tbuckley/cabot-search huggingface dataset:
The validity of 5-aminorevrinic acid as a biomarker for risk screening and supportive diagnostic parameters in lung cancer patients.
Authors: Yoshikane Yamauchi, Yuichi Saito, Koji Murakami, Yasuyuki Kanamoto, Momoko Asami, Fumi Yokote, Takashi Sakai, Yukinori Sakao, Toru Tanaka, Masafumi Kawamura
Journal: Journal of Clinical Oncology (2020)

e21027 Background: Early detection and treatment of cancer is an important issue that affect the prognosis of cancer patients. Photodynamic screening with 5-aminorevrinic acid (ALA-PDS) is simple and non-invasive procedure for risk screening of cancer, and it is gradually recognized as the predictable biomarkers for cancer in Japan. In this study, we examined the predictability of lung cancer by ALA-PDS and its usefulness as a supportive parameter for preoperative diagnosis. Methods: Eighty-five lung cancer patients (48 males and 37 females) just before lung resection were enrolled. 5-aminolevulinic acid phosphate 150mg was taken at night and urine samples were collected in the next morning. The porphyrin metabolites in the urine samples were detected by solid phase extraction method, previously reported from our group. Afterwards, the data was adjusted depending renal function. The data was compared with that from healthy volunteer without any abnormal symptom and physical disorder. Results: The average age of 85 patients was 70 years (46-85). The number of patients in each pathological stage was 2 in Stage 0, 58 in Stage IA and IB, 15 in Stage IIA and IIB, 8 in Stage IIIA and IIIB, and 2 in Stage IV, respectively. The diagnosis was 61 cases of adenocarcinoma and 22 cases of squamous cell carcinoma. Urinary porphyrin metabolites in lung cancer patients increased significantly as compared to those of healthy volunteers (2,847nM/gCRE vs 1,668nM/gCRE, p &lt; 0.001). Increase of urinary porphyrin metabolites was observed even in stage 0 or I patients, but the correlation with stage progression was not clear (Stage 0 and I vs Stage II vs Stage III and IV: 2,757nM/gCRE vs 3,099nM/gCRE vs 3,010nM/gCRE). Furthermore, urinary porphyrin metabolites were confirmed to be significantly increased even in PET-negative cancer patients, compared to healthy volunteers (p &lt; 0.001). Conclusions: ALA-PDS was able to predict lung cancer in our cohort. Moreover, it was also suggested that it may be useful as a supportive parameter for diagnosis of early stage lung cancer or PET negative lung cancer.
Features of chronic daily headache: a clinical analysis of 128 cases
Authors: Tingting Hao, Jingjing Qi
Journal: BMJ (2015)

Objective
To review the clinical features of chronic daily headache (CDH).


Methods
The clinical data of 128 patients with chronic daily headache, including general condition, characteristics of headache, concomitant symptom and disability were analyzed retrospectively. The features of primary chronic daily headache (PCDH) and medication over-dose headache (MOH) were compared.


Results
Among 128 cases females accounted for 79.7% with an average age of 45.2 years and 88 patients were associated with drug overdose. The symptoms included nausea(68/128), photophobia(75/128), phonophobia(102/128), depression(77/128)and irritability(93/128), sleep disorders(94/128), dizziness(75/128), emotional irritability(58/128) and depression(21/128). The migraine disability assessment questionnaire and headache impact test-6 scores showed that disability was resulted from the severe degree of headache in 62.2%(51/82) and 73.2%(82/112) of CDH patients respectively. Compared with PCDH patients, the MOH patients had older age(t=2.59, P=0.011), longer duration(t=2.48, P=0.015) and severer degree of headache(t=5.58, P=0.018), and chronic migraine (t=11.95.P=0.001) was the most common primary headache type.


Conclusions
Most CDH patients are middle-aged women, with moderate to severe pain, usually complicated with depression, dysphoria and asomnia. Chronic daily headache patients are commonly associated with drug overdose.


Key words: 
Headache disorders; Signs and symptoms; Retrospective studies
Tumor lysis syndrome (TLS) in acute myeloid leukemia (AML) patients treated with azacitidine (AZA) and venetoclax (VEN).
Authors: Joanna Q. Huang, Emmeline Academia, Daniel Aaron Pollyea, Jonathan Aaron Gutman, Andrew Hammes, Stephanie Chase, Cindy L. O'Bryant, Jeff Kaiser
Journal: Journal of Clinical Oncology (2020)

e19507 Background: Studies evaluating VEN with hypomethylating agents in AML patients have reported no incidence of clinical TLS. However, little is known about TLS development in a real-world setting. Here, we investigate our institutional incidence of clinical TLS and describe these patients’ presentations. Methods: This is a single-center, retrospective study of 156 adult pts treated with AZA/VEN for AML between 2015-2019. The primary outcome is the absolute incidence of clinical TLS after AZA/VEN administration per Cairo-Bishop (CB) criteria. Secondary outcomes include median time to TLS, CTCAE grade of TLS, and mortality. All patients received TLS mitigation strategies including fluids, uric acid lowering agents, and frequent lab monitoring. VEN was escalated over 3-4 days, starting at 100 mg, and given with AZA at the standard dose and schedule. Results: The median age was 70 years (22-89); 80 pts (51%) were female. 121 pts (78%) were treatment-naïve, 26 pts (17%) were relapsed, and 9 pts (6%) were refractory. Four pts (3%) developed clinical TLS per CB criteria after AZA/VEN administration. Two pts were relapsed, one pt was treatment-naïve, and one pt had mixed phenotype acute leukemia, B/myeloid. All four pts developed renal insufficiency. No seizures, cardiac arrhythmias, or mortality occurred secondary to TLS. Two pts required renal replacement therapy, and two pts required escalation of care to ICU for TLS management. Median time to TLS onset was 12 hours (10-25) after receiving the first dose of VEN. CTCAE grade 3 TLS occurred in 2 pts (1%) and grade 4 TLS occurred in 2 pts (1%). VEN was held in 2 pts (8, 10 days); no pts required permanent discontinuation of VEN. Baseline features for each patient are listed in the table. Conclusions: Though we report higher rates of clinical TLS compared to prior studies, the incidence of clinical TLS with AZA/VEN remains low. These results support close monitoring of pts, particularly in the first 24 hours of receiving VEN. [Table: see text]
Comparison of three surgical modalities in treatment of lumbar spinal stenosis
Authors: Xiaoyi Lin, Fenghui Lin, Fuan Liu
Journal: BMJ (2015)

Objective
To evaluate the clinical outcomes of lumbar spinal stenosis treated with three different surgical modalities.


Methods
One hundred and forty patients were treated with posterior lumbar interbody fusion (PLIF, n=50), transforaminal lumbar interbody fusion (TLIF, n=40) or modified method (n=50). The operation time and intraoperative blood loss were compared. The outcomes were evaluated with Japanese Orthopedic Association (JOA) score and visual analogue scale (VAS), and the radiographic findings were also reviewed.


Results
The operation time was shorter and the intraoperative blood loss was less in modified group than those in other two groups (F=10.02, P 0.05), also in JOA scores after operation among three groups. The VAS scores in TLIF group and modified group 3 and 6 months after operation were significantly lower than those in PLIF group (F=9.46, 10.02, all P<0.05), but there was no significant difference between TLIF group and modified group. Interbody fusion was good in all three groups.


Conclusions
Three surgical methods have good clinical outcomes for lumbar spinal stenosis. But compared with PLIF and TLIF, the modified method has less blood loss, shorter operation time and less pain after operation.


Key words: 
Spinal stenosis, lumbar vwetebrae; Pedicle screw fixation; Interbody fusion
Preclinical evaluation of SIM1803-1A, a small molecule Trk/ROS1 dual inhibitor for wild and mutate <i>NTRK/ROS1</i> fusion solid malignancies.
Authors: Jianfei Wang, xiaohong yu, Shunwei Zhu, Qingying Chen, Jikui Sun, Yuanfeng Xia, Yang Zhang, Chi-Chung Chan, Jian Li, Shuhui Chen
Journal: Journal of Clinical Oncology (2020)

e21663 Background: Fusions and rearrangements of NTRK1/2/3 and ROS1 genes are oncogenic drivers in multiple solid malignancies. Drugs targeting tyrosine kinases TrkA/B/C and ROS1, such as larotrectinib and entrectinib, are proven highly efficacious in diverse adult and pediatric tumor types (ORR &gt; 75%). However, the treatment-related drug resistance, including S.F. mutations, G.K. mutations and DFGx mutations, has been identified in clinical trials. The use of second generation of TKI, such as repotrectinib to against these acquired resistance mutations, has been explored in clinical trials and reported unsatisfied efficacy in patients under acceptable dosages, which might due to its broader inhibition of multiple kinases. Here we report a novel potent Trk/ROS1 dual inhibitor SIM1803-1A, targeting both the wild type and multiple clinical mutations of Trk and ROS1 with clean selectivity profile and expected in vitro and in vivo efficacy for wild and mutant NTRK/ROS1 fusion solid tumors. Methods: Kinase inhibiting potency was determined with Reaction Biology kinase assays. Kinase selectivity was screened on Eurofins Kinase Profiler panel. Cellular anti-proliferative potency was evaluated on relevant fusion cell lines. Antitumor efficacy was evaluated in the related CDX and PDX mice models shown in results. Results: SIM1803-1A displayed high kinase inhibiting potency with IC 50 3.64/1.24 /4.45 nM on TrkA( WT/G595R/G667C) kinase, 0.07/5.03/5.68 nM on TrkC( WT/G623R/L686M), and 0.08/0.10 nM on ROS1( WT/G2032R) respectively. A clean selectivity profile was also identified in 112 enzymes from TK and TKL family at 0.5 µM. The proliferation inhibition IC 50 of SIM1803-1A in following cell lines were: 0.3 nM on KM12 TPM3-NTRK1, 2.2/0.9/5.7/5.6 nM on Ba/F3 LMNA-NTRK1( WT/F589L/G595R/G667A), 2.9/6.2 nM on Ba/F3 ETV6-NTRK3( WT/G623R), and 7.3/15.0 nM on Ba/F3 SLC34A2-ROS1(WT/G2032R) respectively. SIM1803-1A showed high antitumor efficacy in the subcutaneous colon cancer KM12 TPM3-NTRK1 CDX model with 68% and 80% TGI at 1 and 3 mg/kg (bid) dosing, and similar high efficacy in the subcutaneous NSCLC LU-01-0414 SDC4-ROS1 PDX model with 60% and 74% TGI at 1 and 3 mg/kg (bid) dosing. Conclusions: Collectively, these studies have shown SIM1803-1A is a potent Trk/ROS1 dual inhibitor with better safety potentially from improved kinase selectivity. SIM1803-1A is currently at IND submission stage and represents a promising clinical candidate for the treatment-naïve and acquired-resistance NTRK/ROS1 fusion-positive malignancies.
Optimal cumulative cisplatin dose for radio-sensitization in locally advanced head and neck cancer.
Authors: Atanu Bhattacharjee, Vanita Noronha, Vijay Maruti Patil, Anuja Abhayankar, Amit Joshi, Nandini Sharrel Menon, Kumar Prabhash
Journal: Journal of Clinical Oncology (2020)

e18553 Background: Evidence to choose the optimum chemotherapy between weekly and 3 weekly cisplatin for prolonging the duration of progression free survival in head and neck squamous cell carcinoma (HNSCC) is equivocal. This urged us to look into the cumulative dose of chemotherapy rather than the frequency of administration i.e. weekly or 3 weekly. The aim of this study was to determine the optimal cumulative dose of cisplatin to improve the progression-free survival (PFS). Methods: Between January 2011 and January 2018, a total of 836 consecutive patients with histologically proven primary squamous cell carcinoma of the oral cavity, larynx, hypopharynx, and oropharynx were included. The effect of the cumulative dose on progression-free survival was studied to obtain the optimal cumulative dose of cisplatin. Results: A total of 11 cohorts were generated to represent the cumulative doses. The cumulative doses were measured at 30, 60, 90,120,150,180,200,210,240 and 300 mg/m2 respectively. The maximum duration of progression-free survival (PFS) was considered to define the best effective cumulative dose. Conclusions: This study confirms that a cumulative cisplatin dose of ~ 210 mg/m 2 is optimum for increasing PFS in patients with head and neck cancer. Therefore, doses with weekly 30 mg/m 2 for seven cycles or 3-weekly 70 mg/m 2 for 3 cycles could be equally effective to prolong the PFS. Clinical trial information: CTRI/2012/10/003062, CTRI/2014/09/004980.
BASEM: leadership in sport and exercise medicine despite our uncertain times
Authors: Robin Chatterjee, Polly Baker
Journal: British Journal of Sports Medicine (2020)

Timeline: week 4 of UK lockdown. In these unprecedented times, we maintain a semblance of normalcy by continuing to provide the high-quality education you have become used to from the British Journal of Sports Medicine (BJSM) . We are proud to present the British Association of Sport and Exercise Medicine (BASEM) issue for 2020–the 54th year of publishing our journal (figure 1). BASEM is the leading multidisciplinary sport and exercise medicine membership organisation in the UK with a core responsibility to provide relevant, high-quality education to all those involved in this specialty. Our members comprise doctors, physiotherapists, researchers, nurses, radiologists and podiatrists just to name a few, and we editors celebrate this diverse background and experience with our choice of papers.



Figure 1 
As we go to press, British Association of Sport and Exercise Medicine is considering the options for 2020 events and our schedule for 2021.



For those physiotherapists, doctors and physiologists working within elite sport and exercise medicine there is plenty to read. Aspetar’s Professor Sebastien Racinais et al broach the question as to whether athletes should be tested …
社区医生怎样敲开居民的家门
Authors: 张晓林
Journal: BMJ (2007)

2006年 中明确提出,社区卫生服务机构提供公共卫生服务和基本医疗服务,具有公益性质,不以营利为目的.要以社区、家庭和居民为服务对象,以妇女、儿童、老年人、慢性病人、残疾人、贫困居民等为服务重点,以主动服务、上门服务为主,开展健康教育、预防、保健、康复、计划生育技术服务和一般常见病、多发病的诊疗服务。
Udenyca has equivalent efficacy to the pegfilgrastim originator in breast cancer patients receiving highly myelosuppressive chemotherapy.
Authors: Jennifer Webster, Jeffrey A. Scott, Helen Smith, Danielle Wieland, Joseph Donaldson, Casey Catasus, Robert E. Smith
Journal: Journal of Clinical Oncology (2020)

e19273 Background: In late 2019, the Center for Medicare and Medicaid Innovation (CMMI) issued a request for information (RFI) for the Oncology Care First (OCF) program, which will extend the evaluation of value-based care in the community oncology setting for an additional five years, through 2026. We have learned through the Oncology Care Model (OCM) that there are savings to be found by reducing inpatient admissions and emergency department visits and controlling for things such as duplicate labs. However, it has become increasingly clear that further savings will require practices to evaluate their use of both cancer-directed therapy and supportive therapy. To this end, Integra Connect has developed a tool, the Value Monitor, that allows for statistically rigorous comparative effectiveness research at scale, using real world data. As an initial proof of concept, we used the Value Based Care Monitor to compare the efficacy for febrile neutropenia prophylaxis between two pegfilgrastims: Udenyca, a biosimilar, and Neulasta, the originator. Methods: The Integra Connect Value Monitor was used to perform a matched cohort analysis of breast cancer patients receiving Udenyca vs patients receiving Neulasta from 1/1/2017 – 8/31/2019. Patients were matched on age (within 5 years), gender, OCM participation status and date of treatment (within 90 days). Each Udenyca patient (n = 496) was matched to 5 Neulasta patients. The efficacy endpoint was neutropenia rate, where neutropenia was defined as the presence of a neutropenia ICD-10 code (D70*), and/or an Absolute Neutrophil count less than 1,500. We are in the process of adding grade IV neutropenia (ANC &lt; 500) to the tool. Results: Udenyca and Neulasta showed similar rates of neutropenia at 28.6% and 29.1% respectively (McNemar’s p-value 0.82). These rates are likely higher than those reported in the literature due to the very broad definition of neutropenia used in this study. Follow up will include neutropenia rates by grade. Conclusions: This proof of concept study established two key findings. First, that it is possible to do comparative effectiveness research at scale in order to drive value-based decisions in oncology care. Secondly, it confirms that we are seeing equivalent pegfilgrastim efficacy for neutropenia prophylaxis when comparing Udenyca, a biosimilar, to the originator agent.
上矢状窦血栓形成误诊一例
Authors: 陈育英, 王玉芬
Journal: BMJ (2008)

患者男,18岁,学生.主因头痛5 d,反应迟钝1 d,于2007年2月11日入院.患者于5 d前出现头痛,自认为感冒,测体温不高,曾口服感冒伤风胶囊、扑热息痛,1 d前出现反应迟钝,答非所问,伴右上肢无力,恶心,无呕吐、意识障碍,院外用甘露醇、激素治疗1 d无缓解。
Role of the total mutation burden (TMB) and tumor-infiltrating lymphocytes (TILs) on the development of second primary cancer after complete resection of non-small cell lung cancer (NSCLC).
Authors: Marie-Pier Gauthier, Maryam Karimi, Stefan Michiels, Lesley Seymour, Elisabeth Brambilla, Thierry Le Chevalier, Jean-Charles Soria, Robert Arthur Kratzke, Stephen L. Graziano, Ramaswamy Govindan, Ming-Sound Tsao, Frances A. Shepherd
Journal: Journal of Clinical Oncology (2020)

e21092 Background: Risk of developing SPC after complete surgical resection of NSCLC has been reported to be 3-6% per person-year. We hypothesized that genomic instability, as assessed by high TMB, and the absence of TILs in the primary tumor might be associated with SPC. Methods: The LACE [Lung Adjuvant Cisplatin Evaluation])-BIO database was used, which includes 3 randomized trials. TMB and TILs were analyzed on FFPE specimens. TMB was categorized into tertiles (high &gt; 7.8 mutations/MB, moderate i.e. &gt; 4 and &lt; = 7.8, low &lt; 4) and TILs as marked vs. other. Associations on competing time-to-event endpoints (SPC, and death without developing SPC) were evaluated using the Fine and Gray model stratified by trail and adjusted on treatment, age, gender, tumor stage, nodal stage, histology, performance status and surgery type. Results: TMB and TILs assessments were available for 879 patients without missing clinical covariates; 85 patients had marked TILs. During follow-up, 47 SPCs had been observed and 392 deaths without developing SPC. Regarding TMB, a significant association was found between low TMB and death without SPC (sub-distribution hazard ratio SHR = 1.36(1.06-1.74), see Table), suggesting a higher risk of death without SPC among patient with low TMB compared to those with moderate TMB; no strong effect was observed for SPC. Regarding TILs, a trend was observed between marked TILS and a lower risk of death (SHR = 0.70 [0.47-1.04]) but to a lesser extent for SPC (SHR = 0.80 [0.28-2.28]). Conclusions: This is the first study of the effect of genomic instability (measured by TMB) and host immune response (measured by TILs) in completely resected NSCLC on competing events of SPC and death, suggesting associations between TMB, TILs and death-without-SPC . There was no statistically significant association with SPC. However, the number of SPCs was small; these findings requires validation in other early stage lung cancer cohorts. [Table: see text]
The use of surgical &amp; interventional procedures for the diagnosis and treatment of pediatric tumors: An example from an upper middle income country.
Authors: M. Tezer Kutluk, Kübra Çakmakkaya, Fahad Ahmed, Devrim Akıncı, Saniye Ekinci, Berna Oğuz, Mithat Haliloğlu, Diclehan Orhan, Canan Akyüz
Journal: Journal of Clinical Oncology (2020)

e19022 Background: The burden of pediatric cancer is more than 300.000 cases per year in children aged 0-19 years globally. Turkey faces almost 4000 cases per yr in the same age group. The survival rates exceeded 80% in high income countries although it is still a challenge in LMICs at different level of low survivals. The availability, accessibility &amp; affordability of advanced techniques such as interventional procedures are major challenges for successful treatment of pediatric cancers in LMICs. Methods: 279 sequentially diagnosed cancer in children aged 0-18 years in a single institution in 2018 were included. Tumors were classified according to the ICCC-3. Leukemias were not included. The types of interventional &amp; surgical procedures used for diagnosis were recorded. The distribution of procedures according to the type of malignancies were examined &amp; descriptive characteristics of patients were compared. Results: The median age was 5 8/12 yrs, M/F=153/126. The most common tumors were CNS tumors followed by lymphomas &amp; neuroblastoma. Among all, surgery was performed in 189 (67.8) children whereas 45 (16.1%) patients were diagnosed by interventional radiology procedures. Radiological diagnosis was made in 42 (15.1%) children. Conclusions: Early diagnosis &amp; access to best available care is the most essential part of the pediatric cancer control. Current global initiatives have a focus on how to improve the survival in LMICs. Here we report the use of surgery vs interventional radiological procedures for the diagnosis of pediatric tumors. The efficient &amp; timely use of the diagnostic procedures save the patients lives in a cost effective ways with less morbidity &amp; mortality. Since there is limited data from the LMICs, we suggest to the pediatric oncology community to do more detailed evidenced based research for the diagnosis pediatric cancers. [Table: see text]
Pharmacokinetically-guided preoperative FOLFOX chemotherapy for locally advanced colon cancer patients.
Authors: Lucia Ceniceros, Jorge Baixauli, Azucena Aldaz, Jorge Arredondo, Carlos Pastor, Ana Chopitea, Lucia Granero, Patricia Martinez, Mariano Ponz-Sarvisé, Fernando Manuel Lapuente, Jose Luis Hernandez-Lizoain, Javier Rodriguez
Journal: Journal of Clinical Oncology (2020)

4104 Background: Preliminary results from ongoing randomised trials suggest that neoadjuvant chemotherapy (NAC) may be an alternative approach to conventional adjuvant therapy. We assessed the feasibility and activity of incorporating a pharmacokinetically (PK) guided dose adjustment of 5-FU within preoperative Folfox. Methods: Radiologically staged LACC pts, T4 or T3 with extramural depth &gt;5mm beyond the muscularis propia, were planned to receive 4-6 biweekly cycles of Oxalipatin (85mg/m²), Leucovorin (400 mg/m²), bolus 5-FU (400 mg/m2) and infusional 5-FU (initial dose of 2400mg/m² in 46h and subsequent cycles tailored according to PK monitoring in order to reach a target 5-FU area under the curve (AUC) between 20-30 mg∙h∙L-1). Dihidrouracil deshidrogenase was determined before the first cycle in order to detect pts with 5-Fu intolerance. Three serum samples were obtained during the 5-Fu infusion in the first two cycles. Pathological tumor regression was graded according to the MSKCC classification and toxicity to the NCI-CTCAE 4.0. Results: From June 2012 to August 2017, 45 pts (M/F: 35/10; median age 63) with LACC (T3: 66.7%; T4: 31.1%; T2: 2.2%; N+:66.6%) were evaluated. Median dose of 5-FU was 4500 mg. 48.9% of the pts required a 5-FU dose increase to reach the target AUC. Side effects profile included G3 neutropenia (3 pts), G2 diarrhea (2 pts) and G2 asthenia (9 pts). NAC was discontinued in 3 pts due to small bowell obstruction requiring surgery (no progressive disease during NAC). R0 resection rate was 100% (93.3% laparoscopy-assited). MSKCC score included grades 4, 3+ and 3 in 11.1%, 26.7% and 28.9% of pts, respectively. A complete pathological response was found in 5 pts (11.1%). Median number of harvested nodes was 16 (7-51), 80% ypN0. Those pts with AUC 25-30 had a 3-fold higher likelihood of achieving a MSKCC 3, 3+ and 4 responses. Median time to hospital discharge was 7 days (range 4-22). After a median follow-up of 60 months (44-66), 5-year actuarial PFS is 88.8%. Conclusions: Preoperative PK-adjusted FOLFOX in LACC pts is safe and well tolerated, achieving remarkable rates of major pathological responses and R0 resections.