tbuckley/cabot-search huggingface dataset:
Phase I study of NBTXR3 activated by radiotherapy in patients with advanced cancers treated with an anti-PD-1 therapy.
Authors: Colette Shen, Jessica Frakes, Jared Weiss, Jimmy J. Caudell, Trevor G Hackman, Jason A. Akulian, Ghassan El-Haddad, Yun Hu, Robert Dixon, Alexander T. Pearson, Hampartsoum B. Barsoumian, Maria Angelica Cortez, Katherine LaRoque Jameson, Patricia Said, James William Welsh, Tanguy Y. Seiwert
Journal: Journal of Clinical Oncology (2020)

TPS3173 Background: Despite the past decade of transformative advances in immuno-oncology, the response rate to checkpoint inhibitors (ICIs) remains low (~15%). There is significant interest in developing strategies to overcome resistance to these treatments, thus increasing response rate. Emerging evidence suggests that radiation therapy (RT) could potentially augment the antitumor response to ICIs through synergic effect. However, RT dose and ultimate efficacy are limited by toxicity related to exposure of healthy tissues. NBTXR3 is a first-in-class radioenhancer administered by direct intratumoral injection, designed at the nanoscale to increase RT dose deposition within tumor cells and RT-dependent tumor cell killing, without increasing surrounding normal tissue toxicity. Preclinical and early clinical data suggest NBTXR3 activated by RT can trigger an anti-tumor immune response, producing both local and systemic (abscopal) effects. We hypothesize that NBTXR3 activated by RT, in combination with anti-PD-1 therapy (R3/RT/PD-1), will act synergistically to maximize the local RT effect and produce a systemic response sufficient to increase the proportion of ICI responders or convert ICI non-responders to responders. Methods: This trial [NCT03589339] is a multicenter, open-label, phase I study to evaluate safety and tolerability of R3/RT/PD-1 in three cohorts: (1) Locoregional recurrent or recurrent and metastatic head and neck squamous cell carcinoma (HNSCC) amenable to re-irradiation of the HN field, (2) Lung metastases, or (3) Liver metastases, both from any primary cancer eligible for anti-PD-1 treatment. Approximately two-thirds of patients in each cohort will be anti-PD-1 non-responders. NBTXR3 injected volume is based on a percentage of gross tumor volume (GTV). The primary objective is to determine the R3/RT/PD-1 recommended phase 2 dose in each cohort. Secondary objectives are to evaluate anti-tumor response (objective response rate; ORR), safety and feasibility of NBTXR3 injection, and NBTXR3 body kinetic profile. Exploratory objectives will assess biomarkers of R3/RT/PD-1 response, including PD-L1 status by IHC, as well as mRNA and cytokine immune marker profiling. To date, three patients have been treated, one in cohort 1, two in cohort 2. Clinical trial information: NCT03589339 .
Learning strategies for family medicine residents on clinical rotations
Authors: Siqing Lian, Xia Tao, Chunhua Chi, Fetters Michael Derwin
Journal: BMJ (2019)

Many clinical teachers who train general practice residents are specialists from other departments and are not fully familiar with the work of general practitioners. By socio-culturally adapting concepts from the Preceptor Education Project (PEP) developed over the past 25 years in the United States, this paper provides seven principles general practice residents can consider during rotations in other specialties. (1) Having clear learning objectives makes teaching and studying easier; (2) Teaching takes time, (3) Ask to be observed; (4) Teaching physicians should evaluate you; (5) Patients may resent meeting with a medical resident; (6) Make allies and treat them well; (7) Teach others. These principles can guide general practice residents to take responsibility for excellent training.


Key words: 
General practice; Resident training; Clinical training; Learning principles
Metastatic Parathyroid Hormone-Secreting Prostate Adenocarcinoma Mimicking Ectopic Parathyroid Adenoma Demonstrated on 99mTc-MIBI Image
Authors: Yu-Hung Chen, Yung-Hsiang Hsu, Hwa-Tsung Chen, Bee-Song Chang, Shu-Hsin Liu
Journal: Clinical Nuclear Medicine (2020)

Abstract 99m Tc-MIBI has long been used to localize hyperfunctioning parathyroid tissue in patients with hyperparathyroidism. This tracer can also concentrate in various neoplastic tissues including prostate adenocarcinoma. We herein report a case with parathyroid hormone-secreting metastatic prostate cancer mimicking an ectopic parathyroid adenoma on the 99m Tc-MIBI scan. We conclude that metastatic prostate cancer should be included as one of the differential diagnoses when interpreting 99m Tc-MIBI scan.
Impact of chemotherapy alone or in combination with an anti-angiogenic on the immune tumor microenvironment (TME) of ovarian cancer: Data from the randomized CHIVA trial (a GINECO –GINEGEPS study).
Authors: Elisa Yaniz, Catherine Genestie, Christophe Klein, Flore Salviat, Isabelle Laure Ray-Coquard, Florence Joly, Gwenael Ferron, Eric Pujade-Lauraine, Patricia Pautier, Alexandra Leary
Journal: Journal of Clinical Oncology (2020)

6011 Background: The neoadjuvant setting is an excellent opportunity to study ‘ in vivo’ the biological impact of treatment on tumor cells and the immune TME. Both chemotherapy and anti-angiogenics may have immunomodulatory properties which could prime the TME and increase effectiveness of immunotherapeutic agents. We performed comprehensive multiplexed immune biomarker analyses on paired tumor samples at diagnosis and after 3 cycles of neoadjuvant carboplatin+paclitaxel (CP) +/- the anti-angiogenic tyrosine kinase inhibitor nintedanib (N) in the randomized CHIVA trial. Methods: Patients were randomized 2:1 to CP + N or placebo for 3 cycles prior to interval debulking, samples were evaluable for immune profiling for 124 pts at diagnosis and 107 at surgery from the CHIVA trial. For 86 patients matched paired samples were available. Multiplexed IF or IHC panels were performed for CD4, CD3, CD8, CK, Granzyme B, FOXP3, CD68, CD163 and DC-Lamp. Wilcoxon tests were used to compare measurements. Results: At diagnosis the most abundant cells were CD8+ and CD4+ cells (median=118 and 119cells/mm2, respectively) compared to Foxp3+ TRegs (median=30/mm2). Among the myeloid lineage, the proportion of CD68+ (M1) and CD163+ (M2) macrophages was balanced, while mature dentritic cells (DC) represented &lt;5% of myeloid cells. In the whole population, regardless of arm, neoadjuvant platinum-based treatment significantly increased CD4+ (p=0.03) and CD8+ infiltration (p=0.009), decreased FOXP3+ cells (p=0.01), and these differences pre- and post-treatment remained significant when analysis was restricted to pts with paired samples. Mature DC also increased significantly with neoadjuvant treatment (p=0.0003), there was no significant modification in CD68+ or CD163+ macrophages. Changes in immune parameters did not differ significantly between the CP+B vs CP+placebo arms. Conclusions: Neoadjuvant treatment has a profound impact on the immune cell composition of the TME in advanced OC. However this change seems to be mainly mediated by platinum+paclitaxel chemotherapy rather than the anti-angiogenic tyrosine kinase inhibitor nintedanib.
Analyses on the change of medical care and health services utilization of Yayuncun community residents in Beijing
Authors: Xiao-guo Zheng, Feng Xiao, Bo-wen Chen
Journal: BMJ (2010)

Objective To know the change of  care and health services utilization of Yayuncun community residents in Beijing. Methods Using the prospective study, residents above 15 years old were selected to answer the Beijing Typical Community Resident Questionnaire designed by the local researchers. In 2004 and 2005, the baseline survey was carried. From 2006 to 2008, same questionnaire was used to follow-up survey, and 1412 residents were selected into the last study. Results The proportion of people who should see a doctor but not in past month were decreased, the differences among the three years were significant (P ＜ 0. 01 ); The top three reasons that who should see a doctor but not were the medical care costs too high, self- felt the sickness light, self-treatment. The residents who went to the community health agencies increased from 2006 to 2008. The  costs ( drugs,  fees,inspection fees) decreased from 2006 to 2008, the differences were significant (P ＜0. 01 ) ;The satisfaction increased from 2006 to 2008, the differences were significant ( P ＜ 0. 01 ). Conclusion Under the comprehensive promotion of community health services in Beijing, the satisfaction and the utilization of  care and health services were improved.

Key words: 
Community health services;  Health resources;  Follow-up studies
Ways of acquiring and needs of requiring disease-related knowledge among patients with inflammatory bowel disease
Authors: Saizheng Lin, Yan Chen, Qunfen Cao
Journal: BMJ (2018)

Objective
To survey the ways of acquiring and the needs of requiring disease-related knowledge among patients with inflammatory bowel disease (IBD).


Methods
A total of 376 IBD patients visiting the special clinic in the Second Affiliated Hospital of Zhejiang University School of Medicine from May 2013 to March 2016 participated in a questionnaire survey. The self-designed questionnaire included general information, hospital visits and internet use of the IBD patients.


Results
Totally 359 valid questionnaires were returned with a recovery rate of 95.5% (359/376). Among the participants there were 226 men and 133 women with a mean age of 41.8 years (14- 88 years); and 199 cases of Crohn disease (55.4%) and 160 cases of ulcerative colitis 44.6%. The main methods of acquiring IBD-related knowledge were information from IBD specialist (77.7%, 279/359) and using the internet (59.3%, 213/359). The most frequently searched itemsin internet werelong-term prognosis (97.2%, 207/213), medical treatment (76.1%, 162/213), etiology (58.2%, 124/213) and nutrition treatment (51.6%, 110/213); 96.6% (347/359) patients showed strong interest in keeping close connection with IBD specialist and 89.0% (319/359) wanted to join a IBD club.


Conclusion
IBD patients show strong interest indisease-related knowledge, which they acquire most from the doctors and the internet, IBD specialists are expected to provide the detailed health education for patients.


Key words: 
Colitis, ulcerative; Crohn disease; Access to information
Orvacabtagene autoleucel (orva-cel), a B-cell maturation antigen (BCMA)-directed CAR T cell therapy for patients (pts) with relapsed/refractory multiple myeloma (RRMM): update of the phase 1/2 EVOLVE study (NCT03430011).
Authors: Sham Mailankody, Andrzej J. Jakubowiak, Myo Htut, Luciano J. Costa, Kelvin Lee, Siddhartha Ganguly, Jonathan L. Kaufman, David Samuel DiCapua Siegel, William Bensinger, Mariana Cota, Thomas Doerr, Todd DeVries, Sandy Wai Kuan Wong
Journal: Journal of Clinical Oncology (2020)

8504 Background: Orva-cel is an investigational, BCMA-directed CAR T cell product with a fully human binder. Over 100 pts have been treated in the EVOLVE phase 1 study. Pts treated at 50 and 150 × 10 6 CAR+ T cells were previously reported (Mailankody ASH 2018 #957). We now report results of the higher dose levels (DLs) in 51 pts who received orva-cel manufactured using the process intended to support commercial use. Methods: Pts with RRMM who had ≥3 prior regimens, a proteasome inhibitor (PI), an immunomodulatory drug (IMiD), and an anti-CD38 monoclonal antibody (mAb), received orva-cel at 300, 450, and 600 × 10 6 CAR+ T cells after lymphodepletion with fludarabine/cyclophosphamide. Results: Median pt age was 61 (range, 33–77) y; median time from diagnosis was 7.0 (range, 1.7–23.6) y, with a median of 6 (range, 3–18) prior regimens. Overall, 92% of pts were penta-exposed (2 IMiDs, 2 PIs, and an mAb); 61% of pts received bridging therapy (77% were refractory to bridging therapy). Two pts had dose-limiting toxicities: grade 3 neurological event (NE) for &gt;7 d at 300 × 10 6 CAR+ T cells and grade 4 neutropenia for &gt;28 d at 450 × 10 6 CAR+ T cells. Key efficacy and safety outcomes are shown in the Table. Cytokine release syndrome (CRS)/NEs were managed with tocilizumab and/or steroids (78%), anakinra (14%), and/or vasopressors (6%). Grade ≥3 anemia, neutropenia, and thrombocytopenia at 29 d occurred in 21%, 55%, and 44% of pts (median time to resolution to grade ≤2 of any cytopenia, ≤2.1 mo). Grade ≥3 infections occurred in 14%. After a median follow-up (F/U) of 5.9 mo, median progression-free survival was not reached. Conclusions: Orva-cel at 300, 450, and 600 × 10 6 CAR+ T cells demonstrated manageable safety (CRS grade ≥3: 2%; NE grade ≥3: 4%) and compelling efficacy in heavily pretreated pts with RRMM, with a 91% objective response rate (ORR) and 39% complete response (CR)/stringent CR (sCR) rate. Updated results will be presented, including minimal residual disease, durability of response, and recommended phase 2 dose. Clinical trial information: NCT03430011 . [Table: see text]
The impact of integrating an oncology nurse practitioner into an acute care hospital emergency department: An Australian tertiary cancer centre experience.
Authors: Gillian Blanchard, Antonino Bonaventura, Nicholas Dafters, Fiona Day, Craig Gedye, Johann Gildenhuys, Janine Margaret Lombard, James F. Lynam, Girish Mallesara, Ina Nordman, Andre Van Der Westhuizen, Hiren A. Mandaliya
Journal: Journal of Clinical Oncology (2020)

e14029 Background: A significant delay in oncology patient journey through emergency department (ED) due to various reasons such as multiple specialists involved, difficulty in accessing timely advice from extremely busy inpatient/outpatient oncology teams, etc. In order to streamline admissions and discharges for oncology patients, a new model of care was created with the introduction of oncology nurse practitioner (ONP) at Calvary Mater Newcastle ED. This model operated during business hours three days a week with an aim to improve continuity of care, to enhance patients’ experience and meet organisations key performance indicators (KPIs). Limited research into the impact of these services on patient care and patient experience, particularly from service users’ perspective. Methods: A retrospective audit (6 months) has been undertaken to determine the impact of this model of care on time to specialty transfer, number of admissions versus discharges and patients representations through ED when ONP was available versus standard care. Results: During the audit period, ONP reviewed 149 patients. Fifty-four (36%) patients were discharged and of those 6 (11%) returned (within 28 days) with same or related issues. There was an average reduction in time to disposition planning for ED oncology patients of approximately 83 (193 vs 110) minutes when ONP was present at ED (one month review). Using a raw bed day costing, this resulted in a significant financial saving. Further cost analysis of this model is underway. Conclusions: The introduction of ONP into an acute care hospital ED has proven to be effective in terms of continuity of patient care, financial savings and assisted ED in meeting KPIs. The perception within the senior emergency management team is that this new model of care has been an unqualified success. ONP has rapidly and effectively joined emergency team and has seamlessly adjusted practice to the new environment. ED remains highly supportive of this new model of care. This model of care is one that could be translated easily to other specialities. Further analysis will be presented at the time of ASCO meeting.
高血压患者的健康教育和管理
Authors: 王增武, 郭瑞
Journal: BMJ (2012)

对高血压患者进行多种形式的健康教育,有助于患者了解高血压的危害及预防、治疗的措施,明确坚持药物治疗和积极改善生活方式的重要意义,从而积极配合治疗并自觉采取有益于健康的生活方式.规范高效的高血压管理有助于增加患者的信任感和依从性,最终提高高血压控制率。
Whipworm and roundworm infections
Authors: Kathryn J. Else, Jennifer Keiser, Celia V. Holland, Richard K. Grencis, David B. Sattelle, Ricardo T. Fujiwara, Lilian L. Bueno, Samuel O. Asaolu, Oluyomi A. Sowemimo, Philip J. Cooper
Journal: Nature Reviews Disease Primers (2020)

Trichuriasis and ascariasis are neglected tropical diseases caused by the gastrointestinal dwelling nematodes Trichuris trichiura (a whipworm) and Ascaris lumbricoides (a roundworm), respectively. Both parasites are staggeringly prevalent, particularly in tropical and subtropical areas, and are associated with substantial morbidity. Infection is initiated by ingestion of infective eggs, which hatch in the intestine. Thereafter, T. trichiura larvae moult within intestinal epithelial cells, with adult worms embedded in a partially intracellular niche in the large intestine, whereas A. lumbricoides larvae penetrate the gut mucosa and migrate through the liver and lungs before returning to the lumen of the small intestine, where adult worms dwell. Both species elicit type 2 anti-parasite immunity. Diagnosis is typically based on clinical presentation (gastrointestinal symptoms and inflammation) and the detection of eggs or parasite DNA in the faeces. Prevention and treatment strategies rely on periodic mass drug administration (generally with albendazole or mebendazole) to at-risk populations and improvements in water, sanitation and hygiene. The effectiveness of drug treatment is very high for A. lumbricoides infections, whereas cure rates for T. trichiura infections are low. Novel anthelminthic drugs are needed, together with vaccine development and tools for diagnosis and assessment of parasite control in the field. Whipworm and roundworm infections are neglected tropical diseases caused by the gastrointestinal nematode parasites Trichuris trichiura and Ascaris lumbricoides, respectively. These soil-transmitted helminths are prevalent in tropical areas and affect hundreds of millions of people, with substantial morbidity and disease burden.
子宫颈癌流行病学研究进展
Authors: 李广太
Journal: BMJ (2009)

子宫颈癌是全球女性中仅次于乳腺癌的第二位妇科恶性肿瘤,是位于乳腺癌和肺癌之后的常见死亡原因之一.据估计我国每年有宫颈癌新发病例13.15万,占世界新发病例总数的四分之一以上,每年约有5万多患者死亡.现就流行病学进展予以概述。
Validation of an exome and transcriptome based diagnostic platform enabling clinical cancer therapy selection and emerging composite biomarkers for immunotherapy.
Authors: Juan-Sebstian Saldivar, Jason Harris, Sejal Desai, Erin Ayash, Prateek Tandon, Twinkal Marfatia, Robert Power, Massimo Morra, Manju Chinnappa, Michael James Clark, Rena McClory, Richard Chen
Journal: Journal of Clinical Oncology (2020)

e15583 Background: While immunotherapy has become a pillar of cancer treatment, diagnostic biomarkers that consistently predict patient response to these therapies have remained elusive. There is an increasing need for the development of integrative, composite biomarkers that can model the complex biology driving response and/or resistance to immunotherapy more effectively than existing single-analyte approaches. However, the majority of current cancer diagnostic panels, with their focus on a small set of genes, provide limited ability to support these emerging advanced biomarkers. Methods: To address these limitations, we developed and validated NeXT Dx, a comprehensive enhanced exome and transcriptome based diagnostic platform designed to simultaneously characterize tumor and immune genomics from a single limited FFPE sample. To achieve higher accuracy and sensitivity for an exome scale diagnostic platform, we developed an augmented exome assay that improves uniformity of coverage across all ~20,000 genes, including boosted coverage of 248 clinically-relevant cancer genes. We validated this assay using genomic DNA and RNA extracted from tumor-derived cell-lines, constructs, clinical FFPE samples, and proficiency testing samples. The assay utilizes &gt; = 25ng of co-extracted DNA and RNA which were sequenced using Illumina NovaSeq instruments at our CAP-accredited, CLIA-certified laboratory. Additional assay enhancements for HLA, immune repertoire, and oncoviruses were designed to further optimize the platform for immunotherapy biomarker discovery applications. Results: Validation of NeXT Dx demonstrated a performance of 99.5% sensitivity and 99.8% positive predictive value (PPV) for SNVs with &gt; = 5% AF; 98.7% sensitivity and 97.4% PPV for indels with &gt; = 10% AF; 97.2% sensitivity and 94.6% PPV for CNAs in samples with &gt; = 30% tumor content; 94.9% sensitivity and 94.9% PPV for fusions; and a 2.1% error rate for MSI classification. TMB was calculated using gold-standard whole exome data from SNVs and indels. Typical median coverage depth was &gt; 1,000X for 248 clinically-relevant genes, ~300X for the remaining (whole exome) footprint. Conclusions: With NeXT Dx, we demonstrate a exome/transcriptome scale diagnostic platform that can detect current clinical biomarkers with high sensitivity as well as support emerging, advanced biomarkers that integrate across both tumor and immune features.
A randomized multicenter phase II trial to evaluate the safety and efficacy of vaccination with folate receptor alpha (FRα) peptides admixed with GM-CSF as an adjuvant versus GM-CSF alone in patients with platinum-sensitive ovarian cancer (EOC).
Authors: Roisin Eilish O'Cearbhaill, Jason A. Konner, Matthew Stephen Block, James Potts, Gerald Garrett, Richard Kenney, Robert Michael Wenham
Journal: Journal of Clinical Oncology (2020)

6040 Background: FRα is overexpressed on &gt; 90% of high-grade EOC. We conducted a randomized double-blind multicenter phase II clinical trial to evaluate the safety and efficacy of TPIV200 (a multi-epitope FRα peptide vaccine admixed with GM-CSF adjuvant) versus GM-CSF alone as a control in patients with stage III-IV high-grade platinum-sensitive epithelial ovarian, fallopian tube, or primary peritoneal carcinoma in first complete or partial remission, irrespective of baseline level of FRα expression. Methods: Patients with stage III-IV high-grade serous, high-grade endometrioid, carcinosarcoma or poorly differentiated EOC who had previously completed standard upfront therapy without evidence of disease progression and who were within a year of last platinum were randomized 1:1 to intradermal vaccination of TPIV200 versus intradermal GM-CSF alone. The vaccination period included 6 administrations of the study drug at 4-week intervals. Up to 6 booster vaccinations at 12-week intervals were permitted for patients who did not have disease progression. AEs were assessed using CTCAE. Tumor response was assessed via RECIST every 12 weeks. The primary endpoint, progression free survival (PFS), was calculated from date of first vaccination to the date of progression, death or study termination. Results: Of 120 patients randomized, 63 (53%) were treated on the TPIV200 arm. The median age at study entry was 63 years (range 37-88). AEs were generally mild. Injection site reaction was more frequent in the TPIV200 (63%) versus GM-CSF arm (39%). The other most common AEs, abdominal pain (25%) and fatigue (23%), were comparable in both arms. At study termination with a median follow-up of 15.2 months (range: 1.2-28.3 months), 68 of 119 intention-to-treat patients had progressed (55% in the TPIV200 arm and 59% in the GM-CSF arm). The median PFS was 11.1 months (95% CI: 8.3-16.6 months) and there was no statistically significant difference in median PFS between the arms (10.9 months with TPIV200 versus 11.1 months with GM-CSF, HR = 0.85 [upper 90% CI = 1.17]). Conclusions: Although TPIV200 had a manageable safety profile, the study was terminated for futility after the planned interim analysis. Future development of FRα-targeted therapy will likely focus on the careful selection of patients whose cancers show high FRα expression. Clinical trial information: NCT02978222.