tbuckley/cabot-search huggingface dataset:
Long-Term Rituximab Use to Maintain Remission of Antineutrophil Cytoplasmic Antibody–Associated Vasculitis
Authors: Pierre Charles, Élodie Perrodeau, Maxime Samson, Bernard Bonnotte, Antoine Néel, Christian Agard, Antoine Huart, Alexandre Karras, François Lifermann, Pascal Godmer, Pascal Cohen, Catherine Hanrotel-Saliou, Nicolas Martin-Silva, Grégory Pugnet, François Maurier, Jean Sibilia, Pierre-Louis Carron, Pierre Gobert, Nadine Meaux-Ruault, Thomas Le Gallou, Stéphane Vinzio, Jean-François Viallard, Eric Hachulla, Christine Vinter, Xavier Puéchal, Benjamin Terrier, Philippe Ravaud, Luc Mouthon, Loïc Guillevin
Journal: Annals of Internal Medicine (2020)

Biannual rituximab infusions over 18 months effectively maintain remission after a "standard" remission induction regimen for patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV).To evaluate the efficacy of prolonged rituximab therapy in preventing AAV relapses in patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) who have achieved complete remission after completing an 18-month maintenance regimen.Randomized controlled trial. (ClinicalTrials.gov: NCT02433522).39 clinical centers in France.68 patients with GPA and 29 with MPA who achieved complete remission after the first phase of maintenance therapy.Rituximab or placebo infusion every 6 months for 18 months (4 infusions).The primary end point was relapse-free survival at month 28. Relapse was defined as new or reappearing symptoms or worsening disease, with a Birmingham Vasculitis Activity Score greater than 0.From March 2015 to April 2016, 97 patients (mean age, 63.9 years; 35% women) were randomly assigned, 50 to the rituximab and 47 to the placebo group. Relapse-free survival estimates at month 28 were 96% (95% CI, 91% to 100%) and 74% (CI, 63% to 88%) in the rituximab and placebo groups, respectively, an absolute difference of 22% (CI, 9% to 36%) with a hazard ratio of 7.5 (CI, 1.67 to 33.7) (P = 0.008). Major relapse-free survival estimates at month 28 were 100% (CI, 93% to 100%) versus 87% (CI, 78% to 97%) (P = 0.009), respectively. At least 1 serious adverse event developed in 12 patients (24%) in the rituximab group (with 9 infectious serious adverse events occurring among 6 patients [12%]) versus 14 patients (30%) in the placebo group (with 6 infectious serious adverse events developing among 4 patients [9%]). No deaths occurred in either group.Potential selection bias based on previous rituximab response and tolerance.Extended therapy with biannual rituximab infusions over 18 months was associated with a lower incidence of AAV relapse compared with standard maintenance therapy.French Ministry of Health and Hoffmann-La Roche.
Would patients benefit from a decision aid for surgical decision making for rectal cancer? A qualitative analysis.
Authors: Jenaya Goldwag, Catherine Saunders, Jackson Read, Marie-Anne Durand, Glyn Elwyn, Srinivas J Ivatury
Journal: Journal of Clinical Oncology (2020)

e19139 Background: Rectal cancer surgery drastically changes the lives of patients. Decision aids available to guide patients on this decision are limited and of poor quality. We aimed to identify the content and delivery preferences of rectal cancer survivors who have faced this surgical decision and colorectal surgeons to guide future decision aid creation. Methods: We performed semi-structured interviews of survivors and their caregivers, as well as colorectal surgeons from April through August 2019. We purposively sampled patients treated surgically for rectal cancer and colorectal surgeons to include different demographics, surgical experiences, and practice types. We achieved thematic saturation in both groups. We performed dual coding and inductive thematic analysis. Results: A total of 30 participants were interviewed, 15 patients with 5 caregivers, and 10 colorectal surgeons. Patient demographics demonstrated an equal distribution of sex, age categories, and operative type. Physician demographics demonstrated a mean of 10±7 years in practice with 70% academic and 30% private practice. Main themes for both groups stated that a massive patient educational need exists throughout the continuum of disease into survivorship. Participants emphasized the need for a comprehensive educational tool to address these needs rather than a decision aid. Both wanted a tool that was personalized, simple, understandable, visually appealing, interactive, and delivered in a combination of modalities to capture the broadest audience. Patients also desired specific features like care timelines and resources. Surgeons felt than an educational tool would enhance patient/provider interaction by reinforcing material covered in clinic. Conclusions: A surgical decision aid for rectal cancer is not enough. Patients and surgeons acknowledged the need for a comprehensive tool to address the educational gap that exists through the continuum of rectal cancer care.
胸段硬膜外麻醉和术后镇痛对胃肠功能的影响
Authors: 徐然, 吴安石
Journal: BMJ (2010)

胸段硬膜外麻醉(thoracic epidual anesthesia,TEA)复合全身麻醉(全麻)是近10年来广泛使用的胸部和上腹部手术的麻醉方法.硬膜外自控镇痛(patient-controlled epidural analgesia,PCEA)因其镇痛效果确切、用药量少、不良作用少,尤其是减少了疼痛所带来的术后并发症,目前已被外科和麻醉医生接受.以往动物模型和临床应用TEA的研究结果表明,在使用TEA期间,内脏交感神经的活动会减少,但高位TEA对内脏交感神经活动的影响仍然不清楚,因此TEA对胃肠灌注的影响还不是很明确。
Long-term immune-related adverse events under PD-1 inhibitors: a multicenter prospective cohort study (MELBASE).
Authors: Charlee Nardin, Stéphane Dalle, Marie Thérèse Leccia, Laurent Mortier, Sophie Dalac-Rat, Caroline Dutriaux, Delphine Legoupil, Henri Montaudie, Olivier Dereure, Julie De Quatrebarbes, Florence Granel-Brocard, Myrtille Le-Bouar, Julie Charles, Florence Brunet-Possenti, Brigitte Dreno, Wendy Lefevre, Clara Allayous, Celeste Lebbe, Francois Aubin
Journal: Journal of Clinical Oncology (2020)

10057 Background: PD-1 inhibitors (anti-PD1) are frequently associated with immune-related adverse events (IRAE). Since melanoma patients included in clinical trials were frequently treated during two years, data on IRAE occurring after 2 years of treatment are lacking. This study aimed to describe IRAE in melanoma patients treated with anti-PD1 for longer than 2 years in a real-life setting. Methods: Patients were screened from MelBase, a French multicentric biobank dedicated to the prospective follow-up of unresectable stage III or IV melanoma. All patients who received anti-PD1 for at least 2 years between January 2013 and November 2019 were included. Among them, patients who experienced IRAE and long-term IRAE defined as IRAE occurring after 2 years of anti-PD1 were identified. Results: Among 1849 patients with advanced melanoma included in Melbase, 119 patients received anti-PD1 monotherapy during at least 2 years, from January 2013 to November 2019, with a median follow-up of 41.7 months (25.2-57.5). Patients characteristics at treatment initiation were: male gender (61%), mean age of 63 years old, past history of autoimmune disease (11%), BRAF WT (72%), AJCC stage IV (84%), brain metastases (22%), ECOG 0-1 (88%) and normal LDH (56%). Patients were treated with Nivolumab (n = 53) or Pembrolizumab (n = 66). IRAE occurred in 99 patients (83%) with a median time of 13.3 months (0-53.9), including severe IRAE (grade 3 or 4) in 30 patients (30%). Long-term IRAE, mostly grades 1-2, occurred in 52 patients (43%). Long-term IRAE led to 5 hospitalizations (4%) of which 4 were grades 3-4. Among patients with long-term IRAE, 45 patients (87%) previously experienced IRAE within the first 2 years of anti-PD1 and 29 patients (56%) experienced multiple IRAE. Conclusions: Our data demonstrate that long-term IRAE are frequent especially in patients who already experienced IRAE within the first two years of treatment. These data should be taken into account to establish formal recommendations on the duration of anti-PD1 therapy.
Moving beyond PARP Inhibition in ATM-Deficient Prostate Cancer
Authors: Jeremy S. Setton, Simon N. Powell
Journal: Cancer Research (2020)

Abstract DNA repair defects are found in primary and metastatic prostate cancer. Alterations in the ATM gene are the second most common defect after BRCA2, but their sensitivity to PARP inhibitors has been questioned by recent clinical literature. The work by Rafiei and colleagues in this issue of Cancer Research now supports this observation with genetically engineered cells and quantitative responses. ATR inhibitors have not yet found a clear role in the clinic, but the new work suggests that ATM-deficient cancers may be more vulnerable to ATR inhibition rather than PARP inhibitors, which is a testable hypothesis for clinical trials. See related article by Rafiei et al., p. 2094
Quantifying unmeasured confounding in three epidemiological studies associating myelodysplastic syndromes (MDS) with cardiovascular disease (CVD).
Authors: Abhay Singh
Journal: Journal of Clinical Oncology (2020)

e19532 Background: Confounding occurs when an investigator studies the effect of an exposure on the occurrence of an outcome, but in the process measures the effect of another factor (a confounding variable). Knowledge of possible causal pathways assists an investigator to minimize confounding, but despite utmost attempts, errors are frequent. To assess role of a possible confounder (smoking), data from 3 studies (1. Herrera at al. 2019 2. Goldberg et al. 2010 and 3. Brunner et al. 2017) associating MDS (exposure) with CVD (outcome) was used to conduct sensitivity analysis. Methods: 2 x 2 tables were constructed with data from 3 studies (part 2 of table below). A vector defining the proportion of confounder (smoking) among exposed [prop (Smoking+|MDS+)], unexposed [prop (Smoking+|MDS-)] and risk ratio associating smoking status with CVD (part 1) using historical data was deduced. Extracted data was added to online bias analysis tool ( https://sites.google.com/site/biasanalysis/ ) to calculate crude as well as mantel-haenszel (MH) relative risk (RR) adjusted for smoking. Results: RRs unadjusted for smoking status for studies 1, 2 and 3 were 1.31, 1.34 and 2.21, respectively, signifying increased risk of CVD in MDS patients (part 3). Upon adjustment for smoking status, MH-RR for MDS-CVD relationship was 0.95, 0.97 for studies 1 and 2 respectively, signifying no increased CVD risk and 1.59 for study 3 signifying increased CVD risk but lower upon adjustment. Conclusions: Making inference of MDS-CVD association without accounting for smoking status can blur effects and at times result in false associations. Given ambiguity in results from these 3 studies, further evidence is needed to better assess MDS-CVD relationship. A simple online tool allows estimating nonrandom errors, assess magnitude and direction of biases, and help clinicians/researchers quantify these biases for better interpretation of observational data in a time efficient manner. Other bias analyses for these studies will be presented. [Table: see text]
Knowledge and attitude towards hierarchical medical system among patients in Beijing Xicheng district community health service centers
Authors: Yongfeng Tian, Ningyan Li
Journal: BMJ (2018)

Objective
To assess the knowledge and attitude towards hierarchical medical system among patients in Beijing Xicheng district  health service centers.


Methods
A questionnaire survey was conducted between July and August 2016, among randomly-selected patients who were visiting  health service  in Beijing Xicheng district.


Results
A total of 2 770 patients were investigated. The percentage of patients who knew the hierarchical medical system was 62.2% (1 722/2 770). Logistic regression showed that the degree of knowledge was significantly correlated with the visit number in the recent year and the education levels of patients. The percentage of patients who had a positive attitude to the system was 89.5% (2 478/2 770). The main reasons for negative attitude to the system were worry about the delay of  , inconvenience and fewer drugs in  health service centers and weak capacity of  health service centers . Logistic regression showed that the education level was negatively correlated with the attitude. In the case of mild illness, 2, 485 (89.7%) participants would chose community health service center or service station .


Conclusions
The knowledge of hierarchical medical system among patients in  health institutions are moderately high, while most of them have positive attitude towards the system. The service capacity of  health service institutions should be further improved, and publicity should be strengthened to improve the awareness of hierarchical medical system among  residents.


Key words: 
Community health service; Questionnaires; Dividing treatment by diagnosis
Covid-19: Test and trace programmes are important but no silver bullet, say scientists
Authors: Shaun Griffin
Journal: BMJ (2020)

The success of test, trace, and isolate programmes to control the covid-19 pandemic will depend on how quickly tests can be performed and results delivered, public compliance, and monitoring, a data analytics group convened by the Royal Society has said.

A test, trace, and isolate system to tackle the covid-19 outbreak was launched in England and Scotland on 28 May,1 with one planned for Wales and one already operating in Northern Ireland.

The DELVE (data evaluation and learning for viral epidemics) group said that such programmes can only help control the UK covid-19 epidemic if they are effectively implemented and form part of a wider package of interventions that …
心房颤动的抗栓治疗
Authors: 许俊堂, 胡大一
Journal: BMJ (2006)

非瓣膜病性房颤患者使用抗栓药物的目的是防止心房内血栓形成,防止发生脑动脉或者外周动脉栓塞;对已经存在心房内血栓的患者,抗栓治疗能防止血栓延展或新的血栓形成,防止血栓脱落导致脑动脉或外周动脉栓塞;在准备电复律的患者,抗栓治疗的目的是保证电复律前后不发生血栓栓塞事件。
Clinically advanced renal cell carcinoma (RCC) and renal sarcoma (RSC) in young patients: A comprehensive genomic profiling (CGP) study.
Authors: Gennady Bratslavsky, Andrea Necchi, Petros Grivas, Oleg Shapiro, Joseph M Jacob, Julia Andrea Elvin, Jo-Anne Vergilio, Jonathan Keith Killian, Erik Abraham Williams, Shakti H. Ramkissoon, Eric Allan Severson, Amanda Hemmerich, Alexa Betzig Schrock, Kimberly McGregor, Venkataprasanth P. Reddy, Brian Michael Alexander, Natalie Danziger, Mehdi Mollapour, Brian M. Shuch, Jeffrey S. Ross
Journal: Journal of Clinical Oncology (2020)

5066 Background: We queried whether the landscape of genomic alterations (GA) would differ in patients with metastatic RCC under 40 years of age (under40) and patients 40 years of age or older (over40). Methods: FFPE tissues from 2,128 clinically advanced RCC and 25 RSC underwent hybrid-capture based CGP to evaluate all classes of GA. Samples were classified at time of sequencing as the following RCC subtypes: clear cell (ccRCC), papillary (papRCC), chromophobe (chrRCC), medullary (medRCC), collecting duct (cdRC), sarcomatoid (sarcRCC) and NOS (nosRCC). Tumor mutational burden (TMB) was determined on up to 1.1 Mbp of sequenced DNA. Tumor cell PD-L1 expression was determined by IHC (Dako 22C3). Results: The male preponderance increased in the over40 patients. The GA/tumor increased in the over40 cohorts except for medRCC. Similarly, TMB was consistently higher in over40 groups. MSI high status was virtually absent. PD-L1 expression, available only in small subsets, was generally absent although 44% high positive staining in sarcRCC was noteworthy. Differences in GA in under40 vs over40 RCC were seen and included increased PBRM1 and SETD2 GA in over40 vs under40 ccRCC; increased C DKN2A/B and TERT and decreased FH GA in over40 vs under40 papRCC; increased TP53 and decreased VHL, BAP1, SETD2 and PTEN in over40 vs under40 chrRCC; increased TP53, PTEN and TERT GA with decreased NF2 GA in over40 vs under 40 sarcRCC; and increased TP53, VHL and TERT in over40 vs under40 nosRCC. Changes in GA in under40 vs over40 medRCC, cdRCC and RSC were noted but insufficient cases prevented further evaluation. Conclusions: When separately evaluated by under/over 40 years of age, CGP of clinically advanced RCC demonstrates differences in genomic landscapes with over40 cases featuring increasing male preponderance, higher GA/tumor, higher TMB and increases in a variety of GA. These findings may play important roles in the planning of future clinical trials designed to personalize the treatment of metastatic RCC. [Table: see text]
Concurrent docetaxel and S-1 compared with oxaliplatin and s-1 as first-line therapy for advanced gastric adenocarcinoma: A retrospective study.
Authors: Siyi Tan, Jiaqi Xie, Jia Wei, Qin Liu, Juan Du, Baorui Liu, Yang Yang
Journal: Journal of Clinical Oncology (2020)

e16540 Background: The aim of this study was to compare the efficacy and safety between docetaxel plus S-1 with oxaliplatin plus S-1 therapy as first-line treatment for advanced gastric adenocarcinoma. Methods: Patients, who had received docetaxel plus S-1 or oxaliplatin plus S-1 as first-line chemotherapy for advanced gastric adenocarcinoma, were retrospectively reviewed. Kaplan–Meier curve and log-rank test were used to analyze the survival. Prognostic factors were estimated by Cox regression. Adverse events (AEs) were evaluated using CTCAE 4.0. Results: One hundred and twenty-nine patients received concurrent docetaxel plus S-1, whereas 130 received oxaliplatin plus S-1. The median progression-free survival (PFS) and overall survival (OS) in docetaxel and oxaliplatin groups were 6.0 and 8.2 months ( P= 0.025), 14.7 and 15.7 months ( P= 0.697), respectively. Multivariate Cox regression suggested that chemotherapy regimen (docetaxel vs oxaliplatin; HR = 1.535, 95% CI:1.092-2.156, P = 0.014), Eastern Cooperative Oncology Group performance status (ECOG PS 3-4 vs 0-2; HR = 4.213, 95% CI: 2.246–7.903, P&lt; 0.001), Lauren type (Intestinal vs Diffuse, HR = 0.471, 95% CI: 0.307–0.725, P= 0.001, Mixed vs Diffuse, HR = 0.649, 95% CI: 0.442–0.953, P= 0.028), and number of metastases (HR = 2.097, 95% CI: 1.421–3.095, P&lt; 0.001) had significant effects on PFS. Multivariate Cox regression suggested that pathologic types (signet-ring cell carcinoma vs adenocarcinoma; HR = 1.688, 95% CI:1.152-2.472, P = 0.007), Lauren type (Intestinal vs Diffuse, HR = 0.637, 95% CI: 0.414–0.982, P= 0.041), number of metastases (HR = 1.7, 95% CI: 1.154–2.504, P= 0.007) had significant effects on OS.The most common grade 3-4 adverse events were leukopenia (3.1% vs 7.8%), neutropenia (7.7 vs 12.3%), anemia (13.2% vs 14.6%), thrombocytopenia (2.3% vs 10.8%), peripheral neuropathy(0.8% vs 7.8%)and Nausea/vomiting/ anorexia (1.6% vs 3.8%). Conclusions: Concurrent oxaliplatin plus S-1 therapy appears to be effective as first-line treatment in advanced gastric and has an acceptable safety profile. For patients in good physical condition, we prefer to recommend oxaliplatin combined with S-1 for treatment.
Adherence to post-surgery follow-up assessment and its association with sociodemographic and disease characteristics in patients with breast cancer in China.
Authors: Ran Feng, Jingfeng Jing, Haibo Yang, Xiaojun Zhang, Ming Li, Jinnan Gao
Journal: Journal of Clinical Oncology (2020)

e19232 Background: The incidence of breast cancer has increased more than 30% in the past decades in China. Epidemiological studies based on international and Chinese data have showed that breast cancer is the most common in female malignant tumors. Breast cancer patients with early breast cancer have better survival, lower recurrence and metastasis rate due to early diagnosis and improved treatment. As an important element in the comprehensive management of breast cancer patients, follow-up can eliminate treatment-related complications, detect recurrence and metastasis as early as possible, and improve mental health and quality of life. It is increasingly recognized as a distinct phase of cancer care. However, follow-up adherence after breast surgery has not been studied in China. The aim of this study is to investigate the loss of follow-up after breast cancer surgery and its association with patients', tumor and treatment characteristics. Methods: A total of 711 patients underwent surgical treatment in Shanxi Bethune Hospital from March 2012 to May 2018 were included in this study. Baseline socio-demographic, tumor, and treatment characteristics were obtained from the hospital electronic medical records. The post-surgery follow-up was reviewed and assessed from the patients’ follow-up examination record. Factors associated with the first three-year follow-up was evaluated using logistic regression analysis. Results: The annual follow-up rate after surgery decreased gradually from 67.1% at the 1st year, 60.2% at the 3rd year to 51.9% at the 4th year, and 43.5% at the 5th year. Loss of follow-up during the first three years after surgery was significantly associated with older age &gt;65 years(OR=2.34, 95% CI:1.14-4.82), lower medical insurance coverage(OR=4.26, 95%CI:1.77-10.25), axillary lymph node dissection(OR=2.52, 95%CI:1.39-4.55), no chemotherapy(OR=3.55, 95% CI:1.87-6.75) and no radiotherapy(OR=3.85, 95%CI:2.11-7.03). Conclusions: This study indicated that the annual follow-up rate after curative surgery for breast cancer survivors decreased significantly within five years, and that the risk of poor adherence to follow-up examinations was significantly increased in patients aged over 65 years with lower medical insurance coverage, having extensive axillary lymph node dissection, and lack of systematic treatments. These results suggest potential for improving adherence to follow-up in higher-risk subgroups and help clinicians to develop tailored patient management.
CNS outcomes in EGFR/ALK wild-type NSCLC patients with brain metastases treated with immune checkpoint inhibitors (ICI).
Authors: David Benjamin Shultz, Sally CM Lau, Christopher Poletes, Lisa W Le, Kate MacKay, Frances A. Shepherd, Penelope Ann Bradbury, Natasha B. Leighl, Geoffrey Liu, Adrian G. Sacher
Journal: Journal of Clinical Oncology (2020)

e14505 Background: Anti-tumor lymphocytes activated in response to ICIs may cross the blood brain barrier with effect on brain metastases (BM). Preliminary evidence suggests that ICIs alone are effective for melanoma BMs. However, the ability of ICI to effectively control NSCLC BMs without radiotherapy is controversial. By comparing serial MRIs and patterns of progression in ICI and chemotherapy treated patients, we sought to investigate the role of ICI in BM control in NSCLC patients. Methods: Serial MRIs were reviewed in ICI treated NSCLC patients with known BMs. Eligible patients must have a minimum of one baseline MRI and a follow-up within 3 months of CNS directed treatment. Patients with EGFR/ ALK mutations were excluded. A control cohort of patients who had never received ICIs was selected using the same criteria. The primary outcome was cumulative CNS progression and intracranial progression free survival (iPFS) analyzed using an accelerated failure time model and competing risk analysis. Results: We identified 137 ICI treated NSCLC patients with known BMs. After excluding for patients without serial MRIs, we analyzed 40 ICI treated patients and 39 controls. All patients received upfront radiotherapy or surgery and the modality used was similar (p = 0.13). CNS failure was less common in the ICI group (p = 0.02). ICI treated patients had a trend to longer iPFS in the PD-L1 ≥50% subgroup (p = 0.058). Cumulative incidence of progressive BM at 12 and 24 months were significantly lower in the ICI treated PD-L1 ≥50% subgroup: 19%/19% vs 50%/56% (p = 0.02). Patients in the PD-L1 ≥50% subgroup who achieved a systemic partial response (n = 10) did not experience any CNS events despite extracranial progression in some. Conclusions: Durable CNS disease control is observed with ICIs in NSCLC with PD-L1 ≥50% and demonstrates a high level of concordance with systemic response. The need for radiotherapy in PD-L1 ≥50% disease should be investigated and may be reasonably delayed in asymptomatic patients with small BMs. Importantly, the same trend was not observed in PDL1 &lt; 50% patients and caution is needed in employing this strategy in this subset of patients.