tbuckley/cabot-search huggingface dataset:
Effect of obesity on oxidative stress system in patients with diabetic nephropathy and analysis of related factors
Authors: Ying-ying Zhang, Shou-gang Zhuang, Xiao-jun Li, Feng Liu, Lu Fang, Na Liu, Yi Wang
Journal: BMJ (2013)

Objective
To explore the relationship between obesity and oxidative stress in patients with diabetic nephropathy (DN).


Methods
We selected 76 cases with diabetic nephropathy (DN). All cases were at CKD stage Ⅱ-Ⅳ. And another 61 healthy controls (CON) were matched. According to body mass index (BMI), each group was further divided into three sub-groups of normal weight, overweight and obesity. The serum levels of isoprostane F 2α (PGF2α) was measured by enzyme linked immunosorbent assay (ELISA). And the serum levels of advanced oxidation protein products (AOPP) and vitamin E (VitE) were quantified by spectrophotometry.


Results
The serum levels of PGF2α and AOPP significantly increased in DN patients than those of healthy controls while the serum level of VitE was lower in DN patients (P<0.05). The serum levels of PGF2α and AOPP in overweight group were higher than those in normal weight group while the serum level of VitE was lower than that in normal weight group (P<0.05). BMI, smoking history, age, triglyceride and total cholesterol were associated with the level of oxidative stress in DN patients.


Conclusion
Oxidative stress is present in DN patients. Increased adiposity may amplify oxidative stress in diabetic nephropathy. Besides BMI, diabetes, age, smoking history, hypertensive history, triglyceride, total cholesterol also affect the level of oxidative stress in CKD patients.


Key words: 
Diabetic nephropathy; Obesity; Oxidative stress
Performance of a Nu.Q H3.1 assay for lung cancer detection.
Authors: Anne Louise Louise Sibille, Monique Henket, Marielle Herzog, Natalie Hardat, Jean-Louis Corhay, Renaud Louis, Bernard Duysinx
Journal: Journal of Clinical Oncology (2020)

e15542 Background: Lung cancer diagnosis relies on invasive methods and often occurs at a late stage of disease, explaining its poor outcome. Nucleosomes are DNA fragments wrapped around histones. They may constitute a non-invasive and early diagnostic method for lung cancer. We investigated the clinical and statistical performance of nucleosome assay levels alone and in combination with cytokines in plasma from untreated lung cancer (LC) patients and what their discriminant power was towards chronic obstructive pulmonary disease (COPD) and healthy (H) subjects. Methods: 142 plasma samples were prospectively collected: H, n = 45; LC, n = 44 and COPD, n = 53. The circulating level of intact nucleosomes containing the histone H3.1 isoform (Nu.Qª-H3.1) was individually tested and in combination with cytokines for its performance in discriminating subjects for their underlying condition. Then, statistical performance of each model was tested with binary logistic regression models for the best combination of biomarkers for the following groups: cancer vs control (group A), cancer vs COPD+control (group B) and for cancer vs COPD (group C). The best model for each group was then applied to two independent biobank cohorts for validation. Results: Results for Nu.Q-H3.1 was an area under the curve (AUC) of 0.79, for group A, B and C; a sensitivity of 68%, 66% and 66% for group A, B and C, respectively, for 80% specificity. For group A the H3.1+IL-10 model achieved a sensitivity of 77% for 80% specificity with an AUC of 0.88 (R² = 55.8%). For group B the H3.1+IL-6+IL-10 model achieved a sensitivity of 70% with an AUC of 0.85 (R² = 40.6%). For group C the H3.1+IL-6+IL-10 model achieved a sensitivity of 79% with an AUC of 0.85 (R² = 46.1%). The validation cohort performed similarly. Results for the 3 cohorts taken together were: AUC of 0.83, 0.87 and 0.90 for group A, B and C, respectively; sensitivity of 75%, 76 % and 84% for group A, B and C, respectively, for 80% specificity. Conclusions: Nucleosomes are detected in the plasma of H, LC and COPD patients. Combination with cytokines as described in these models allows for a good power ofdiscrimination between the three groups. Based on these encouraging results, we believe further studies with larger numbers of patients should be performed to confirm and validate the usefulness of these biomarkers and models.
Treatment effectiveness of two Chinese herbal medicine formulae in upper respiratory tract nfections: a randomized double-blind placebo-controlled tria
Authors: 刘岚
Journal: BMJ (2013)

目的
以安慰剂为对照，探讨两种中草药治疗急性上呼吸道感染疾病的疗效。


方法
两个随机、双盲、安慰剂对照的临床试验入选了香港地区327例诊断为上呼吸道感染的患者。这些患者由中医医师分类为两种不同的中医症候群，并分别随机接受中草药治疗或安慰剂治疗，疗程至多10 d。以治疗的第4天和第7天时患者痊愈的比例作为主要终点，而症状痊愈所需的时间、由健康调查简表(SF–36)和中华生活质量量表(ChQOL)方法测量的生存质量评分以及临床不良反应作为次要终点。


结果
治疗的第4天和第7天中药治疗组与安慰剂组的疾病痊愈率比较，差异无统计学意义。无论是风寒型或风热型症候群患者，症状好转的中位时间均为第10天。中药和安慰剂治疗的患者都随时间的延长，其生存质量评分均有显著改善；但对于风寒型症候群患者的SF–36生存质量评分，中药治疗组的改善程度优于安慰剂组(P＝0.01)。


结论
常用于治疗上呼吸道感染的两种中成药无论在治愈或缓解上呼吸道感染症状方面未能证实优于安慰剂。然而，对于风寒型症候群患者中药荆防败毒散(jing fan bai du san)能较安慰剂更好地改善总体健康状况。两种中药未显示不良反应。
Registrational dataset from the phase I/II ARROW trial of pralsetinib (BLU-667) in patients (pts) with advanced RET fusion+ non-small cell lung cancer (NSCLC).
Authors: Justin F. Gainor, Giuseppe Curigliano, Dong-Wan Kim, Dae Ho Lee, Benjamin Besse, Christina S Baik, Robert C Doebele, Philippe Alexandre Cassier, Gilberto Lopes, Daniel Shao-Weng Tan, Elena Garralda, Luis G. Paz-Ares, Byoung Chul Cho, Shirish M. Gadgeel, Michael Thomas, Stephen V. Liu, Corinne Clifford, Hui Zhang, Christopher D. Turner, Vivek Subbiah
Journal: Journal of Clinical Oncology (2020)

9515 Background: Pralsetinib is an investigational, highly potent, selective RET kinase inhibitor targeting oncogenic RET alterations. We provide the registrational dataset for pts with RET fusion+ NSCLC with and without prior treatment from the global ARROW study. Methods: ARROW (75 sites in 11 countries; NCT03037385) consists of a phase I dose escalation to establish recommended phase II dose (400 mg once daily [QD] orally) and phase II expansion cohorts defined by tumor type and/or RET alteration. Primary objectives were overall response rate (ORR; blinded independent central review per RECIST v1.1) and safety. Efficacy analyses are shown for response-evaluable pts (REP) with RET fusion+ NSCLC who initiated 400 mg QD pralsetinib by July 11 2019 and safety for all pts (regardless of diagnosis) treated with 400 mg QD. Results: As of November 18 2019, 354 pts with advanced solid tumors had received pralsetinib at starting dose of 400 mg QD with median follow-up 8.8 months. ORR, disease control rate (DCR), and % of pts with tumor size reduction are shown in the table for pts with metastatic RET fusion+ NSCLC (n=116; 72% KIF5B; 16% CCDC6; 12% other/fusion present but type unknown) and with prior platinum treatment (n=80) or without prior systemic treatment (n=26). ORR was similar regardless of RET fusion partner, prior therapies, or central nervous system involvement. Overall there were 7 (6%) complete responses, 4 (5%) in prior platinum pts and 3 (12%) in treatment naïve pts; median time to response overall was 1.8 months and median duration of response (DOR) was not reached (95% CI, 11.3–NR). In the safety population (n=354), most treatment-related adverse events (TRAEs) were grade 1-2, and included increased aspartate aminotransferase (31%), anemia (22%), increased alanine aminotransferase (21%), constipation (21%) and hypertension (20%). 4% of pts in the safety population (all tumor types) discontinued due to TRAEs. Conclusions: Updated, registrational, centrally reviewed data demonstrate that pralsetinib has rapid, potent, and durable clinical activity in pts with advanced RET fusion+ NSCLC regardless of RET fusion genotype or prior therapies, and QD oral dosing is well-tolerated. Clinical trial information: NCT03037385 . [Table: see text]
Outcomes of patients with primary plasma cell leukemia (pPCL) in the era of novel agent therapy.
Authors: Bharat Nayar Nandakumar, Shaji Kumar, Angela Dispenzieri, Francis Buadi, David Dingli, Martha Lacy, Prashant Kapoor, Yi Lin, Taxiarchis Kourelis, Eli Muchtar, John Anthony Lust, Ronald S. Go, Rahma M. Warsame, Suzanne R. Hayman, Nelson Leung, Dragan Jevremovic, Morie A. Gertz, Robert A. Kyle, S. Vincent Rajkumar, Wilson I. Gonsalves
Journal: Journal of Clinical Oncology (2020)

e20510 Background: pPCL is a rare and aggressive form of multiple myeloma (MM) with dismal survival outcomes compared to the remainder of MM patients. Several studies have validated the optimal cutoff for defining pPCL to be &gt;5% circulating plasma cells (cPCs) on a peripheral blood smear due to equally poor outcomes in this less restrictive cohort. We evaluated the clinical outcomes and cytogenetic features of patients diagnosed with pPCL at our institution that were treated with novel agent induction therapies. Methods: We evaluated patients with pPCL diagnosed between 2000 – 2018 (using the 5% cut off) at Mayo Clinic, Minnesota. Data was extracted from a prospectively maintained database and from the review of electronic medical records. Patients were categorized as having high risk (HR) cytogenetics if any of the following abnormalities were present: del 17p, t(4;14), t(14;16) or t(14;20). Chi-square tests and Fisher exact tests were used to compare differences between sub-groups. Survival analysis was performed by the Kaplan-Meier method and differences assessed using the log rank test. Results: This cohort consisted of 67 patients with pPCL with a median age of 62 years (range: 34-91) of which 33 (46%) were male. The median follow up was 46 months (95% CI: 41 – 90). The median bone marrow plasma cell involvement was 84% (Range: 10 – 100) and the median cPCs percentage on the peripheral blood was 23% (range: 5 - 93). Data on primary cytogenetic abnormalities were available in 60 (85%) patients and the distribution was as follows: t(11;14) – 27 (45%), t(4;14) – 5 (8%), t(14;16) – 8 (13%), t(14;20)- 3(5%) and del 17p- 15(25%). All patients received novel agent induction therapy with 36 (54%) having received autologous stem cell transplant and 4 undergoing an allogeneic stem cell transplant. The median time to next therapy (TTNT) and overall survival (OS) for all patients was 13 months (95% CI: 9 – 17) and 24 months (95% CI: 19 – 40) respectively; 16 months and 51 months for standard risk (SR) vs. 10 months and 19 months for HR (P = 0.005 for OS), when stratified by cytogenetic risk. There were only 17 (31%) patients who were alive for ≥48 months since diagnosis (i.e. twice the median OS of this cohort); The absence of high risk cytogenetics (P = 0.049) and non-elevated LDH level (P = 0.047) at diagnosis predicted for achieving this survival goal. Conclusions: The outcomes of patients diagnosed with pPCL remain poor despite the use of novel agent induction therapy. However, some patients appear to do better than expected and this phenomenon may be influenced by the presence of HR cytogenetics.
Technology-enabled longitudinal monitoring of patient-reported outcomes (PROs) to individualize care of immune-related adverse events (irAEs) in patients (pts) treated with immune checkpoint inhibitors (ICIs).
Authors: Pavlos Msaouel, Michael L. Van Alstine, Clara Oromendia, Jianjun Gao, Yinghong Wang, Bilal A. Siddiqui, Arlene O. Siefker-Radtke, Amishi Yogesh Shah, Leah Shaw, Lidia Lopez, Andrew Leonard Laccetti, Nizar M. Tannir, Michael Elashoff, Christopher Logothetis
Journal: Journal of Clinical Oncology (2020)

TPS2088 Background: ICIs have become the therapeutic standard for many cancers but are associated with unique and diverse irAEs that often occur at home. Appropriately timed and specific interventions are critical to recovery. Thus, there is a need to effectively &amp; efficiently monitor in real time pts treated with ICIs. To improve outcomes, we have activated a clinical trial developed to determine the feasibility and safety of an electronically enabled strategy to remotely monitor symptoms and prompt communication that will guide and inform specific patient-driven “course corrections” in response to potential irAEs. Methods: This is an adaptive prospective trial that uses a mobile irAE-specific PRO application we developed to monitor and alert the care team in real time when severe symptoms are reported. In parallel with the mobile symptom collection, serum and urine biomarkers are collected at baseline, first tumor restaging, and upon the development of irAEs. Optional stool microbiome analyses are also performed. To facilitate the generalizability of our inferences, we are using broad inclusion criteria: ECOG performance status ≤3; any line of ICI given as standard of care or as part of therapeutic clinical trials; elderly pts are included. Because the relationship between PROs and irAEs is currently undefined, we designed our trial to use adaptive symptom thresholds that will notify the healthcare team of suspicion for irAEs. The mobile application will use these dynamic thresholds to determine whether or not to alert the healthcare team. The positive and negative predictive value of each symptom for identifying subsequent irAEs will be assessed at scheduled interim analysis time points. The care teams’ responses to the alerts, and all of the clinical outcomes for the pts over time will be collected as part of the trial. The primary goal of the trial is the assessment of the predictive power of the mobile PRO symptom collection in combination with serum and urine markers to identify grade 2 or higher adverse events that require intervention (e.g., dose modifications, hospitalizations, and therapeutic interventions) within two weeks of symptom onset. Effective remote monitoring of irAEs will leverage our understanding of ICI toxicity and empower pts to be effective partners in their care. The trial has currently enrolled 17 pts towards the enrollment target of 100 pts. Clinical trial information: PA19-0095 .
Fractures of the scaphoid
Authors: Onur Berber, Imtiaz Ahmad, Sam Gidwani
Journal: BMJ (2020)

### What you need to know

A 25 year old man sustains an extension injury of his right wrist while playing football as a goalkeeper, and presents to the emergency department the same day with wrist pain. Examination reveals tenderness over the radial side of the wrist, including within the “anatomical snuffbox,” as well as tenderness over the tubercle of the scaphoid. However, he has no pain on longitudinal compression of his thumb. Standard posteroanterior and lateral wrist radiographs are performed ( fig 1 ) and as no fracture is seen, he is discharged. He re-attends six weeks later with ongoing pain, and a series of scaphoid radiographs ( fig 2 ) show a fracture of the proximal third of the scaphoid. 



Fig 1 
Initial radiographs obtained in the emergency department with and without labels. These only included standard (a) posteroanterior and (b) lateral views of the wrist. No scaphoid fracture was visible on these views. Scaphoid (Sc) marked with a dashed white line; trapezium (Tm) marked with dotted white line, and trapezoid (Td) marked with dotted black line





Fig 2 
Scaphoid views performed six weeks after the injury. Three of the standard scaphoid series are presented including (a) posteroanterior, (b) pronated oblique, and (c) Ziter views. A proximal pole fracture is clearly seen on the pronated oblique and the Ziter views. The fracture is …
视触叩听急腹症:急性胰腺炎
Authors: 吴东, 韩显林, 朱峰
Journal: BMJ (2012)

我国急性胰腺炎的病因多为胆石症或饮食不当.患者常有不同程度的上腹痛和腹部压痛.通过仔细询问病史、准确查体以及淀粉酶检测,多数患者可得到及时正确的诊断.物理诊断还有助于区分轻症急性胰腺炎和重症急性胰腺炎,这是正确施治的关键。
Can sentinel node biopsy after neoadjuvant systemic chemotherapy (NAC) be safely omitted in selected patient with early breast cancer?
Authors: Atsushi Yoshida, Yasuyuki Kojima, Mizuho Tazo, Naoko Matsuda, Koichiro Tsugawa, Hideko Yamauchi, Seigo Nakamura, Naoki Hayashi
Journal: Journal of Clinical Oncology (2020)

564 Background: There is a recent trend of performing minimum axillary surgery considering the prognostic value and fewer complications for primary breast cancer patients since the results of ACOSOG Z011. Nodal status after NAC is not be useful for postoperative treatment in most of cN0 patients. Therefore, sentinel node biopsy (SNB) may be omitted if ypN0 after NAC can be predicted in cN0 patients. We assessed clinicopathological factors associated with ypN0 after NAC in cN0 primary breast cancer patients. Methods: Two-institutional retrospective cohort study of clinically N0 breast cancer patients before NAC and who underwent breast surgery was conducted, including 419 consecutive patients between 2009 and 2016 in St. Luke's International Hospital and St. Marianna University School of Medicine hospital. Each institutional review board approved this study. In the patients with or without nodal metastasis on SNB after NAC, we compared clinicopathological factors including Estrogen Receptor (ER), Progesterone Receptor (PgR), human epidermal growth factor receptor 2 (HER2), Ki-67 on needle biopsy specimens, and tumor size before and after NAC on MRI findings. Results: Of the 419 patients, 380 patients (90.7%) were ypN0 and 39 patients (9.3%) were ypN+ after NAC. In univariate analysis, clinical complete response of primary tumor on MRI findings (MRI-CR) (p&lt;0.01), ER-negative (p&lt;0.01), PgR-negative (p&lt;0.01), and high-Ki-67 &gt;30% (p&lt;0.01) were significantly associated with ypN0 on SNB after NAC. In multivariate analysis, MRI-CR (HR 5.12, p&lt;0.01) and high-Ki-67 (HR 2.86, p&lt;0.01) were independent predictive factors of ypN0 after NAC.According to breast cancer subtype, only one of 72 ER-negative and HER2-positive had significantly low risk of ypN+ (1.3%) comparing other subtypes (p&lt;0.01). Conclusions: Achieving cCR of primary tumor after NAC and high-Ki67 in cN0 patients, especially in HER2 type breast cancer, might have ypN0. We are conducting prospective study to omit SNB for these populations based on these results,
Utilization of a cardio-oncology clinic: A single center experience.
Authors: Peter Doukas, Sadiya S Khan, Nausheen Akhter
Journal: Journal of Clinical Oncology (2020)

e19192 Background: Many systemic anti-cancer therapies (chemotherapy, immunotherapy and radiation) have known cardiac toxicities. The field of cardio-oncology aims to optimize the cardiac health of cancer patients. Our goal was to evaluate baseline clinical characteristics, referral patterns and the rate of adverse cardiac outcomes in patients referred to a single cardio-oncology clinic at a tertiary care academic center. Methods: We performed a retrospective review of 100 consecutive patients who established care at a cardio-oncology clinic between 2011-2019. Baseline clinical data was collected from the initial presentation. Interventions and subsequent adverse cardiac events that occurred within a 6-24 month follow-up period were recorded. Fisher’s exact test was used to compare the measured variables. Results: Of the 100 patients, the median age was 63 years old and 69% were women. The most common reasons for referral were echocardiographic changes in systolic function or symptomatic congestive heart failure (HF) (54%; 54/100). Of patients who received anti-cancer therapy, only 18% (17/95) were referred for a pre-treatment cardiac evaluation. The rate of new HF diagnoses or worsening HF symptoms, defined by decreased NYHA class or HF-related hospitalizations, was 6% in the cancer treatment naïve group and 12% in the group that was not (p=0.68). Anti-cancer therapy was stopped or changed in 6 patients who were diagnosed with HF at any point. Conclusions: Our study provides insight into referral practices, interventions and outcomes at a single cardio-oncology clinic at a tertiary care academic center. Patients were often referred after the initiation of anti-cancer therapy, with the majority already experiencing a decline in systolic function. There was a higher rate of new HF events in patients who had already been treated with anti-cancer therapy before their first cardio-oncology visit. This may suggest the need for a change in referral practices to optimize cardiac health, specifically a shift in cardio-oncology evaluation prior to initiation of anti-cancer therapy. [Table: see text]
A retrospective single-center evaluation of the safety and efficacy of direct oral anticoagulants versus low molecular weight heparin in patients with cancer-associated thrombosis.
Authors: Melissa McShane, Jordan Senchak, Anthony Stack, Justina Frimpong, Van T Hellerslia, Huaqing Zhao
Journal: Journal of Clinical Oncology (2020)

e24102 Background: Over the past decade, there has been an increase in the use of direct oral anticoagulants (DOACs) in the cancer population despite limited data comparing its use against low molecular weight heparin (LMWH), the standard of care in cancer patients. Increasing data supporting DOACs in cancer-associated thrombosis has emerged over the past few years. Nonetheless, this study will evaluate the relative safety and efficacy of DOACs versus LMWH in cancer-associated thrombosis within an urban setting associated with low socioeconomic status. Methods: This is a retrospective chart review of medical records from patients treated at an urban academic medical center from October 2010 through October 2018. Patients met study inclusion if they had a diagnosis of venous thromboembolism occurring after the date of diagnosis of active cancer and were prescribed a direct oral anticoagulant (rivaroxaban, apixaban, dabigatran, edoxaban) or a low molecular weight heparin (dalteparin, enoxaparin, or fondaparinux) as monotherapy for the treatment of venous thromboembolic disease. Patients were excluded if they had less than 6 months of follow up data for reasons other than death. The primary outcomes were recurrent venous thromboembolism, major bleeding and death. Results: Of the 914 patients who met inclusion criteria, 286 were excluded due to lack of follow up data. The remaining patients included 472 in the LMWH arm and 156 in the DOAC arm. At 6 months, recurrent thromboembolism occurred in 5 of the 472 patients (1.1%) in the LMWH group as compared with 4 of the 156 patients (2.6%) in the DOAC group (p = 0.170). Major bleeding occurred in 36 patients (7.6%) in the LMWH group and 11 patients (7.0%) in the DOAC group (p = 0.813). Death within 6 months of starting anticoagulation occurred in 76 patients (16.1%) in the LMWH group and 16 patients (9.6%) in the DOAC group (p = 0.046). Discontinuation before 6 months of treatment occurred in 241 patients (51.2%) in the LMWH group and 46 patients (29.5%) in the DOAC group. Conclusions: The LMWH and DOAC groups had similar rates of recurrent thromboembolism and major bleeding. The mortality rate within 6 months of starting anticoagulation was significantly higher in the LMWH group and this difference requires further evaluation. These results help support the continued use of DOACs for the treatment of cancer-associated thrombosis and demonstrate that DOACs are as safe and effective as LMWH in this patient population.
肝硬化患者黏附分子水平及其与肝功能状况的关系
Authors: 贾道全, 粱若玲, 郑雪莲, 毛咏秋
Journal: BMJ (2004)

检测70例乙型肝炎后肝硬化患者血清细胞黏附分子-1(sICAM-1)和血管细胞黏附分子-1(sVCAM-1),并与20例健康者对照,发现肝硬化患者该指标较正常组增高,其水平与肝功能Child-puph分级变化呈正相关.提示sICAM-1和sVCAM-1水平能较好反映肝功能状况,对肝硬化病情判断有一定的参考价值。