tbuckley/cabot-search huggingface dataset:
Efficacy of add-on treosulfan and melphalan high-dose therapy in patients with high-risk metastatic Ewing sarcoma: Report from the International Ewing 2008R3 trial.
Authors: Uta Dirksen, Vivek Bhadri, Bénédicte Brichard, Trude Butterfass-Bahloul, Sona Cyprova, Andreas Faldum, Hans Gelderblom, Jendrik Hardes, Peter Hauser, Lianne Havemann, Lars Hjorth, Heribert Juergens, Jukka Kanerva, Thomas Kuehne, Ruth Lydia Ladenstein, Anna Raciborska, Jelena Rascon, Beate Timmermann, Andreas Ranft, Raphael Koch
Journal: Journal of Clinical Oncology (2020)

11501 Background: Ewing 2008R3 (EudraCT2008-003658-13) was conducted in 12 countries. It evaluated the effect of treosulfan and melphalan high dose chemotherapy followed by re-infusion of autologous hematopoietic stem cells (HDTreoMel) on event-free (EFS, primary endpoint) and overall survival (OS) in high-risk Ewing Sarcoma (EwS). Methods: Phase III, open label, prospective, multi-center, randomized controlled clinical trial. Eligible patients (pts) had disseminated EwS with metastases to bone and/or other sites, excluding pts with only pleuropulmonary metastases. Pts received 6 cycles of VIDE induction and 8 cycles of VAC consolidation therapy. Patients were randomized to receive additional HDTreoMel chemotherapy or no further treatment (control), They were further stratified by number of bone metastases (1, 2-5, &gt; 5). One-sided adaptive inverse-normal 4-stage design, changed after the 1 st interim analysis via Müller-Schäfer method. Initial sample size 185 pts, type I error rate 2.5%, power 80%. Results: 109 pts were randomized between 2009 and 2018: 55 were randomized to HDTreoMel. With a median follow-up of 3.3 years, the primary endpoint EFS was not significantly different between HDTreoMel and control in the adaptive design (HR 0.85, 95% CI 0.55-1.32, intention-to-treat). 3-year (3y) EFS was 20.9 % (95% CI 11.5-37.9%) in HDTreoMel and 19.2 % (95% CI 10.8-34.4%) in control pts. Results were similar in the per protocol collective. Subgroup analyses showed that independent of treatment, male patients had a worse outcome than female patients: 3y EFS 13.3% (95% CI 5.7-31.1%) vs 25.2% (95% CI 15.5-40.8%); p = 0.07. Patients aged &lt; 14 had a better outcome when treated in the HDTreoMel group: 3y EFS 39.3% (95% CI 20.4-75.8%) vs 9% (95% CI 2.4-34%); p = 0.016; HR 0.40 (0.19-0.87). These effects were similar in the per protocol collective. Severe toxicities of hematology, gut, general condition and infection were more pronounced in the HDTreoMel group (p &lt; 0.05). Conclusions: In patients with very high risk EwS, additional HDTreoMel was of no benefit for the entire cohort of patients. HDTreoMel may be of benefit for children age &lt; 14. This observation is supported by comparable results from a non-randomized trial EE99 R3 (Ladenstein et al. JCO, 2010). Clinical trial information: NCT00987636 .
The humanistic burden reported by first-line (1L) head and neck cancer patients diagnosed with recurrent/metastatic squamous cell carcinoma (R/M SCCHN) in europe: A real-world study.
Authors: Prianka Singh, Bryan Bennett, Tom Bailey, Gavin Taylor-Stokes, Ivana Rajkovic, Roelien Postema, Sharon Curtis, Chris Curtis
Journal: Journal of Clinical Oncology (2020)

e18514 Background: R/M SCCHN is associated with substantial humanistic burden and limited tolerable treatment options that are able to preserve heath-related quality of life (HRQoL). Real world evidence is lacking to characterize and quantify burden in these patients by geographic region and treatment. Methods: A cross-sectional study was conducted in France, Germany, Italy, Spain and the UK from Jan to May 2019. Physicians (n = 184) recruited patients to complete a survey assessing the impact of their SCCHN and completed medical charts for corresponding patients. Patient burden and HRQoL was captured through the patient survey, which included the Functional Assessment of Cancer Therapy Head and Neck Cancer (FACT H&amp;N) (range: 0-148; sub scores physical/social/functional: 0-28, emotional 0-24). Higher scores for instruments indicate better HRQoL. Patients were identified as 1L platinum eligible according to clinical characteristics and treatments captured in the medical charts. Results: Physicians recruited 577 (99 UK, 114 France, 117 Germany, 117 Spain, and 130 Italy) 1L platinum eligible patients of mean age 62.8 years, most were male (72%) and had ECOG score 0-1 (79%) or 2 (21%). Over half (52%) received the EXTREME regimen, 9% received a separate cetuximab-based regimen. Patients experienced a high symptom burden, most commonly fatigue (43%), weight loss (40%), pain (35%), and difficulty swallowing (32%). Dry mouth and persistent sore throat were reported by 19% patients. Most patients reported at least some problems with performing usual activities (62%), at least moderate pain/discomfort (79%), and at least moderate anxiety/depression (71%). Patients had a diminished HRQoL in every FACT-H&amp;N domain: total score, 73.2; physical, 15.0; social, 16.5; emotional, 11.7; functional well-being, 10.7. Conclusions: In Europe, patients treated for 1L R/M SCCHN experience considerable humanistic burden and diminished HRQoL. These data suggest an unmet need in this patient population for novel treatments that are able to maintain or even improve HRQoL.
A report of 23 cases of middle and lOW rectal carcinoma in the elderly treated with trans-sphincteric local resection(Mason's operation)
Authors: Xi-shui Wang, Yan-mei Han, Zhi-yong Jiang, Shou-he Zhao, Qiang-pu Chen, Chun-sheng Qi
Journal: BMJ (2008)

Clinical data of 23 elderly patients with rectal cancer undergoing trans-sphincteric local resection(TSLR, Mason's operation)were retrospectively analyzed. All the 23 patients were followed-up for three to seven years after operation, 18 with normal or good fecal continence(78%), five just in fair condition(22%)and none in fecal incontinence. Three-year survival was 83 percent(19/23)and 5-year survival was 78 percent(18/23)for them. It is suggested that TSLR is a safe, feasible and effective treatment for middle and low rectal cancer in the elderly with a long term survival and satisfactory quality of life. 

Key words: 
Anus neoplasms; Digestive system surgical procedures
Gynecologic oncology, gender and relevant leadership in academic medicine.
Authors: Sarah Madhu Temkin, Lisa Rubinsak, Michelle F. Benoit, Uma Chandavarkar, Linda Hong, Laurel K Berry, Christine A Heisler, BJ Rimel, William P. McGuire
Journal: Journal of Clinical Oncology (2020)

e19056 Background: Within academic medicine, there has been increasing attention to diversity and inclusion. We sought to characterize gynecologic oncologist (GO) faculty inclusion, with attention to gender in relevant academic leadership roles. Methods: Using the American Association of Medical Colleges list of accredited schools of medicine academic institutions were identified. Observational data was obtained through institutional websites in 2019. Results: Of 154 accredited medical schools, 144 contain a department of obstetrics and gynecology (OBG) with a chair; 103 a GO division with a director; 98 a clinical cancer center with a director. GO divisions included an average of 3.1 faculty. 55% of GO faculty were women, compared to 66% of OBG faculty (p &lt; 0.01). 38% of the GO division directors were women which was an under-representation (p &lt; 0.01). GOs made up 10% of OBG faculty and 15.4% of OBG chairs (NS). Women GOs made up 7.9% of women OBG faculty and 8 (5.6%) women GOs were OBG chairs (NS). 9.9% of GO faculty (11.6% of women GO faculty) report to women GOs at the chair level. OBG departments with a GO chair were more likely to have a woman GO division director (68.4 vs 31.7%, p &lt; 0.01), and GO fellowship (59.1 vs 32%, p &lt; 0.01). The majority (59%) of cancer centers directors were medical oncologists (see Table). 2 (2%) of cancer center directors were GOs; 1 at an NCI designated cancer center. Neither GO directors were women. Incidence to leadership and mortality to leadership ratios were calculated compared to expected rates by SEER 2019. By these measures GOs were underrepresented in cancer center leadership (p &lt; 0.01, p &lt; 0.01). Conclusions: Despite representative leadership of GO and women GO within in OBG leadership, most GOs report to non-oncologists at the department chair level. Potential benefits of GO leadership within OBG departments were identified. The practice of gynecologic oncology includes complex medical and surgical cancer care making these physicians uniquely qualified for cancer center, but representation of GOs in cancer center leadership is low and women GO were absent from cancer center director positions. Without inclusion of GO in cancer center leadership, existing inequities in clinical care, research and funding for gynecologic malignancies may be amplified. [Table: see text]
金匮肾气丸治疗中老年男性部分雄激素缺乏综合征的临床研究
Authors: 车文骏, 何小舟, 经浩, 巢志复, 蔡文元, 薛钟, 丁涛, 姜建平
Journal: BMJ (2007)

对58例中老年男性部分雄激素缺乏综合征(PADAM)患者应用金匮肾气丸治疗3个月;治疗后国际勃起功能指数评分提高,PADAM评分体能症状+血管舒缩症状评分降低,精神心理症状评分显著降低,性功能减退症状评分降低,血睾酮水平升高,而黄体生成素水平降低,卵泡刺激素水平降低,前列腺特异性抗原无明显变化.表明金匮肾气丸治疗PADAM可使症状全面明显改善,精神心理症状和体能症状、血管舒缩症状的改善优于性功能减退症状的改善,对前列腺不产生明显影响。
Chinese expert consensus on the application of Troponin in patients with acute coronary syndrome Expert Group of Chinese expert consensus on the application of Troponin in patients with acute coronary syndrome
Authors: 《基层医院急性冠状动脉综合征临床诊疗中心肌肌钙蛋白检测应用专家共识》撰写专家组
Journal: BMJ (2016)
Dose Timing of <scp>D</scp>-Cycloserine to Augment Exposure Therapy for Social Anxiety Disorder
Authors: Jasper A. J. Smits, Mark H. Pollack, David Rosenfield, Michael W. Otto, Sheila Dowd, Joseph Carpenter, Christina D. Dutcher, Elizabeth M. Lewis, Sara M. Witcraft, Santiago Papini, Joshua Curtiss, Leigh Andrews, Shelley Kind, Kristina Conroy, Stefan G. Hofmann
Journal: JAMA Network Open (2020)

Findings suggest that the efficacy of D-cycloserine (DCS) for enhancing exposure therapy may be strongest when administered after sessions marked by low fear at the conclusion of exposure practice. These findings have prompted investigation of DCS dosing tailored to results of exposure sessions.To compare tailored postsession DCS administration with presession DCS administration, postsession DCS administration, and placebo augmentation of exposure therapy for social anxiety disorder.This double-blind randomized clinical trial involved adults with social anxiety disorder enrolled at 3 US university centers. Symptom severity was assessed at baseline, weekly during treatment, and at 1-week and 3-month follow-up. Data analysis was performed from September 2019 to March 2020.Participants completed a 5-session treatment and received pills commensurate with their condition assignment at sessions 2 through 5, which emphasized exposure practice.Symptom severity was evaluated by the Liebowitz Social Anxiety Scale and Social Phobic Disorders-Severity Form as administered by independent evaluators.A total of 152 participants were enrolled (mean [SD] age, 29.24 [10.16] years; 84 men [55.26%]). Compared with placebo, presession and postsession conditions showed greater symptom improvement (b = -0.25; 95% CI, -0.37 to -0.13; P < .001; d = 1.07; and b = -0.20; 95% CI, -0.32 to -0.07; P = .002; d = 0.85) and lower symptom severity (b = -0.51; 95% CI, -0.81 to -0.21; P < .001; d = 0.76; and b = -0.49; 95% CI, -0.80 to -0.18; P = .002; d = 0.72) at 3-month follow-up. No differences were found between presession and postsession conditions. The tailored condition showed no advantage over placebo. Compared with the tailored condition, presession and postsession conditions evidenced greater decreases (b = -0.22; 95% CI, -0.34 to -0.10; P < .001; d = 0.94; and b = -0.17, 95% CI, -0.29 to -0.04; P = .008; d = 0.72) and lower symptom severity (b = -0.44, 95% CI, -0.73 to -0.14; P = .004; d = 0.64; and b = -0.41, 95% CI, -0.72 to -0.11; P = .008; d = 0.61) at 3-month follow-up.Administration of DCS enhanced exposure therapy for social anxiety disorder when given before or after the exposure session. However, the study failed to achieve the aim to develop a tailored clinical application.ClinicalTrials.gov Identifier: NCT02066792.
Neutropenia analysis of venetoclax monotherapy in patients with relapsed or refractory chronic lymphocytic leukemia: Pooled data from VENICE-I and -II Phase IIIb trials.
Authors: Mary Ann Anderson, Matthew Steven Davids, Arnon P. Kater, Tara Cochrane, Fatih Demirkan, Yair Herishanu, Brian Leber, Eugene Nikitin, Abdullah A. Masud, Tanya S. Rosenberg, Simon Sharmokh, Stan Fort, Francesco Forconi
Journal: Journal of Clinical Oncology (2020)

e20011 Background: Neutropenia is a common hematologic Grade (Gr) 3+ adverse event (AE) recorded in patients with chronic lymphocytic leukemia (CLL) receiving venetoclax (VEN). In this analysis, we evaluated fixed duration VEN monotherapy given to patients with relapsed or refractory (R/R) CLL with and without pre-existing Gr3+ neutropenia. Methods: This post-hoc analysis pooled data from patients in the ongoing Phase 3b trials VENICE-I and VENICE-II with R/R CLL who had received ≥1 dose of VEN monotherapy (ramp-up to 400 mg QD). Gr4 hematologic AEs and Gr3+ neutropenia ( &lt; 1000 cells/mm 3 ) with infection or fever were managed using dose interruption/reduction. Granulocyte colony stimulating factor (G-CSF) was used in Gr3+ neutropenia. Results: At data cutoff (June 30, 2019), 44/468 (9%) patients had Gr3+ neutropenia at baseline (BL; Gr3+ neutropenia group), 80% of whom received G-CSF during the study vs 38% of those with &lt; Gr3 neutropenia at BL ( &lt; Gr3 neutropenia group). Median on-study duration for VEN was 20.2 months (range: 0.1–36.1). Median number of prior CLL therapies was 2 for both groups (range: 1–10). Serious infections were experienced by 10/44 (23%) and 69/424 (16%) of patients in the Gr3+ and &lt; Gr3 neutropenia groups, respectively. The most common AEs leading to discontinuation overall were second primary malignancies (13/468; 3%). 5/468 (1%) patients in the total population discontinued due to neutropenia/febrile neutropenia. One case of Gr5 infection with concomitant Gr3 neutropenia was reported in the &lt; Gr3 neutropenia group post-VEN discontinuation. See Table. Conclusions: In this large post-hoc analysis, discontinuation due to neutropenia was rare (1%) in the overall population and accounted for 3/11 AE discontinuations in the Gr3+ neutropenia group; 10 patients had a serious infection. Patients with pre-existing neutropenia can be managed on VEN, though concurrent use of G-CSF is likely to be required. Additional data to follow. Clinical trial information: NCT02756611; NCT02980731 . [Table: see text]
Impact of premature rupture of membranes on fetal lung development
Authors: Ying Liu
Journal: BMJ (2018)

Premature rupture of membranes (PROM) is a common complication of pregnancy, seriously affecting the growth and development of fetus and newborns, even leading to death. PROM may disturb lung maturation and cause a variety of serious lung disease due to the infection and inflammation factors, which is one of the causes of poor prognosis or death in fetus and newborns. The awareness and knowledge of the impact of PROM on the fetal lung development may be of value for clinicians to improve neonatal survival rate.


Key words: 
Fetal membranes, premature rupture; Fetus; Bronchopulmonary dysplasia
Clinical characteristics in juvenile gout patients
Authors: Fuyong Qiang, Xiaowan Wang, Zhi Li, Dan Xuan
Journal: BMJ (2018)

To analyze the clinical characteristics of juvenile gout, 101 gout patients in Affiliasted First Hospital of Wanan Medical College from 2016 January to Decemder were divided into juvenile group (≤20 years, n=41) and adult group (>20 years, n=60), the clinical data and related biochemical tests were collected. The body mass index (BMI), fasting blood glucose (FBG), TC, TG, uric acid, urea nitrogen, creatinine, cystatin C, glomerular filtration rate (GFR) and C-reactive protein (CRP), the first gout position, the duration of disease, the family history, the number of involved joints and the tophi were compared between two groups. Compared with the adult group, the juvenile group had significantly higher BMI [(25.6±1.3) vs. (22.8±1.0), t=-12.51)], TC [(5.55±0.51) vs. (5.07±0.54), t=-4.44), TG [(2.04±0.32) vs. (1.83±0.39), t=-2.92), uric acid[606.0 (541.0,641.0) vs. 502.5 (447.5,542.2), Z=-5.65]and C-reactive protein[68.0(57.0,83.5) vs. 46.0 (36.0,59.8), Z=-4.64], while lower FBG [(4.83±0.68) vs. (5.74±1.23),t=4.31)] and the number of involved joints[1(1,1) vs.2(1,4), Z=5.45]. The GFR was higher in the juvenile group [(140.4±31.0) vs. (77.7±22.5), t=-11.81, P 0.05) .The proportion of family history of gout was higher in juvenile group (χ2=6.174, P<0.05) but the proportion of tophi was lower (χ2=16.564, P<0.01) than those in adult group. The characteristics of juvenile gout are significantly different with those of adult gout patients, so the juvenile patients should be managed differently from the adult patients.


Key words: 
Gout; Adolescent; Disease attributes
Association Between Malignant Mitral Valve Prolapse and Sudden Cardiac Death
Authors: Lakshmi Muthukumar, Arshad Jahangir, M. Fuad Jan, Ana Cristina Perez Moreno, Bijoy K. Khandheria, A. Jamil Tajik
Journal: JAMA Cardiology (2020)

Malignant arrhythmic mitral valve prolapse (MVP) phenotype poses a substantial risk of sudden cardiac death (SCD), and an estimated 26 000 individuals in the United States are at risk of SCD per year. Thus, identifying risk-stratification strategies for SCD is imperative.Patients with MVP have a heterogenous clinical spectrum, ranging from a benign course to a devastating complication such as SCD. Some of the high-risk markers of MVP, which are identified electrocardiographically, include inverted or biphasic T waves, QT dispersion, QT prolongation, and premature ventricular contractions originating from the left ventricular outflow tract and papillary muscles. Morphofunctional characteristics of SCD are leaflet thickness of 5 mm or greater, mitral annulus disjunction, paradoxical systolic increase of the mitral annulus diameter, increased tissue Doppler velocity of the mitral annulus, and higher mechanical dispersion on echocardiography and fibrosis identified by late gadolinium enhancement on cardiac magnetic resonance imaging.Findings from this review suggest that SCD can occur earlier in the course of MVP from complex arrhythmias that are triggered by the repeated tugging and traction of the chordopapillary muscle unit and basal mid-myocardium, even before macrofibrosis can be identified in these regions by late gadolinium enhancement on cardiac magnetic resonance imaging. Some of the newer markers identified by speckle-tracking Doppler, such as mechanical dispersion, myocardial work index, and postsystolic shortening, need further validation in a larger population.
Hookworm diagnosed during colonoscopy and terminal ileum intubation
Authors: Pezhman Alavinejad, Amir Hossein Sina, Mehrdad Nikfam
Journal: Endoscopy (2020)

A 38-year-old man attended the gastrointestinal outpatient clinic with a 3-month history of bloating, nonspecific abdominal pain, and irregular bowel habit. His laboratory findings included the following: hemoglobin 12.1 g/dL, mean corpuscular volume 81 fL, white blood cell count 5.4 × 109/L, platelet count 245 × 109/L, stool exam normal. Based on the recent onset of his complaints and lack of response to symptomatic management, he was referred for colonoscopy. Apart from mild erythema in the transverse colon ([Fig. 1]), colonoscopy showed no significant findings, but at terminal ileum intubation multiple hookworms were seen attached to the mucosa ([Video 1]). During withdrawal of the scope, several biopsy samples were obtained from the mid transverse colon. The pathologist reported mild to moderate infiltration of eosinophils in the colonic mucosa ([Fig. 2]). Treatment with albendazole 400 mg twice daily was started, and 2 weeks later all of the patient’s symptoms had disappeared.
Osimertinib for patients with poor performance status and <i>EGFR</i> T790M mutation-positive advanced non-small-cell lung cancer (NSCLC): A phase II clinical trial.
Authors: Yuichi Ozawa, Kazuhisa Nakashima, Haruko Daga, Hisao Imai, Motohiro Tamiya, Takaaki Tokito, Takahisa Kawamura, Hiroaki Akamatsu, Yuko Tsuboguchi, Toshiaki Takahashi, Nobuyuki Yamamoto, Keita Mori, Haruyasu Murakami
Journal: Journal of Clinical Oncology (2020)

e21704 Background: Osimertinib has been shown to be effective against epidermal growth factor receptor ( EGFR) T790M-positive non-small cell lung cancer (NSCLC), but so far all clinical trials have targeted performance status (PS) 0 to 1 cases. The efficacy and safety of osimertinib in EGFR T790M-positive NSCLC patients with poor PS remain elusive. Methods: We conducted an open-label, multi-center, single-arm phase II study to evaluate the efficacy and safety of osimertinib in patients with EGFR T790M mutation-positive NSCLC who had Eastern Cooperative Oncology Group PS scores of 2 to 4. Patients received 80 mg of osimertinib once daily. The primary endpoint was progression-free survival (PFS). The planned sample size was 18 patients to achieve power of at least 80% with one-sided alpha of 0.05 and expected and threshold PFS as 8.2 months and 3.0 months. Results: Eighteen patients (4 men and 14 women) were enrolled between June 2017 and November 2018. The median age was 77 years (range: 55–85 years). Ten, six, and two patients had PS scores of 2, 3, and 4, respectively. All patients had adenocarcinoma with common EGFR mutations and were previously treated with first- or second-generation EGFR- tyrosine kinase inhibitors, and 10 patients (56%) had central nervous system (CNS) metastasis. The overall median PFS was 7.0 months (90% confidence interval: 5.5-8.9 months). The overall response rate (ORR) was 53%, the median time to first response was 1.5 months, the median duration of response was 6.7 months, and the median overall survival (OS) was 12.7 months. Moreover, improved PS scores were observed in 13 patients (72%) including six with PS 2, six with PS 3, and one with PS 4. Osimertinib also showed an ORR of 60% in the patients with CNS metastasis, and the median PFS and OS were 6.5 months and 22.0 months, respectively. Although anemia, rash, and anorexia were frequently reported, the incidence of grade 3 adverse events was low, and no grade 4 or 5 events were observed. Interstitial lung disease (ILD) was observed in three patients (two with grade 2, one with grade 1). All three patients discontinued osimertinib treatment and recovered from ILD. Conclusions: Osimertinib therapy could be a promising treatment option for patients with EGFR T790M mutation-positive advanced NSCLC who have poor PS. Clinical trial information: UMIN000027655.