open-label, phase 2 trial recruited patients with advanced TNBC who failed to receive first or second-line treatment. A total of 66 patients were randomly assigned, in a 1:1 ratio, to receive vinorelbine 25 mg/m 2 (days 1, 8, 15) or vinorelbine 20 mg/m 2 (days 7, 14, 21) with apatinib (250 mg once daily, days 1-5, 8-12, 15-19, if tolerable, the second cycle started with 500 mg per day) in 28-day cycles. The efficacy was evaluated every two treatment cycles (8 weeks ± 3 days). According to the RECIST criterion, patients with CR, PR and SD continued treatment until disease progression or unacceptable toxicity or withdrawal of consent. The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS), overall response rate (ORR) and safety. Results: Between Sep 14, 2017 and Dec 08, 2020, 66 patients underwent randomization. Median follow-up was 21.3 months. 33 received apatinib plus vinorelbine and 32 received vinorelbine (1 was withdrawal of consent). Median PFS was significantly longer in the apatinib plus vinorelbine group than in the vinorelbine group (3.8 months vs. 1.9 months; hazard ratio for disease progression or death, 1.76; 95% confidence interval [CI], 1.02 to 3.05; P= 0.039). Median OS was 14.6 months with apatinib plus vinorelbine and 14.1 months with vinorelbine (HR,1.34; 95% CI, 0.60 to 3.00; P= 0.469). The ORR was 48.5% in the apatinib plus vinorelbine group and 31.3% in the vinorelbine group ( P= 0.156). The most common treatment-related hematologic grade 3–4 adverse events in those treated with apatinib plus vinorelbine versus vinorelbine, respectively, were leukopenia (42.4% vs. 34.4%), granulocytopenia (57.6% vs. 28.1%), anemia (9.1% vs. 12.5%) and thrombocytopenia (3.1% vs. 3.0%). The most frequent grade 3 nonhematologic toxicities were hand–foot syndrome (21%), proteinuria (9%), hypertension (9%) and increased ALT (9%) and which only occurred in apatinib plus vinorelbine group. No treatment-related nonhematologic grade 4 adverse events or treatment-related deaths were observed. Conclusions: Collectively, among patients with advanced TNBC with failed first/second-line treatment, apatinib plus vinorelbine show a promising benefit in PFS compared to vinorelbine monotherapy. Apatinib plus vinorelbine regimen shows promising efficacy and manageable toxicity, which might be a previously unappreciated therapeutic option for advanced TNBC. Clinical trial information: NCT03254654 .
A phase 3, single-arm study of CG0070 in subjects with nonmuscle invasive bladder cancer (NMIBC) unresponsive to Bacillus Calmette-Guerin (BCG).
Authors: Edward M. Uchio, Donald L. Lamm, Neal D. Shore, Ashish M. Kamat, Mark Tyson, Ben Tran, Paul Anderson, Paola Grandi, James M. Burke
Journal: Journal of Clinical Oncology (2022)

TPS598 Background: CG0070 is a serotype 5 adenovirus engineered to express GM-CSF and replicate in cells with mutated or deficient RB, with response rates (RR) of approximately 45% observed in patients with recurrent NMIBC after BCG (J Urol. 2012;188:2391–7; Urol Oncol. 2018;36(10):440–7). This single arm phase 3 study (NCT04452591) was launched to confirm the clinical activity of CG0070 in patients with BCG Unresponsive NMIBC. Methods: 110 patients with BCG-unresponsive CIS with or without concurrent Ta or T1 disease will be treated with intravesical (IVe) CG0070 at a dose of 1x10 12 vp. CG0070 will be administered as follows: induction weekly x 6 followed by weekly x 3 maintenance instillations at months 3, 6, 9, 12, and 18. Patients with persistent CIS or HG Ta at 3 months (m) may receive re-induction with weekly x 6 CG0070. Assessment of response will include q 3 m cystoscopy with biopsy of areas suspicious for disease, urine cytology, CTU/MRU, and mandatory bladder mapping at 12 m. Detection of high grade disease within the bladder will be enumerated as recurrence or non-response. The primary endpoint of the study is CR at any time on study as assessed by biopsy (directed to cystoscopic abnormalities and mandatory mapping at 12 m), urine cytology, and radiography, as above. Secondary endpoints include CR at 12 m, duration of response, progression free survival, cystectomy free survival and safety. Correlative assessments include changes in the tumor immune microenvironment, systemic immune induction as reflected in the peripheral blood and urine, as well as viral replication and transgene expression. Baseline expression of coxsackie adenovirus receptor, E2F transcription factor as well as anti-adenovirus antibody titer will be correlated with tumor response. Study enrollment globally is ongoing including in North America, Taiwan, Japan, and South Korea. Refs. Burke JM, Lamm DL, Meng MV, Nemunaitis JJ, Stephenson JJ, Arseneau JC, Aimi J, Lerner S, Yeung AW, Kazarian T, Maslyar DJ, McKiernan JM. A first in human phase 1 study of CG0070, a GM-CSF expressing oncolytic adenovirus, for the treatment of nonmuscle invasive bladder cancer. Clinical trial information: NCT04452591.
超音波血管内視鏡(IVUS)ガイド下方向性冠動脈内粥腫切除術(DCA)後の自己拡張可能ステント(Radiusステント)の効果
Authors: Itou Y, Muramatsu T, Tsukahara R, Ho M, Hirano K, Nakano M, Matsushita M, Shida K
Journal: Circulation (2003)
Kailash Chand: general practitioner, NHS campaigner, and medical politician
Authors: Rebecca Wallersteiner
Journal: BMJ (2021)

Born in the hills of Shimla, northern India, on 10 June 1948, Kailash Chand Malhotra grew up in a large family. His father, Harish Chander, worked on the railways, and his mother, Hem Lata, was a housewife. The eldest of four brothers and one sister, Chand was educated in the village school of Adhoya, in the Kurukshetra district in the state of Haryana. Athletic, as well as academic, he excelled at cricket and both founded and captained the school’s first cricket team at the age of 15. A gregarious, popular, and driven student, he was a natural leader.

In 1968 Chand entered the Government Medical School, in Patiala, Punjab, through the “sports quota” on the back of his cricketing prowess, a sport that he continued to enjoy playing throughout his impressive career. An admired paternal uncle who was involved in politics and keen to help disadvantaged people sparked his own interest in politics.

In the early 1970s, Chand, along with other medical students, became involved in two uprisings when they stood up for farmers’ rights after the Indian government imposed harsh landowning restrictions. Wearing his white doctor’s coat, Chand was arrested twice and released on bail. Thankfully, his medical studies were unaffected.

In Delhi, after a year’s internship at the Northern Railway Hospital, …
Endotyping Sleep Apnea One Breath at a Time: An Automated Approach for Separating Obstructive from Central Sleep-disordered Breathing
Authors: Ankit Parekh, Thomas M. Tolbert, Anne M. Mooney, Jaime Ramos-Cejudo, Ricardo S. Osorio, Marcel Treml, Simon-Dominik Herkenrath, Winfried J. Randerath, Indu Ayappa, David M. Rapoport
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

Rationale: Determining whether an individual has obstructive or central sleep apnea is fundamental to selecting the appropriate treatment. Objectives: Here we derive an automated breath-by-breath probability of obstruction, as a surrogate of gold-standard upper airway resistance, using hallmarks of upper airway obstruction visible on clinical sleep studies. Methods: From five nocturnal polysomnography signals (airflow, thoracic and abdominal effort, oxygen saturation, and snore), nine features were extracted and weighted to derive the breath-by-breath probability of obstruction (Pobs). A development and initial test set of 29 subjects (development = 6, test = 23) (New York, NY) and a second test set of 39 subjects (Solingen, Germany), both with esophageal manometry, were used to develop Pobs and validate it against gold-standard upper airway resistance. A separate dataset of 114 subjects with 2 consecutive nocturnal polysomnographies (New York, NY) without esophageal manometry was used to assess the night-to-night variability of Pobs. Measurements and Main Results: A total of 1,962,229 breaths were analyzed. On a breath-by-breath level, Pobs was strongly correlated with normalized upper airway resistance in both test sets (set 1: cubic adjusted [adj.] R2 = 0.87, P < 0.001, area under the receiver operating characteristic curve = 0.74; set 2: cubic adj. R2 = 0.83, P < 0.001, area under the receiver operating characteristic curve = 0.7). On a subject level, median Pobs was associated with the median normalized upper airway resistance (set 1: linear adj. R2 = 0.59, P < 0.001; set 2: linear adj. R2 = 0.45, P < 0.001). Median Pobs exhibited low night-to-night variability [intraclass correlation(2, 1) = 0.93]. Conclusions: Using nearly 2 million breaths from 182 subjects, we show that breath-by-breath probability of obstruction can reliably predict the overall burden of obstructed breaths in individual subjects and can aid in determining the type of sleep apnea.
Unchanged Prevalence of Preeclampsia After Implementation of Prophylactic Aspirin for All Pregnant Women With Preexisting Diabetes: A Prospective Cohort Study
Authors: Nicoline C. Do, Marianne Vestgaard, Björg Ásbjörnsdóttir, Sidse K. Nørgaard, Lise Lotte T. Andersen, Dorte M. Jensen, Lene Ringholm, Peter Damm, Elisabeth R. Mathiesen
Journal: Diabetes Care (2021)

OBJECTIVE To evaluate the prevalence of preeclampsia after implementation of prophylactic aspirin for all pregnant women with preexisting diabetes compared with the prevalence in a previous risk-based prophylaxis. RESEARCH DESIGN AND METHODS A prospective observational cohort study of 410 consecutive pregnant women with preexisting diabetes categorized according to aspirin prophylaxis strategy, with the prevalence of preeclampsia as primary outcome. In total, 207 women were included after implementation of prophylactic aspirin for all pregnant women with preexisting diabetes in February 2018 (all-cohort). The 203 women included before this date, where aspirin prophylaxis was risk based and only prescribed to selected women (selected-cohort), were studied for comparison. RESULTS Aspirin was prescribed at ∼10 gestational weeks for 88% (all-cohort) compared with 25% (selected-cohort). HbA1c, parity, chronic hypertension, home blood pressure, microalbuminuria/diabetic nephropathy, and smoking were similar in the two cohorts in early pregnancy. In the all-cohort, fewer women had type 2 diabetes (32% vs. 42%, respectively; P = 0.04) and BMI tended to be lower (P = 0.05). The prevalence of preeclampsia was similar (12% vs. 11%, P = 0.69) in the two cohorts, and this was also the case with stratification for diabetes type. Prevalence of preterm delivery &amp;lt;37 weeks (23% vs. 27%, P = 0.30), preterm preeclampsia (7% vs. 7%, P = 0.96), and infants large (40% vs. 32%, P = 0.07) and small (7% vs. 6%, P = 0.88) for gestational age was similar in the two cohorts. CONCLUSIONS Implementation of prophylactic aspirin for all pregnant women with diabetes did not reduce the prevalence of preeclampsia compared with the previous risk-based prophylaxis in this cohort study.
Effect of Training on Peak Oxygen Consumption in Patients With Heart Failure With Preserved Ejection Fraction
Authors: Arik Bernard Schulze, Georg Evers, Michael Mohr
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
Mask-Wearing Behavior at the 2021 NCAA Men’s Basketball Tournament
Authors: Joshua R. Vest, Justin Blackburn, Shama Cash-Goldwasser, Eleanor Peters Bergquist, Peter J. Embi
Journal: JAMA (2021)

This cross-sectional study examines the mask-wearing behavior of attendees at the 2021 NCAA men's basketball tournament in an attempt to help other venues prepare for future events during the pandemic.
Insulin signaling establishes a developmental trajectory of adipose regulatory T cells
Authors: Yangyang Li, Ying Lu, Shu-Hai Lin, Ning Li, Yichao Han, Qianru Huang, Yi Zhao, Feng Xie, Yixian Guo, Biaolong Deng, Andy Tsun, Juan Du, Dan Li, Joanne Sun, Guochao Shi, Fang Zheng, Xiao Su, Shengzhong Duan, Song Guo Zheng, Gang Wang, Xuemei Tong, Bin Li
Journal: Nature Immunology (2021)
26843 Carbon dioxide laser excision for hidradenitis suppurativa patients—Healing, complications, and recurrence in patients with diabetes mellitus and history of smoking
Authors: Taylor L. Braunberger, Paras Vakharia, Nneamaka Ezekwe, Cynthia L. Nicholson, Angela Parks-Miller, Iltefat H. Hamzavi
Journal: Journal of the American Academy of Dermatology (2021)
25423 Improvements in work productivity following baricitinib treatment in patients with moderate-to-severe atopic dermatitis: Results from BREEZE-AD5
Authors: Lawrence F. Eichenfield, Emanual Maverakis, Jerry Tan, Lorne Albrecht, Andrew Buchanan, Amy M. DeLozier, Jinglin Zhong, Luna Sun, David Rosmarin
Journal: Journal of the American Academy of Dermatology (2021)
Immune functions as a ligand or a receptor, cancer prognosis potential, clinical implication of VISTA in cancer immunotherapy
Authors: Eunji Im, Deok Yong Sim, Hyo-Jung Lee, Ji Eon Park, Woon Yi Park, SeongGyu Ko, Bonglee Kim, Bum Sang Shim, Sung-Hoon Kim
Journal: Seminars in Cancer Biology (2021)

Since cancer immunotherapy with immune checkpoint inhibitors of PD/PDL-1 and CTLA-4 limited efficacy to the patients due to resistance during the current decade, novel target is required for customized treatment due to tumor heterogeneity. V-domain Ig-containing suppressor of T cell activation (VISTA), a programmed death protein-1(PD-1) homolog expressed on T cells and on antigen presenting cells(APC), has emerged as a new target in several cancers. Though VISTA inhibitors including CA-170 are considered attractive in cancer immunotherapy to date, the information on VISTA as a potent biomarker of cancer prognosis and its combination therapy is still lacking to date. Thus, in this review, we discussed extracellular domain, ligands, expression, immune functions and clinical implications of VISTA and finally suggested conclusion and perspectives.
Standardized measurement of coronary inflammation using cardiovascular computed tomography: integration in clinical care as a prognostic medical device
Authors: Evangelos K Oikonomou, Alexios S Antonopoulos, David Schottlander, Mohammad Marwan, Chris Mathers, Pete Tomlins, Muhammad Siddique, Laura V Klüner, Cheerag Shirodaria, Michail C Mavrogiannis, Sheena Thomas, Agostina Fava, John Deanfield, Keith M Channon, Stefan Neubauer, Milind Y Desai, Stephan Achenbach, Charalambos Antoniades
Journal: Cardiovascular Research (2021)

Abstract Aims Coronary computed tomography angiography (CCTA) is a first-line modality in the investigation of suspected coronary artery disease (CAD). Mapping of perivascular fat attenuation index (FAI) on routine CCTA enables the non-invasive detection of coronary artery inflammation by quantifying spatial changes in perivascular fat composition. We now report the performance of a new medical device, CaRi-Heart®, which integrates standardized FAI mapping together with clinical risk factors and plaque metrics to provide individualized cardiovascular risk prediction. Methods and results The study included 3912 consecutive patients undergoing CCTA as part of clinical care in the USA (n = 2040) and Europe (n = 1872). These cohorts were used to generate age-specific nomograms and percentile curves as reference maps for the standardized interpretation of FAI. The first output of CaRi-Heart® is the FAI-Score of each coronary artery, which provides a measure of coronary inflammation adjusted for technical, biological, and anatomical characteristics. FAI-Score is then incorporated into a risk prediction algorithm together with clinical risk factors and CCTA-derived coronary plaque metrics to generate the CaRi-Heart® Risk that predicts the likelihood of a fatal cardiac event at 8 years. CaRi-Heart® Risk was trained in the US population and its performance was validated externally in the European population. It improved risk discrimination over a clinical risk factor-based model [Δ(C-statistic) of 0.085, P = 0.01 in the US Cohort and 0.149, P &amp;lt; 0.001 in the European cohort] and had a consistent net clinical benefit on decision curve analysis above a baseline traditional risk factor-based model across the spectrum of cardiac risk. Conclusion Mapping of perivascular FAI on CCTA enables the non-invasive detection of coronary artery inflammation by quantifying spatial changes in perivascular fat composition. We now report the performance of a new medical device, CaRi-Heart®, which allows standardized measurement of coronary inflammation by calculating the FAI-Score of each coronary artery. The CaRi-Heart® device provides a reliable prediction of the patient's absolute risk for a fatal cardiac event by incorporating traditional cardiovascular risk factors along with comprehensive CCTA coronary plaque and perivascular adipose tissue phenotyping. This integration advances the prognostic utility of CCTA for individual patients and paves the way for its use as a dual diagnostic and prognostic tool among patients referred for CCTA.
The microbial one-hit wonder
Authors: Brigida A. Rusconi, Rodney D. Newberry
Journal: The Journal of Experimental Medicine (2021)

Intestinal inflammation, in the absence of infection, occurs from contributions by genetics and environment. Chen et al. (2021. J. Exp. Med.https://doi.org/10.1084/jem.20210324) challenge this concept by demonstrating that a dominant transmissible dysbiotic microbial community predisposes to intestinal inflammation in absence of genetic alterations.
Off-pump or on-pump coronary-arterybypass grafting at 30 days
Authors: André Lamy, P. J Devereaux, Dorairaj Prabhakaran, David Tagart, Shengshou Hu, Ernesto Paolasso, Zbynek Straka, Leopoldo S Piegas, Ahmet Ruchan Akar, Anil R Jain, Nicolas Noiseux, Chandrasekar Padmanabhan, Juan-Carlos Bahamondes, Novick Richard J, Prashant Vaijyanath, Sukesh Reddy, Liang Tao, Pablo A Olavegogeascoechea, Balram Airan, Toomas-Andres Sulling, Richard P Whitlock, Yongning Ou, Jennifer Ng, Susan Chrolavicius, Salim Yusuf
Journal: New England Journal of Medicine (2012)
ZFP91 disturbs metabolic fitness and antitumor activity of tumor-infiltrating T cells
Authors: Feixiang Wang, Yuerong Zhang, Xiaoyan Yu, Xiao-Lu Teng, Rui Ding, Zhilin Hu, Aiting Wang, Zhengting Wang, Youqiong Ye, Qiang Zou
Journal: Journal of Clinical Investigation (2021)

Proper metabolic activities facilitate T cell expansion and antitumor function; however, the mechanisms underlying disruption of the T cell metabolic program and function in the tumor microenvironment (TME) remain elusive. Here, we show a zinc finger protein 91–governed (ZFP91-governed) mechanism that disrupts the metabolic pathway and antitumor activity of tumor-infiltrating T cells. Single-cell RNA-Seq revealed that impairments in T cell proliferation and activation correlated with ZFP91 in tissue samples from patients with colorectal cancer. T cell–specific deletion of Zfp91 in mice led to enhanced T cell proliferation and potentiated T cell antitumor function. Loss of ZFP91 increased mammalian target of rapamycin complex 1 (mTORC1) activity to drive T cell glycolysis. Mechanistically, T cell antigen receptor–dependent (TCR-dependent) ZFP91 cytosolic translocation promoted protein phosphatase 2A (PP2A) complex assembly, thereby restricting mTORC1-mediated metabolic reprogramming. Our results demonstrate that ZFP91 perturbs T cell metabolic and functional states in the TME and suggest that targeting ZFP91 may improve the efficacy of cancer immunotherapy.
26032 Sustained and rapid improvements in patient reported outcomes for moderate-to-severe psoriasis patients with moderate and high BSA treated with ixekizumab: Side-by-side results from UNCOVER-3 and IXORA-S
Authors: Jerry Bagel, Alice B. Gottlieb, Russel Burge, Kyoungah See, Alyssa Garrelts, Missy McKean-Matthews, Kim Papp
Journal: Journal of the American Academy of Dermatology (2021)
Double Trouble: Combined Cardiovascular Effects of Particulate Matter Exposure and COVID-19.
Authors: Vineeta Tanwar, Jeremy M Adelstein, Loren E Wold
Journal: Cardiovascular Research (2020)

The coronavirus disease-2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly grown into a pandemic. According to initial reports, the lungs were thought to be the primary target, but recent case studies have shown its reach can extend to other organs including the heart and blood vessels. The severity of cardiac complications of COVID-19 depends on multiple underlying factors, with air pollutant exposure being one of them as reported by several recent studies. Airborne particulate matter attracts heightened attention due to its implication in various diseases, especially respiratory and cardiovascular diseases. Inhaled particulate matter not only carries microorganisms inside the body but also elicits local and systemic inflammatory responses resulting in altering host's immunity and increasing susceptibility to infection. Previous as well as recent studies have documented that particulate matter acts as a carrier for the virus and aids in spreading viral infections. This review presents the mechanisms and effects of viral entry and how pollution can potentially modulate pathophysiological processes in the heart. We aimed to concisely summarize studies examining cardiovascular (CV) outcomes in COVID-19 patients and postulate on how particulate matter can influence these outcomes. We have also reviewed evidence on the use of rennin-angiotensin system (RAS) inhibitors, namely, ACE inhibitors and angiotensin receptor blockers, in patients with COVID-19. The interplay of pollution and SARS-CoV-2 is essential to understanding the effects of accentuated cardiovascular effects of COVID-19 and deserves in depth experimental investigations.