tbuckley/cabot-search huggingface dataset:
Relationship between <i>Helicobacter pylori</i> and development of hepatocellular carcinoma: A systematic review and meta-analysis.
Authors: Samragnyi Madala, Kira MacDougall, Balarama Krishna Surapaneni, Robin Park, Anup Kasi, Mohit Girotra
Journal: Journal of Clinical Oncology (2021)

4091 Background: The relationship between Helicobacter pylori (H.pylori) and hepatocellular carcinoma (HCC) was first proposed in 1994. Since then, several studies have been performed to explore the association. The role of Hepatitis C (HCV) viruses coexisting with H.pylori in causing HCC was also studied. With the emergence of data in this regard, a causal relationship has been postulated, but not confirmed, and hence the relationship remains controversial. Our meta-analysis aims to summarize the research on this topic and investigate if there exists a relationship between H. pylori infection and the development of HCC and if the presence of HCV along with H.pylori plays a role in liver carcinogenesis. Methods: Following PRISMA guidelines, we performed a systematic review of all relevant studies published in the literature using keywords “Helicobacter pylori” and “Hepatocellular carcinoma” on major literature databases, including PubMed, EMBASE, Web of Science, and Cochrane controlled trials register. A total of 656 studies were identified between 1994 to March 2020, out of which 26 studies qualified under our selection criteria. Patients positive for HCC are included as cases and patients that did not have HCC under control group. In both groups, H.pylori positive patients and their HCV status, was identified. Results: Out of the 26 studies included in the final analysis, the prevalence of H. pylori infection was 64.78% (561 of 866) amongst HCC cases and 47.92% (1718 of 3585) in the non-HCC control group. The summary odds ratio for the association of H. pylori infection with the risk for HCC using the random-effects model was determined to be 4.75 (95% CI, 3.06-7.37), I²=63%. Subgroup analysis to determine the odds of developing HCC in the presence of H.pylori and HCV coinfection, was 13.97 (95% CI, 3.94-49.61), I²=81%. Whereas, the odds of developing HCC in the presence of only HCV without H.pylori was found to be 2.21 (0.70-6.94), I²=79. Subgroup analysis by study design showed no significant difference between the study groups (P= 0.5705). Conclusions: Our meta-analysis showed a positive association between H. pylori infection and the development of HCC. It showed a significantly higher risk of developing HCC in the presence of HCV infection along with H.pylori. Further prospective cohort studies are needed to prove the causal relationship, especially in cases of Hepatitis B, C coinfection, and cirrhotic patients.[Table: see text]
Use of critically important antibiotics class has more than doubled on UK pig farms
Authors: Elisabeth Mahase
Journal: BMJ (2021)

The use of a class of antibiotics critically important to human health more than doubled on UK pig farms between 2015 and 2019, raising concerns over the impact this could have on the rise of antimicrobial resistant infections.

The unpublished industry data—uncovered by the Bureau of Investigative Journalism, Vet Record , and the Guardian , and seen by The BMJ —shows the use of aminoglycosides rose from 2.607 mg/PCU (mg per kilogram of body weight) to 5.957 mg/PCU over four years.

Aminoglycosides—a class which includes amikacin, gentamicin, …
Covid-19: an economic perspective on vaccinating the world
Authors: Cam Donaldson, Olga Biosca
Journal: BMJ (2021)

The most recent vulnerability of societal structures exposed by covid-19 is the inability of pharmaceutical regulation systems to ensure global vaccine coverage. We are currently seeking to resolve problems related to demand (exacerbated by vaccine nationalism) with alternative solutions such as fair and equitable priority setting,1 none of which helps achieve universal coverage. The solution is to combine priority setting with the other side of the economic equation—supply.23

Vaccines for all, as proposed by prominent campaigns, …
Real-world starting dose and outcomes of palbociclib plus an aromatase inhibitor for metastatic breast cancer.
Authors: Debra A. Patt, Xianchen Liu, Benjamin Li, Lynn McRoy, Rachel M. Layman, Adam Brufsky
Journal: Journal of Clinical Oncology (2021)

e13021 Background: Palbociclib (PA) has been approved for HR+/HER2–advanced/metastatic breast cancer (mBC) in combination with an aromatase inhibitor (AI) or fulvestrant for more than 6 years. Regardless of the labeled recommended starting dose of 125mg/day, some patients initiate palbociclib at lower doses in routine practice. This study described real-world starting dose, patient characteristics, and effectiveness outcomes of first line PA+ AI for mBC in the US clinical setting. Methods: We conducted a retrospective analysis of Flatiron Health’s nationwide longitudinal electronic health records, which came from over 280 cancer clinics representing more than 2.2 million actively treated cancer patients in the US. Between February 2015 and September 2018, 813 HR+/HER2– mBC women initiated PA+AI as first-line therapy and had ≥ 3 months of potential follow-up. Patients were followed from start of PA+AI to December 2018, death, or last visit, whichever came first. Real-world progression-free survival (rwPFS) was defined as the time from the start of PA+AI to death or disease progression. Real-world tumor response (rwTR) was assessed based on the treating clinician’s assessment of radiologic evidence for change in burden of disease over the course of treatment. Multivariate analyses were performed to adjust for demographic and clinical characteristics. Results: Of 813 eligible patients, 68.3% were white, median age was 65.0 years, and 42.9% had visceral disease (lung and/or liver). Median duration of follow-up was 21.0 months. 805 patients had records of PA starting dose, with 125mg and 75/100mg/day being 86.5% and 13.5%, respectively. Patients who started at 75/100mg/day were more likely to be ≥75 years than those who started at 125mg/day (38.5% vs 17.1%). Other baseline and disease characteristics were generally evenly distributed. Patients who started at 125mg/day had longer median rwPFS (27.8 vs 18.6 months, adjusted HR=0.74, 95%CI=0.52-1.05) and higher rwTR (54.0% vs. 40.4%) than those patients who started 100/75mg/day (adjusted OR=1.76, 95%CI=1.13-2.74). Table presents results in detail. Conclusions: Most patients in this study initiated palbociclib at 125mg/day and dose adjustment was similar regardless of starting dose. These real-world findings may support initiation of palbociclib at a dose of 125mg/day in combination with AI for the first-line treatment of HR+/HER2- mBC. [Table: see text]
Intraoperative digital single-operator cholangioscopy – extra-anatomical biliary access and insights into severe sclerosing cholangitis in a pediatric patient
Authors: Philipp Dobsch, Stefan M. Brunner, Birgit Knoppke, Hans J. Schlitt, Arne Kandulski
Journal: Endoscopy (2021)

A 3-year-old boy with Downʼs syndrome, born prematurely with atrial septal defect type II and stenosis of the pulmonary artery, presented with hepatopathy and fibrosis. Magnetic resonance imaging (MRI) showed diffuse dilations of the biliary system, with large cystic changes suspicious for Caroli syndrome ([Fig. 1]). Endoscopic retrograde cholangiography (ERC) presented signs of secondary sclerosing cholangitis of the right liver lobe with missing contrast enhancement of the left biliary system ([Fig. 2]). Because there was no communication of the left liver lobe with the central biliary system, the patient underwent surgery to drain the left liver lobe by peripheral hepaticojejunostomy. Access to the biliary system was gained by the open biliary system of segment II and intraoperative cholangioscopy was performed using the newly developed, short digital system (SpyGlass Discover; Boston Scientific Corp., Marlborough, Massachusetts, USA) ([Video 1], [Fig. 3]). Intraoperative cholangioscopy revealed cystic dilated bile ducts, partly filled with biliary casts in accordance with the MRI imaging ([Fig. 4]). These findings further supported the diagnosis of systemic sclerosis due to severe postnatal respiratory insufficiency and circulatory problems.
Pre-clinical evaluation of PV-10 for <i><i>in vitro</i></i> anti-tumor activity in refractory and high-risk adult solid tumors.
Authors: Son Tran, Satbir Thakur, Mohit Jain, Chunfen Zhang, Aru Narendran
Journal: Journal of Clinical Oncology (2021)

e14544 Background: PV-10 (10% rose bengal disodium; 4,5,6,7-tetrachloro-2’,4’,5’,7’-tetraiodofluorescein) is a novel therapeutic agent previously shown to have potent anti-tumor activity following intratumoral injection in melanoma and refractory neuroblastoma, and currently is undergoing clinical testing as a single-agent for refractory metastatic neuroendocrine cancer (NCT02693067) and in combination with checkpoint inhibitors for metastatic melanoma (NCT02557321) and metastatic uveal melanoma (NCT00986661). Given the established clinical efficacy of PV-10 in adult melanoma and hepatic cancers via intratumoral injection, there is a need to evaluate the therapeutic potential of PV-10 in high-risk and refractory adult solid tumors via systemic administration. Our study aims to identify the clinical potential of systemically-delivered PV-10 by first generating prerequisite in vitro data for adult malignancies. Methods: Cytotoxicity assays were performed using the Alamar Blue assay to study the effects of PV-10 in vitro 96-hours post-treatment against a panel of adult solid tumor cell lines derived from breast (MCF-7, T-47D, MDA-MB-231), colorectal (HCT-116, LoVo, T-84), head and neck (CAL-27, Detroit-562, FaDu, UM-SCC-1), and testicular (NCC-IT, NTERA-2, TCAM-2) tissues. Light microscopy and Western blotting were used to investigate apoptosis induction and target modulation in tumor cells after PV-10 treatment. Results: In vitro results from our study demonstrate that PV-10 is cytotoxic at pharmacologically relevant concentrations across the indicated cell lines. Specifically, tumor cell lines originating from testicular tissues were highly sensitive to PV-10 treatment (Mean ± SD IC 50 : 37.5 ± 16.4 µM; n = 3) compared to breast (117.5 ± 71.0 µM; n = 3), colorectal (64.79 µM; n = 3), and head and neck (106.6 ± 29.2 µM; n = 4) cell lines. Western blot analyses showed dose- and time-dependent activation of pro-apoptotic protein markers in caspase-3 and PARP cleavage, indicating drug-induced apoptosis. Conclusions: This study provides the first pre-clinical results of PV-10 as a novel systemically-delivered therapeutic agent for a range of high-risk and refractory adult solid tumors. Data obtained from our in vitro experiments using a broad repertoire of cell lines that represent diverse molecular and phenotypic subtypes of solid tumors in adults can serve as prerequisite pre-clinical data to establish clinical testing in these populations.
Trial in progress: A phase I/II trial of novel MDM2 inhibitor alrizomadlin (APG-115), with or without platinum chemotherapy, in patients with p53 wild-type salivary gland carcinoma.
Authors: Paul Swiecicki, Yuefen Tang, Alexander T. Pearson, Jameel Muzaffar, Mary J. Fidler, Robert Winkler, Tommy Fu, Mingyu Li, Mohammad Ahmad, Dajun Yang, Yifan Zhai
Journal: Journal of Clinical Oncology (2021)

TPS6094 Background: Salivary gland carcinoma is a rare tumor that accounts for 6% of all head and neck cancers. This histologically and anatomically heterogeneous malignant tumor type is largely resistant to platinum and other chemotherapies but commonly has wild-type TP53 based on next-generation sequencing analysis. Alrizomadlin is a novel, orally active, small molecular agent that binds to MDM2, restoring p53 tumor suppressor function and inducing apoptosis in tumor cells retaining wild-type p53. Preliminary clinical evidence suggests promising antitumor activity and a favorable safety profile for alrizomadlin in the treatment of solid tumors (Rasco 2019). Methods: This US multicenter open-label trial is evaluating alrizomadlin with or without platinum chemotherapy in adults with histologically documented wild-type TP53 salivary gland carcinoma, including primary or metastatic lesions, an ECOG performance status 0-1, and a life expectancy of at least 12 weeks. In addition, subjects need to have measurable disease by computed tomography according to RECIST v1.1, with radiographic disease progression within the prior 12 months, high-grade status with or without metastases, and/or not amenable to curative treatment. An initial randomized phase (Part 1) will be followed by a single-arm phase (Part 2). Treatment arms include a cycle length of 21 days, and the study is using a time-to-event continual reassessment method. In Part 1 (42 patient target), patients are randomly allocated (in a 1:2 ratio) to one of two arms: single-agent alrizomadlin at a starting dose of 150 mg (Arm A) or at a starting dose of 150 mg with concomitant IV carboplatin administered at starting AUC = 4.5 (Arm B). Based on overall response rate (ORR; complete or partial response after Cycle 2) and safety profile, the most promising treatment arm will be advanced to Part 2, which has a target enrollment of 20 patients. Study endpoints are (1) dose-limiting toxicity (DLT), which is defined by the rate of drug-related grade ≥ 3 adverse events (by NCI CTCAE v5.0) over the first 2 cycles (6 weeks) of study treatment; (2) maximum tolerated dose based on these DLTs; and (3) ORR by RECIST v1.1 observed at up to 12 months. As of January 27, 2021, 11 of 42 patients had been enrolled in Part 1. Internal study identifier APG-115SG101. Clinical trial registration: NCT03781986. Clinical trial information: NCT03781986.
IMMU-08. MICROENVIRONMENT MODULATION BY TIM-3 BLOCKADE IMPROVES THE OUTCOME OF PRECLINICAL DIPG MODELS
Authors: Iker Ausejo-Mauleon, Sara Labiano, Virginia Laspidea, Marc Garcia-Moure, Daniel de la Nava, Montserrat Puigdelloses, Oren J Becher, Li Jiang, Mariella G Filbin, Fernando Pastor, Marta M Alonso
Journal: Neuro-Oncology (2021)

Abstract Diffuse Midline Gliomas (DMGs), encompassing Diffuse Intrinsic Pontine Gliomas (DIPGs), are the most aggressive pediatric brain tumors. Their meagre survival has not changed despite the combination of radiotherapy with targeted therapies emphasizing the urgent need for effective treatments. Recent research suggested that the DIPG tumor microenvironment is neither highly immunosuppressive nor inflammatory. These analyses showed the lack of infiltrating lymphocytes and the abundance of CD11b+ cells. TIM-3 (HAVCR2) is a member of the T-cell immunoglobulin and mucin domain protein family which is expressed on multiple immune cell types including T cells, Tregs, NK cells, monocytes, dendritic cells and microglia, where it potently regulates not only adaptive immunity but also innate immunity. Therefore, the central hypothesis of this study is that TIM-3 inhibitors could stimulate a cytotoxic immune effect and challenge several components in the tumor microenvironment including microglia, thereby providing a potential effective treatment for DMGs. In silico assessment of TIM-3 expression in a DIPG datasets showed a robust expression of this gene. Moreover, single-cell sequencing analyses of DIPG biopsies uncover its expression on tumor cells, especially in the OPCs compartment. In vivo efficacy studies showed that treatment with anti-TIM-3 antibody significantly increase the overall survival in two DIPG immunocompetent orthotopic animal models (doubling the median), lead to long-term survivors (50%) and showed immune memory. Analyses of CD45+ populations in the tumor microenvironment showed a significant increase in B, NK and CD8+ cells corresponding with a T-cell activate phenotype in treated-mice. The potential therapeutic involvement of NK cells was certified using nude mice and functional studies. Involvement of microglia in currently being analysed. In summary, these data underscore TIM-3 as a potential target DIPGs and uncover the potential involvement of NKs and other immune mechanisms in the efficacy of anti-TIM-3 therapy.
Abstract 11277: Systemic High-Mobility Group Box 1 Administration Might Suppress Ventricular Remodeling in a Rat Heart Failure With Preserved Ejection Fraction Model by Enhancing Self-Renewing System
Authors: Takasumi Goto, Shigeru Miyagawa, Katsuto Tamai, Takayoshi Ueno, Koichi Toda, Toru Kuratani, Yoshiki Sawa
Journal: Circulation (2018)

Introduction: High-mobility group box 1 (HMGB1), a necrotic cell-derived damage-associated molecular-pattern protein molecule, reportedly enhances bone marrow mesenchymal stem cell (MSC) recruitmen...
Validation of the RSClin risk calculator using the National Cancer Database (NCDB).
Authors: Frederick Howard, Alexander T. Pearson, Rita Nanda, Olufunmilayo I. Olopade, Dezheng Huo
Journal: Journal of Clinical Oncology (2021)

549 Background: Clinical practice guidelines recommend the use of genomic assays to aid decision making regarding the use of adjuvant chemotherapy (CT) for hormone receptor-positive, HER2-negative (HR+/HER2-) early breast cancer (EBC). Recently, the RSClin clinical tool, which integrates the 21-gene recurrence score (RS) and clinicopathologic features, was developed using data from the TAILORx trial. By integrating clinical and genomic risk, RSClin demonstrated greater precision in guiding adjuvant CT use in HR+/HER2- EBC than the 21-gene RS alone. As outcomes differed by race and ethnicity in TAILORx, further validation in real world datasets of diverse populations is needed. Methods: This study includes patients (pts) from the NCDB who were diagnosed with HR+/HER2- EBC from 2010-2017 and received adjuvant endocrine therapy (ET) with or without CT. RSClin provides a predicted absolute reduction in distant recurrence at 10 years with CT, while the NCDB database only provides overall survival (OS) metrics. While OS underestimates distant recurrence, we correlated RSClin predictions with survival differences between pts receiving ET versus those who received ET plus CT. Inverse probability of treatment weighting was used to correct for differences in age, comorbidity index, insurance, and race/ethnicity. OS benefit of CT was assessed in pts with low (&lt; 2%), intermediate (2-5%), and high (&gt;5%) absolute CT benefit (ACB) per RSClin using the log-rank test. Results: 150,268 pts with EBC were included. Average (avg) age was 59 yrs; 84% were white, 8% black, 4% Hispanic, and 4% Asian/Pacific Islander. Avg tumor size was 1.7 cm, avg RS 17, and 82% had lymph node (LN) negative disease. A significant OS benefit with CT was seen in the intermediate (HR 0.70) and high (HR 0.66) RSClin predicted ACB in the LN negative pts. When analyzed by racial / ethnic subgroup, all pts with a high RSClin ACB had improvement in survival with CT; in pts with an intermediate RSClin ACB, only white pts demonstrated significantly higher OS with CT (HR 0.72). Conclusions: Although developed to predict distant recurrence rates, the RSClin tool also correlates with OS in pts receiving ET with or without CT, which can aid in clinical decision making in pts with HR+/HER2- EBC. Predictive accuracy of RSClin differs by race/ethnicity. Accurate risk stratification in diverse populations is essential in ensuring equitable treatment and mitigating disparities in breast cancer outcomes in different racial/ethnic groups.
Pott’s disease in the atlas and posterior thoracic vertebral plate
Authors: Liyuan Jiang, Jianzhong Hu
Journal: BMJ (2021)

This magnetic resonance image shows tuberculosis spondylitis, known as Pott’s disease, in a woman in her 20s (fig 1). Pott’s disease characteristically causes destruction of the spinal vertebrae, which is visible here at the T10 level.



Fig 1 

The …
18F-FDG PET/CT of Primary Tracheal Adenoid Cystic Carcinoma
Authors: Junhao Wu, Yi Tao, Ya Liu, Yingwei Wang, Chunyin Zhang
Journal: Clinical Nuclear Medicine (2021)

Abstract Primary adenoid cystic carcinoma in the trachea is a very rare tumor. A 40-year-old woman presented with persisting cough and wheezing over 2 months. A CT scan showed a mass in the tracheal wall. The bronchoscopic biopsy confirmed adenoid cystic carcinoma. 18 F-FDG PET/CT was performed to evaluate the tracheal mass, which showed an FDG-avid mass in the right posterior tracheal wall.
Efficacy and safety of anlotinib hydrochloride in the treatment of advanced bone and soft tissue sarcoma after failure of first-line chemotherapy.
Authors: Weitao Yao, Jiaqiang Wang, Peng Zhang, Xin Wang, Qiang Yan, Xinhui Du, Zhichao Tian, Xiaoying Niu
Journal: Journal of Clinical Oncology (2021)

e23504 Background: There were limit treatments for bone and soft tissue sarcomas that have failed chemotherapy. Anlotinib hydrochloride is a multi-targeted receptor of tyrosine kinase inhibitors (TKI), which has shown therapeutic effects on soft tissue sarcoma. Methods: This is a single-arm, prospective, single-center clinical study. The included criteria were patients with pathological diagnose of bone and soft tissue sarcoma, at least one measurable lesion (criteria of RECIST 1.1), failed of more than one line therapy (except for sarcoma subtypes insensitive to chemotherapy), with the normal function of main organs. All patients received 12mg of anlotinib once daily, 2 weeks on and 1 week off until progression or unacceptable toxicity. The primary endpoint was ORR. We also observed PFS, OS, DCR and AEs. Results: From October 2018to October 2020, a total of 40 patients were enrolled. 25 were men and the median age of the patients was 43.28 (8-79) years. The tumor was located on the trunk in 14 cases, on the limbs in 24 cases and on the abdominal wall in 2 cases. 77.5%, 10%, 7.5% and 5% of patients have lung metastases, bone metastasis, liver metastasis and lymph node metastasis, respectively. The main subtypes included synovial sarcoma (20%), alveolar soft tissue sarcoma (15%), osteosarcoma (12.5%), fibrosarcoma (10%), undifferentiated pleomorphic sarcoma (7.5%). 32.5% of patients had received for at least second-line prior therapy and 25% of patients had received apatinib as a previous treatment. The ORR was 15% and the DCR was 77.5%. Patients who had received apatinib had an ORR of 10% and a DCR of 80% in this group. mPFS were 7.0 months (95%CI = 5.07-8.93) and 7.13 months (95%CI = 5.28-8.98) in overall patients and patients who had received apatinib respectively. The mPFS of ASPS, synovial sarcoma, fibrosarcoma, and osteosarcoma were 17.0 months, 8.2 months, 7.1 months, 2.9 months (p = 0.017). The mOS has not been reached. Adverse events were mainly in grades I and II, The ≥3 AEs were hypertension (2.5%), proteinuria (2.5%), leukopenia (2.5%), thrombocytopenia (2.5%), anorexia (2.5%) and elevated transaminase (5.0%). Conclusions: Anlotinib is effective and safe in the treatment of bone and soft tissue sarcoma, and its efficacy is positively correlated with special types (such as ASPS, synovial sarcoma), effectiveness can also be observed in patients who have failed in other targeted therapy. Clinical trial information: NCT04223583.