tbuckley/cabot-search huggingface dataset:
Treatment of Patients with Relapsed or Refractory Mantle–Cell Lymphoma with Zanubrutinib, a Selective Inhibitor of Bruton's Tyrosine Kinase
Authors: Yuqin Song, Keshu Zhou, Dehui Zou, Jianfeng Zhou, Jianda Hu, Haiyan Yang, Huilai Zhang, Jie Ji, Wei Xu, Jie Jin, Fangfang Lv, Ru Feng, Sujun Gao, Haiyi Guo, Lei Zhou, Rebecca Elstrom, Jane Huang, William Novotny, Rachel Wei, Jun Zhu
Journal: Clinical Cancer Research (2020)

Abstract Purpose: Mantle-cell lymphoma (MCL) is an incurable mature B-cell neoplasm with high initial response rates followed almost invariably by relapse. Prognosis for patients following relapse is poor, and treatment choices are limited. We evaluated the efficacy and safety of zanubrutinib, an investigational selective Bruton's tyrosine kinase (BTK) inhibitor. Patients and Methods: Patients with relapsed/refractory MCL were enrolled in this ongoing phase II, single-arm, open-label study, and treated with oral zanubrutinib 160 mg twice daily. The primary endpoint is overall response rate (ORR) assessed by an independent review committee (per Lugano 2014 classification); secondary endpoints include duration of response (DOR), time to response, progression-free survival (PFS), and safety. Results: Eighty-six patients (median age, 60.5 years) were enrolled after a median of 2 prior lines of therapy, received ≥1 dose of the study drug, and were evaluable for safety and efficacy. After a median follow-up of 18.4 months, 72 (84%) patients achieved an objective response, with 59 (68.6%) achieving a complete response (CR). Median DOR and PFS were 19.5 and 22.1 months, respectively; 12-month event-free estimates for DOR and PFS are 78% and 76%, respectively. Most common grade ≥3 adverse events (AE) were neutropenia (19.8%) and lung infection/pneumonia (9.3%). Three patients experienced major bleeding events, and there were no reports of atrial fibrillation. Eight (9.3%) patients discontinued zanubrutinib for AEs. Conclusions: These results demonstrate high and durable ORR and CR rates in patients with relapsed/refractory MCL. Zanubrutinib was generally well tolerated; grade ≥3 BTK inhibitor-associated toxicities (hemorrhage, rash, hypertension, diarrhea, atrial fibrillation) were uncommon.
MRI in diagnosis of cervical posterior longitudinal ligament rupture
Authors: Song Lin, Rui Chen, Qiang Wu, Jixian Miao, Junyan Teng
Journal: BMJ (2018)

Magnetic resonance imaging (MRI) data of 87 patients with suspected cervical posterior longitudinal ligament (PLL) rupture, who underwent cervical spine surgery in Luoyang Orthopedic Hospital from January 2015 to September 2017, were analyzed retrospectively. The criteria of MRI diagnosis for PLL rupture were the low signal image of the PLL on the posterior margin of the vertebral body, the discontinuity or continuous interruption, or the local highlighting signal on the T2 weighted image. According to intraoperative findings, the diagnostic accuracy of MRI for PLL rupture was examined. Among 87 patients, 31 cases were diganosed as PLL rupture by preoperative MRI; and 38 cases were confirmed by intraoperative exploration, of whom 30 were diagnosed with MRI, and 8 were missed by MRI. The accuracy, sensitivity and specificity of MRI in the diagnosis of ruptured PLL were 0.90, 0.79 and 0.98 respectively. MRI has a good diagnostic efficiency in PLL rupture, which can be used for preoperative investigation.


Key words: 
Magnetic resonance imaging; Longitudinal ligaments; Diagnosis
Sintilimab for relapsed/refractory (r/r) extranodal NK/T cell lymphoma (ENKTL): Extended follow-up on the multicenter, single-arm phase II trail (ORIENT-4).
Authors: Jianyong Li, Rong Tao, Lei Fan, Yongping Song, Yu Hu, Wei Zhang, Yafei Wang, Linxinyu Xu, Xing Sun, Hui Zhou
Journal: Journal of Clinical Oncology (2020)

8050 Background: Patients with r/r ENKTL have a poor prognosis after failing an asparaginase-based regimen. The overexpression of PD-L1 induced by EBV infection is a potential mechanism for ENKTL to avert immune surveillance. Sintilimab, a fully human anti-PD-1 monoclonal antibody, has demonstrated efficacy in r/r ENKTL after the primary analysis of the ORIENT-4 study. Here, we report the updated efficacy and safety results with extended follow-up. Methods: Patients with pathologically confirmed r/r ENKTL were enrolled. Sintilimab was given 200 mg IV Q3W, until PD, death, unacceptable toxicity, or withdrawal from the study. Treatment beyond PD is allowed. Tumor response evaluation was performed by both PET-CT and CT/MRI with contrast. The primary endpoint was objective response rate per Lugano 2014. Data cut-off date for this analysis was Jan 17, 2020. Results: A total of 28 patient were enrolled and treated. With a median follow-up of 26.9 months (range, 23.3 to 28.6), the median treatment duration was 24.15 months (range, 1.4 to 28.7). Of 20 patients with progressive disease (PD) by investigator per Lugano 2014 criteria, 19/20 (95%) patients received treatment beyond PD. The median OS has not been reached and 24-month OS rate was 78.6% (95% CI, 58.4% to 89.8%). ORR was 67.9% (95% CI, 47.6% to 84.1%), including 4 pts who experienced PD prior to having a response. DCR was 85.7%, including 5 pts who experienced PD before SD or response. Median duration of response was 4.1 months (range, 1.9 to 15.2+). After treatment, the mean EQ-5D-5L VAS Score (from 79.3 to 90.8), EQ-5D-5L Index Value (from 0.8 to 0.9) and EORTC QLQ-C30 (from 70.5 to 87.3) were all increased. The Treatment-related adverse events (TRAEs) of any grade occurred in 28 (100%) pts; grade 3 occurred in 11 (39.4%) pts, most commonly, decreased lymphocyte count (2 [7.1%]) and diabetes (2 [7.1%]); no grade 4-5 TRAE. Conclusions: In addition to an encourage response, sintilimab also demonstrated long-term clinical benefit, with 78.6% of 24-month OS rate, and favorable long-term safety profile after extended follow-up. Considering the high rate (95%) of treatment beyond PD, Lugano 2014 may not be a suitable criteria for evaluating the efficacy of anti-PD-1 antibody in r/r ENKTL. Clinical trial information: NCT03228836 .
Pembrolizumab versus placebo after complete resection of high-risk stage III melanoma: New recurrence-free survival results from the EORTC 1325-MG/Keynote 054 double-blinded phase III trial at three-year median follow-up.
Authors: Alexander M. Eggermont, Christian U. Blank, Mario Mandalà, Georgina V. Long, Victoria Atkinson, Stéphane Dalle, Andrew Mark Haydon, Andrey Meshcheryakov, Muhammad Khattak, Matteo S. Carlino, Shahneen Kaur Sandhu, Susana Puig, Paolo Antonio Ascierto, Alexander Christopher Jonathan Van Akkooi, Clemens Krepler, Nageatte Ibrahim, Sandrine Marreaud, Michal Kicinski, Stefan Suciu, Caroline Robert
Journal: Journal of Clinical Oncology (2020)

10000 Background: We conducted the phase 3 double-blind EORTC 1325/KEYNOTE-054 trial to evaluate pembrolizumab vs placebo in patients (pts) with resected high-risk stage III melanoma. Based on 351 recurrence-free survival (RFS) events and at a median follow-up of 1.25 years (yrs), pembrolizumab improved RFS (hazard ratio (HR) 0.57, P&lt;0.0001) as compared to placebo (Eggermont, NEJM 2018). This led to the approval of pembrolizumab adjuvant treatment by EMA and FDA. Methods: Eligible pts included those ≥18 yrs of age with complete resection of cutaneous melanoma metastatic to lymph node(s), classified as AJCC-7 stage IIIA (at least one lymph node metastasis &gt;1 mm), IIIB or IIIC (without in-transit metastasis). A total of 1019 pts were randomized (stratification by stage and region) to pembrolizumab at a flat dose of 200 mg (N=514) or placebo (N=505) every 3 weeks for a total of 18 doses (~1 year) or until disease recurrence or unacceptable toxicity. The 2 co-primary endpoints were RFS in the intention-to-treat overall population and in pts with PD-L1-positive tumors. Here, we report an updated RFS analysis based on a longer follow-up. Results: Overall, 15%/46%/39% of pts had stage IIIA/IIIB/IIIC. At 3.05-yr median follow-up, pembrolizumab (190 RFS events) compared with placebo (283 RFS events) prolonged RFS, in the overall population and in the PD-L1 positive tumor subgroup (see Table). RFS was consistently prolonged across subgroups, in particular according to AJCC-7 staging, BRAF-V600 E/K mutation status. Conclusions: Pembrolizumab, administered at 200 mg every 3 weeks for up to 1 year as adjuvant therapy, provided, at a 3-yr median follow-up, a sustained improvement in RFS, which was clinically meaningful, in resected high-risk stage III melanoma. This improvement was consistent across subgroups. In the overall population, the 3-yr cumulative incidence of distant metastasis being the first recurrence was 22.3% (pembrolizumab group) vs 37.3% (placebo group) (HR 0.55, 95% CI 0.44-0.69). Clinical trial information: NCT02362594. [Table: see text]
The role of communication in acquisition, curation, and transmission of culture
Authors: Hyowon Gweon
Journal: Behavioral and Brain Sciences (2020)

Abstract Veissière et al.'s proposal aims to explain how cognition enables cultural learning, but fails to acknowledge a distinctively human behavior critical to this process: communication . Recent advances in developmental and computational cognitive science suggest that the social-cognitive capacities central to TTOM also support sophisticated yet remarkably early-emerging inferences and communicative behaviors that allow us to learn and share abstract knowledge.
Updated results from BELLINI, a phase III study of venetoclax or placebo in combination with bortezomib and dexamethasone in relapsed/refractory multiple myeloma.
Authors: Shaji Kumar, Simon J. Harrison, Michele Cavo, Javier de La Rubia, Rakesh Popat, Cristina Gasparetto, Vania Hungria, Hans Salwender, Kenshi Suzuki, Inho Kim, Francesca Gay, Gabor Mikala, Elizabeth Punnoose, Wan-Jen Hong, Anjla Sood, Muhammad Jalaluddin, Jeremy A. Ross, James M Pauff, Paulo Cesar Maciag, Philippe Moreau
Journal: Journal of Clinical Oncology (2020)

8509 Background: Venetoclax (Ven) is a selective, potent, oral BCL-2 inhibitor. In the Phase 3 BELLINI trial, addition of Ven to bortezomib (B) + dexamethasone (d) significantly improved response rates and progression-free survival (PFS) vs placebo (Pbo) and showed significant efficacy in patients (pts) with either t(11;14) or BCL2high gene expression. Here we present updated safety and efficacy data from the prespecified second interim overall survival (OS) analysis. Methods: In this multicenter, randomized, double-blind study (NCT02755597), pts with relapsed/refractory multiple myeloma (RRMM) with 1-3 prior lines of therapy were randomized 2:1 to Ven (800 mg) or Pbo in combination with B (1.3 mg/m2) and d (20 mg). The primary endpoint was PFS; key secondary endpoints included overall response and overall survival (OS). Results: 291 pts were randomized; 194 to Ven, 97 to Pbo. Pt characteristics were well balanced among arms. In the Ven arm, median age was 66, 17% had high-risk cytogenetics, 11% had t(11;14), and 34% had BCL2high gene expression. As of 13 Sept 2019, 59 pts were still on study, 45 (23%) Ven vs 14 (14%) Pbo. At a median follow-up of 28.6 months, there were 64 (33%) deaths in the Ven arm vs 24 (25%) in Pbo. At the initial data cutoff (26 Nov 2018), PFS HR was 0.63 (0.44,0.90) and OS HR was 2.03 (1.04,3.95). Table shows updated PFS and OS. Most common treatment-emergent adverse events (TEAEs) with Ven were diarrhea (59%), nausea (37%), and constipation (35%). Most common grade 3/4 AEs (Ven/Pbo) were neutropenia (21%/8%), thrombocytopenia (15%/30%), anemia (16%/15%), diarrhea (15%/12%), and pneumonia (18%/13%). Serious AEs occurred in 54% Ven and 52% Pbo pts. 24% discontinued Ven due to AEs vs 12% Pbo. There were 14 treatment-emergent deaths in the Ven arm and 1 in Pbo. Conclusions: The addition of Ven to Bd significantly improves PFS but resulted in increased mortality vs Pbo in the total population. Greatest PFS improvement with Ven was observed in pts with t(11;14) or BCL2high gene expression, where Ven shows a favorable benefit-risk profile. The study continues for final OS analysis. Clinical trial information: NCT02755597 . [Table: see text]
葡萄糖调节受损人群血糖与血压的关系
Authors: 俞春芳, 葛军, 刘钧钧, 刘文斌, 王宝珍, 史京衡, 史虹莉
Journal: BMJ (2006)

将符合入选条件的居民1 853人按口服葡萄糖耐量试验分为正常糖耐量、糖尿病、糖耐量低减、空腹血糖受损、糖耐量低减合并空腹血糖受损,后三者统称糖调节受损.测定血压、血脂等,以不同糖代谢状态人群的血糖与血压、年龄等指标进行统计学分析.结果显示,正常糖耐量、糖调节受损、糖尿病者的高血压患病率依次逐渐上升,年龄、体重指数、空腹血糖、糖负荷后2 h血糖与是否患高血压相关。
Exploration of Chinese early-onset renal cancer predisposed genetic features.
Authors: Yu Gong, Yifan Zhou, Bei Zhang, Yuezong Bai, Jianming Guo
Journal: Journal of Clinical Oncology (2020)

e17087 Background: The population of early-onset renal cancer patients is increasing in China and they need early genetic screening test to give risks management. In order to avoid the bias of focusing on the patients younger than 45 years old without comparing the genetic features of the patients over 45y and to find more biomarkers, we explored both germline and somatic variations of patients without age limitation. Methods: Ages at confirmed diagnoses and renal tissue samples were collected from 701 patients. The next generation sequencing (NGS) was performed using validated commercial panels containing over 300 genes or WES. Variations were classified into four groups: germline-MUT/ VLM (pathogenic or very like pathogenic mutations), germline-VOUS (variations of unknown significance), somatic-MUT/ VLM and somatic-VOUS. Statistical analysis was performed by t-test (single tail), and p≤ 0.05 was considered statistically significant. Results: In 701 renal cancer patients, with the median age of 55 (12, 86) years old, 114 (16.26%) patients confirmed diagnoses under 45y. The germline MUT/ VLM of 21 genes (FH, VHL, CHEK2, BRCA2, FLCN, ATM, TSC2, SDHB, MUTYH, SDHA, FANCA, RAD50, APC, BARD1, JAK2, LRP1B, TP53, FANCD2, PALB2, MSH6 and CDH1) were observed, more than previous studies. As two aggressive potential predisposed genes in early-onset renal cancer, VHL and FH were studied comprehensively. There were 29 (4.14%) and 369 (52.6%) patients carried FH variations and VHL variations (either germline or somatic), respectively. The median age of patients harbored VHL germline MUT/ VLM was 33.5 (23, 52), significantly lower than other groups (Table). Interestingly, in 6 patients harboring VHL germline MUT/ VLM, 3 of them carried large region deletion. The median age of FH germline-MUT/ VLM group was 33 (21, 59), significantly lower than patients carried germline VOUS (Table). In addition, germline variations or copy number variations of SDHB gene or germline variations of FLCN gene might be associated with early onset. However, the patients No. was small to give conclusion. Conclusions: Genetic test of FH and VHL genes might be necessary in early screening of renal cancer in China. The role of variations of SDHB and FLCN genes and large region deletion needs more explorations. [Table: see text]
The potentially inappropriate medications among elderly patients with chronic diseases in Shanghai communities and its influence factors
Authors: Chenyi Zhang, Zhigang Pan, Shi Chen, Liu Cheng, Lihua Xu, Yongfeng Yang, Wei Qin, Hongmei Gai
Journal: BMJ (2020)

Objective
To investigate the potentially inappropriate medication(PIM)among elderly patients with chronic diseases in Shanghai communities and related influence factors.


Method
Six community Health service Centers were choosen using stratified sampling. Total 968 elderly patients with chronic diseases who visited to the outpatient clinic of Shanghai Community Health Service Centers from July to August 2018 were included in the study. The PIM was investigated according to the 2015 Beers criteria. The χ2 test and multivariate logistic regression model were used to analyze factors related to the PIM.


Results
The survey showed that 317 elderly patients had PIM with 412 person-doses. In 134 person-doses, the PIM was unrelated to the disease; in 18 person-doses, PIM was caused by interaction of drug with disease/symptoms; in 259 person-doses PIM was related to the drugs that should be cautiously used for elderly; only in 1 person-dose the PIM was caused by the interaction between drugs. The drugs with the highest proportion of PIM were diuretics, benzodiazepines and aspirin. There were significant differences in age, kinds of diseases, kinds of drugs and times of visiting community health service centers between elderly patients with PIM and those without PIM (χ2=42.28, 35.51, 46.47, 38.46; all P<0.05). The main PIM-related factors were age, kinds of diseases, kinds of drugs and times of visiting community health service centers.


Conclusion
The study shows that the prevalence of PIM among elderly chronic diseases patients in Shanghai communities is relatively high, which is associated with the age, kinds of diseases, kinds of drugs and times of visiting community health service centers.


Key words: 
Chronic disease; Aged; Potentially inappropriate medications; Beers criteria; Influence factors
Scalp cooling to prevent chemotherapy induced alopecia (CIA) in black patients: Differences in efficacy?
Authors: Asma Ali Dilawari, Princess Alintah, Richard Paxman, Ami Chitalia, Christopher Gallagher, Shruti Rakesh Tiwari, Chiranjeev Dash, Lucile L. Adams-Campbell
Journal: Journal of Clinical Oncology (2020)

12101 Background: The Paxman scalp cooling device has been used for over 20 years to prevent CIA, obtaining FDA clearance in the U.S. in 2017. Prior studies reported 50-80% success and high patient satisfaction yet included few or no black patients. In the U.S. this may reflect disparities in access due to cost, awareness, or availability. We opened a prospective observational study combining patient-reported outcomes with clinical assessments of alopecia and planned to deliver scalp cooling to 30 black patients receiving chemotherapy for breast cancer. Methods: Patients who self-identified racially as black, had a new diagnosis of stage I-III breast cancer, and planned to receive chemotherapy with taxane-containing regimens were eligible. Anthracycline (AC) and non-anthracycline (NAC) chemotherapy agents were included; costs for the intervention were covered by Paxman and internal philanthropic funding. Patients who declined scalp cooling were approached for enrollment as controls. Primary endpoints were grade of alopecia as measured by providers and patient self-report using Modified Dean Scale and Visual Analog Scale (VAS) respectively. Hair preservation was defined as &lt;50% hair loss (&lt;grade 2) by Dean and score &lt; 50 on VAS. Secondary endpoints were alopecia by NCI grading scale and psychosocial from CADS and EORTC QLQ BR45 questionnaires. Results: 15 out of 30 planned participants enrolled by February 2020 with interim analysis and hold in accrual due to lack of efficacy. Four patients remain on treatment. Of 11 scalp cooling patients who completed chemotherapy, 0 prevented significant alopecia. Nine discontinued use of scalp cooling before completion (1 due to scheduling, 8 due to &gt;grade 3 alopecia). The 2 patients who used scalp cooling for the duration had &gt;grade 3 alopecia before the last cycle of treatment. Conclusions: Scalp cooling is an important supportive therapy that can reduce chance of alopecia, a bothersome side effect for patients. Our experience indicates decreased efficacy in black patients with both AC and NAC regimens. This is an important negative result to explore. Discussions with the Paxman team and providers with expertise in alopecia are underway to explore contributing factors such as hair thickness, prior hair treatments, and cap design. [Table: see text]
Efficacy and safety of fractional laser combined with smooth mode laser for treatment of facial photoaging
Authors: Huijie Qi, Zhanwei Gao, Xiaojun Wang
Journal: BMJ (2019)

Objective
To evaluate the efficacy and safety of fractional laser combined with smooth mode laser for the treatment of facial photoaging.


Methods
Thirty subjects with facial photoaging treated in Department of Plastic Surgery of China-Japan Friendship Hospital were enrolled. All subjects received treatment with fractional Nd: YAG laser combined with smooth mode Er: YAG laser,once every 4 weeks for 3 sessions. Subjects were followed up before the first treatment(V1), 4 weeks after the second treatment (V2), 4 weeks after the third treatment(V3)and 12 weeks after the third treatment(V4).During each follow-up,Global Scores for Photoaging (GSP) were used to evaluate the photoaging degree on the whole face, Global Aesthetic Improvement Scale(GAIS) were applied to evaluate the improvement degree of facial photoaging, and the Visual Analogue Scale(VAS)was adopted to assess pain induced by treatment.After the last treatment,self-assessment on the degree of satisfaction with therapeutic effects was conducted.


Results
All 30 subjects completed the treatments and follow-up. GSP decreased with the increase of visiting time after treatment (r=-0.736,P<0.01). GAIS increased with the increase of visiting time after treatment (r=0.616, P<0.01).There were significant differences in the measurements of VISIA Skin Detector at V1,V2,V3 and V4(all P<0.01). There was a positive correlation between GAIS and VISIA measurements at V2,V3 and V4; the correlation coefficients were 0.453 (P=0.012), 0.552 (P=0.002) and 0.564 (P=0.001), respectively. The average VAS score of 30 subjects after treatment was 1.2±0.1. No side effect was observed. The self-satisfaction rate was 76.7% (23/30).


Conclusion
Fractional Nd: YAG laser combined with smooth mode Er: YAG laser can be applied to treat facial photoaging safely and effectively.


Key words: 
Skin aging; Laser therapy; Treatment outcome
Gender impact on renal cell carcinoma survival: A population-based analysis.
Authors: Firas Baidoun, Inas A. Ruhban, Anas M Saad, Mohamed Gad, Muneer J. Al-Husseini, Moshe Chaim Ornstein, Shilpa Gupta, Brian I. Rini
Journal: Journal of Clinical Oncology (2020)

e17099 Background: Prior evidence has suggested that females diagnosed with renal cell carcinoma (RCC) present at an earlier stage compared to males, but a survival difference between males and females has been controversial. We aimed to evaluate the impact of gender on RCC survival in the US. Methods: Data of RCC patients diagnosed between 1973 and 2015 in the US was obtained using Surveillance Epidemiology and End Results (SEER) database. We studied the overall and cancer-specific survival of patients diagnosed with RCC in the US according to gender using multivariable covariate-adjusted Cox models and Kaplan-Meier test. Results: We reviewed 155,430 RCC patients, of which 96,656 were males, and 58,774 were females. The median overall survival of female patients was 122 months and was significantly higher than male patients (98 months). Cancer-specific survival showed similar trends with females having significantly higher survival (p-value &lt; 0.001). Adjusted for age, race, stage and grade of cancer, undergoing cancer-targeted surgery, and marital status, female sex was associated with improved overall and cancer-specific survival outcomes; HR = 0.829 (p-value &lt; 0.001), and HR = 0.923 (p-value &lt; 0.001), respectively. Conclusions: Females have a significantly better overall and cancer specific survival compared to males diagnosed with renal cell carcinoma. In previous studies this disparity was attributed to the lower grade and earlier stage of RCC presentation in females, but gender-based disparity persisted in this analysis after adjusting for patient baseline and tumor characteristics. This raises the question of the hormonal effects on the progression of RCC.