tbuckley/cabot-search huggingface dataset:
Dynamic changes of the immune infiltrate after neoadjuvant avelumab/axitinib in patients (pts) with localized renal cell carcinoma (RCC) who are at high risk of relapse after nephrectomy (NeoAvAx).
Authors: Axel Bex, Yasmin Abu-Ghanem, Johannes V. Van Thienen, Niels Graafland, Brunolf Lagerveld, Patricia Zondervan, Harrie Beerlage, Jeroen van Moorselaar, Mark Kockx, Pieter-Jan Van Dam, Bernadett Szabados, Christian U. Blank, Thomas Powles, John B. A. G. Haanen
Journal: Journal of Clinical Oncology (2021)

4573 Background: Antibodies targeting PD-1/PD-L1 combined with vascular endothelial growth factor (VEGF) inhibitors are a front-line standard of care for metastatic RCC. Neoadjuvant use of these combinations is associated with tumor downsizing, but dynamic effects on key immune biomarkers are uncertain. We report early dynamic changes in the tumour immune environment after neoadjuvant treatment with avelumab/axitinib. Methods: Neoavax is an open label, single arm, phase II trial, investigating 12 weeks of neoadjuvant avelumab/axitinib prior to nephrectomy in patients with high-risk non-metastatic clear-cell (cc) RCC (cT1b-4N0-1M0). Partial primary tumour response (RECIST 1.1) occurring in ≥25% is the primary endpoint. Biomarker analysis on sequential tissue is an exploratory endpoint. Expression of PD-L1 (SP263), CD8+, CD8-granzyme-B (CD8/GZMB)+, Foxp3+ cells, CD8/CD39+ and major histocompatibility complex class I (MHC-I) were compared on paired samples (pre-treatment biopsy and nephrectomy) (NCT03341845). Results: Paired, sequential tissue from the first 24 patients was analysed for immune biomarker expression. Of these patients, 70% were ≥pT3a, 30% pN1, 58% had ISUP/WHO grade ≥3 with 8% sarcomatoid features. Compared to pre-treatment biopsy there was a significant increase in PD-L1 (p = 0.0002) and CD8+ expression (p = 0.0003) after therapy, whereas changes in CD8/GZMB+, MHC-I and CD8/CD39+ were not significant. Furthermore, neoadjuvant avelumab/axitinib therapy was associated with a significant decrease in Foxp3+ cells (p = 0.009). Conclusions: 12 weeks of neoadjuvant axitinib/avelumab treatment in ccRCC leads to significant dynamic changes in the tumour microenvironment for CD8+, PD-L1 and Foxp3+ expression. High baseline Foxp3+ infiltration is associated with an unfavorable outcome in the majority of solid tumours. The significant on-treatment decrease in Foxp3+ may account for the positive interaction seen between VEGF targeted therapy and immune checkpoint inhibitors in mRCC. If these cells represent regulatory T cells (Tregs), activated CD4 T cells or fragile Tregs remains to be determined. Clinical trial information: NCT03341845.
Encapsulation of lyophilized platelet-rich fibrin in alginate-hyaluronic acid hydrogel as a novel vascularized substitution for myocardial infarction
Authors: Bei Qian, Qi Yang, Mingliang Wang, Shixing Huang, Chenyu Jiang, Hongpeng Shi, Qiang Long, Mi Zhou, Qiang Zhao, Xiaofeng Ye
Journal: Bioactive Materials (2021)

Cardiovascular diseases such as myocardial infarction (MI) are among the major causes of death worldwide. Although intramyocardial injection of hydrogels can effectively enhance the ventricular wall, this approach is limited because of its restriction to the poor vascularization in the infarcted myocardium. Here, we reported a new type of hydrogel composed of alginate (ALG) and hyaluronic acid (HA) with lyophilized platelet-rich fibrin (Ly-PRF) for releasing abundant growth factors to realize their respective functions. The results of in vitro studies demonstrated favorable mechanical property and release ability of ALG-HA with Ly-PRF. When injected into the infarcted myocardium, this composite hydrogel preserved heart function and the Ly-PRF within the hydrogel promoted angiogenesis and increased vascular density in both infarcted and border zone, which rescued the ischemic myocardium. These beneficial effects were also accompanied by macrophage polarization and regulation of myocardial fibrosis. Moreover, the autologous origin of Ly-PRF with ALG-HA hydrogel offers myriad advantages including safety profile, easiness to obtain and cost-effectiveness. Overall, this study demonstrated the versatile therapeutic effects of a novel composite hydrogel ALG-HA with Ly-PRF, which optimizes a promising vascularized substitution strategy for improving cardiac function after MI.
Associated factors for poor response in advanced EGFR-mutated NSCLC patients under tirosine kinasa inhibitors: Peruvian real-world data.
Authors: Rodrigo Motta Guerrero, Carlos Aliaga, Thanya Katherine Runciman Gozzer, Carlos F. Carracedo, Virgilio Failoc, Alejandro Leon
Journal: Journal of Clinical Oncology (2021)

e21214 Background: Although tirosine kinasa inhibitors (TKI) are the first line of therapy in patients with non-small cell lung cancer (NSCLC) harboring EGFR mutations, some patients do not have benefit with TKI. The aim of this study is to determinate if there are associated factors with poor response with TKI. Methods: This is an observational study of a single institution patient cohort. Clinical records of advanced NSCLC patients harboring EGFR mutations that have received TKI as first line therapy in ALIADA cancer center since january 2015 until december 2019 were evaluated. Clinical records with incomplete data were excluded. Type of EGFR mutation, type of TKI agent, BMI, neutrophil, lymphocyte, platelets, neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) were evaluated in all cases. Poor responders where defined as NSCLC patients who progressed within 3 months with erlotinib or afatinib and 6 months within osimertinib. The statistical analysis was performed with SPSS version 20 and MINITAB 14. Results: 46 patients were finally included. Mean age was 63.6 ± 11.7 years, 54.4% of patients were female and 93% had adenocarcinoma histology. Mean neutrophil, lymphocyte and platelet counts were 4.82, 1.96 and 396.07 respectively; meanwhile mean NLR was 4.85 and mean PLR 282.36. 45% of patients were overweight or obese. 65.2% of all mutations were EGFR exon 19 deletions, 19.6% were exon21 L858R substitution and 10% EGFR uncommon mutations (de novo exon20 T790 mutations and exon18 G719X substitution). 45.7% of patients received erlotinib, 37% received afatinib and 17.3% osimertinib. 61.5% of patients achieved partial response, 17.3% achieved complete response, 9.6% stable disease and 28.3% of patients were poor responders to TKI treatment. In bivariate analysis, odds ratio for poor response was more associated with uncommon mutations (OR = 8.21, IC95% = 1.94-97.18; p = 0.025) and patients with neutrophil &gt; 4.82 (OR = 1.65, IC 95% = 1.08-2.52; p = 0.020). Odds ratio for poor response decreases 95% with erlotinib (OR = 0.05, IC95% = 0.00-0.58; p = 0.016). There was no statistical association with the rest factors. In the logistic regression model, poor response to TKI are related to uncommon EGFR mutations (OR = 8.21, 95% CI = 1.3-51.99; p = 0.009) and neutrophils &gt; 4.82 (OR: 1.85, 1.13 -3.05). Conclusions: Disease progression is a phenomenon present in patients with EGFR-mutated NSCLC. According to our data, poor response is associated with uncommon EGFR mutations, TKI agent (erlotinib) and neutrophil count level. We need larger studies to validate our results.
A Review of Acute Pancreatitis
Authors: Jairo Moyano, Daniela Abondano, Veronica Echavarria
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
High-grade glioma of central nervous system: Single center treatment experience.
Authors: Nur Olgun, Deniz Kızmazoğlu, Batuhan Özdoğar, Emre Çeçen, Ceren Kızmazoğlu, Sefika Akyol, Ayşe Demiral, Rıza Çetingöz, Ayşe Önal, Handan Güleryüz Uçar, Erdener Özer, Dilek İnce
Journal: Journal of Clinical Oncology (2021)

e14040 Background: To evaluate characteristics and treatment responses of patients with high grade gliomas (HGG) in our center Methods: Medical files of patients with malignant CNS tumors between 1987-2020 were analyzed retrospectively. There were 44 patients with HGG. Results: Diagnosis of patients as follows: 21 pons glioma, 2 anaplastic astrocytoma, 11 anaplastic ependimoma, 7 glioblastoma multiforme, 1 glioblastoma, 2 gliomatosis cerebri. The median age at diagnosis was 6,5 yrs (7 – 17 yrs), M/F:25/19. Age distrubution: &lt;5 yrs 12 patients, 5-10 yrs 18 patients, 10-18 yrs 14 patients. The most frequent complaints for pons gliomas: cranial nerve paralysis (52%), visial impairment (48%), headache (38%), power loss (43%) and speech disorder (30%). Surgery was performed to extrinsic component of mass in 3 patients of pons gliomas. For other HGG: 7 subtotal resection and 16 gross total resection had performed. Seven patients died before RT. And other 37 patients received radiotherapy. RT total doses varied between 50-60 Gy. Seven patients were not received chemotherapy, 3 of them died before chemo, and others received only RT. Chemotherapy protocoles were changed over the years: For pons gliomas, MOPP (Mechlorethamine, vincristine, prednisone, procarbazine) in 3 patients, NOPP (nitrosourea, vincristine, prednisone, procarbazine) in 2 patients, only ICE (Ifosfamide, carboplatin, cisplatin) in five patients, oral cyclophosphamide in one patient, temozolamide in one patient and temo + bevacizumab in one patient. Last 3 patients received nimotuzumab-vinorelbine after ICE and temo. For other HGGs, platin based regimens used fort he first line treatment. Temozolamide-bevacizumab, irinotecan-temsirolimus combinations were the other options as second and also third line treatments. Median progression free survival time was 6 mos (2 weeks -25 mos) for pons gliomas, for other gliomas median progression free survival time was 14 mos (0 -74 mos). For pons gliomas: Event free survival rate for 6 mos was 75%, for one year was 17%, One year, 18 mos, and two years overall survival rates were 84%, 52% and 10% respectively. For other HGGs: Event free survival rate for one year and two years were 57% and 17% respectively. One year and two years overall survival rates were 73% and 36% respectively. Conclusions: High grade glioma is a group of tumor in which still the helplessness experienced in treatment. Despite radiotherapy and chemotherapy, prognosis is very poor. The progression free and overall survival rates of patients were similar to literature. With new developments in molecular pathology, as the use of molecular target therapies, the progression free survival rates newly will improve.
Clinical burden, risk factor impact and outcomes following myocardial infarction and stroke: A 25-year individual patient level linkage study
Authors: Anoop S.V. Shah, Kuan Ken Lee, Jesús Alberto Rodríguez Pérez, Desmond Campbell, Federica Astengo, Jennifer Logue, Peter James Gallacher, Srinivasa Vittal Katikireddi, Rong Bing, Shirjel R. Alam, Atul Anand, Catherine Sudlow, Colin M Fischbacher, Jim Lewsey, Pablo Perel, David E. Newby, Nicholas L. Mills, David A. McAllister
Journal: The Lancet Regional Health - Europe (2021)

Understanding trends in the incidence and outcomes of myocardial infarction and stroke, and how these are influenced by changes in cardiovascular risk factors can inform health policy and healthcare provision. We identified all patients 30 years or older with myocardial infarction or stroke in Scotland. Risk factor levels were determined from national health surveys. Incidence, potential impact fractions and burden attributable to risk factor changes were calculated. Risk of subsequent fatal and non-fatal events (myocardial infarction, stroke, bleeding and heart failure hospitalization) were calculated with multi-state models. From 1990 to 2014, there were 372,873 (71±13 years) myocardial infarctions and 290,927 (74±13 years) ischemic or hemorrhagic strokes. Age-standardized incidence per 100,000 fell from 1,069 (95% confidence interval, 1,024-1,116) to 276 (263-290) for myocardial infarction and from 608 (581-636) to 188 (178-197) for ischemic stroke. Systolic blood pressure, smoking and cholesterol decreased, but body-mass index increased, and diabetes prevalence doubled. Changes in risk factors accounted for a 74% (57-91%) reduction in myocardial infarction and 68% (55-83%) reduction in ischemic stroke. Following myocardial infarction, the risk of death decreased (30% to 20%), but non-fatal events increased (20% to 24%) whereas the risk of both death (47% to 34%) and non-fatal events (22% to 17%) decreased following stroke. Over the last 25 years, substantial reductions in myocardial infarction and ischemic stroke incidence are attributable to major shifts in risk factor levels. Deaths following the index event decreased for both myocardial infarction and stroke, but rates remained substantially higher for stroke. British heart foundation
Abstract 16120: Pericardiocentesis and Pericardiotomy: A National Comparison of Utilization, Cost and Outcomes
Authors: Swiri Konje, Lingling Wu, Wojciech Rzechorzek, Alba Munoz Estrella, Eyal Herzog
Journal: Circulation (2019)

Objectives: Pericardiocentesis and pericardiotomy remain the two main treatment modalities for cardiac tamponade and malignant pleural effusions. However, there is little current evidence comparing...
Correlation between different levels of HER2 expression in circulating tumor cells (cHER2 ratio) and metastatic behavior in stageIV<sub>aggressive</sub> breast cancer.
Authors: Paolo D'Amico, Carolina Reduzzi, Sara Gandini, Lorenzo Gerratana, Wenan Qiang, Qiang Zhang, Frederique St-Pierre, Youbin Zhang, Ami N. Shah, Andrew A. Davis, Saya Jacob, Elena Vagia, Firas Hazem Wehbe, Amir Behdad, Giuseppe Curigliano, Massimo Cristofanilli
Journal: Journal of Clinical Oncology (2021)

3036 Background: The presence of HER2 expressing (HER2+) circulating tumor cells (CTCs) occurs often in metastatic breast cancer (MBC) patients (pts). We have previously showed that the ratio among CTCs expressing high level of HER2 and the total number of HER2+ CTCs (circulating HER2 ratio, cHer2 ratio) has a prognostic role in MBC patients. Here we further investigate the role of the cHER2 ratio in the process of metastatic spread. Methods: Under IRB-approved study we prospectively analyzed blood samples of patients with MBC enrolled before starting a new line of therapy. Samples were collected from pts treated at Northwestern University (Chicago, IL) between 2016 and 2020. CTCs were enumerated through CellSearch (Menarini Silicon Biosystems, Bologna, Italy) and characterized for HER2 expression using the CellSearch CXC Kit. HER2+ CTCs were divided in 3 different categories (1+,2+,3+) leaning on fluorescence intensity. Pts with &lt;5 CTCs (stage IV indolent ) were excluded from the analysis. The cHER2 ratio, defined as the sum of 2+ CTCs and 3+ CTCs divided by the total number of HER2+ CTCs, was used to split the remaining pts in 2 different cohorts: cHER2 ratio high (&gt; 0.75) (cHER2 high ) and cHER2 ratio low (≤0.75) (cHER2 low ). The frequency of each metastatic site (i.e. liver, lung, central nervous system, bone, lymph nodes, skin/soft tissue, serosa) and the total number of different sites involved (1-7, ≤2 and &gt;2 sites) were compared among the two sub-populations and analyzed through Fisher exact test. Results: Out of 98 pts enrolled, 77 were classified as cHER2 low and 21 as cHER2 high . We observed a higher frequency of oligometastatic pts (≤2 sites involved) in the cHER2 high cohort (16, 76%), compared to only 29 (37%) in the cHER2 low (p&lt;0.005). Moreover, the cHER2 ratio was associated with a tropism toward specific sites of disease spread with higher incidence of liver, lung and lymph nodes metastases in the cHER2 low cohort (p&lt;0.05). No other statistical associations were observed in respect of specific organ tropism. The frequency of involvement for each metastatic site among the two cohorts are reported in the table. Conclusions: Measuring CTCs enumeration and HER2 expression we identified two cohorts, cHER2 high and cHER2 low , associated with distinct patterns of metastatic spread. The cHER2 low pts were correlated to multiple sites of metastatic involvement, with particular tropism toward liver, lung and lymph nodes. These results confirm the prognostic role of the cHER2 ratio, suggesting a peculiar biological meaning of the HER2+ 1+ CTCs.[Table: see text]
Concerns About Recommendations for Perioperative Cannabis Use—Reply
Authors: Camille Stewart, Yuman Fong
Journal: JAMA Surgery (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 Surgery 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 Surgery journal
Socio-economic disparities and accessibility to age-appropriate screening tools.
Authors: Noha Soror, Amany Keruakous
Journal: Journal of Clinical Oncology (2021)

1529 Background: Pervasive racial and ethnic health disparities continue to be reported throughout the U.S. population. An increasing number of studies have discussed racial disparities in cancer statistics as well as socio-economic differences. The purpose of this study is to investigate sociodemographic health care disparities and the prevalence of cancer diagnosis in the context of challenges in medical services accessibility due to financial burden. Methods: Analysis of pooled cross-sectional data using 2017 Behavioral Risk Factor Surveillance System (BRFSS). Differences between our comparison groups were computed using chi square test for categorical values and t-test for continuous variables. Demographic factors were analyzed through weighted regression for accessibility to cancer treatment and prior cancer screening. Results: We report data from a total of 436,198 respondents to the 2017 BRFSS survey, with cancer prevalence 9.8% and higher prevalence of cancer among females and elderly population (70 years and older). Racial disparities differed significantly between respondents with and without history of cancer, with higher prevalence in Hispanic and multiracial minorities, 19% and 14%, respectively. We also report, differences in annual income are significantly associated with increased cancer prevalence in lower socioeconomic populations. Nineteen percent of participants who had annual income less than 25k were diagnosed with cancer. Additionally, analyzing the association between delayed medical care due to financial burden and its correlation with accessibility to age-appropriate cancer screening tools. We report significant differences in receipt of cancer screening among respondents, with consistently lower probabilities of receiving age-appropriate screening tools among participants who experienced delays in medical care due to cost, that applies to all screening tools. Among respondents who did not receive screening mammograms, 17% reported delays in medical care due to medical cost. Twelve percent of participants who did not receive screening colonoscopy suffered delays in medical care due to cost. Also, among participants who did not receive screening for prostate cancer with PSA testing, 11% reported delays in medical care due to cost. Conclusions: Health care disparities in cancer screening continue to persist including differences in socioeconomic classes and access to medical services. In this study, we report that patients with delayed access to medical services due to cost are not adequately receiving age-appropriate screening for cancer. Given the deleterious effects of delayed diagnosis and treatment of cancer, it is important that public health and clinical professionals utilize tools to improve cancer screening accessibility to minorities with socio-economic disparities.
A study on the genomic alterations of transformation from colorectal adenoma to colorectal cancer.
Authors: Qingjian Chen, Pan Yang, Linna Luo, Wenhua Fan, Chen Wei, Qi Zhao, Huiyan Luo
Journal: Journal of Clinical Oncology (2021)

e15607 Background: Colorectal cancer is one of the most common malignancies worldwide. Approximately 85% of colorectal cancers are thought to result from adenoma. However, the molecular mechanism of adenoma transformation into colorectal cancer is still unclear. Methods: Ninety-nine adenoma patients aged from 25 to 78 years old were enrolled in this study. We collected tissue sample from each patient and 77 matched blood samples. Pathological subtypes included tubular villous adenomas, villous adenomas, tubular adenomas, high-grade intraepithelial neoplasia, and polyps. Eighty-one stage I colorectal cancer patients (CRC I) were also enrolled in this study. All samples underwent Next-generation sequencing with a panel of 405 cancer related genes. Results: Mutational profiles of adenoma and CRC I patients were compared. The top 5 most frequently mutated genes in adenoma were APC (71%), KRAS (41%), ATM (33%), RIF1 (31%), SYNE1 (28%). While in CRC I patients, top 5 mutated genes were APC (78%), TP53 (57%), TTN (35%), KRAS (33%) and TCF7L2 (22%). There were significant differences between TP53 and TTN by chi-square test. The frequency, number and TMB of mutations in stage I colorectal cancer patients were significantly higher than those in various adenoma subtypes. Stage I colorectal cancer patients have more mutated genes enriched in the Wnt and Notch pathways than adenoma patients. We analyzed mutation signatures in CRC I and adenoma patients, and CRC I were more focused on mutation signatures of mismatch repair such as signature 1, signature 6, signature 10, and signature 15. A total of 391 mutations were identified in tissue samples, while 130 mutations were found in plasma cell-free DNA, with 116 mutations shared between them. The two genes with the highest consistency between tissue and blood were PAX7 and KMT2D. Conclusions: TP53 and TTN are associated with the transition from CRC I to adenoma, and Wnt and Notch pathways may also be involved. PAX7 and KMT2D mutations frequently found in adenoma tissue and blood cfDNA demonstrate the diagnostic potential of these two genes in clinic.