tbuckley/cabot-search huggingface dataset:
Composite Hydrogels: Prolonged Local In Vivo Delivery of Stimuli‐Responsive Nanogels That Rapidly Release Doxorubicin in Triple‐Negative Breast Cancer Cells (Adv. Healthcare Mater. 4/2020)
Authors: Yi Zhang, Pere Dosta, João Conde, Nuria Oliva, Mian Wang, Natalie Artzi
Journal: Advanced Healthcare Materials (2020)

In article number 1901101 by Natalie Artzi and co-workers, dual-sensitive nanogels rapidly dislodge the chemotherapy drug inside cancer cells through pH and redox sensitivities, enabling efficient cancer-cell killing. Their incorporation into an injectable hydrogel, delivered to tumor-adjacent areas, enables prolonged release of the nanogels, with instantaneous action once taken up by cancer cells, resulting in increased therapeutic efficacy.
Nasal Allergen Neutralizing Antibodies Correlate Closely with Tolerated Intranasal Allergen Challenge Dose Following Grass Pollen Subcutaneous Immunotherapy in Patients with Local Allergic Rhinitis
Authors: Rebecca Parkin, Ibon Eguiluz-Gracia, Maria Torres Jaen, Stephen Durham, Lina Mayorga, Carmen Rondon Segovia, Mohamed Shamji
Journal: Journal of Allergy and Clinical Immunology (2020)
Global and regional burdens of oral cancer from 1990 to 2017: Results from the global burden of disease study
Authors: Zhen‐Hu Ren, Chuan‐Yu Hu, Hai‐Rong He, Yuan‐Jie Li, Jun Lyu
Journal: Cancer Communications (2020)

Abstract Background Data on the incidence, mortality, and other burden of oral cancer as well as their secular trends are necessary to provide policy‐makers with the information needed to allocate resources appropriately. The purpose of this study was to use the Global Burden of Disease (GBD) 2017 results to estimate the incidence, mortality, and disability‐adjusted life years (DALYs) for oral cancer from 1990 to 2017. Methods We collected detailed data on oral cancer from 1990 to 2017 from the GBD 2017. The global incidence, mortality, and DALYs attributable to oral cancer as well as the corresponding age‐standardized rates (ASRs) were calculated. The estimated annual percentage changes in the ASRs of incidence (ASRI) and mortality (ASRM) and age‐standardized DALYs of oral cancer were also calculated according to regions and countries to quantify the secular trends in these rates. Results We tracked the incidence, mortality, and DALYs of oral cancer in 195 countries/territories over 28 years. Globally, the incidence, mortality, and DALYs of oral cancer increased by about 1.0‐fold from 1990 to 2017. The ASRI of oral cancer showed a similar trend, increasing from 4.41 to 4.84 per 100,000 person‐years during the study period. The ASRM remained approximately stable at about 2.4 per 100,000 from 1990 to 2017, as did the age‐standardized DALYs, at about 64.0 per 100,000 person‐years. ASRI was highest in Pakistan (27.03/100,000, 95% CI = 22.13‐32.75/100,000), followed by Taiwan China, and lowest in Iraq (0.96/100,000, 95% CI = 0.86‐1.06/100,000). ASRM was highest in Pakistan (16.85/100,000, 95% CI = 13.92‐20.17/100,000) and lowest in Kuwait (0.51/100,000, 95% CI = 0.45‐0.58/100,000). Conclusions The ASRI of oral cancer has increased slightly worldwide, while the ASRM and age‐standardized DALY have remained stable. However, these characteristics vary between countries, suggesting that current prevention strategies should be reoriented, and much more targeted and specific strategies should be established in some countries to forestall the increase in oral cancer.
Gender disparity in authorship of guidelines and recommendations in rheumatology
Authors: Giovanni Adami, Camilla Benini, Elisabetta Vantaggiato, Denise Rotta, Ombretta Viapiana, Davide Gatti, Maurizio Rossini, Annamaria Iagnocco
Journal: Annals of the Rheumatic Diseases (2020)

Women are generally less represented as first author among original medical researches and clinical guidelines. Indeed, women are first authors in only 30% of clinical guidelines published in high impact medical journals.1 2 Nevertheless, the trend seems to be improving over the last 20 years but it has plateaued in recent years.3 It is not known if a comparable under-representation occurs also in rheumatological guidelines. We have conducted a bibliometric analysis to evaluate the representation of female authors in rheumatological guidelines and recommendations over a period of time between 2004 and 2019. We searched PubMed for guidelines and recommendations published in English in the rheumatological field from 1 January 2004 to 1 January 2019. We included …
SGLT2 Inhibitors Produce Cardiorenal Benefits by Promoting Adaptive Cellular Reprogramming to Induce a State of Fasting Mimicry: A Paradigm Shift in Understanding Their Mechanism of Action
Authors: Milton Packer
Journal: Diabetes Care (2020)

There is compelling evidence that sodium–glucose cotransporter 2 (SGLT2) inhibitors exert cardioprotective and renoprotective effects that are far greater than expected based on their effects on glycemia or glycosuria. In large-scale randomized controlled trials, SGLT2 inhibitors reduce the risk of hospitalizations for heart failure by ∼30% and often decrease the risk of cardiovascular death (1). This benefit is particularly striking in patients who have the most marked impairment of systolic function prior to treatment. In parallel, SGLT2 inhibitors also reduce the risk of end-stage renal events, including the occurrence of renal death and the need for dialysis or renal transplantation by ∼30% (2). This benefit is seen even when glomerular filtration rates are sufficiently low to abolish the glycosuric effect of these drugs.

These cardiorenal benefits cannot be explained by an action of SGLT2 inhibitors to lower blood glucose, since similar effects are not seen with antidiabetes drugs that have greater antihyperglycemic actions. Additionally, they cannot be ascribed to a natriuretic action, since these drugs exert only a modest effect on plasma volume or on circulating natriuretic peptides (3).

In 2016, two articles published in Diabetes Care proposed the “thrifty fuel hypothesis” to explain the cardiorenal benefits of SGLT2 inhibitors. Ferrannini et al. (4) and Mudaliar et al. (5) postulated that the action of SGLT2 inhibitors to promote ketogenesis might account for their favorable effects on the heart and kidney because enhanced ketone bodies formation might possibly provide an efficient fuel that could boost the energy state of organs under stress. However, type 2 diabetes represents a state of nutrient overabundance and not energy deprivation, as is evidenced by the enhancement of molecular pathways that promote both energy retention (e.g., through SGLT2 upregulation) and energy storage (6,7). In fact, the stressed heart already preferentially utilizes ketone bodies, …
Mitochondrial dysfunction during loss of prohibitin 1 triggers Paneth cell defects and ileitis
Authors: Dakota N Jackson, Marina Panopoulos, William L Neumann, Kevin Turner, Brandi L Cantarel, LuAnn Thompson-Snipes, Themistocles Dassopoulos, Linda A Feagins, Rhonda F Souza, Jason C Mills, Richard S Blumberg, K Venuprasad, Winston E Thompson, Arianne L Theiss
Journal: Gut (2020)

Objective Although perturbations in mitochondrial function and structure have been described in the intestinal epithelium of Crohn’s disease and ulcerative colitis patients, the role of epithelial mitochondrial stress in the pathophysiology of inflammatory bowel diseases (IBD) is not well elucidated. Prohibitin 1 (PHB1), a major component protein of the inner mitochondrial membrane crucial for optimal respiratory chain assembly and function, is decreased during IBD. Design Male and female mice with inducible intestinal epithelial cell deletion of Phb1 ( Phb1 iΔIEC ) or Paneth cell-specific deletion of Phb1 ( Phb1 ΔPC ) and Phb1 fl/fl control mice were housed up to 20 weeks to characterise the impact of PHB1 deletion on intestinal homeostasis. To suppress mitochondrial reactive oxygen species, a mitochondrial-targeted antioxidant, Mito-Tempo, was administered. To examine epithelial cell-intrinsic responses, intestinal enteroids were generated from crypts of Phb1 iΔIEC or Phb1 ΔPC mice. Results Phb1 iΔIEC mice exhibited spontaneous ileal inflammation that was preceded by mitochondrial dysfunction in all IECs and early abnormalities in Paneth cells. Mito-Tempo ameliorated mitochondrial dysfunction, Paneth cell abnormalities and ileitis in Phb1 iΔIEC ileum. Deletion of Phb1 specifically in Paneth cells ( Phb1 ΔPC ) was sufficient to cause ileitis. Intestinal enteroids generated from crypts of Phb1 iΔIEC or Phb1 ΔPC mice exhibited decreased viability and Paneth cell defects that were improved by Mito-Tempo. Conclusion Our results identify Paneth cells as highly susceptible to mitochondrial dysfunction and central to the pathogenesis of ileitis, with translational implications for the subset of Crohn’s disease patients exhibiting Paneth cell defects.
Endosonography-guided fine-needle aspiration for re-evaluation of lymph node status after neoadjuvant therapy in patients with esophageal cancer: is there any role for it?
Authors: Enrique Vazquez-Sequeiros
Journal: Endoscopy (2020)

Preoperative staging of esophageal carcinoma usually relies on the sequential assessment of the tumor TNM stage by computed tomography (CT) scan and/or positron emission tomography (PET)-CT, followed by endoscopic ultrasound (EUS) [1]. Identification of patients with locally advanced cancer (T3 and, more importantly, N1 disease) is crucial to indicate preoperative neoadjuvant therapy and increase the chances of cure [1]. EUS appears to be superior to other techniques for locoregional (TN) staging of these patients [1]. However, although highly accurate (80 % – 85 %), lymph node (LN) status assessment relies on subjective EUS criteria such as echogenicity, and roundness or sharpness of the LN border, which has somehow limited the credibility and reproducibility of EUS nodal stage assessment [1]. EUS-guided fine-needle aspiration (EUS-FNA) of LNs for cytologic confirmation of nodal status has been shown to be the best technique in patients with esophageal cancer [1].
Second-line VEGF TKI after IO combination therapy: Results from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC).
Authors: Igor Stukalin, Shaan Dudani, Connor Wells, Chun Loo Gan, Sumanta K. Pal, Nazli Dizman, Thomas Powles, Frede Donskov, Lori Wood, Ziad Bakouny, Christian K. Kollmannsberger, Naveen S. Basappa, Aaron Richard Hansen, Guillermo de Velasco, Benoit Beuselinck, Christina M. Canil, Ulka N. Vaishampayan, Neeraj Agarwal, Toni K. Choueiri, Daniel Yick Chin Heng
Journal: Journal of Clinical Oncology (2020)

684 Background: Immuno-Oncology (IO) combinations are standard of care first-line treatment for metastatic renal cell carcinoma (mRCC). Data on therapy with vascular endothelial growth factor (VEGF) tyrosine kinase inhibitors (TKI) post-progression on IO-combination therapy are limited. Methods: Using the IMDC, a retrospective analysis was done on mRCC patients treated with second-line VEGF TKIs after receiving IO combination therapy. Patients received first-line ipilimumab+nivolumab (IOIO) or anti-PD(L)1+anti-VEGF (IOVE). Baseline variables and second-line IMDC risk factors were collected. Overall response rates (ORR), time to treatment failure (TTF) and overall survival (OS) were determined. Multivariable Cox regression analysis was performed. Results: 142 patients were included. 75 patients received IOIO and 67 received IOVE pretreatment. The ORR of 2nd line therapy was 17/46 (37%) and 7/57 (12%) in the IOIO and IOVE pretreated groups, respectively (p&lt;0.01). 2nd-line TTF was 5.4 months (95% CI 4.1-8.3) for the IOIO- and 4.6 months (95% CI 3.7-5.8) for the IOVE-pretreated group (p=0.37). 2nd-line median OS was 17.2 months (95% CI 10.8-35.1) and 11.8 months (95% CI 9.9-21.3) for the prior IOIO and IOVE groups, respectively (p=0.13). The hazard ratio adjusted by IMDC for IOVE vs IOIO pretreatment was 1.22 (95% CI 0.73-2.07, p=0.45) for 2nd line TTF and 1.43 (95% CI 0.74-2.8, p=0.29) for 2nd line OS. Conclusions: VEGF TKIs show activity after combination IO therapy. Response rates are higher in patients treated with VEGF TKIs after first-line IOIO compared to after IOVE. In patients with VEGF TKI after IOIO or IOVE, no difference in OS and TTF was observed.[Table: see text]
Risk Stratification Using High-Sensitivity Cardiac Troponin T in Patients With Suspected Acute Coronary Syndrome
Authors: Andrew R. Chapman, Dennis Sandeman, Amy V. Ferry, Stacey Stewart, Fiona E. Strachan, Ryan Wereski, Anda Bularga, Atul Anand, Anoop S.V. Shah, Nicholas L. Mills
Journal: Journal of the American College of Cardiology (2020)

High-sensitivity cardiac troponin assays allow the early recognition of myocardial injury, and they have facilitated the development of early rule-out pathways to identify patients who do not have acute myocardial infarction. Although international guidelines recommend using the sex-specific 99th
Phase 1b Study of AK002, an Anti-Siglec-8 Monoclonal Antibody, in Patients with Severe Allergic Conjunctivitis (KRONOS Study)
Authors: H. Terry Levine, Joseph Tauber, Quan Nguyen, Stephen Anesi, Peter Chang, Gregg Berdy, Charles Lin, David Chu, Andrea Kantor, Henrik Rasmussen, Bhupinder Singh, Alan Chang, Bennie Jeng, Vishal Jhanji, C. Stephen Foster
Journal: Journal of Allergy and Clinical Immunology (2020)
Semi-ResMass Study: Residual masses after salvage chemotherapy in men with pure seminoma—A multicenter retrospective analysis.
Authors: Giulia Baciarello, Caroline Brard, Mihaela Aldea, Christoph Oing, Ugo De Giorgi, Franco Morelli, Damien Pouessel, Simona Secondino, Bruno Vincenzi, Magalie Pascale Tardy, Laurence Crouzet, Sylvain Ladoire, Stéphanie Foulon, Karim Fizazi
Journal: Journal of Clinical Oncology (2020)

420 Background: Only scarce data exist on the management of residual masses in men who have received two lines of chemotherapy for advanced seminoma. Due to the lack of data, the role of PET scanning, surgery and other additional treatments is controversial in these men. Methods: Data from men with pure seminoma and residual masses after salvage chemotherapy were retrospectively collected from 10 high-volume centers in 3 European countries. We analyzed the clinical management of residual masses (imaging, surgery, pathological data, and additional treatment modalities) and long-term outcomes. Residual mass was defined as a lesion of ≥1 cm after two lines of platin-based chemotherapy. Results: To date, data from 48 patients (pts) with non-progressing residual masses after second line (salvage) chemotherapy have been collected and are included in this analysis. Median age at diagnosis was 36 years (range 31; 42). A post-chemotherapy PET-FDG was performed in 32 (67%) pts. Surgery was performed in 20/48 (41%) pts irrespectively of FDG uptake (no, n=8; yes, n=5). Complete necrosis was found in 16 (80%), viable seminoma in 3 (15%), and teratoma in 1 pt, respectively. All pts with a negative PET (PET-) who underwent surgery (8/8) had complete necrosis. 5/11 pts with a positive PET (PET+) underwent surgery: 3 had a complete necrosis while 2 had viable seminoma. Among those with a PET+, 3 pts (28%) experienced either viable seminoma in residual masses or a subsequent relapse. The absence of FDG uptake correlated with absence of viable cancer (p=0.04). A second relapse occurred in 5/48 pts (10%). Only 2/20 pts who had residual masses resected post 1st salvage chemotherapy subsequently relapsed (one had viable seminoma in the residuals). At a median follow up of 4 years (IC95% [3.5-5.5]), 41/48 pts (87%) were alive. 7/48 patients died of cancer progression. Conclusions: Most men with residual masses after 1st salvage chemotherapy for advanced seminoma may achieve a cure. Pending validation with more pts in this rare situation, PET-FDG may help guide who should be selected for post-chemotherapy resection. Updated results will be presented at the congress.
Racial disparities in the outcomes of transitional cell carcinoma of the bladder: A population-based analysis.
Authors: Firas Baidoun, Inas A. Ruhban, Anas M. Saad, Mohamed M. Gad, Khalid Jazieh, Muneer J. Al-Husseini, Moshe Chaim Ornstein, Brian I. Rini, Shilpa Gupta
Journal: Journal of Clinical Oncology (2020)

577 Background: Bladder cancer is the most common type of genitourinary malignancy and is the fourth most common cancer in men in the US. Transitional cell carcinoma (TCC) of the bladder accounts for most bladder cancer cases. Previous studies have observed racial disparities in the prognosis between white and black populations with very little mentioned about other ethnicities and race groups that are part of the United States population. We hereby, present a detailed and comprehensive analysis of racial disparities in TCC survival in the US. Methods: Using the data from surveillance Epidemiology and End results (SEER) database, we identified patients with TCC between 1992 and 2015. We used multivariable covariate-adjusted Cox models to analyze the overall and TCC-specific survival of patients according to their race. Results: We evaluated 176,388 patients with TCC and after we adjusted for age, sex, race, stage, grade, and undergoing cancer-targeted surgery, we found that Asians/Pacific Islanders and Hispanics had a better overall survival when compared to whites (HR= 0.792, 95% CI [0.761-0.824], P&lt;.001 and HR = 0.941, 95% CI [0.909-0.974], P = .001, respectively). Asians/Pacific Islanders also showed better TCC specific survival (HR = 0.843, 95% CI [0.759-0.894], P&lt;.001). Blacks had worse overall survival and TCC-specific survival (HR =1.221, 95% CI [1.181-1.262], P &lt;.001 and HR =1.325, 95% CI [1.268- 1.384], P &lt;.001, respectively). When stage IV TCC was analyzed separately, only Hispanics showed better overall and TCC specific survival when compared to whites (HR = 0.896, 95% CI [0.806-0.997], P = 0.044 and HR = 0.891, 95% CI [0.797-0.996], P = 0.42). Conclusions: Asians/Pacific Islanders have better overall and TCC-specific outcome while blacks have the worst outcome compared to whites. Hispanics have better overall and cancer specific survival in stage IV TCC. These disparities likely related to different and complex factors from lifestyle and chemical exposure to genetic factors. Further studies can help us more in understanding and approaching this malignancy in different race groups.
CaboPoint, a phase II, open-label study of cabozantinib as second-line therapy for patients with clear cell metastatic renal cell carcinoma (RCC), whose disease progressed after therapy with checkpoint inhibitors (CPIs).
Authors: Laurence Albiges, Manuela Schmidinger, Naila Taguieva Pioger, David Pérol, Viktor Grünwald
Journal: Journal of Clinical Oncology (2020)

TPS772 Background: Cabozantinib, a tyrosine kinase inhibitor with activity against vascular endothelial growth factor (VEGF) receptors, MET and AXL, is approved for the treatment of advanced RCC (in the USA) in treatment-naïve patients with intermediate or poor risk, as well as following VEGF-targeted therapy (in Europe). Here we present the design of the CaboPoint study evaluating the efficacy and safety of cabozantinib in patients with clear-cell metastatic RCC, whose disease progressed after CPI therapy. Methods: CaboPoint is a phase II, open-label (OL), single-arm study of cabozantinib in adults with unresectable, locally advanced or metastatic RCC with a clear-cell component, whose disease progressed after CPI therapy with ipilimumab and nivolumab alone (cohort A) or in combination with VEGF-targeted therapy (cohort B). The primary endpoint is objective response rate, evaluated by independent review committee. Secondary endpoints include time to response, duration of response, disease control rate, progression-free survival and overall survival. Change in disease-related symptoms and safety/tolerability will also be assessed. During the pre-treatment period, potential participants will attend a screening visit within 15 days of treatment initiation to determine eligibility status. During the treatment period, a target of 250 eligible patients (n = 125 per cohort) at 50 sites across AT, CH, DE, ES, FR, NL and UK will receive OL cabozantinib (60 mg once daily; self-administered at home) for up to 18 months after the last recruited patient has received their first dose. Safety assessments will be conducted every 2 weeks up to week 4, and every 4 weeks thereafter. Patients may continue on cabozantinib after disease progression if clinical benefit is observed. During the post-treatment follow-up period, patients who discontinue early will be contacted at visits every 12 weeks to assess survival status and subsequent anticancer therapy. Each cohort will have an interim analysis when 60% of the patients have reached 12 months of follow-up. The study is funded by Ipsen Pharma. Clinical trial information: NCT03945773.
Nivolumab (NIVO) in combination with stereotactic body radiotherapy (SBRT) in pretreated patients (pts) with metastatic renal cell carcinoma (mRCC): First results of phase II NIVES study.
Authors: Cristina Masini, Cinzia Iotti, Ugo De Giorgi, Roberto Salvatore Bellia, Sebastiano Buti, Francesco Salaroli, Ilaria Zampiva, Renzo Mazzarotto, Claudia Mucciarini, Cinzia Baldessari, Alessio Bruni, Giuseppe Procopio, Stefania Kinspergher, Franco Nole, Franco Morelli, Susanne Baier, Consuelo Buttigliero, Annalisa Berselli, Carmine Pinto
Journal: Journal of Clinical Oncology (2020)

613 Background: NIVO showed an increased on OS in pre-treated mRCC. The introduction of metastasis SBRT could improve the clinical outcomes. NIVES Study evaluated the efficacy and safety of SBRT in combination with NIVO in II and III line of mRCC pts. Methods: This is a phase II, single arm, multicentre study in mRCC pts with PD after ≤2 prior anti-angiogenic therapies with measurable metastatic sites, and at least one suitable for SBRT. The pts received hypofractionated radiation in 1 lesion at dose of 10 Gy/3 fractions after 7 days from the first infusion of NIVO. NIVO is given as flat dose of 240 mg on day 1 every 14 days for 6 months, then 480 mg q4-weekly in responding pts until PD or unacceptable toxicity. The primary end point is ORR. Secondary endpoints are PFS, OS, ORR of irradiated and non-irradiated metastasis and safety profile. Results: 69 pts were enrolled from July 2017 to March 2019 in 12 Italian centers. Pt characteristics were: 79.7% clear cell histology, 82.6% males, 79.7%% IMDC intermediate/poor, median age 67 yrs (43-85), 18.8% third line, 21.7% non-nephrectomy. The most frequent sites of SBRT were lung (37.7%), lymphonodes (15.9%), bone (11.6%). At the time of this analysis, median number of NIVO doses received was 12 (1-32). The ORR was 19% (1 CR) and DCR 63.5% (no statistically difference between site of SBRT and ORR); the largest benefit in pts with clear cell histology (p=0.01). Median PFS was 4 months (95%CI, 2.8-7.1), median OS 22.1 months (95%CI, 18.1-NR). With a median follow-up of 15 months (0-25.6), 6-month and 9-month survival rates were 80.3% and 56.1% respectively. 7 pts (10.1%) discontinued treatment due to AEs; grade(G) 3-4 toxicities related to NIVO were experienced in 17 pts (24.6%). The most frequent G3-4 toxicities included diarrhea (5.8%), amylase/lipase increased (4.3%) and hypothyroidism (4.3%); no G3-4 toxicities related to SBRT. Conclusions: The NIVES Study represents the first prospective trial of NIVO and SBRT combination in pre-treated mRCC pts. At present the Study showed a high DCR and no-increase of toxicity. It is ongoing the analysis of correlation between efficacy and PD-L1 expression. Clinical trial information: NCT03469713.