tbuckley/cabot-search huggingface dataset:
Real-world outcomes of second-line ramucirumab plus paclitaxel in patients with advanced gastric or gastroesophageal junction adenocarcinoma: A nationwide retrospective study in Korea (KCSG-ST19-16).
Authors: Dae Young Zang, Hye Sook Han, Bum Jun Kim, Hee-Jung Jee, Young Ju Suh, Hyonggin An, Ji-Hye Byun, Dong Sook Kim, Se Hoon Park, Sun Young Rha, Do-Youn Oh, Jong Gwang Kim, Woo Kyun Bae, In-Ho Kim, Sun Jin Sym, So Yeon Oh, Hyeong Su Kim, Keun Wook Lee, Min-Hee Ryu
Journal: Journal of Clinical Oncology (2021)

4056 Background: Ramucirumab as monotherapy or in combination with paclitaxel is a second-line treatment option recommended for patients with locally advanced unresectable or metastatic gastroesophageal junction (GEJ) or gastric adenocarcinoma. However, real-world data of large samples focused on ramucirumab plus paclitaxel in gastric cancer are limited. We conducted a nationwide retrospective study to evaluate the efficacy, safety, and factors potentially associated with survival in patients with gastric or GEJ adenocarcinoma who received second-line ramucirumab plus paclitaxel in a real-world setting. Methods: The study population comprised all patients with gastric or GEJ cancer who received ramucirumab plus paclitaxel in South Korea between May 1, 2018, and December 31, 2018. We included patients with advanced gastric or GEJ adenocarcinoma and disease progression after first-line platinum and fluoropyrimidine-containing combination chemotherapy. Results: A total of 1,063 patients with advanced gastric or GEJ adenocarcinoma who received ramucirumab plus paclitaxel were included. The objective response rate and disease control rate were 15.1% and 57.7%, respectively; the median progression-free survival was 4.03 months (95% CI, 3.80–4.27), and the median overall survival was 10.3 months (95% CI, 9.33–10.73). The common treatment-related adverse events (TRAEs) at any grade were neutropenia (44.7%), anemia (41.8%), neuropathy (29.1%), fatigue (25.9%), and anorexia (25.0%). Grade 3 or higher TRAEs with incidences of ≥5% were neutropenia (35.1%) and anemia (10.5%). Adverse events of special interest were infrequent, including hypertension (2.1%) and proteinuria (3.0%). Based on multivariate analysis, overall survival was negatively associated with Eastern Cooperative Oncology Group performance status ≥2, weight loss in the previous 3 months ≥10%, GEJ of primary tumor, poor or unknown histology grade, number of metastatic sites ≥3, presence of peritoneal metastasis, no prior gastrectomy, and time to second-line since first-line treatment &lt; 6 months. Conclusions: Our large-scale, nationwide, real-world data analysis of an unselected real-world population added evidence for the efficacy and safety of second-line ramucirumab plus paclitaxel in patients with locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma. Clinical trial information: NCT04192734.
PolyTLR7/8a-conjugated, antigen-trapping gold nanorods elicit anticancer immunity against abscopal tumors by photothermal therapy-induced in situ vaccination
Authors: Xiang Liu, Qi Su, Huijuan Song, Xiaoguang Shi, Yumin Zhang, Chuangnian Zhang, Pingsheng Huang, Anjie Dong, Deling Kong, Weiwei Wang
Journal: Biomaterials (2021)
Comparison of care process for newly diagnosed breast cancer in insured versus uninsured populations: Opportunities for improving health equity.
Authors: Gehan Botrus, Natalie Ertz-Archambault, Nellie Nafissi, Miguel Gonzalez Velez, Heidi E. Kosiorek, Brenda Ernst, Donald W. Northfelt
Journal: Journal of Clinical Oncology (2021)

e18518 Background: Initiatives enhancing equitable oncologic care are an increasingly emphasized priority. Our study aims to identify aspects of breast cancer (BC) care in which differences exist based on insurance coverage status. Methods: We performed a retrospective, case control study consisting of 39 Hispanic ethnicity uninsured patients (UP) with newly diagnosed BC at federally qualified health centers and 119 insured patients (IP) diagnosed at Mayo Clinic Arizona (MCA). Patients were matched 3:1 for age, stage, year of diagnosis, ER and HER2 status. Demographic information, clinical variables, and zip code level specific socioeconomic information were compared. Continuous variables were compared by Wilcoxon rank-sum test and categorical variables by chi-square test. All patients ultimately received their cancer treatment at MCA. Results: Similar treatment patterns with chemotherapy, surgery, and radiation treatment were observed between groups. Primary language was Spanish for 94% of UP and English for 97.5% of IP. The majority of UP were of Hispanic ethnicity (97.4%); IP were 83.2% non-Hispanic White, 9.2% Hispanic, 3.4% African American. Zip code level information reflected more unemployment with a median of 10.6% versus 6.9% p ˂ 0.001, percent of high school or lower (53.0 % v 23.2 %, p ˂ 0.001), and lower income for UP (33733.5 v 64728.0 p values ˂ 0.001). UP BMI was significantly higher (30.6 V 24.7, p=0.005), with presence of more co-morbidities; diabetes (28.2% v 5.0%, p ˂ 0.001), hypertension (35.9 % v 20.2%, p= 0.046), dyslipidemia (28.2% v 12.6%, p = 0.023), metabolic syndrome (p 23.7% v 8.5, p= 0.013), and tobacco use (17.9% v 2.5%, p ˂ 0.001). IP had higher alcohol use (52.9% v 5.3%, p ˂ 0.001). Genetics consultation was performed for 62.2% IP versus 35.9% UP (p=0.004), lower acceptance of oncology nutrition consultation for UP (29.4% vs 7.4%, p= 0.024) Median time from abnormal mammogram to biopsy (25.5 days vs. 14 days, p=0.056), and interval from diagnosis to treatment (62 days vs. 39 days) (p=0.001) were less favorable for UP compared to IP. Conclusions: In comparing the status of UP (primarily Hispanic, Spanish-speaking) and IP (primarily non-Hispanic White, English-speaking) with newly diagnosed BC we identified greater prevalence of co-morbidities and adverse social determinants of health in the former group. We identified access to genetic counseling services, access to oncology nutrition consultation, and timeliness of diagnostic biopsy and initiation of treatment as disparate features in the care pathway. These observations can allow development of tailored interventions to achieve greater equity in delivery of BC care.
Destination shapes antibiotic resistance gene acquisitions, abundance increases, and diversity changes in Dutch travelers
Authors: Alaric W. D’Souza, Manish Boolchandani, Sanket Patel, Gianluca Galazzo, Jarne M. van Hattem, Maris S. Arcilla, Damian C. Melles, Menno D. de Jong, Constance Schultsz, Martin C. J. Bootsma, Perry J. van Genderen, Abraham Goorhuis, Martin P. Grobusch, Nicky Molhoek, Astrid M. L. Oude Lashof, Ellen E. Stobberingh, Henri A. Verbrugh, Gautam Dantas, John Penders
Journal: Genome Medicine (2021)

Abstract Background Antimicrobial-resistant bacteria and their antimicrobial resistance (AMR) genes can spread by hitchhiking in human guts. International travel can exacerbate this public health threat when travelers acquire AMR genes endemic to their destinations and bring them back to their home countries. Prior studies have demonstrated travel-related acquisition of specific opportunistic pathogens and AMR genes, but the extent and magnitude of travel’s effects on the gut resistome remain largely unknown. Methods Using whole metagenomic shotgun sequencing, functional metagenomics, and Dirichlet multinomial mixture models, we investigated the abundance, diversity, function, resistome architecture, and context of AMR genes in the fecal microbiomes of 190 Dutch individuals, before and after travel to diverse international locations. Results Travel markedly increased the abundance and α-diversity of AMR genes in the travelers’ gut resistome, and we determined that 56 unique AMR genes showed significant acquisition following international travel. These acquisition events were biased towards AMR genes with efflux, inactivation, and target replacement resistance mechanisms. Travel-induced shaping of the gut resistome had distinct correlations with geographical destination, so individuals returning to The Netherlands from the same destination country were more likely to have similar resistome features. Finally, we identified and detailed specific acquisition events of high-risk, mobile genetic element-associated AMR genes including qnr fluoroquinolone resistance genes, bla CTX-M family extended-spectrum β-lactamases, and the plasmid-borne mcr-1 colistin resistance gene. Conclusions Our results show that travel shapes the architecture of the human gut resistome and results in AMR gene acquisition against a variety of antimicrobial drug classes. These broad acquisitions highlight the putative risks that international travel poses to public health by gut resistome perturbation and the global spread of locally endemic AMR genes.
The BMJ Awards: Deadline approaches for 13th annual excellence awards
Authors: Zosia Kmietowicz
Journal: BMJ (2021)

Healthcare teams across the UK have until midnight on 21 June to submit their entries to the 13th annual BMJ Awards that recognise innovative and patient centred care.

The awards give clinicians a chance to showcase their team’s achievements in transforming care and to accelerate the integration of innovative ideas into practice and secure further research funding.

Winners of the Stroke and Cardiovascular Team of the Year …
Pathophysiology of Coagulopathy in Hematological Malignancies and in COVID-19
Authors: Marcel Levi
Journal: HemaSphere (2021)

Many severe illnesses with a systemic impact may cause activation of coagulation. While systemic activation of coagulation leads to a coagulopathy that follows many common activation pathways and failure of endogenous regulatory anticoagulant systems, underlying conditions may utilize distinctive pathogenetic routes and may vary in clinical manifestations of the coagulopathy. The coagulation derangement associated with hematological malignancies and the coagulopathy of coronavirus disease 2019 (COVID-19) clearly demonstrate such differences. Malignancies are associated with venous thromboembolism due to the biological effect of malignant cells, frequent medical interventions, or the presence of indwelling vascular catheters. The underlying pathogenesis of cancer-associated coagulopathy relies on tissue factor-mediated activation of coagulation, cytokine-controlled defective anticoagulant pathways, fibrinolytic changes, and dysfunctional endothelium. There is an additional risk caused by anti-cancer agents including chemotherapy and immunotherapy. The underlying pathogenetic factor that contributes to the thrombotic risk associated with chemotherapy is endothelial cell injury (or loss of protection of endothelial integrity, for example, by vascular endothelial growth factor inhibition). In addition, individual anti-cancer agents may have specific prothrombotic effects. One of the remarkable features of severe COVID-19 infections is a coagulopathy that mimics but is not identical to the disseminated intravascular coagulation and thrombotic microangiopathy and has been identified as a strong marker for an adverse outcome. Severe COVID-19 infections cause inflammation-induced changes in coagulation in combination with severe endothelial cell injury. This coagulopathy likely contributes to pulmonary microvascular thrombosis, bronchoalveolar fibrin deposition (which is a hallmark of acute respiratory distress syndrome) and venous thromboembolic complications.
Tick Bites Send Concerned Patients to the Emergency Department
Authors: Bridget M. Kuehn
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
Superior overall survival (OS) and disease-free survival (DFS) predictions for patients with glioblastoma multiforme (GBM) using Cellworks Singula: myCare-022-03.
Authors: Patrick Y. Wen, Michael Castro, Drew Watson, Shweta Kapoor, Ashish Agrawal, Aftab Alam, Kunal Ghosh Roy, Swaminathan Rajagopalan, Kabya Basu, Deepak Anil Lala, Nirjhar Mundkur, Jim Christie, Anusha Pampana, Sayani Basu, Diwyanshu Sahu, Yugandhara Narvekar, Divya Singh, Prashant Nair, Manmeet Singh Ahluwalia
Journal: Journal of Clinical Oncology (2021)

2017 Background: The Cellworks Singula Therapeutic Response Index (TRI) has been developed to assist clinicians and GBM patients in choosing between competing therapeutic options. In contrast to approaches that consider single aberrations, which often yield limited benefit, Cellworks utilizes an individual patient’s next generation sequencing results and a mechanistic multi-omics biology model, the Cellworks Omics Biology Model (CBM), to biosimulate downstream molecular effects of cell signaling, drugs, and radiation on patient-specific in silico diseased cells. For any individual patient and alternative therapy, Cellworks integrates this biologically modeled multi-omics information into a continuous Singula TRI Score, scaled from 0 (low therapeutic benefit) to 100 (high therapeutic benefit). We demonstrate that Singula is strongly associated with OS and DFS beyond standard clinical factors, including patient age, patient gender, and physician prescribed treatments (PPT). Methods: In this study, Singula’s ability to predict response was evaluated in a retrospective cohort of 100 GBM patients with OS and DFS data from The Cancer Genome Atlas (TCGA) project, treated with PPT. As a primary analysis of the CBM and TRI Score, Cox Proportional Hazards (PH) regression and likelihood ratio (LR) tests were used to assess the hypothesis that Singula is predictive of OS and DFS above and beyond patient age, patient gender, and PPT. A p-value &lt; 0.05 for the corresponding likelihood ratio statistic was required to be considered significant. Results: Multivariate analyses were performed to assess the performance of the Singula Therapy Response Index after adjusting for the contribution of standard clinical factors. The same Singula TRI algorithm and clinical cutoffs were used for all clinical outcome measures. These analyses, shown in the table, suggests that the proposed Singula TRI provides predictive value of OS and DFS above and beyond patient age, patient gender, and PPT. Conclusions: The Singula TRI Score provides a continuous measure scaled from 0 (low benefit) to 100 (high benefit) for alternative GBM therapeutic options. In this retrospective cohort, Singula was strongly predictive of OS and DFS and provided predictive value beyond PPT, patient age and gender. These results will be further validated in larger scale, prospectively designed clinical studies.[Table: see text]
Pancreatic cancer surveillance and its ongoing challenges: is it time to refine our eligibility criteria?
Authors: Thomas P Potjer
Journal: Gut (2021)

Individuals at high risk for pancreatic cancer (PC) could potentially benefit from regular surveillance, as the first clinical symptoms of PC often appear only at an advanced stage, at which point the prognosis is often dismal. PC surveillance is therefore aimed at the timely detection and surgical resection of still curable lesions in usually asymptomatic patients. In a guideline developed by the International Cancer of the Pancreas Screening (CAPS) Consortium, high-risk individuals (HRIs) eligible for surveillance are defined as those with either a strong family history of PC ( familial pancreatic cancer ; FPC) or those with a germline mutation in a high-risk PC susceptibility gene such as CDKN2A , STK11 or BRCA2 . The preferred imaging modality is endoscopic ultrasound (EUS) and/or MRI/magnetic resonance cholangiopancreatography (MRCP).1 2 In a series of mostly small and short-term studies published since the early 2000s, the diagnostic yield of PC surveillance varied widely.2 However, more recent, larger studies with long-term follow-up have found evidence of increased survival among CDKN2A mutation carriers3 and HRIs from FPC families,4 thereby supporting continued PC surveillance of HRIs in a research setting.

In Gut , Overbeek et al 5 now report the yield of long-term surveillance in one of the largest cohorts of HRIs to date (n=366). A major strength of the study design was the routine genetic counselling and testing of individuals prior to enrollment, which allowed the authors to compare the yield of surveillance between HRIs …
ENGOT-ov60/GOG3052/RAMP 201: A phase 2 study of VS-6766 (dual RAF/MEK inhibitor) alone and in combination with defactinib (FAK inhibitor) in recurrent low-grade serous ovarian cancer (LGSOC).
Authors: Susana N. Banerjee, Bradley J. Monk, Els Van Nieuwenhuysen, Kathleen N. Moore, Ana Oaknin, Michel Fabbro, Nicoletta Colombo, David M. O'Malley, Robert L. Coleman, Jonathan A. Pachter, Andrew G. Koustenis, Gloria Patrick, Lorna Leonard, Rachel N. Grisham
Journal: Journal of Clinical Oncology (2021)

TPS5603 Background: VS-6766 is a unique small molecule inhibitor that blocks MEK kinase activity and RAF phosphorylation of MEK. This mechanism of blockade has been shown to limit compensatory MEK activation, thereby potentially enhancing efficacy of MEK inhibition. Defactinib, (VS-6063), an orally active small molecule, is a potent adenosine 5'- triphosphate (ATP) competitive, reversible inhibitor of focal adhesion kinase (FAK). Defactinib has shown synergistic activity with BRAF and MEK inhibitors in both in vitro and in vivo solid tumor models. Prior molecularly unselected studies with single agent MEK inhibitors have shown response rates up to 26% in recurrent LGSOC. A third of patients with recurrent LGSOC harbor somatic KRAS mutations. FAK inhibition has been shown to induce tumor regression when combined with RAF, MEK or RAF/MEK inhibitors in in vivo models of KRAS mutant ovarian cancer. The combination of VS-6766 and defactinib is currently being evaluated in the ongoing Investigator Sponsored FRAME study (NCT03875820). In this proof of concept study, durable objective responses have been reported in recurrent LGSOC patients, particularly those with KRAS mutations including patients who have had a prior MEK inhibitor (Banerji et al AACR 2020). Based on preclinical studies demonstrating efficacy of both VS-6766 and the VS-6766/defactinib combination and preliminary results of the FRAME study, the phase II ENGOT-ov60/GOG3052 has been developed in recurrent LGSOC. Methods: This is a Phase II, adaptive, two-part, multicenter, parallel cohort, randomized, open label study designed to evaluate the efficacy and safety of VS-6766 versus VS-6766 in combination with defactinib (NCT04625270). The study will be conducted in two parts. Part A will determine the optimal regimen based on confirmed overall response rate (independent radiology review) in KRAS-mutated LGSOC. Part B will determine the efficacy of the optimal regimen identified in Part A in KRAS-mutated and KRAS wild-type LGSOC. The minimum expected enrollment is 52 subjects with KRAS-mutated tumors (32 subjects in Part A and 20 in Part B) and 36 with KRAS wild-type tumors in Part B. Patients will be randomized to receive VS-6766 (4.0 mg PO, twice weekly 3 weeks on, 1 week off) or VS6766 with defactinib (VS-6766 3.2 mg PO, twice weekly + defactinib 200 mg PO BID 3 weeks on, 1 week off) till progression. Key inclusion criteria include histologically confirmed LGSOC, presence of KRAS mutation (Part A), prior systemic therapy for metastatic disease and up to 1 prior line of MEK/RAF inhibitor therapy permitted. This international study is open to enrollment. Clinical trial information: NCT04625270.
Impact of COVID-19 on work-related fatigue and satisfaction among oncology providers in Latin America: An analysis of the HOLA COVID-19 study.
Authors: Ana I. Velazquez Manana, Carolina Bernabe Ramirez, Coral Olazagasti, Paulo Gustavo Bergerot, Enrique Soto Perez De Celis, Jose Francisco Corona-Cruz, Ivy Riano, Christina Adaniel, Francisca Ramirez, Jesus Del Santo Anampa Mesias, Carmen Cajina, Evelin Mena, Elias Gracia, Alvaro G. Menendez, Raimundo Bezares, Omar Orlando Castillo Fernandez, Liseth Duque Duran, Luis-Alberto Corrales, Cristiane Decat Bergerot, Narjust Duma
Journal: Journal of Clinical Oncology (2021)

11014 Background: The well-being of oncology providers (OP) is in jeopardy with increasing workload, limited resources, and personal challenges that result from the COVID-19 pandemic. We aim to evaluate the impact of COVID-19 on work-related (WR) satisfaction and fatigue among OP in Latin America. Methods: We conducted an international cross-sectional online survey of OP practicing in Latin America. The survey was administered in English, Spanish, and Portuguese. Data was analyzed using descriptive statistics and Chi-square tests. Results: In August 2020, 704 OP from 20 Latin American countries completed the survey (77% of 913 who started the survey). Table outlines baseline characteristics. Higher frequency of WR fatigue (67% vs. 58%, p=0.010) and exhaustion (81% vs. 70%, p=0.001) were reported by OP who cared for patients with COVID-19, compared to OP who cared for patients without COVID-19. Providers that observed delays in referrals to radiation (p=0.002) and surgery (p=0.04) reported WR fatigue at higher rates than their counterparts. Higher exhaustion (p=0.016) and dissatisfaction (p=0.046) were reported by OP who lacked access to supportive services, as social work. A significantly higher proportion of women reported WR fatigue (72% vs. 56%, p=0.003) and exhaustion (86% vs. 68%, p=0.001), when compared to men. Women were more likely than men to endorse higher current levels of fatigue when compared to pre-COVID-19 (61% vs. 46%, p=0.0001). To reduce stress, women were more likely than men to cut the time spent watching the news (p=0.002). Both genders declined research collaborations and speaking opportunities. Conclusions: Fatigue and dissatisfaction with work-life were prevalent among OP in Latin America. Higher rates of WR fatigue were seen in women, OP caring for patients with COVID-19, and OP with patients who experienced cancer care delays. Our data imply that OP may be a prime target for psychosocial support, particularly as current challenges will continue for the foreseen future. Baseline characteristics (N=704).[Table: see text]