tbuckley/cabot-search huggingface dataset:
Prevalence of delay to seeking medical attention in patients with synovial sarcoma and association with inferior outcomes.
Authors: Tiffany Seto, Meena Song, Elisabeth Russell, Danny Sam, Minggui Pan
Journal: Journal of Clinical Oncology (2020)

e23556 Background: Synovial sarcoma is an aggressive soft tissue sarcoma that predominantly affects young patients with high rate of relapse and mortality. Systemic study of patients’ presenting symptoms and possible delay of seeking medical attention is lacking. Methods: We retrospectively reviewed the electronic records of all patients diagnosed with synovial sarcoma from 2005 to 2016 within Kaiser Permanente Northern California to identify the pattern of presenting symptoms and its correlation with outcomes. Results: Of the 77 patients with synovial sarcoma, 64 had early stage disease and 13 had metastatic disease at diagnosis, with median age at diagnosis of 47 years. Anatomically, 48 patients had primary disease at the extremity, 12 trunk, and 17 visceral. Median duration of follow up is 40 months. The median time from symptom to first medical appointment (TTM) is 3 months (range 0.1 to 180 months). Nine out of 13 patients who presented with metastatic disease were visceral primary. For the 60 patients with an extremity/trunk primary, patients who presented with pain without a palpable mass had a median duration of TTM of 12 months, compared to the TTM of 3 months for patients who presented with a palpable mass. The relapse rate (RR) and disease-free survival (DFS) for patients with an extremity/trunk primary who presented with pain but without a palpable mass were significantly worse when compared to patients who presented with a palpable mass (RR 50% vs. 26.5%, and DFS 27 vs. 42.5 months, p &lt; 0.005). TTM was inversely correlated with DFS for the 64 cases with early stage disease and for the 60 cases with extremity/trunk primary (p &lt; 0.00000001). Of the 11 patients with a foot primary, a similar pattern of TTM and DFS was also observed. Conclusions: Patients with synovial sarcoma who presented with pain but without a palpable mass had longer TTM, worse DFS and higher RR compared to patients who presented with a palpable mass. Longer TTM was associated with worse DFS.
Hydroxychloroquine for the Prevention of Covid-19 — Searching for Evidence
Authors: Myron S Cohen
Journal: New England Journal of Medicine (2020)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (Covid-19), has generated a worldwide pandemic.The interruption of its spread depends on a combination of pharmacologic and nonpharmacologic interventions.Initial SARS-CoV-2 prevention includes social distancing, the use of face masks, environmental hygiene, and hand washing. 1 Although the most important pharmacologic interventions to prevent SARS-CoV-2 infection are likely to be vaccines, the repurposing of established drugs for short-term prophylaxis is another, more immediate option.Some researchers have promoted chloroquine and hydroxychloroquine for the treatment and prevention of illness from a variety of microorganisms, including SARS-CoV. 2 Hydroxychloroquine can inhibit replication of SARS-CoV-2 in vitro. 3Some observational studies have suggested benefits of hydroxychloroquine for the treatment of Covid-19, whereas other treatment reports have described mixed results. 4oulware et al. now report in the Journal the results of a randomized trial testing hydroxychloroquine as postexposure prophylaxis for Covid-19. 5This is described by the investigators as a "pragmatic" trial in which participants were recruited through social media and almost all data were reported by the participants.Adults who described a high-risk or moderate-risk exposure to someone with Covid-19 in their household or an occupational setting were provided hydroxychloroquine or placebo (by mail) within 4 days after the reported exposure, and before symptoms would be expected to develop.The
Phase Ib study: APL-1202 (APL) in combination with Bacillus Calmette-Guerin (BCG) in recurrent non-muscle invasive bladder cancer (NMIBC).
Authors: John Sfakianos, Neal D. Shore, John Zhuang
Journal: Journal of Clinical Oncology (2020)

e17039 Background: APL is a selective human methionine aminopeptidases II (MetAP2) inhibitor. In preclinical studies, APL has demonstrated both anti-angiogenic and anti-tumor activities as well as a potential synergistic effect with BCG or PD-1. A. This phase 1b study assesses the tolerability and pharmacokinetics (PK) characteristics of oral APL and intravesical BCG combination in HR NMIBC pts. Methods: Pts who had received a prior induction course of BCG within 12 weeks (wks) of enrollment and were scheduled to receive either maintenance or another induction course of BCG were given 750 mg/day APL (2x125 mg tablet, TID) for 12 wks. The tolerability and PK of APL was evaluated one wk prior to first BCG instillation and during combination use with BCG. AEs were evaluated to assess safety and tolerability. Wilcoxon matched-pair signed-rank test was used for PK analysis. Results: Six pts (4M, 2F) with a median age of 72.5 yrs (range 58-81 yrs) were enrolled; 4 pts had grade 3 Ta and 2 pts had Tis. Four and 2 pts received induction and maintenance course of BCG, respectively. Six AEs of grade 1 or 2 were reported by 3 pts, and they were respiratory and head congestion, acid reflux, rash, bronchitis, nausea, and cystitis. None of these AEs were judged to be related to APL. Five pts completed the study and 1 pt dropped out due to a grade 1 cystitis after receiving 4 wks of APL and 2 doses of BCG. The PK results suggested similar PK characteristics (plasma AUC tau, C max and t 1/2 , and urinary excreted faction Ae%). Conclusions: APL was well tolerated when given for 12 wks to NMIBC pts who also received induction or maintenance BCG. Further study of APL in combination with BCG is warranted. Clinical trial information: NCT03672240.
跟骨旁肿瘤性钙盐沉积症一例
Authors: 隋旭蕾, 梁鹏, 唐小锋, 黄兴文, 孙晓苑, 冯佩佩
Journal: BMJ (2012)

本例跟骨旁肿瘤性钙盐沉积症的影像学表现,与常见部位的肿瘤性钙盐沉着症具有共同点,即X线及CT示关节旁软组织内密度不均匀的钙化团块,MRI扫描显示病灶主体呈长T1、短T2信号,周围呈长T1、等T2环形信号,邻近骨质及软组织无异常改变。
Tri-ratna Man Tuladhar
Authors: Swayambhu Tuladhar
Journal: BMJ (2020)

Tri-ratna Man Tuladhar was one of the pioneers of anaesthesiology in Nepal. He was only the second doctor in Nepal to attain the postgraduate fellowship degree in anaesthesia from the royal college in the UK. He returned to his country and developed the then less appreciated specialty, encouraging many others to take up the profession.

Born into a merchant family in the heart of Kathmandu, he passed his school leaving certificate examination at age 14. He studied medicine at Patna University in India and went to London in 1963, …
Effects of iso-osmolar contrast media on renal function in elderly patients
Authors: Ying Sun, Aiqun Chen, Jiyang Wang, Yongjun Li, Jihong Yang
Journal: BMJ (2018)

Objective
To investigate the effect of iso-osmolar contrast media (IOCM) on renal function in elderly patients.


Methods
The clinical data of 77 patients aged over 65 years undergoing vascular angiography and interventional therapy using IOCM with a dose>100 ml from September 2016 to May 2017 were retrospectively analyzed. Serum creatinine (CRE), urea and uric acid were measured before angiography, within 48 h and 3-7 d after angiography. The incidence of contrast-induced nephropathy (CIN) and the renal function before and after angiography were compared.


Results
Among the 77 patients, 58 were males and 19 were females, with an average age of (73.8±7.2) years. The mean serum CRE values before and 3-7 days after angiography were (84.55±39.92) μmol/L and (83.87±38.45) μmol/L respectively (t=0.140, P=0.889); the mean serum urea levels were (5.64±2.36) mmol/L and (6.44±3.15) mmol/L (t=3.041, P=0.003); the mean serum uric acid levels were (281.39±85.30) μmol/L and (333.29±89.89) μmol/L (t=7.297, P<0.001), respectively. CIN occurred in 7 patients with an incidence of 9.1%. In 7 patients with CIN, the mean CRE values increased from (135.71±102.41) μmol/L before angiography, to (180.00±100.45) μmol/L within 48 h and (142.86±92.97) μmol/L 3-7 d after angiography (F=9.876, P=0.011); and the uric acid levels progressively decreased from (353.43±86.73) μmol/L before angiography, to (339.14±85.69) μmol/L within 48 h after angiography and (299.57±95.71) μmol/L 3-7 d after angiography (F=5.713, P=0.029).


Conclusion
In elderly patients, IOCM has relatively mild effect on renal function during vascular angiography or interventional therapy.


Key words: 
Contrast media; Aged; Acute kidney injury
The natural history of fibroblast growth factor receptor (FGFR)-altered cholangiocarcinoma (CCA).
Authors: Lipika Goyal, Angela Lamarca, John H. Strickler, Michael Cecchini, Daniel H. Ahn, Islam Baiev, Alice Boileve, Melodie Tazdait, Lindsay Marie Hannan, Jingquan Jia, Hetal Desai Marble, Afsaneh Barzi, Vaibhav Sahai, Jochen K Lennerz, Robin Kate Kelley, Tanios S. Bekaii-Saab, Milind M. Javle, Nataliya Volodymyrivna Uboha, William P. Harris, Antoine Hollebecque
Journal: Journal of Clinical Oncology (2020)

e16686 Background: Genetic alterations in the FGFR pathway are emerging as promising therapeutic targets in CCA. The clinical and molecular features of patients (pts) with CCA harboring FGFR genetic alterations are reported here. Methods: A retrospective chart review was performed in pts with CCA who were found to have an FGFR alteration on tumor molecular profiling as part of routine care between 9/2007 and 12/2019. Data on demographics, risk factors, pathology, molecular characteristics, systemic therapies, radiographical response, time on treatment, and overall survival (OS) were collected in a multi-center collaborative effort across seven academic centers. Results: Among 135 pts with FGFR-altered CCA, the median age at diagnosis was 57 years old (range = 25-92 years), and 80 (59.3%) pts were female, 129 (95.6%) had intrahepatic CCA, and 6 (5.6%) had chronic HBV. At presentation, 28.2% of pts had resectable disease, including 65.0% with Stage I-II, 22.5% with Stage III, and 5.0% with Stage IV. At the time of initial diagnosis, CA19-9 was &lt; 35U/mL in 42.6% of pts. Bone metastases were observed in 41 (30.6%) pts with advanced disease. FGFR2 fusions were the most common FGFR alteration (68.2%), followed by FGFR2 mutations (21.5%), FGFR3 mutations (3.7%), FGFR2 rearrangements (1.5%), FGFR1 amplification (1.5%), and FGFR2 amplification (1.5%). The most common FGFR2 fusion partners were BICC1 (28.3%), SORBS1 (4.4%), POC1B (3.3%), and TACC2 (3.3%). The median lines of palliative systemic therapies received was 3 (range = 0-8), and 40/135 (29.6%) pts received a liver-directed therapy. For the 55 (59.8%) pts with FGFR2 fusions who received gemcitabine/cisplatin as first-line palliative systemic therapy, the median time on treatment was 6.2 months (95% CI: 4.1-9.3). The median OS from time of initial diagnosis was 36.1 months (95% CI: 28.3-51.6) in the FGFR2 fusion positive cohort. Among the 92 pts with FGFR2 fusions, 70 (76.1%) pts received an FGFR inhibitor on a clinical trial; 12 (17.1%) were subsequently treated with a second FGFR inhibitor, and 58.3% stayed on the second FGFR inhibitor for ≥4 months. Pts with a BICC1 fusion partner (n = 16) had an overall response rate of 42.9% on FGFR-selective inhibitors compared to 30.8% in non-BICC1 fusion partners (n = 54). Conclusions: Pts with CCA harboring FGFR alterations were found to have a high rate of normal CA19-9, high rate of bone metastases, and short median time on treatment on first-line palliative gemcitabine/cisplatin. Additional comparative studies are necessary to evaluate these findings.
A functional precision medicine 3D microtumor platform to identify and personalize novel indications.
Authors: Christian Apfel, David Chen, Juliana Baratta, Dhruva K. Mishra
Journal: Journal of Clinical Oncology (2020)

e15588 Background: We have previously validated our 3D microtumor platform that captures the tumor heterogeneity of a patient's primary tumor biopsy using a patient-derived xenograft model (Nikolov et al. ASCO 2019, e17076). Here we describe its utility to identify FDA approved therapies that may be effective for tumors previously not considered. Methods: A fresh tumor sample of a liver metastasis of a 45-year-old colorectal cancer patient was shipped overnight and processed to create hundreds of live 3D microtumors. These microtumors were treated with a panel of 12 commonly used drugs including chemotherapies and targeted therapies. Treatment effects were quantified and validated on fresh and cryopreserved/thawed samples using our metabolic and proprietary multiplexed fluorescent staining technologies to quantify the ratio of live and dead cells in those microtumors. Results: None of the conventional treatments in the 12-panel drug test suggested any efficacy as determined by the log of efficacy concentrations (in µmol/l): Oxaliplatin 2.59, 5-FU 3.00 (upper cut-off value), paclitaxel 1.72, topotecan 3.00, irinotecan (SN-38) 2.33, gemcitabine 2.44, and bevacizumab 3.00. The microtumors also appeared resistant to several targeted therapies that are not commonly given, ranging from 1.85 to 2.44. However, abemaciclib had an efficacy of 0.49, which was confirmed on thawed samples with all drug efficacy concentrations again suggesting resistance, except for abemaciclib at 0.67. Conclusions: Our 3D microtumor platform may be a useful tool a) to identify rescue treatment options for metastatic patients that have multi-resistant tumors and b) to identify novel indications to personalize FDA-approved cytotoxic or targeted therapies as a companion diagnostic.
Delivery of cancer survivorship education to community health care professionals.
Authors: Ashley Pariser, Javin Brita, Maura Harrigan, Scott Capozza, Angela Khairallah, Tara B. Sanft
Journal: Journal of Clinical Oncology (2020)

11032 Background: Cancer survivorship care is an integral part of oncology care. Although oncologists overwhelmingly demonstrate a desire to be a part of their cancer survivors’ care and management, only 60% of oncologists feel comfortable promoting healthy lifestyle behaviors, screening and prevention care. There is currently no standard of care for survivorship care education and data evaluating current educational models is limited. Methods: Project ECHO (Extension for Community Healthcare Outcomes) utilizes telehealth to promote long-distance learning and sharing of best practices. We utilized the Project ECHO model to deliver a survivorship curriculum in 6 hourly, biweekly sessions from October 2019 to December 2019. The curriculum was aligned with the 4 central tenets of survivorship care and was developed based on a needs assessment. Recruited participants included registered nurses (RN), registered dietitians (RD), advanced practice providers (APP), radiation oncologists and medical oncologists. Participants were enrolled in either a local ECHO curriculum or a national ECHO curriculum. Local Connecticut participants were invited to participate in semi-structured interviews to evaluate their experience. Results: Eight participants including 3 MDs, 1 APP, 1 SW and 3 RNs from 3 community oncology clinics in suburban Connecticut enrolled in the local ECHO curriculum. Twenty-eight participants including 17 RDs, 2 MDs, and 3 APPs from 13 hospital and community practices enrolled in the national ECHO curriculum. Four participants (50%) agreed to participate in semi-structured interviews. Motivations to participate included ease of participation and interest in survivorship. Participants described a positive experience, citing a well-structured curriculum and sense of community as highlights. Two participants described the sessions as empowering, leading to more discussions and engagement with survivors. All participants described an increased awareness of resources available for cancer survivors. Areas for improvement included greater assistance with technology and session time management. Concomitant patient care was the most cited barrier to participation. Conclusions: This pilot study is the first to demonstrate the feasibility of the Project ECHO model for delivering cancer survivorship education to community oncology providers. Further research evaluating the correlation between improved provider knowledge and survivorship care outcomes is needed.
Risk factors of chronic disease for high-risk population and its application in community
Authors: Rui-an Chen, Yan-ling Fu, Jia-li Bao, Xin-hua Tang, Yi Zheng, Chao-yang Zhu
Journal: BMJ (2013)

The individual intervention control of risk factors in high-risk population is one of key preventive measures of chronic disease. A total of 312 volunteers consulted physicians in one selected community. And 23 high-risk individuals of chronic disease were screened. The physicians customized the limit or requirement of diet, activity, tobacco and alcohol for each individual and made interventions of life behaviors according to the plans. The results showed that physical state of 20 (87%) of them converted from high-risk to health after interventions. Therefore customized control plan of individual risk factors is an effective control method of chronic disease.


Key words: 
Chronic disease; High-risk population
Becoming Your Healthiest Self: An Eat-Well, Get-Fit, Feel-Great Guide for Teens
Authors: Michelle Cardel, Aaron S. Kelly, Lindsay A. Thompson
Journal: JAMA Pediatrics (2020)

Becoming Your Healthiest Self: An Eat-Well, Get-Fit, Feel-Great Guide for Teens Parents, empower your adolescents so they can make choices that promote their healthiest self.Teens, getting older means making decisions about what matters to you most.Making healthy choices is a great place to start.Taking care of your physical, emotional, and mental health is what makes it possible for you to do all the things you want to do.
Gastric inflammatory prognostic index (GIPI) to predict efficacy of PD-1/PD-L1 immune checkpoint inhibitors in metastatic gastroesophageal junction (GOJ)/gastric cancer (GC) patients.
Authors: Cristina Morelli, Vincenzo Formica, Anna Patrikidou, Carmen Murias, Sabeeh-Ur-Rehman Butt, Antonella Nardecchia, Jessica Lucchetti, Nicola Renzi, Kai-Keen Shiu, Mario Roselli, Tobias Arkenau
Journal: Journal of Clinical Oncology (2020)

4530 Background: ICIs demonstrated improved overall survival (OS) in heavily pre-treated mGOJ/GC pts. Pts selection exclusively based on PD-L1 tissue expression appears to be suboptimal, despite data from subgroup analyses of KEYNOTE trials. Strong rationale suggests a potential predictive role of inflammatory biomarkers in ICIs treated mGOJ/GC pts. Methods: Ten systemic inflammatory markers [platelets, monocytes, neutrophil/lymphocyte ratio (NLR), platelets-lymphocyte ratio, lymphocytes, sum of mononuclear cells, albumin, lactate dehydrogenase, c-reactive protein (CRP) and serum globulin] were retrospectively analyzed at baseline in 57 mGOJ/GC pts with unknown PD-L1 status treated in second-line with ICIs, and correlated with OS. Least Absolute Shrinkage and Selection Operator (LASSO) method was used to select variables (preliminarily subject to optimal coding using HR smoothed curves for OS) with the highest prognostic value. Selected variables were then analyzed in a multivariate Cox Regression Model and used to build a GIPI nomogram. Results: NLR and CRP taken as continuous variables and albumin categorized as &lt; vs &gt; 30 g/dL were found as the most meaningful independent predictors of OS and used to build the GIPI nomogram. Nomogram-based lowest (l), mid-low, mid-high and highest (h) risk quartiles were associated with median(m)OS of 14.9, 7.1, 5.6 and 2.1 months (mos), respectively [HR of l vs h 4.94, p 0.0002]. By optimally dichotomizing CRP and NLR, pts with one or more of the following risk factors: NLR &gt;6, CRP &gt;15 mg/L, albumin &lt;30 g/dL (n: 29) had a mOS of 3.9 mos vs 14.2 mos of pts with no risk factor (n: 28) (HR 2.48, p 0.001). Conclusions: GIPI, combining NLR, CRP and Albumin, is the first inflammatory index with a significant prognostic value in mOGJ/GC pts receiving second-line ICIs. Its implementation in correlation with PD-L1 expression in the present cohort is ongoing. GIPI merits validation in independent cohorts and prospective clinical trials.
The HLA Ligand Atlas: A novel immuno-oncology resource for T-cell antigen discovery.
Authors: Ana Marcu, Leon Bichmann, Leon Kuchenbecker, Linus Backert, Daniel J Kowalewski, Lena-Katharina Freudenmann, Markus W. Löffler, Maren Lübke, Juliane Walz, Julia Velz, Holger Moch, Luca Regli, Manuela Silginer, Michael Weller, Andreas Schlosser, Oliver Kohlbacher, Stefan Stevanovic, Hans-Georg Rammensee, Marian Christoph Neidert
Journal: Journal of Clinical Oncology (2020)

3128 Background: The human leukocyte antigen (HLA) complex regulates the adaptive immune response by showcasing the intracellular and extracellular protein content to the immune system, which is the basis for T cell-dependent tumor rejection. Therefore, a comprehensive map of the entirety of both HLA class I- and class II-presented peptides from various benign tissues is a highly sought after resource, as it enables the definition of tumor-association on the immunologically pivotal level of the HLA ligandome. Methods: Human tissue samples were snap frozen post mortem during autopsy. The study was approved by the local IRB. HLA ligands were immunopurified and characterized using an Orbitrap Fusion Lumos mass spectrometer coupled to an Ultimate 3000 RSLC Nano UHPLC System. Data acquisition was performed as technical triplicates in data-dependent mode, and data were analyzed using the containerized, computational pipeline MHCquant. Results: In this work, we describe the HLA Ligand Atlas, a comprehensive collection of matched HLA class I and class II ligandomes from 29 non-malignant tissues and 13 human subjects (208 samples in total), covering 38 HLA class I, and 17 HLA*DRB alleles and comprising 48,381 HLA class I and 16,146 HLA class II peptides. Nearly 50% of HLA ligands have not been previously described. The HLA Ligand Atlas is publicly available as a raw data resource, but also in the form of a user-friendly web interface that allows users to quickly formulate complex queries against the data set. Both downloadable data and the query interface are available at www.hla-ligand-atlas.org. Conclusions: This data set provides a valuable tool for research in diverse fields such as systems biology, general immunology, autoimmune disease and organ transplantation. Most importantly, the HLA Ligand Atlas provides essential information for translational applications in immuno-oncology. The knowledge of HLA ligands from benign tissues strongly supports the informed design of proteogenomic HLA-dependent target discovery approaches.
Correlation of plasma PAC-1 and CD62P levels with diabetic nephropathy in type 2 diabetes mellitus
Authors: Dong-ying Li, Xiu-jun Bu, Hong Yang
Journal: BMJ (2010)

Three hundred and thirty eight patients with type 2 diabetes mellitus( DM) admitted from January 2006 to June 2009 and 50 healthy subjects (control group) were enrolled in the study. Platelet glycoprotein PAC-1 and CD62P levels were measured in both groups. Compared with control group, plasma PAC-1 and CD62P levels of DM patients increased significantly (P ＜0.01). Patients were divided into three groups according to their urinary albumin excretion rate ( UAER) . PAC-1 and CD62P levels in macroalbuminuria group (UAER≥200μg/min) were significantly higher than those in normoalbuminuria group( UAER <20μg/min) and microalbuminuria group (20μg/min≤UAER ＜ 200μg/min) (both P＜ 0.05). The results indicate that plasma levels of PAC-1 and CD62P, which reflect platelet activation, are the independent risk factors for diabetic nephropathy.

Key words: 
Diabetic nephropathy;  Platelet activating factor