tbuckley/cabot-search huggingface dataset:
Biosimilar trastuzumab active post-marketing surveillance real-world data update: Results from a patient support program for patients under treatment with the first biosimilar trastuzumab approved in Brazil.
Authors: Allisson Monteiro da Silva, Jaqueline Amália de Paulo, Thais Tiemi Watanabe, Gislaine Villarta Capeleti Dib
Journal: Journal of Clinical Oncology (2020)

e15626 Background: In 2017, biosimilar trastuzumab (Zedora) became the first biosimilar trastuzumab approved in Brazil. In 2019, biosimilar trastuzumab early data from an active postmarketing surveillance program were presented in ASCO. Now, with an extended follow up and more patients included, we present updated data from the surveillance program. Methods: This is a prospective observational study based on a patient support program. HER2 + breast cancer (BC) who received prescription for biosimilar trastuzumab were invited to participate. After agreement of informed consent, they were followed by periodical phone calls after each infusion and up to 3 months after the end of treatment. Treatment related data and adverse events (AEs) were collected. Results: A total of 76 female patients with HER2 + BC were enrolled in the program between May 2018 and December 2019. 74 patients with median age 51 (range 30 to 80) received at least one biosimilar trastuzumab infusion. Out of these, 52 (70.3%) patients reported 385 AEs all-causality (Table 1). Regarding severity and expectedness, 344 (89.4%) were non-serious AE (243 expected / 101 unexpected) and 41 (10.6%) were serious AE (29 expected / 12 unexpected). Considering all serious unexpected AEs (12), 8 were assessed as unlikely and 4 as likely. For the non-serious unexpected AEs (101) causality assessment was unlikely in 32 AEs, likely in 68 AEs and conditional in 1 AE. The three most frequently reported AEs according to SOC (System Organ Classification) were gastrointestinal disorders 59 (15.3%), general disorders and administration site conditions 57 (14.8%). The five most reported symptoms (PT - Preferential Term) were nausea 15 (3.9%), fatigue 14 (3.6%), infusion reactions 14 (3.6%), diarrhea 9 (2.3%) and insomnia 9 (2.3%). Further monitoring is continued. Conclusions: Nature of AEs for biosimilar trastuzumab are consistent with the label in female patients with HER2 + BC. The risk benefit remains consistent with the label and no new safety signals were detected. [Table: see text]
口服左氧氟沙星致严重药物过敏一例
Authors: 王纯
Journal: BMJ (2010)

患者女,61岁,因咳嗽、咳痰1周于2008年11月25日早8:00就诊.患者1周前咽痒、咳嗽,无畏寒、发热、胸痛、气喘等不适,未予重视,3 d后痰色转黄、黏稠,不易咳出.自服沐舒坦、复方甘草合剂3 d,未见好转,痰色灰黄,遂来院就诊。
Association of Neighborhood Disadvantage in Childhood With DNA Methylation in Young Adulthood
Authors: Aaron Reuben, Karen Sugden, Louise Arseneault, David L. Corcoran, Andrea Danese, Helen L. Fisher, Terrie E. Moffitt, Joanne B. Newbury, Candice Odgers, Joey Prinz, Line J. H. Rasmussen, Ben Williams, Jonathan Mill, Avshalom Caspi
Journal: JAMA Network Open (2020)

<h3>Importance</h3> DNA methylation has been proposed as an epigenetic mechanism by which the childhood neighborhood environment may have implications for the genome that compromise adult health. <h3>Objective</h3> To ascertain whether childhood neighborhood socioeconomic disadvantage is associated with differences in DNA methylation by age 18 years. <h3>Design, Setting, and Participants</h3> This longitudinal cohort study analyzed data from the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally representative birth cohort of children born between 1994 and 1995 in England and Wales and followed up from age 5 to 18 years. Data analysis was performed from March 15, 2019, to June 30, 2019. <h3>Exposures</h3> High-resolution neighborhood data (indexing deprivation, dilapidation, disconnection, and dangerousness) collected across childhood. <h3>Main Outcomes and Measures</h3> DNA methylation in whole blood was drawn at age 18 years. Associations between neighborhood socioeconomic disadvantage and methylation were tested using 3 prespecified approaches: (1) testing probes annotated to candidate genes involved in biological responses to growing up in socioeconomically disadvantaged neighborhoods and investigated in previous epigenetic research (stress reactivity–related and inflammation-related genes), (2) polyepigenetic scores indexing differential methylation in phenotypes associated with growing up in disadvantaged neighborhoods (obesity, inflammation, and smoking), and (3) a theory-free epigenome-wide association study. <h3>Results</h3> A total of 1619 participants (806 female individuals [50%]) had complete neighborhood and DNA methylation data. Children raised in socioeconomically disadvantaged neighborhoods exhibited differential DNA methylation in genes involved in inflammation (β = 0.12; 95% CI, 0.06-0.19;<i>P</i> &lt; .001) and smoking (β = 0.18; 95% CI, 0.11-0.25;<i>P</i> &lt; .001) but not obesity (β = 0.05; 95% CI, −0.01 to 0.11;<i>P</i> = .12). An epigenome-wide association study identified multiple CpG sites at an arraywide significance level of<i>P</i> &lt; 1.16 × 10<sup>−7</sup>in genes involved in the metabolism of hydrocarbons. Associations between neighborhood disadvantage and methylation were small but robust to family-level socioeconomic factors and to individual-level tobacco smoking. <h3>Conclusions and Relevance</h3> Children raised in more socioeconomically disadvantaged neighborhoods appeared to enter young adulthood epigenetically distinct from their less disadvantaged peers. This finding suggests that epigenetic regulation may be a mechanism by which the childhood neighborhood environment alters adult health.
Community nutrition support for discharged patients
Authors: Zhiyun Zhao, Yongdong Wu
Journal: BMJ (2019)

It is important to find the patients with malnutrition or at risk of malnutrition, so that the appropriate nutrition support would be given in time. The nutritional status of inpatients isexamined by various nutrition assessment methods and laboratory indexes. If necessary, when the patient sare discharged the home enteral nutrition therapy should be given under the supervision of community doctors and nurses following the established nutrition support program. With this program the nutritional status can be further improved, the disease recovery and quality of life can be promoted, as well as the economical burden of patients can be reduced.


Key words: 
Nutritional support; Community health services
Carboplatin versus cisplatin for the treatment of extensive-stage small cell lung cancer (SCLC): A National VA Database analysis.
Authors: Ibrahim Azar, Adam Austin, Seongho Kim, Hyejeong Jang, Amit Chopra, Syed Arzoo Mehdi, Hirva Mamdani
Journal: Journal of Clinical Oncology (2020)

9061 Background: Current standard of care first line treatment for extensive stage SCLC includes combination of platinum-etoposide doublet with an immune checkpoint inhibitor. Carboplatin is preferred over cisplatin in the extensive stage disease because of its favorable toxicity profile. Data comparing the efficacy of carboplatin with cisplatin in the metastatic setting are limited. Methods: Data from the National VA Cancer Cube database were compiled. Only pathologically confirmed cases of extensive stage SCLC that received platinum-based multiagent chemotherapy were included. Interval-censored Weibull and Cox proportional hazard regression models were used to estimate median overall survival (OS) and hazard ratio (HR), respectively. Two survival curves were compared by a Wald test. Results: Overall, 2600 SCLC cases were studied: 1968 received carboplatin-based therapy (Carbo-SCLC) while 632 received cisplatin-based therapy (Cis-SCLC). Median OS of Carbo-SCLC and Cis-SCLC was 0.71 years (95% CI 0.68-0.75) versus 0.70 years (95% CI 0.64-0.76), respectively (HR = 0.99; 95% CI 0.90-1.10; p = 0.90). Median OS of patients with ECOG-PS of 0, 1, 2 and 3 was similar for Carbo-SCLC and Cis-SCLC. HR of death for Carbo-SCLC compared to Cis-SCLC stratified by performance status were: ECOG-PS 0: 1.04 (95% CI 0.78-1.38; p = 0.80); ECOG-PS 1: 0.87 (95% CI 0.71-1.06; p = 0.17); ECOG-PS 2: 0.92 (95% CI 0.69-1.24; p = 0.6); ECOG- PS 3: 1.13 (95% CI 0.66-1.92; p = 0.66). Multivariable regression analysis accounting for age and ECOG-PS shows a HR of 0.92 (95% CI 0.80-1.05; p = 0.24). Conclusions: Cisplatin-based chemotherapy was not associated with a survival advantage over carboplatin-based chemotherapy in extensive-stage SCLC., including in patients with robust performance status and young patients. The findings from this large dataset along with the favorable toxicity profile of carboplatin support its use as the platinum agent of choice in extensive stage SCLC.
Electrical Impedance Tomography for Positive End-Expiratory Pressure Titration in COVID-19–related Acute Respiratory Distress Syndrome
Authors: Philip van der Zee, Peter Somhorst, Henrik Endeman, Diederik Gommers
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

To the Editor:Coronavirus disease (COVID-19) spreads rapidly and has already resulted in severe burden to hospitals and ICUs worldwide.Early reports described progression to acute respiratory distress syndrome (ARDS) in 29% of cases (1).It is unknown how to titrate positive end-expiratory pressure (PEEP) in patients with ARDS.Patient survival improved if higher PEEP successfully recruited atelectatic lung tissue (2).However, excessive PEEP caused alveolar overdistention, resulting in reduced patient survival (3).Therefore, PEEP should be personalized to maximize alveolar recruitment and minimize the amount of alveolar overdistention.Electrical impedance tomography (EIT) provides a reliable bedside approach to detect both alveolar overdistention and alveolar collapse (4).We describe a case series of patients with COVID-19 and moderate to severe ARDS in whom EIT was applied to personalize PEEP based on the lowest relative alveolar overdistention and collapse.Subsequently, we compared this PEEP level with the PEEP that could have been set according to the lower or higher PEEP-FI O 2 table from the ALVEOLI trial (5).These early experiences may help clinicians to titrate PEEP in patients with COVID-19 and ARDS. MethodsStudy design and inclusion criteria.We conducted this case series between March 1, 2020, and March 31, 2020, in our tertiary referral ICU (Erasmus Medical Center, Rotterdam, the Netherlands).All consecutive mechanically ventilated patients admitted to the ICU with COVID-19 and moderate to severe ARDS (according to the Berlin definition of ARDS) were included in this study.COVID-19 was defined as a positive result on a PCR of sputum, nasal swab, or pharyngeal swab specimen.The local medical ethical committee approved this study.Informed consent was obtained from all patients' legal representatives.Study protocol.A PEEP trial was performed daily in all patients according to our local mechanical ventilation protocol.Patients were fully sedated with continuous intravenous infusion of propofol, midazolam, and opiates.Persisting spontaneous breathing efforts were prevented with increased sedation or neuromuscular blockade.Arterial blood pressure was measured continuously.
Accuracy of 68Ga-PSMA-11 for pelvic nodal metastasis detection prior to radical prostatectomy and pelvic lymph node dissection: A multicenter prospective phase III imaging study.
Authors: Thomas A Hope, Wesley R Armstrong, Vishnu Murthy, Courtney Lawhn Heath, Spencer Behr, Francesco Barbato, Francesco Ceci, Andrea Farolfi, Sarah Schwarzenboeck, Marcus Unterrainer, Helle Zacho, Matthew R. Cooperberg, Hao Gia Nguyen, Peter Carroll, Robert Evan Reiter, Stuart Holden, Wolfgang Peter Fendler, Matthias Eiber, Johannes Czernin, Jeremie Calais
Journal: Journal of Clinical Oncology (2020)

5502 Background: To determine the accuracy of 68Ga-PSMA-11 PET for the detection of pelvic nodal metastases (N1) compared to histopathology at time of radical prostatectomy (RP). Methods: This is a prospective multicenter single-arm open-label phase 3 imaging trial. Patients with intermediate to high risk prostate cancer (PCa) considered for RP with lymph node dissection (PLND) were enrolled at the University of California, Los Angeles (UCLA) and at the San Francisco (UCSF) (NCT03368547, NCT02611882, NCT02919111), and underwent one 68Ga-PSMA-11 PET. The primary endpoint was the sensitivity (Se) and specificity (Sp) of 68Ga-PSMA-11 PET for the N1 detection compared to PLND histopathology (reference-standard) on a per patient basis using nodal region-based correlation. Each scan was read by three blinded independent central readers (BICR). Consensus was based on majority rule. Results: From December 2015 to August 2019, 633 patients underwent one 68Ga-PSMA-11 PET for primary staging, and 277/633 (44%) subsequently underwent RP and PLND. The median initial PSA was 11.1 [0.04-147]. 75/277 patients (27%) had N1 disease per histopathology. Using a regional based analysis, Se, Sp, positive predictive value (PPV) and negative predictive value (NPV) for N1 detection was 0.40 [0.34, 0.46], 0.95 [0.92, 0.97], 0.75 [0.70, 0.80], 0.81 [0.76, 0.85], respectively. Se was higher for patients with higher PSA: 0.29 [0.24, 0.35] for PSA &lt; 11 ng/ml versus 0.48 [0.42, 0.54] for PSA &gt; 11. Se was higher when the nodes were larger: 0.30 [0.25, 0.36] for nodes &lt; 10 mm versus 0.68 [0.63, 0.74] for nodes &gt; 10. The average node size in true positive patients was 10 mm versus 4 mm in false negative patients. Conclusions: In intermediate to high risk PCa patients who underwent RP and PLND, 68Ga-PSMA-11 PET detected pelvic nodal metastases with a sensitivity of 0.40 and a specificity of 0.95. Higher PSAs and larger node size correlated with increased sensitivity. Clinical trial information: NCT03368547, NCT02611882, NCT02919111 .
肺气肿的影像表现
Authors: 马大庆
Journal: BMJ (2011)

肺气肿是终末细支气管远端气腔(包括呼吸性细支气管、肺泡导管和肺泡)持续异常扩张,常合并气腔壁破坏.肺气肿属于慢性阻塞性肺疾病(COPD).多数肺气肿病例与吸烟有关,其他原因有长期吸入有害物质和粉尘,呼吸道反复感染等。
Evaluation of TKI toxicity according to inflammatory markers and body mass index in patients with non-small cell lung cancer (NSCLC) harboring an EGFR mutation: A retrospective observational study.
Authors: Thanya Runciman, Rodrigo Motta Guerrero, Carlos Aliaga Macha, Carlos F. Carracedo
Journal: Journal of Clinical Oncology (2020)

e21522 Background: The standard treatment for patients with advance EGFR mutated NSCLC are Tirosine Kinasa inhibitors (TKI), we face in our clinical practice a different profile of toxicity; there is limited data of Inflammatory markers in this especial population. The aim of our study is to determine whether neutrophil lymphocyte ratio (NLR), lymphocyte platelet ratio(PLR), RDW-CV and body mass index (BMI) are related to the develop of this toxicity. Methods: We retrospectively analyzed data of patients with EGFRm NSCLC at Aliada Clinic between January 2016 to December 2019. Inflammatory markers were obtained from laboratory tests performed during the first visit as outpatient. The BMI kg/m2 at the start of the treatment was defined as the weight (kg) divided by the height (m) squared. Adverse event (AE) were graded according CTCAE v5.0. Results: A total of 164 patients were diagnosed with advanced NSCLC, of these 50 patients were assessed, 29 women and 21 men. The average age was 58.9 years, median of 59.5 ( 38 to 83; SD: 11.7). The most frequent EGFR mutation was deletion 19 (59.6%) followed by L858R mutation ( 23.1%) . The median BMI was 25.18 (16.2 to 41.3 kg/m2) 46.2% were normal, 36.5% were overweight, and 11.5 % were obese. 80% present any grade of AE. The most frequent AE was skin related: 75% (90 % grade I or II) follow by gastrointestinal: 57.6% (74 % grade I or II). There were no significant differences between NLR according to toxicity grade I-II vs III-IV (media: 3.44 and 4.32; P = 0.46); PLR according toxicity grade I-II vs III-IV (media: 229.41 and 251-50; P = 0.78); and RDW-CV according to toxicity grade I-II vs III-IV (media: 14.17 and 14.4; P = 0.74). Similarly, no significant differences were observed among toxicity profiles in relation to BMI (p = 0.2). Finally, there was no impact of severity of toxicity on progression-free survival (p = 0.64) or overall survival 24,33 months (IC 95% 16,05 – 32,6; p = 0.9). Conclusions: There was no relation between inflammatory markers and the grade of toxicity in patients with EGFRm advance NSCLC receiving TKIs. We suggest increase the population to validate our results.
ALCHEMIST: Adjuvant targeted therapy or immunotherapy for high-risk resected NSCLC.
Authors: Jacob Sands, Sumithra J. Mandrekar, Geoffrey R. Oxnard, David E. Kozono, Shauna L Hillman, Suzanne Eleanor Dahlberg, Zhuoxin Sun, Jamie E. Chaft, Ramaswamy Govindan, David E. Gerber, Jhanelle Elaine Gray, Shakun M. Malik, Margaret M. Mooney, Pasi A. Janne, Everett E. Vokes, Karen Kelly, Suresh S. Ramalingam, Tom Stinchcombe
Journal: Journal of Clinical Oncology (2020)

TPS9077 Background: ALCHEMIST (Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trial) is a clinical trial platform of the National Cancer Institute that offers biomarker analysis for high-risk resected non-small cell lung cancer (NSCLC) to support randomized trials of novel adjuvant therapies within the National Clinical Trials Network (NCTN). EA5142, a trial of adjuvant nivolumab for patients (pts) without EGFR / ALK alterations, has completed enrollment. Given the survival benefit seen with 1st-line chemo-immunotherapy (chemo-IO) for advanced NSCLC without EGFR / ALK alterations, there was compelling rationale for the launch of a trial offering concurrent immunotherapy with adjuvant chemo. Here we report updated enrollment to ALCHEMIST as of Jan 14, 2020. Methods: ALCHEMIST includes a screening trial (A151216, 5362 registered) that enrolls pts with completely resected clinical stage IB (≥4 cm)–IIIA (per AJCC 7) NSCLC. Tissue and blood are collected, biomarker testing includes EGFR sequencing, ALK FISH and PD-L1 IHC. 733 active sites are enrolling across the NCTN. Pts with EGFR mutations may enroll to adjuvant erlotinib vs observation (A081105, 352 randomized); those with ALK fusions may enroll to adjuvant crizotinib vs observation (E4512, 99 randomized). A trial offering adjuvant nivolumab vs observation regardless of PD-L1 status (EA5142, 935 randomized) recently completed enrollment. To support ongoing investigation of adjuvant immunotherapy, ALCHEMIST is adding A081801 (opens spring 2020). Pts will be randomized to one of 3 arms: chemo-IO with pembrolizumab during and after chemo vs sequential chemo followed by pembrolizumab vs chemo alone. Pts with pathological N2 nodes are eligible and can undergo postoperative radiotherapy after completing chemo. Pts are eligible if enrolled to A151216, negative for EGFR and ALK alterations, and with PD-L1 testing completed (required for stratification). Local testing for EGFR, ALK and PD-L1 will be accepted for enrollment; central testing will not delay randomization. Pts may not have received any therapy except surgery for the lung cancer and must be age &gt;18, Eastern Cooperative Oncology Group performance status 0-1, have no active autoimmune disease requiring systemic treatment within 2 years, must not be pregnant or nursing, have no active second malignancy within 3 years and meet standard organ function values. By building off the ongoing ALCHEMIST platform, we hope to facilitate rapid enrollment to A081801 across participating NCTN sites. Clinical trial information: NCT02194738.
Effect of early integration of diabetic services in primary brain tumor patients receiving radical radiotherapy on steroid-induced diabetic complications and hospital admission.
Authors: Karim Keshwani, Lorna Raymond, Marianne Shawe-Taylor, Hannah Lowe, Piers N. Plowman, Rachel Lewis
Journal: Journal of Clinical Oncology (2020)

e14522 Background: Corticosteroids are commonly used in neuro-oncology both in the perioperative setting and with chemotherapy and radiotherapy to manage cancer and treatment-associated cerebral oedema and neurological deficits. Corticosteroids are associated with significant morbidity. We sought to identify primary brain tumour patients affected by steroid complications within our centre, the repercussions on their treatment and whether these consequences are avoidable. Methods: This retrospective study curated the last 50 primary brain tumour patients treated radically and therefore at risk of long term steroid use between November 2018 and August 2019. Patient demographics, tumour and treatment type, as well as diabetic and steroid history were collected. A second cohort of primary brain patients undergoing radical radiotherapy were recruited between November 2019 and January 2020. HbA1c blood tests were performed and NICE guidelines used for HbA1c diagnostic criteria with referral to diabetic services and outcomes recorded. Results: Tumour types ranged from Glioblastoma (36%), meningioma (32%), oligodendroglioma (16%), astrocytoma (14%) and hemangioblastoma (2%). 12 (24%) had a known diabetes diagnosis. Forty-two (84%) had an operation (biopsy (30%), partial (18%) or full debulking (16%). 82% of patients were exposed to dexamethasone at some point during their neurosurgical or oncological treatment. Initial doses varied but 36% were placed on 8mg twice daily. Steroid-induced hyperglycaemia occurred in 8 (16% of the cohort) with admission to hospital as a consequence in half of these cases, of whom two were newly diagnosed diabetes patients. HbA1c testing prior to or during treatment occurred in 16 (32%) patients. In the second cohort, All 15 patients (100%) had HbA1c testing with 5 (33%) patients diagnosed with diabetes or at risk of diabetes. Diabetic team advice was sought and recommended blood glucose testing in all these patients with oral hypoglycaemic and/or insulin dose modification in 3 (60%). There were no hyperglycaemic recordings or subsequent admissions to hospital in this cohort. Conclusions: We therefore recommend HbA1c testing and early diabetic team involvement in all primary brain tumour patients receiving radical radiotherapy.