tbuckley/cabot-search huggingface dataset:
Efficacy of DNA versus RNA NGS-based Methods in MET Exon 14 skipping mutation detection.
Authors: Magdalena Jurkiewicz, Anjali Saqi, Mahesh M Mansukhani, Vaishali Hodel, Anamaria Krull, Catherine A. Shu, Helen D’Silva Fernandes
Journal: Journal of Clinical Oncology (2020)

9036 Background: Exon 14 skipping mutations in the mesenchymal-epithelial transition ( MET) gene are reported in 2-5% of lung adenocarcinomas and are mutually exclusive of other driver mutations. Small-molecule MET tyrosine kinase inhibitors, capmatinib and tepotinib, showed durable responses in previously treated and treatment-naïve patients harboring MET-exon-14 skipping mutations. Studies suggest that for detection of MET-ex14 mutations, DNA-based assays alone may be sub-optimal when compared to RNA-based NGS assays. We compared the performance of DNA and RNA-based assays for detection of MET-ex14 variants. Methods: We examined NGS-based profiling data of lung adenocarcinomas (or when this diagnosis could not be excluded) to identify MET-ex14 mutations missed by DNA but identified by RNA analysis. The carcinomas were profiled by a DNA-based NGS panel that targets MET exons 2, 14, 16, 18 and 19. Cases without driver mutations were reflexed to an NGS-based RNA fusion panel (Archer’s Anchored Multiplex PCR). Results: Over a 21-month period, MET-ex14 skipping events were detected in 16/644 (2.5%) lung carcinomas by DNA profiling. RNA analysis on driver-negative cases identified 9 additional MET-ex14 mutations. All 16 MET-ex14 DNA variants occurred at or around the intron 14 splice donor site, as the assay did not include the intron 13 splice acceptor site. Clinical characteristics of the MET positive cohort include a male to female ratio of 0.8:1.0, an average age of 76.5 years and 52% non-smoker status. All tumors were adenocarcinomas (including one with a &lt; 10% spindle/pleomorphic component) with the exception of 3 adenosquamous carcinomas and 1 squamous cell carcinoma. Conclusions: DNA based NGS-panels can potentially miss MET-ex14 skipping events in lung carcinomas, when the primers do not target both 3′ splice site of intron 13, and the 5′ splice site of intron 14. A reflex work flow interrogating RNA fusions can potentially capture such events. The clinical and molecular characterization of the variants detected only by RNA NGS assays warrants further exploration.
Percutaneous hepatic injection of rose bengal disodium (PV-10) in metastatic uveal melanoma.
Authors: Sapna Pradyuman Patel, Brett W. Carter, Ravi Murthy, Rahul Sheth, Sanjiv S. Agarwala, Gary Lu, Ellen Redstone, Gener C Balmes, Helene Rider, Dominic Rodrigues, Eric Andrew Wachter
Journal: Journal of Clinical Oncology (2020)

3143 Background: PV-10 is a small molecule autolytic immunotherapy in clinical development for treatment of solid tumors. When administered by intralesional (IL) injection, PV-10 can produce immunogenic cell death that may induce a T cell-mediated immune response against treatment refractory and immunologically cold tumors. Given this mechanism of action and clinical data that metastatic uveal melanoma (MUM) generates low response rates to immune checkpoint blockade (CB), we investigated treatment of MUM with percutaneously-delivered PV-10. Methods: This open-label Phase 1 basket study (NCT00986661) is evaluating the safety, tolerability, and preliminary efficacy of intralesional PV-10 in patients (pts) with solid tumors of the liver. PV-10 is injected into one or more designated hepatic tumor(s) with a maximum sum of diameters ≤4.9 cm. Response assessments using 2D EASL criteria are performed at Day 28, then every 3 months. Pts with additional injectable tumors are eligible to receive further PV-10 after Day 28. Pts can receive standard of care CB immunotherapy during treatment with PV-10. Results: As of February 1, 2020, the initial cohort of 15 pts with MUM to the liver was fully enrolled. Pts had received at least 1 IL injection of PV-10, with an average of 2 hepatic lesions injected per pt (range 1-4). Of these, 4 pts were refractory to prior CB. Three pts received PV-10 alone, 3 received PV-10 + anti-PD-1 and 9 received PV-10 + anti-PD-1 + anti-CTLA-4. Adverse events (AEs) were consistent with established patterns for PV-10 and CB: AEs attributed to PV-10 were transient and included 3 cases of Grade 3/4 transaminitis that resolved within 72 hrs, injection site pain, photosensitivity, and pink discoloration of skin, urine or feces; AEs attributed to CB included nausea, decreased WBC, and fatigue. Response assessments on 24 injected tumors were: 2 complete response (8%), 7 partial response (29%) and 11 stable disease (46%), per 2D EASL. Among the 4 CB-refractory pts, median overall survival (OS) was 9.2 months (range 5.3 - 11.4 months, with 2 pts alive at 5.3 months each), while among the 11 CB-naïve pts OS was undefined (range 0.5 - 21.9+ months, with 1 death at 7.9 months). Pts receiving PV-10 alone (1 CB-refractory, 2 naïve) achieved a median OS of 7.9 months with one CB-naïve pt alive with partial overall response at 21.9 months. Conclusions: Response indicative of regression or stabilization in a majority (83%) of injected lesions is encouraging in a disease of major unmet need. Enrollment and follow-up for safety, duration of response and survival are ongoing. Clinical trial information: NCT00986661 .
Intestinal microbiota in patients with acute leukemia (AL) and allogeneic hematopoietics stem cell transplantation (allo-HSCT).
Authors: Brenda Lizeth Acosta-Maldonado, Fernando Vallejo-Leucona, Felipe Vaca-Paniagua, Liliana Rivera-Fong, Elizabeth Hernández-Urzúa, Jaime G. De La Garza, Luis Manuel Valero-Saldana, Alinne Venegas-Olvera, Luis Lozano-Aguirre, Consuelo Velazquez, Angel Herrera, Jose Luis Aguilar
Journal: Journal of Clinical Oncology (2020)

e19518 Background: Microbiome is a challenging study area due to its influence on the multiple host functions. The majority of human-associated microbes reside within the colon. Our understanding about the complex interplay between host and environmental factors to shaping the microbiota is evolving rapidly AL is an unfavorable prognosis disease whose only cure possibility is the allo-HSCT. This procedure uses high doses of chemotherapy and multiple drugs such as antibiotics, antiviral, antifungals, and immunosuppressants that damage the mucous membranes and alter the intestinal microbiome balance. These events have been linked to bacterial resistance, relapse risk, Graft Versus Host Disease (GVHD), and poor Overall Survival (OS). The present study’s objective was to identify the intestinal microbiome bacteria groups during allo-HSCT and to evaluate their impact on patients outcome. Methods: Observational and prospective study was performed. Eleven patients with acute leukemia under alloHSCT and 11 health control (relatives) were enrolled. Gut faecal samples were collected in both groups; three for patients (at income day (ID), neutropenic period (N) and 30 days after discharge (+30D) and one in healthy donor (HD) at income day of their relatives. Bacterial 16S rRNA gene sequences were characterized by illumina and QUIIME 2. Biodiversity of microbiome was evaluated by OTUS, Shannon index and dominance. This proyect was supported by CONACyT. Results: We analyze 11 patients, 55% were male, with a median of 25 years-old at allo-HSCT. 7/10 received a HLA-identical and 4/10 an haploidentical HSCT. 82% had GVHD (I-IV), 1/11 died (two due to infections-GVHD and one of disease relapse). We analyzed 44 samples. There are no difference between healthy control group and income day patients’ samples. Statistical differences in the patients’ microbiome were identified among HSCT moments. According OTUS and Shannon Index the biodiversity decrease at neutropenia, and increase at day +30 outcome but it doesn’t represent a complete recovery. Greater bacterial dominance was observed in neutropenia period. (Table). 3/10 patients who died didn’t recovery biodiversity at day +30. Conclusions: Our results suggest that poor microbiome biodiversity recovery could be a worst prognostic [Table: see text]
甘露醇联合活性炭治疗急性口服中毒效果
Authors: 张金桥, 李品银
Journal: BMJ (2012)

将468例急性口服中毒患者分为治疗组和对照组,各234例,均常规洗胃,治疗组洗胃后经胃管注入20％甘露醇250 ml和活性炭50 g的混悬液,每日3次,此后若患者神智清楚改为口服,疗程3～5d.治疗组住院时间及病死率均明显低于对照组(均P＜0.05)。
A phase I study of AK112, a bispecific antibody that targets PD-1 and VEGF co-expressing T cells, in patients with advanced solid tumors.
Authors: Jermaine Coward, Charlotte Rose Lemech, Anna Rachelle Austria Mislang, Sagun Parakh, Craig Underhill, Adnan Nagrial, Xiaoping Jin, Baiyong Li, Zhongmin Maxwell Wang, Kon Yew Kwek, Yu Xia
Journal: Journal of Clinical Oncology (2020)

TPS3155 Background: AK112 is a humanized IgG1 bispecific anti-PD-1/VEGF antibody. VEGF blockade potentiates PD-1 inhibition by, inter alia, opposing the immunosuppressive effects of VEGF-A, which include suppression of dendritic cell activity and enhancement of checkpoint molecule expression on CD8+ T cells and proliferation of regulatory T cells. Combination therapies involving PD-(L)1 and VEGF inhibitors have been approved for the treatment of selected patients with metastatic non-small cell lung carcinoma, advanced renal cell carcinoma and advanced endometrial carcinoma. A supplemental Biologics License Application has been submitted for an anti-PD-L1 + anti-VEGF combination for the first-line treatment of unresectable hepatocellular carcinoma. Given the strong correlation between VEGF and PD-1 expression in the tumor microenvironment, the simultaneous blockade of these 2 targets by AK112 as a single agent might achieve higher target binding specificities and synergistically produce enhanced antitumor activity compared to co-administration of anti-PD-(L)1 and anti-VEGF therapies. Methods: This is a Phase 1a/1b, first-in-human, multicenter, open-label study in patients with advanced or metastatic solid tumor that is refractory/relapsed to standard therapies. The primary objective is to assess safety, tolerability and DLTs; and to determine the Maximum Tolerated Dose (MTD) or Maximum Administered Dose of AK112. Antitumor activity, PK and immunogenicity of AK112 will be studied as secondary objectives. As exploratory endpoints, tumor tissue samples may be evaluated for PD-L1 expression, mRNA expression profile and biomarkers (e.g. CD8+, FoxP3, Granzyme B, apelin and EPHB4). PD-1 receptor occupancy on circulating T-cells and serum VEGF level may also be measured as indications of target engagement. The dose-escalation phase will evaluate 5 dose levels of AK112 (up to 20 mg/kg Q2W IV) using a 3+3+3 study design. Additional subjects (up to 18 subjects) may be enrolled at any dose level not exceeding the MTD for additional PK, PD and safety evaluations to determine the optimal dose level for the dose-expansion phase. Cohorts 1 and 2 have been completed and enrollment to Cohort 3 began in January 2020. The dose-expansion phase will be performed in patients with selected advanced solid tumors who had no prior exposure to drugs targeting T-cell co-stimulation or immune checkpoint pathways. Clinical trial information: NCT04047290 .
Tocilizumab not associated with increased infection risk after CAR T-cell therapy: implications for COVID-19?
Authors: Matthew J. Frigault, Sarah Nikiforow, Michael K. Mansour, Zhen-Huan Hu, Mary M. Horowitz, Marcie L. Riches, Peiman Hematti, Cameron J. Turtle, Mei-Jie Zhang, Miguel-Angel Perales, Marcelo C. Pasquini
Journal: Blood (2020)
Efficacy of computer plus humanities in the treatment of cognitive dysfunction after brain injury
Authors: Jian-bo Yu, Xiao-fen Wu, Xiao-mei Yang, Li-juan Zhang, Hong-yan Qi
Journal: BMJ (2013)

A total of 60 patients with cognitive impairment were divided randomly into observation and control groups. Both groups were treated by conventional exercise therapy and computer-assisted cognitive rehabilitation while humanities therapy was combined in the observation group. After 8-week treatment, Loewenstein occupational therapy cognitive assessment (LOTCA) and modified Barthel index (MBI) scores were enhanced in both groups (P<0.05) while the scores of self-rating anxiety scale (SAS) and self-rating depression scale (SDS) declined obviously in observation group (P<0.05). The thought operation function, optomotor tissue, consciousness, concentration and total score of cognitive function in observation group were higher than control group (P<0.01) while the scores of SAS and SDS obviously lower (P<0.01). The scores of SAS were (50±4),(55±5) and SDS (53±4),(56±5) in two groups respectively. Therefore the therapy of computer cognitive rehabilitation plus humanities has the significant effect on improving cognitive function.


Key words: 
Cognitive therapy; Rehabilitation
Abstract 11497: Focal Hibernating Myocardium -A Novel Method to Assess Ventricular Arrhythmogencity Using Molecular Imaging
Authors: Mohammed Abdulghani, Brian Miller, Mark Smith, Wengen Chen, Kiddy L Ume, Tamunoinemi Bob-Manuel, Hasan Imanli, Anastasios Saliaris, Vincent See, Stephen Shorofsky, Vasken Dilsizian, Timm Dickfeld
Journal: Circulation (2015)

Introduction: Hibernating myocardium is associated with increased ventricular tachyarrhythmias and sudden cardiac death. Current algorithms aim to detect only large areas of left ventricular hibernation, likely to respond to revascularization and improve LV EF. However, no current tools allow the determination of small and focal hibernating areas within the ischemic substrate, which could act as VT trigger and substrate modulators, and initiate or maintain ventricular arrhythmias. Methods: Custom-made Matlab-based software was developed to perform quantitative segmental analysis. Patients with ischemic cardiomyopathy undergoing VT ablation underwent pre-procedural FDG and Rubidium-PET/Technicum SPECT to determine the metabolic and perfusion characteristics of the LV myocardium. After co-registering the voxel-based tracer intensity information was transferred into a 36 x 21 +1 matrix (757 segments analysis). After normalization comparative analysis identified functional categories of LV myocardium (normal:&gt;75% uptake perfusion[p]/metabolism[M]; hibernation: P and MP+20% or P&gt;50% but P+20%; matched scar P and M&lt;50%). Results: Software was evaluated on metabolism/perfusion scans of 8 patients undergoing VT ablation. While all patients had reported scar, only 2/8 patients (25%) had clinically identified area of hibernation using the currently clinically employed nuclear medicine algorithm. All DICOM files were successfully uploaded into the software module, transformed and analyzed using the pre-specified functional categories of LV myocardium. Post-analysis polar plots of all patients demonstrated matched scar as seen during the clinical read. However, focal areas of hibernation were detected in all patients using the 757 algorithm analytical tool (100% vs. 25% for 757 segmental vs. standard clinical analysis, P&lt;0.001) often adjacent to pre-specified scar category. ConclusioN: The novel quantitative 757 segmental analysis is able to detect and localize focal areas of hibernation in all patients with ischemic VT substrate. This allows the use of molecular imaging techniques to identify potentially proarrhythmic VT trigger and modulators and design novel diagnostic and therapeutic strategies.
Myelopreservation and reduced use of supportive care with trilaciclib in patients with small cell lung cancer.
Authors: Jared Weiss, Jerome Goldschmidt, Andric Zoran, Konstantin H. Dragnev, Yili Pritchett, Shannon R. Morris, Rajesh K. Malik, Davey B. Daniel
Journal: Journal of Clinical Oncology (2020)

12096 Background: Chemotherapy (CT) is a mainstay of cancer treatment; however, its side effects, notably myelosuppression, cause significant suffering. Trilaciclib (T) is an IV CDK4/6 inhibitor that protects hematopoietic stem and progenitor cells by preventing proliferation during CT administration. Results from three randomized, double-blind, placebo (P)-controlled phase II trials in patients (pts) with extensive-stage small cell lung cancer (ES-SCLC) have previously been reported. Data from these studies were pooled to understand the effects of T on specific myelosuppression endpoints with greater statistical precision. Methods: All pts received standard CT (etoposide/carboplatin [E/C], E/C/atezolizumab, or topotecan) plus T or P. Analyses were conducted on pooled intent-to-treat datasets from three ES-SCLC studies (NCT02499770; NCT03041311; NCT02514447). Results: 123 pts were treated with T and 119 with P. Median age in both groups was 64 years. Addition of T decreased measures of myelosuppression and the need for supportive care interventions (Table). From the pooled dataset, median OS and PFS (months [95% CI]) were comparable between pts treated with T vs P (OS: 10.6 [9.1, 11.7] vs 10.6 [7.9, 12.8]; PFS: 5.3 [4.6, 6.1] vs 5.0 [4.4, 5.5], respectively). Fewer pts on T had grade 3/4 hematologic events (54 [44.3%]) vs P (91 [77.1%]). Among pts who continued after cycle 1, 11 pts (9.2%) treated with T had ≥1 CT dose reduction vs 36 (30.8%) with P. Conclusions: T significantly and meaningfully reduced both CT-induced myelosuppression and its consequences, with no detrimental effect on PFS or OS, thus improving the patient experience with CT in ES-SCLC. T has potential to become a new standard of care for preventing myelosuppression in SCLC. [Table: see text]
Lung Cancer in Peru
Authors: Rossana Ruiz, Marco Galvez-Nino, Ebert Poquioma, Abel Limache-García, Edgar Amorin, Mivael Olivera, Natalia Valdiviezo, Juan M. Trejo, Adela Heredia, Gustavo Sarria, Alfredo Aguilar, Luis Raez, Silvia P. Neciosup, Henry L. Gomez, Eduardo Payet, Luis Mas
Journal: Journal of Thoracic Oncology (2020)
Insulin administration for pregnant women with hyperglycemia
Authors: Honghua Wu
Journal: BMJ (2019)

妊娠期高血糖包括妊娠期糖尿病（GDM）、妊娠期显性糖尿病（ODM）及孕前糖尿病（PGDM）。妊娠期高血糖患病率高。几乎所有PGDM、绝大多数ODM及20%~30%GDM孕期需用胰岛素控制血糖。可应用于孕期的胰岛素包括所有人胰岛素及胰岛素类似物（门冬、地特胰岛素）。孕期胰岛素应用需遵循个体化原则，小剂量起始，结合孕周及孕期胰岛素抵抗特点，及时调整胰岛素治疗方案及胰岛素剂量。强调血糖达标同时避免低血糖发生。孕期血糖目标：空腹<5.3 mmol/L，餐后2 h<6.7 mmol/L。孕期低血糖诊断标准：血糖<4.0 mmol/L视为血糖偏低，需调整胰岛素治疗方案；<3.3 mmol/L必可诊断为低血糖且需即刻处理。
High-Dose Chemotherapy With Hematopoietic Stem Cell Transplant in Patients With High-Risk Breast Cancer
Authors: Natalie Ertz-Archambault, Donald W. Northfelt, Mohamad Bassam Sonbol
Journal: JAMA Oncology (2020)

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 Oncology HomeNew OnlineCurrent IssueFor Authors Podcast 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 Oncology journal
Artificial intelligence-assisted CT characterizations and quantitative analysis for differentiating pre-invasive lesions from invasive adenocarcinomas in pulmonary subsolid nodules ≤ 2cm.
Authors: Bingyu Zhang, Fenglei Yu, Muyun Peng
Journal: Journal of Clinical Oncology (2020)

e21614 Background: The use of artificial intelligence (AI) in medical imaging has dramatically improved the quality of segmentation including accuracy, efficiency and reproducibility. This study sought to determine whether AI-assisted computed tomography (CT) features and quantitative analysis of pulmonary subsolid nodules (SSNs) under 2cm could be used to differentiate preinvasive lesions from invasive adenocarcinomas. Methods: Clinical data and CT images of 297 preinvasive lesions and early invasive lung adenocarcinomas confirmed by surgery pathology with CT manifestations of SSNs under 2cm were retrospectively analysed. The nodules were divided into two groups: the preinvasive lesions (PILs, N = 115) including 7 cases of atypical adenomatous hyperplasia (AAH), 30 cases of adenocarcinoma in situ (AIS) and 78 cases of minimally invasive adenocarcinoma (MIA), and the invasive adenocarcinomas (IACs, N = 182). All CTs were processed by AI and the volume, mean CT value, consolidation-to-tumor ratio (CTR), mass and maximum diameter of each SSN were obtained. Results: The volume, mean CT value, CTR, maximum diameter and mass of nodules showed significant difference between the two groups (Table). Multivariate analysis was determined by logistic regression. The regression model between the two groups was logit(p) = -1.439-2.927Volume +0.0005(mean CT value)-0.463(CTR &gt; 0.5) +0.238(maximum diameter)+6.298(mass).The receiver operating characteristic curve (ROC) showed that the mass can do the best prediction among all the independent factors with the areas under the curve(AUC) 0.748 at a cut-off value of 0.154, with the sensitivity of 70.9% and specificity of 70.4% .The AUC of the ROC using the regression probabilities of regression model was 0.769. Conclusions: AI-assisted CT characterizations may be promising tools to predict if SSNs under 2 cm have invaded. [Table: see text]
Immunologic mechanisms underlying sepsis
Authors: Lihua Dong, Shiji Wang, Guang Wang
Journal: BMJ (2017)

Sepsis remains the leading cause of death in intensive care unit.The pathogenesis of sepsis is extremely complex. Immune dysfunction plays an important role in the occurrence and development of sepsis. Many mechanisms are responsible for sepsis induced immune-suppression, including apoptotic depletion of immune cells, increased T regulatory and myeloid-derived suppressor cells, and cellular exhaustion. The article provided a brief review on the advance of immunologic mechanisms underlying sepsis.


Key words: 
Sepsis; Immune