tbuckley/cabot-search huggingface dataset:
Association of pancreatic adenocarcinoma location (head/body/tail) with DDR mutation status and response to platinum-based therapy.
Authors: Ida Micaily, Edik Matthew Blais, Steven J Cohen, Shawnna Cannaday, Geoffrey Krampitz, Raymond Couric Wadlow, Rachna T. Shroff, Autumn Jackson McRee, Jennifer W. Chuy, Lei Zheng, Andrew Eugene Hendifar, Lynn McCormick Matrisian, Gary Lee Gregory, Dzung Thach, Jonathan Robert Brody, Emanuel Petricoin, Michael J. Pishvaian, Harish Lavu, Charles Yeo, Atrayee Basu Mallick
Journal: Journal of Clinical Oncology (2022)

612 Background: Pancreatic adenocarcinoma is an aggressive disease with poor clinical prognosis that can originate from either the head (H) or body/tail (BT). Potential prognostic implications for H versus BT tumors have been reported; however, the molecular underpinnings associated with these differences in survival have not fully been explored. Using a large-scale real-world cohort of H and BT tumors with NGS results available from commercial labs, we retrospectively aim to identify potential differences between H and BT tumors in their response to standard therapies to help understand whether the treatment prioritization for pancreatic adenocarcinoma should take into account anatomical sidedness, as is recognized today with left-sided versus right-sided colorectal cancers. Methods: We analyzed outcomes across 1540 pts with NGS results from Perthera’s Real-World Evidence database who were diagnosed with PDAC originating from the H or BT. Progression-free survival (PFS) was evaluated from initiation of 1st line for advanced disease until discontinuation due to disease progression. Hazard ratios and p-values were computed via Cox regression when comparing PFS between 1st line FOLFIRINOX and gemcitabine/nab-paclitaxel. Differences in frequencies of genomic alterations between proximal and distal were analyzed by Fisher’s exact test. Results: Mutations in BRCA1/ BRCA2/ PALB2 were enriched (unadjusted p-value=0.017) in BT tumors (8.6% of 619) relative to H tumors (5.4% of 921). An expanded set of DDR pathway alterations (e.g. ATM, FANCA, CHEK2, BAP1, BRIP1, etc) were also enriched (unadjusted p-value=0.003) in BT tumors (21.4% of 619) relative to H tumors (15.6% of 921). In BT tumors, mPFS on 1st line FOLFIRINOX was longer (Table) than 1st line gemcitabine/nab-paclitaxel (p=0.0078) but this difference was not observed in H tumors (p=0.34). Overall survival data in these patients and an independent institutional cohort which motivated these analyses will also be discussed. Conclusions: DDR pathway alterations are known predictors of increased benefit from platinums and these real-world insights preliminarily suggest that DDR mutations are more common in BT vs. H. Prospective studies may be warranted to confirm the hypothesis-generating findings that platinum-based regimens should be prioritized in patients with BT tumors while underscoring the importance of routine NGS testing in both BT and H tumors given the prevalence of DDR pathway alterations on both sides of the pancreas.[Table: see text]
Case 1-2022: A 67-Year-Old Man with Motor Neuron Disease and Odd Behaviors during Sleep
Authors: Aleksandar Videnovic, Suma Babu, Brian Zhao, Haatem M. Reda, Jenny J. Linnoila
Journal: New England Journal of Medicine (2022)

A 67-year-old man with progressive motor neuron disease was evaluated in the sleep clinic because of dream enactment, daytime sleepiness, and apnea detected on a sleep study. Four months earlier, he had fallen asleep while washing dishes; this resulted in a fall and unstable C1 spinal fracture. A diagnostic test was performed.
COVID-19: protecting health-care workers
Authors: None The Lancet
Journal: The Lancet (2020)

Worldwide, as millions of people stay at home to minimise transmission of severe acute respiratory syndrome coronavirus 2, health-care workers prepare to do the exact opposite. They will go to clinics and hospitals, putting themselves at high risk from COVID-2019. Figures from China's National Health Commission show that more than 3300 health-care workers have been infected as of early March and, according to local media, by the end of February at least 22 had died. In Italy, 20% of responding health-care workers were infected, and some have died.
LAG3–PD-1 Combo Impresses in Melanoma
Journal: Cancer Discovery (2021)

Immune checkpoint inhibitors targeting PD-1, PD-L1, and CTLA4 have dramatically improved melanoma treatment-and the LAG3 immune checkpoint inhibitor relatlimab may soon be added to the mix. In a phase III trial, adding relatlimab to the PD-1 inhibitor nivolumab more than doubled progression-free survival, and the combination had relatively manageable side effects.
<i>History of Circumcision from the Earliest Times to the Present. Moral and Physical Reasons for its Performance, with a History of Eunnchism, Hermaphrodism, etc., and of the Different Operations Practiced upon the Prepuce</i>. By P. C. Remondino, M. D. Philadelphia and London: F. A. Davis, Publisher, 1891
Journal: American Journal of Psychiatry (1892)
Human brain mapping with multithousand-channel PtNRGrids resolves spatiotemporal dynamics
Authors: Youngbin Tchoe, Andrew M. Bourhis, Daniel R. Cleary, Brittany Stedelin, Jihwan Lee, Karen J. Tonsfeldt, Erik C. Brown, Dominic A. Siler, Angelique C. Paulk, Jimmy C. Yang, Hongseok Oh, Yun Goo Ro, Keundong Lee, Samantha M. Russman, Mehran Ganji, Ian Galton, Sharona Ben-Haim, Ahmed M. Raslan, Shadi A. Dayeh
Journal: Science Translational Medicine (2022)

Electrophysiological devices are critical for mapping eloquent and diseased brain regions and for therapeutic neuromodulation in clinical settings and are extensively used for research in brain-machine interfaces. However, the existing clinical and experimental devices are often limited in either spatial resolution or cortical coverage. Here, we developed scalable manufacturing processes with a dense electrical connection scheme to achieve reconfigurable thin-film, multithousand-channel neurophysiological recording grids using platinum nanorods (PtNRGrids). With PtNRGrids, we have achieved a multithousand-channel array of small (30 μm) contacts with low impedance, providing high spatial and temporal resolution over a large cortical area. We demonstrated that PtNRGrids can resolve submillimeter functional organization of the barrel cortex in anesthetized rats that captured the tissue structure. In the clinical setting, PtNRGrids resolved fine, complex temporal dynamics from the cortical surface in an awake human patient performing grasping tasks. In addition, the PtNRGrids identified the spatial spread and dynamics of epileptic discharges in a patient undergoing epilepsy surgery at 1-mm spatial resolution, including activity induced by direct electrical stimulation. Collectively, these findings demonstrated the power of the PtNRGrids to transform clinical mapping and research with brain-machine interfaces.
Evaluation of plaque instability using intravascular ultrasound images Tomokazu Okimoto, Michinori Imazu, Yasuhiko Hayashi, Hitoshi Fujiwara, Hironori Ueda, Kotaro Sumii, Mamoru Toyofuku, Kenji Kajiwara, Yoshito Shimizu, Tomoki Shokawa, Shinji Omura. The Second Department of Internal Medicine, Hiroshima University School of Medicine, Hiroshima, Japan, The Division of Cardiology, Tsuchiya General Hospital, Hiroshima, Japan
Journal: Journal of the American College of Cardiology (2001)
The contribution of itch and skin severity improvements to the Dermatology Life Quality Index in patients with atopic dermatitis in baricitinib phase <scp>III</scp> trials
Authors: Gil Yosipovitch, Kim Papp, Seth Forman, George Han, Jill Waibel, Maria J. Rueda, Luna Sun, Yun‐Fei Chen, Orin Goldblum, Evangeline Pierce, Jonathan I. Silverberg
Journal: British Journal of Dermatology (2022)

With data from three monotherapy baricitinib phase III randomized clinical trials (RCTs), we conducted a posthoc mediator analysis to assess whether changes in itch or skin severity mediated the treatment effect over placebo on changes in health-related quality of life. In this analysis, baricitinib demonstrated significant improvement in the Dermatology Life Quality Index for which itch mediated approximately half of the changes at weeks 4 and 16.
ACCF/AHA 2011 Key Data Elements and Definitions of a Base Cardiovascular Vocabulary for Electronic Health Records
Authors: William S. Weintraub, Ronald P. Karlsberg, James E. Tcheng, Jeffrey R. Boris, Alfred E. Buxton, James T. Dove, Gregg C. Fonarow, Lee R. Goldberg, Paul Heidenreich, Robert C. Hendel, Alice K. Jacobs, William Lewis, Michael J. Mirro, David M. Shahian
Journal: Journal of the American College of Cardiology (2011)
Abetalipoproteinemia
Authors: Daniel J. Rader
Journal: JAMA (1993)

<h3>SELECTED CASE</h3> A 30-year-old woman was referred to the National Institutes of Health (NIH) with malabsorption, ataxia, visual impairment, and low serum cholesterol level. As an infant, she had frequent colic and diarrhea, which improved when the amount of fat in her diet was decreased. She continued to have malabsorptive symptoms after ingesting a fatty meal and was diagnosed at 8 years of age as having celiac disease. A gluten-free diet did not, however, improve her symptoms. During her late teens and twenties, she experienced slowly progressive difficulty maintaining her balance, numbness in her legs below the knee, and difficulty in seeing at night with worsening color vision. At age 28 years she had a small-intestine biopsy; the findings were not consistent with celiac disease but rather revealed lipid-engorged enterocytes. Her family history was remarkable in that her parents were fourth cousins and her three younger sisters had similar, though
Clinical features and outcomes of tumor lysis syndrome in patients with gastrointestinal cancers.
Authors: Neil Kelkar, Jue Wang
Journal: Journal of Clinical Oncology (2022)

655 Background: In recent years, tumor lysis syndrome (TLS), an oncologic emergency typically associated with cytotoxic therapies, has been increasingly reported across a spectrum of cancer types including GI cancers. The objective of this study was to investigate the clinical characteristics and outcomes of TLS in GI cancers. Methods: Systematic review of the literature and pooled analysis of published cases of TLS in solid tumors. Two additional cases treated in our intuition are also included. Results: A total of 246 patients with TLS in solid tumors were included in this study. The median age was 56 years (7 months -94 years). The male: female ratio was 1.3. The most common sites were gastrointestinal (29%), followed by genitourinary (24%), lung (12%), melanoma (10%), breast cancer (8.1%), and GYN tumors (7.8%). Liver metastasis was documented in 70% of patients. TLS occurred after various cancer-directed therapies in 69% of subjects, and spontaneously in 31% of subjects. Older age and liver metastasis predict high mortality. The clinical features, treatment, and outcomes of TLS in 74 cases of GI cancers including HCC (n = 27), colorectal (n = 22), gastric (n = 8), cholangiocarcinoma (n = 6), pancreatic cancer (n = 4), GIST (n = 3), and PNET (n = 2) were compared. The mortality rate of TLS in this cohort was 100% in pancreases and cholangiocarcinoma, 66.7% in GIST, 57.7% in HCC, 54.5% in CRC, 50% in Gastric cancer. Conclusions: Documented across different sites consistently, TLS in GI cancers is associated with very high mortality. The development of a wider range of novel therapies and the application of more intensive therapy for the treatment of GI cancers likely contributed to the increased risk of TLS.[Table: see text]
Corrigendum
Journal: BMJ (1942)

The annual session for 1942 of the American Medical Association will be held at Atlantic City in the week June 8-12.In an editorial discussing the plans for this meeting the Journal of the Amlericani Medical Association says that long before the United States entered the war the authorities of the A.M.A. had agreed to endeavour to make it an inter-American meeting, as an indication of the close relationship in medicine prevailing among all the American nations.The Brazilian Government has offered exhibits dealing particularly with yellow fever and malaria, and, subject to the difficulties of travel in wartime, there is promise of the attendance of some cf the leading figures in medicine in South America, Canada, the West Indies, Mexico, and Central America.Several events of special interest in relation to the war are being scheduled, and official representatives of Governmental agencies concerned witlh medical participation in the war have undertaken to be present and to contribute to the pr-ogramme.
PrEP Awareness Is Low Among Heterosexual People
Authors: Bridget M. Kuehn
Journal: JAMA (2022)

Although nearly one-third of heterosexually active adults in cities with high HIV prevalence are aware of preexposure prophylaxis (PrEP), less than 1% use it, according to a CDC analysis of 2019 National HIV Behavioral Surveillance (NHBS) data.
Leads from the MMWR. Measles--Puerto Rico
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
Childhood Cancer Drugs for the World
Journal: Cancer Discovery (2022)

St. Jude Children's Research Hospital and the World Health Organization have launched an initiative to provide cancer drugs for children receiving treatment at medical centers in low- and middle-income countries at no charge. The Global Platform for Access to Childhood Cancer Medicines, launched with a $200 million investment from St. Jude, also aims to ensure that the centers have a steady supply of high-quality medications.
CD70 as an actionable immunotherapeutic target in recurrent glioblastoma and its microenvironment
Authors: Mathieu Seyfrid, William Thomas Maich, Muhammad Vaseem Shaikh, Nazanin Tatari, Deepak Upreti, Deween Piyasena, Minomi Subapanditha, Neil Savage, Dillon McKenna, Nicholas Mikolajewicz, Hong Han, Chirayu Chokshi, Laura Kuhlmann, Amanda Khoo, Sabra Khalid Salim, Blessing Archibong-Bassey, William Gwynne, Kevin Brown, Nadeem Murtaza, David Bakhshinyan, Parvez Vora, Chitra Venugopal, Jason Moffat, Thomas Kislinger, Sheila Singh
Journal: Journal for ImmunoTherapy of Cancer (2022)

Glioblastoma (GBM) patients suffer from a dismal prognosis, with standard of care therapy inevitably leading to therapy-resistant recurrent tumors. The presence of cancer stem cells (CSCs) drives the extensive heterogeneity seen in GBM, prompting the need for novel therapies specifically targeting this subset of tumor-driving cells. Here, we identify CD70 as a potential therapeutic target for recurrent GBM CSCs.
Reply
Authors: Teruo Inoue, Toru Kato, Toshihiko Uchida, Masashi Sakuma, Atsuko Nakajima, Mitsuei Shibazaki, Yoshitaka Imoto, Masahiko Saito, Shigemasa Hashimoto, Yutaka Hikichi, Koichi Node
Journal: Journal of the American College of Cardiology (2006)
Memorandum on the management of accidents in childhood. Prepared by the Standing Committee on Accidents in Childhood of the British Paediatric Association.
Journal: BMJ (1967)

Throughout this memorandum the word "accident" includes accident, poisoning, and violence.females and 48 % of all burns in males occur in children (Hospital In-patient Enquiry for 1959, quoted in Platt Com- mittee's Report on Accident and Emergency Services, 1962, Appendix III, Table III).A high proportion of accidents involve very young children.According to the British Medical Association's Report on Accidents in the Home (1964), 40% of all home accidents occur in those under 5 years of age: accidents to boys aged 1 and 2 years make up 22 % of all reported accidents to males.Of home accidents in Aberdeen, more than half were among children below school-leaving age, though children composed less than one-quarter of the population (MacQueen, 1960).It should be noted that not all injuries to young children are accidental.Deliberate, serious, and often fatal injury to children by adults seems to be more common than formerly (Brit.med.7., 1966).
Plasma hPG<sub>80</sub> (circulating progastrin) as a novel prognostic biomarker for hepatocellular carcinoma at early to intermediate stages (BCLC 0 to B).
Authors: Alexandre Prieur, Marie Dupuy, Sarah Iltache, Eric Assenat
Journal: Journal of Clinical Oncology (2022)

472 Background: Alpha-fetoprotein (AFP) is the most widely used biomarker for hepatocellular carcinoma (HCC) prognosis. However, AFP is not useful in establishing a prognosis for patients with a tumor in the early stages. hPG 80 (circulating progastrin) is a tumor promoting peptide present in the blood of patients with various cancers including HCC, even at early stages. In this study, we evaluated the prognostic value of plasma hPG 80 in patients with HCC at early and intermediate stages. Methods: A total of 79 HCC patients including 44 BCLC from 0 to A and 35 BCLC B managed with local or systemic treatments, (“Liverpool” biobank) were enrolled prospectively and analyzed retrospectively. hPG 80 was quantified using DxPG 80 Lab kit (ECS-Progastrin) with a limit of detection at 1 pM and AFP was quantified using Cobas E411 in the blood of HCC patients. An optimal cutoff value of hPG 80 was identified at 4.5 pM by calculating the minimal p-value based on the log-rank method. For AFP, a cutoff of 100 ng/mL was used as for liver transplantation (Notarpaolo, 2016). The prognostic impact of hPG 80 and AFP levels on patient overall survival (OS) was assessed using Kaplan-Meier curves and log-rank tests. Results: hPG 80 was detected in 36 of 44 (81.8%) HCC patients at stages BCLC 0 to A and 29 of 35 (82.9%) at stage BCLC B by contrast to AFP present in only 5 (11.4%) and 9 (25.7%) patients respectively. The median of hPG 80 was 5.7 pM (IQR: 1.7-22.4 pM) at stages BCLC 0 to A, 6.0 pM (IQR: 1.5-22.2 pM) at stage BCLC B and significantly different from a non-HCC age-range matched control group cohort (median value: 1.5 pM, IQR 0.6-3.2 pM, p &lt; 0.0001). When combining BCLC 0 to B, the median OS for hPG 80 + patients (n = 46) was significantly shorter than that of hPG 80 - patients (n = 33) (25 months versus undefined, HR: 3.07, 95% CI: 1.46-6.43; p = 0.0064). AFP+ patients were also significantly correlated with poorer OS (17.5 months versus undefined, HR: 3.16, 95% CI: 1.06-9.47; p = 0.0030). Then, we evaluated the prognostic significance of hPG 80 in combination with AFP levels. hPG 80 + patients with AFP &gt; 100 ng/mL (n = 46) had a worse OS than that of patients with AFP &lt; 100 ng/mL patients (n = 33) (15.8 months versus undefined, HR: 6.38, 95% CI: 1.74-23.41; p = 0.0052). Conclusions: Our findings show that hPG 80 could serve as a new prognostic biomarker for HCC patients at early to intermediate stages. These results will need to be confirmed in a prospective study, but it opens the possibility to use hPG 80 as a biomarker for HCC patients at early stage at a time they can be treated to be cured.
A phase Ib, multicenter, open-label study to assess the safety, tolerability, and preliminary efficacy of sintilimab plus IBI310 (anti-CTLA4 mAb) in patients with advanced hepatocellular carcinoma.
Authors: Jian Zhou, Ying-Hong Shi, Baorui Liu, Wei-Dong Jia, Shanzhi Gu, Yanru Qin, Ying Liu, Zhengxiang Han
Journal: Journal of Clinical Oncology (2022)

421 Background: Immune checkpoint inhibitors (ICI) targeting PD-1/L1 or in combination with CTLA-4 have shown therapeutic benefit in patients with advanced hepatocellular carcinoma (aHCC). This study aimed to evaluate the safety, tolerability, and preliminary efficacy of IBI310, an anti-CTLA-4 monoclonal antibody (mAb), combined with sintilimab, in patients with aHCC who failed or intolerant to previous systemic therapy. Methods: Three cohorts were pre-designed to explore recommended dose of IBI310 in de-escalation order: sintilimab 200 mg plus IBI310 3, 2 or 1 mg/kg every 3 week (q3w). Patients will receive the combined treatment up to 4 cycles, followed by sintilimab 200 mg q3w up to 24 months. Primary endpoint was safety. Key secondary endpoints included objective response rate (ORR), disease control rate (DCR), progress free survival (PFS) and overall survival (OS) by RECISTv1.1 per investigators. Results: 9 subjects were initially treated with sintilimab 200 mg plus IBI310 3 mg/kg q3w without predefined adverse event (AE) observed. 3 mg/kg was determined as recommended dose of IBI310 and no subject was assigned to other cohorts. As of the data cut-off of August 30, 29 subjects were enrolled (median age 51.4 years, 86.2% male, 96.6% BCLC C, 24.1% ICI treated). The average treatment cycles of IBI310 and sintilimab were 2.8 and 5.7. The most frequent treatment related adverse events (TRAEs) of any grade were alanine transaminase increases (34.5%), aspartate transaminase increases (34.5%), thrombopenia (24.1%), and lipase increases (24.1%). Grade ≥3 TRAEs occurred in 34.5% of subjects (including one grade 5 immune-mediated pneumonitis). Dose interruption and discontinuation rates due to AE were 55.2% and 6.9%. With a median follow-up of 9.89 months, investigator confirmed ORR and DCR were 17.2% (all partial response, including one anti-PD1 mAb failed) and 72.4%. The median PFS was 3.9 months (95% CI: 2.6, NR) and median OS not reached (95% CI: 11.4, NR). The 6-month PFS and OS rates were 45.8% (95%CI 25.2%, 64.2%) and 93.1% (95%CI 75.1%, 98.2%) respectively. 6 patients remain on treatment at cutoff date. Conclusions: The combination of sintilimab and IBI310 shows promising efficacy and managable safety profile in aHCC patients. Our results are comparable to that have been published in the same setting. This regimen is currently being evaluated in phase II study. Clinical trial information: NCT04401813.