tbuckley/cabot-search huggingface dataset:
Immunotherapy combining NK and T cell activation with IL-15 super agonist (N-803), off-the-shelf high-affinity CD16 NK (haNK) or PDL1 targeted haNK and checkpoint inhibitor in relapsed/refractory advanced pancreatic cancer.
Authors: Tara Elisabeth Seery, Mira Kistler, Chaitali Singh Nangia, Christina Ann To, Sandeep K. Reddy, Leonard S. Sender, John H. Lee, Patrick Soon-Shiong
Journal: Journal of Clinical Oncology (2020)

e15015 Background: Pancreatic cancer is the third leading cause of cancer-related deaths in the US. Patients who relapse after first/second-line chemotherapy have a 2 month median survival. In this relapsed population, there is no approved therapy. Effective response requires a coordinated approach that orchestrates both the innate and adaptive immune system. We hypothesize that by orchestrating the activation of the entire immune system, we could accomplish immunogenic cell death with clinical benefit. We describe a first-in-human novel combination immunotherapy protocol of chemoradiation, cytokine-induced NK and T cell activation, checkpoint inhibition, and off-the-shelf allogeneic high-affinity NK cell infusion (haNK). We report the first complete response (CR) to an NK-based immunotherapy combination in pancreatic cancer. Methods: QUILT-3.039/3.060/3.070/3.080 enrolled a total of 12 patients (8M/4F), median age 57.5 (35-74), ECOG 0-2) with advanced pancreatic with progressive disease after prior chemotherapy. There were differences in the dose and schedule of agents used across the various protocols. Common elements were: 1. Reduced dose metronomic chemotherapy (combinations of aldoxorubicin, gemcitabine, abraxane, oxaliplatin, 5FU, and cyclophosphamide) 2. SBRT, 3. Avelumab, 4. N803 (IgG1 Fc-engineered IL-15-fusion protein), 5. Allogeneic haNK cells. This experience led to a SPIND substituting allogeneic haNK cells with allogeneic haNK cells targeted against PDL-1. All treatment was in an outpatient setting. A median of 6 cycles of haNK cells (2-15) were delivered for a cumulative median dose of 29.0 x 10 9 cells per patient (8.0-56.0 x 10 9 ). Results: In 12 patients across 4 studies, a median of 6 (2,15) cycles of treatment were delivered, resulting in median PFS of 6.6 mo (3.3-12.4), OS 8.1 mo (5.0-27.0). 11/12 (92%) patients experienced stable disease (SD) for &gt; 8 weeks. 11/12 (92%) also experience at least 1 grade 3 AE: neutropenia (92%), anemia (50%), febrile neutropenia (17%), diarrhea (8%), hyperglycemia (25%), hyponatremia (17%), and elevated alkaline phosphatase (8%). The SPIND patient (79 yo M, ECOG 1) received 7 cycles and achieved a CR by PET with 5 months follow-up to date. No grade 4 AEs were seen. No severe immune related AE’s were seen. Conclusions: Orchestrated immunomodulatory outpatient combination treatment is feasible and results in clinical benefit and CR in selected patients with acceptable toxicity.
幽门螺杆菌感染与术后反流性胃炎的关系
Authors: 李西启, 孙妍琳, 刘淑皎, 崔敏, 宫兆松, 张玲
Journal: BMJ (2004)

胃术后反流性胃炎一直被认为是由于肠液及胆汁反流所致,但通过控制饮食、促进胃排空、减少胃酸和胆汁分泌等措施仍不能取得较好的疗效.近年来研究证明,幽门螺杆菌(HP)感染是胃炎和胃十二指肠溃疡的一个重要致病因素,根除HP有助于治愈胃炎和胃十二指肠溃疡.那么,HP与术后反流性胃炎是否有关?我们对几家医院1999年以前收治的182例患者的资料进行了回顾性分析。
Transplantation of free latissmus dorsi osteocutaneous flap using bridge-like vascular anastomosis in treatment of tibial defect:5-case report
Authors: Gong-lin Zhang, Ming Zhang, Ao Guo, Ling-zhi Zhang, Fa-ming Ding
Journal: BMJ (2008)

From September 2002 to May 2006, five patients ( age range, 24 to 46; mean, 32) with tibial defect underwent transplantation of free latissmus dorsi osteocutaneous flap using bridge-like vascular anastomosis. All the osteocutaneous flaps survived without any serious complications, and tibial defects were improved completely. After 1.5 to 4.5 years' follow-up ( mean, 2.6), no remarkable dysfunction was found at donor sites, and local injury was reduced. This study indicates that transplantation of free latissmus dorsi osteocutaneous flap using bridge-like vascular anastomosis might be useful in leg reconstructive surgery if only one vessel is remained.

Key words: 
Reconstructive surgical procedures;  Tibial
An investigation and analysis for dietary pattern and action in 80 type 2 diabetics
Authors: Li Li, Qian Zhang, Zhe Xu
Journal: BMJ (2010)

Eighty patients with T2DM hospitalized at Tongren Hospital, Beijing during June to December 2009 were chosen for survey by FFQ (food frequency questionnaire).Their daily food intake and nutrient intake were collected and percentage of energy generated from carbohydrate, protein and fat were estimated for each participant, and analyzed based on the criteria of dietary intake for T2DM, the dietary guidelines and the recommendations for dietary nutritional structure for Chinese residents.Among 80 patients with T2DM, 27 (34%) were found insufficient daily protein intake, 39 (49%) insufficient carbohydrates,40 (50%) excessive fat, and 74 (93%) insufficient dietary fiber, respectively.There was a significant gap between their daily total energy intake and that recommended for patients with T2DM ( P ＜ 0.01 or 0.05 ).No significant difference was found in daily intake of total energy, protein, fat carbohydrate and dietary fiber among T2DM patients with varied body mass index ( P ＞ 0.05 ).Dietary pattern and actions and selfmanagement in the patients with T2DM surveyed are not so reasonable.

Key words: 
diabetes mellitus,type 2;  Diet surveys
Mammographic screening and socio-epidemiological profile of Amerindian riverside women in the Amazon forest.
Authors: Juliana Ramos Chaves, Maria Isabel Zemero, Matheus Dinelly Ribeiro dos Reis, Taynah Cascaes Puty, Bruno Melo Fernandes, Rodnei Jose Macambira Martins Junior, Lorena Lira Tavares dos Santos de Lima, Luis Eduardo Werneck De Carvalho
Journal: Journal of Clinical Oncology (2020)

e13573 Background: Breast cancer still represents the most common tumor among women in the world and in Brazil. Screening coverage in Brazil is much lower than what is recommended by the World Health Organization (WHO), which makes it difficult to perform an early diagnosis. Thus, the current work aims to carry out mammographic screening and the socio-epidemiological profile of Amerindian riverside women in the Amazon region. Methods: This study is characterized as sectional and the sample consists of 260 female patients, living riverside, from the communities of the Amazon Forest, Xingu and Tapajos rivers, interviewed after the mammography screening in a task force promoted by the Brazilian Navy. Results: The median patients age was 49 years (p25-75: 45-58), menarche was around 13 years (p25-75: 12-14), menopause was 48 years (p25-75: 43-50) and the median of pregnancies was four (p25-75: 2-6). Most patients were classified as BIRADS 1 (41.32%), 4 of the 8 suspected and highly suspected cases were confirmed as breast cancer, and these patients had no complaints (82.98%), did not use therapy hormonal (97.15%), and did not use oral contraceptives (60.57%) and breastfed during pregnancy (97.52%). Conclusions: There is a high prevalence of protective factors against cancer, related to lifestyle and local culture. However, these communities have minimal access to health services, which demonstrates actual need of public policies to assist Amerindian riverside women, in order to promote better health care and, thus, reduce one of the most prevalent diseases in the Amazon region. [Table: see text]
Evaluation of clinical characteristics of genitourinary syndrome in postmenopausal women
Authors: Jiao Cheng, Biao Wang, Zhenyu Zhang, Xiaodong Zhang
Journal: BMJ (2016)

One hundred and ten postmenopausal women, complaining vaginal discomfort, recurrent urinary tract infections or painful intercourse and visiting the hospital between March 2014 and February 2015 were enrolled in the study. Among them, 58 patients received vaginal administration of estriol estriol ointment (group A) and 52 patients received conventional treatment (group B). There were no significant differences in mean age of menopause and mean menopause duration between two groups. The clinical symptoms, vaginal health scores, pelvic organ prolapse were observed after treatment. After 6-month treatment, the female vaginal health score was significantly improved in women group A, the rate of urinary orifice was reduced (78% vs. 7%), and the rate of pelvic organ prolapse was decreased (36% vs. 21%). The geritourinary syndrome of menopause is a new term for vulvovaginal atrophy with clinical characteristics of multi-system changes in postmenopausal women, including atrophic vaginitis, female urogenital diseases, and pelvic organ prolapse. The new diagnostic criteria are needed for evaluation and management of geritourinary syndrome.


Key words: 
Postmenopause; Vulvovaginal atrophy; Female urogenicla diseases
First-in-human (FIH) phase I study of GST-HG161, a potent and highly selective c-met inhibitor, in patients with advanced solid tumor.
Authors: Jin Li, Ye Guo, Junli Xue, Wenqiang Wu, Shikui Chen, Yanan Tang, Xiongbin Xu, Gang Li, Lihong Hu, Yunfei Lin, Liang Shen, Yuanfeng Xia, Chi-Chung Chan, Zhouchong Wang, Dawen Ni, Charles Ding, Shuhui Chen
Journal: Journal of Clinical Oncology (2020)

e16126 Background: GST-HG161 is an orally bioavailable novel potent and highly selective c-Met inhibitor, which displayed significant antitumor activity in preclinical models as well as very desirable pharmaceutical properties for oral dosing. Preclinical studies demonstrated that GST-HG161 has the potential to be effective in HCC patients with active c-Met signaling. Methods: This is an open label, first-in-human, single center, dose-escalation study (NCT04228406) utilizing an accelerated dose escalation design using single patient cohorts for the first two dose levels (60 and 150 mg) followed by a conventional 3+3 design at the 3 rd dose cohort (300 mg). Dose escalation is expected to continue to the proposed 7 th dose cohort (900 mg). The objective of the study is to determine the maximum tolerated dose and/or recommended Phase II dose, dose limiting toxicities (DLT), safety, pharmacokinetics, pharmacodynamics and preliminary signals of anticancer efficacy of GST-HG161 in patients with advanced solid tumors. Eligible patients are adults with advanced solid tumors refractory to standard therapies with confirmed c-Met positive. The definition of c-Met positive is a) IHC expression of c-Met (positive criteria: 1+ and above) and/or b) FISH amplification of c-Met and/or c) MET exon 14 (METex14) skipping. GST-HG161 is administered orally once-a-day starting on day 1 of each 21 days cycle. Results: To date, 6 patients (CRC 2, Gastric 1, NSCLC 1, HCC 1, Cholangiocarcinoma 1) were enrolled to 3 dose levels (60, 150, and 300 mg). Of these 6 patients, 4 had discontinued GST-HG161 treatment at the data cut-off date of Feb 1, 2020, due to progressive disease (3) and adverse event (1). Two patients at the 300 mg cohort are still on treatment. Overall, 4/6 patients showed no drug-related AEs &gt; Grade 1. One patient reported a DLT: asymptomatic Grade 3 lipase elevation after a single dose of 60mg. To date, no other patients showed elevations of lipase and amylase. Bioanalysis of PK samples from study patients are currently ongoing. PK summary will be reported in the presentation. Conclusions: GST-HG161 has been well tolerated to date in study patients with a manageable safety profile. The dose escalation is expected to continue to the proposed 7 th cohort at 900 mg. Clinical trial information: NCT04228406 .
Randomized phase II study of stereotactic body radiotherapy and interleukin-2 versus interleukin-2 in patients with metastatic melanoma
Authors: Brendan Curti, Marka Crittenden, Steven K Seung, Christopher B Fountain, Roxanne Payne, ShuChing Chang, Jessica Fleser, Kimberly Phillips, Ian Malkasian, Lyn B Dobrunick, Walter J Urba
Journal: Journal for ImmunoTherapy of Cancer (2020)

A pilot study of stereotactic body radiation therapy (SBRT) followed by high-dose interleukin-2 (IL-2) showed a higher than anticipated objective response rate (ORR) among patients with metastatic melanoma (MM). We performed a prospective randomized study to determine if the ORR of SBRT + IL-2 was greater than IL-2 monotherapy in patients with advanced melanoma. Patients with MM who had adequate physiological reserve for IL-2 and at least one site suitable for SBRT were eligible. There was a 1:1 randomization to SBRT + IL-2 or IL-2 monotherapy. Patients received one or two doses of SBRT (20 Gy per fraction) with the last dose administered 3 days before starting the first cycle of IL-2. IL-2 (600,000 IU per kg via intravenous bolus infusion) was given every 8 hours for a maximum of 14 doses with a second cycle after a 2-week rest. Responding patients received up to six IL-2 cycles. Patients assigned to IL-2 monotherapy who exhibited progression of melanoma after cycle 2 were allowed to crossover and receive SBRT and additional IL-2. Response Evaluation Criteria in Solid Tumors 1.1 criteria were applied to non-irradiated lesions for response assessment. 44 patients were included in the analysis. The ORR in the SBRT + IL-2 group was 54%: 21% complete response (CR), 33% partial response (PR), 21% stable disease (SD) and 25% progressive disease (PD). The ORR in patients receiving IL-2 monotherapy was 35%: 15% CR, 20% PR, 25% SD and 40% PD. Seven patients assigned to IL-2 subsequently received SBRT + IL-2. One CR and two PRs were observed in the crossover group. There was no difference in progression-free or overall survival (OS). At 5 years the OS was 26% in the SBRT + IL-2 group and 25% in the IL-2 monotherapy group. The disease control rate (DCR) was higher in the SBRT + IL-2 group (75% vs 60%, p=0.34). SBRT + IL-2 induced more objective responses with a higher DCR compared to IL-2 monotherapy in MM. IL-2 monotherapy resulted in a significantly higher ORR than anticipated. Some patients in the crossover group also achieved objective responses. NCT01416831.
A rare case of metastatic testicular adult granulosa cell tumor.
Authors: Guido Natoli, Jasna Metovic, Stefano Taraglio, Stefania Miraglia, Francesca Misischi, Luisa Delsedime
Journal: Journal of Clinical Oncology (2020)

e15506 Background: Adult granulosa cell tumour (AGCT) is a rare disease that develops in the testis, composed of sex cord cells, accounting for less than 0.5% of all sex cord-stromal neoplasias (WHO 2016). To our knowledge, 48 cases of AGCT of the testis have been published up to date reporting follow-up (Table 1). Infrequently, these tumors can metastasize, usually to retroperitoneal lymph nodes, but also liver, lungs and bones. Methods: In 2015 a 60-year-old Caucasian male with unilateral, painless slowly growing mass underwent to orchioectomy. A diagnosis of malignant ADTC was rendered. After 19 months metestatic spread to lung was hystologically confirmed. After cytotoxic treatment a compassionate use of pazopanib was sterted and the was in complete response today. Results: The patient is still on pazopanib treatment with complete response that is well tolerated and has improved quality of life 55 months after the initial AGCT diagnosis. Conclusions: Our case report could offer an important source of information for clinicians who are currently facing this rare entity. In summary in case of tumor larger than 4-5 cm adjuvant treatment may be considered and, more importantly, systemic treatments, including pazopanib, could be suggested as a treatment apporach to a metastatic AGCT patient. In the future, other reports containg long-term follow up will be of vital importance to understand the best management of patient with AGCT.
Clinical study of adefovir dipivoxil in renal impairment
Authors: Junlan Liu, Yisheng Ling
Journal: BMJ (2014)

To elucidate the incidence of renal impairment in chronic hepatitis B (CHB) patients on adefovir dipivoxil (ADV). We retrospectively enrolled 127 CHB patients on ADV alone (38.6%) or in combination with lamivudine (61.4%) for over 12 months.Renal function was measured by estimated glomerular filtration rate (eGFR). And renal dysfunction was defined as mild ( 50%). During a treatment duration of 12 months, 2 patients (1.6%) developed mild renal impairment.At Month 36, there were 13 patients with renal damage (10.4%) and one case of hypertension with severe renal impairment plus bone pain.The characteristic of renal pathology was tubule injury.Modification of dosing interval or discontinuation of ADV may arrest a further decline of eGFR in CHB patients.


Key words: 
Nucleotides; Nephrosis
The cardiac auscultation proficiency in residents before and after training
Authors: De-jun Sun, Yi-qing Wang, Ya-qiang Zhang, Hua-xiu Shi, Wen-jiang Xu
Journal: BMJ (2008)

The study is designed to investigate the progress in cardiac auscultation proficiency of residents after training program.Thirty eight residents were selected to test their ability of cardiac auscultation.There were 13 cardiac events(or murmurs)in 15 patients,and the auscultation proficiency was expressed as the percentage of recognizing cardiac events accurately.The results showed that the highest auscultation proficiency was whole systolic and diastolic murmurs(up to 79 percent and 61 percent respectively)before training.The percentage of recognizing continuous murmurs,click,mitral stenosis and regurgitation,aortic stenosis increased significantly after training program(P＜0.05).

Key words: 
Heart auscultation; Teaching
Axitinib plus pembrolizumab in patients with advanced renal cell carcinoma: Long-term efficacy and safety from a phase Ib study.
Authors: Michael B. Atkins, Igor Puzanov, Elizabeth R. Plimack, Mayer N. Fishman, David F. McDermott, Daniel C. Cho, Ulka N. Vaishampayan, Saby George, Jamal Christo Tarazi, William Duggan, Rodolfo F. Perini, Kathrine C. Fernandez, Toni K. Choueiri
Journal: Journal of Clinical Oncology (2020)

5080 Background: Axitinib (AXI) plus pembrolizumab (pembro) showed superior overall survival (OS), progression-free survival (PFS) and response rate compared with sunitinib in a randomized Phase 3 trial in advanced renal cell carcinoma (RCC). Here, we report long-term efficacy and safety data of the combination AXI/pembro from the Phase 1 trial, with almost 5 years of follow-up. Methods: 52 treatment-naïve patients with advanced RCC were enrolled between 23 September 2014 and 13 October 2015, and were treated with oral AXI 5 mg twice daily and intravenous pembro 2 mg/kg every 3 weeks. Planned treatment duration was 2 years for pembro and not limited for AXI. Based on International Metastatic Database Consortium (IMDC) criteria, 46.2%, 44.2% and 5.8% of patients were reported as having favourable, intermediate and poor risk. Results: At data cut-off date (July 3, 2019), median OS was not reached; 38 (73.1%) patients were alive. 14 (26.9%) patients had died, none were related to treatment. The probability of being alive was 96.1% (95% CI 85.2–99.0) at 1 year, 88.2% (95% CI 75.7– 94.5) at 2 years, 82.2 % (95% CI 68.5– 90.3) at 3 years, and 66.8 % (95% CI 49.1–79.5) at 4 years. Median PFS was 23.5 (95% CI 15.4–30.4) months. Median duration of response was 22.1 (95% CI 15.1–not evaluable) months. Median time on treatment with the combination AXI/pembro was 14.5 months (n=52), median time on pembro after AXI discontinuation was 9.0 months (n=10), and median time on AXI after pembro discontinuation was 7.5 months (n=11). After stopping study treatment, 22 patients received subsequent systemic therapy, including nivolumab and cabozantinib (n=6 each). Grade 3/4 AEs were reported in 38 (73.1%) patients. 20 (38.5%) patients discontinued either drug due to AEs: 17 (32.7%) patients discontinued AXI, and 13 (25.0%) patients discontinued pembro with 10 (19.2%) discontinuing both drugs. Dose reduction of AXI due to AEs was reported in 16 (30.8%) patients. The most common AEs reported were diarrhea (84.6%), fatigue (80.8%), hypertension (53.8%), cough (48.1%), and dysphonia (48.1%). Increased alanine aminotransferase and aspartate aminotransferase occurred in 44.2% and 36.5% of patients, respectively. With this longer follow-up, there were no cumulative AEs or new AEs. OS by IMDC risk group will be presented. Conclusions: In patients with advanced RCC with almost 5 years of follow-up, the combination of AXI/pembro continues to demonstrate clinical benefit with no new safety signals. Clinical trial information: NCT02133742 .
Modulation of CT-genes transcriptional activity in HT-29 cells by irradiation with a linear accelerator.
Authors: Denis S. Kutilin, Natalia G Kosheleva, Marina A. Gusareva, Vladislav M. Legostaev, Olga V. Shlyakhova, Vladimir A. Dontsov, Umar Muhmadovich Gaziev, Irina A. Udalenkova, Lyudmila Y. Rozenko, Aliya K. Donskaya, Olga G. Rodionova, Natalya B. Fatkina, Oleg Ivanovich Kit
Journal: Journal of Clinical Oncology (2020)

e15218 Background: Cancer-testis antigens (CTAs) are used as targets in immunotherapeutic approaches based on gene-cell vaccines (GCV). In some cases, it is possible to use experimental combinatorial therapy regimens that combine radiation and GCV. Despite numerous studies of the expression of CTA in tumors of various locations, including colon tumors, the transcriptional activity of CT-genes in tumor tissue of the colon after radiation therapy remains poorly studied. The aim of the study was to analyze changes in the expression of CT-genes in HT-29 cells after irradiation with a linear accelerator. Methods: The study used human cell culture HT-29. For the model experiment, 7 Gy fractionation option was used (irradiation was carried out 5 times every 24 hours). Irradiation was performed on a Novalis TX linear accelerator (Varian, USA). The ratio of living and dead cells was calculated in a Goryaev chamber using a 0.4% trypan blue dye solution. After microscopy on the 5th day of irradiation, the cell line was removed from the vial substrate by Trypsin/Versen solution. RNA was isolated by the Chomczynski&amp;Sacchi method. For cDNA synthesis a set of "REVERTA-L" reagents used. Expression of 16 CT genes (MAGE-A1, -A2, -A3, -A4, MAGE-B1, -B2, GAGE-1, -3, -4, MAGEC1, BAGE, XAGE3, NYESO1, SSX2, SCP1, PRAME1) was determined using the Real-Time qPCR method (reference genes — GAPDH and B2M). Statistical analysis was performed using univariate analysis of variance (ANOVA) with repeated measurements. Results: After 5 days of exposure at a dose of 7 Gy, only 20% of the initial number of HT-29 cells remained viable. It was found that irradiation was statistically significantly (p &lt; 0.05) influenced the increase in the expression of genes MAGEA1 by 1.8 times, MAGEB1 by 6.8 times, BAGE by 1.6 times, CTAGE1 by 3.3 times and SSX2 by 5.8 times relative to intact cells. Conclusions: Thus, tumor cells exposed to radiation at a dose of 7 Gy show an increase in the expression of 5 CT-genes, which, in turn, can increase their immunogenic potential.