tbuckley/cabot-search huggingface dataset:
Efficacy and safety of ABP 798 compared with rituximab: Results from the comparative clinical study in patients with non-Hodgkin’s.
Authors: Dietger Niederwieser, Caroline M. Hamm, Patrick Cobb, Mindy Mo, Cecily Forsyth, Alessandra Tucci, Vladimir Hanes, Vincent Delwail, Roman Hajek, David Chien
Journal: Journal of Clinical Oncology (2020)

8044 Background: ABP 798* is being developed as a biosimilar to rituximab, a CD20-directed cytolytic antibody. A randomized, double-blind, active-controlled study compared the efficacy, safety, and immunogenicity of ABP 798 with rituximab reference product (RP) in subjects with CD20-positive NHL; results of the final analysis are presented here. Methods: Adult subjects with grade 1, 2, or 3a follicular B-cell NHL and low tumor burden were randomized to receive intravenous ABP 798 or RP (375 mg/m 2 ) once weekly for 4 weeks, then at weeks 12 and 20. The primary endpoint was risk difference (RD) of overall response rate (ORR) by week 28. Secondary endpoints included RD of ORR at week 12, pharmacokinetics, pharmacodynamics, safety, and immunogenicity. Results: 254/256 randomized subjects were treated with at least one infusion of ABP 798 (n = 128) or RP (n = 126); ORR by week 28, based on independent central blinded assessment of the modified full analysis set, was comparable between the ABP 798 and RP groups (78% vs. 70%, respectively). The 2-sided 90% confidence interval of RD of ORR (-1.4%; 16.8%) was within the pre-specified margin (-15%; 35.5%) thereby establishing clinical equivalence between ABP 798 and RP. This result was supported by analyses of the secondary efficacy endpoint of RD of ORR at week 12. In the two groups, the geometric least squares means for serum concentrations over time (e.g., week 12, pre-dose: ABP 798, 21.89 vs. RP, 20.57; week 12 post-dose: ABP 798, 201.30 vs. RP, 203.52) and the extent of B-cell depletion from day 1 to day 8 (ABP 798, 98.3% vs. RP, 98.3%) were similar. Frequency, type, and severity of adverse events (AEs) were comparable between ABP 798 and RP groups; grade ≥3 AEs were reported in 10.9% and 10.3% of subjects and serious AEs in 3.9% and 4.0%, respectively. Most common AEs were headache, fatigue, and nausea; the most common AE of interest was infusion reactions. No new or unexpected safety signals were observed. Binding and neutralizing anti-drug antibodies were comparable between groups. Conclusions: Results of this study demonstrated clinical similarity between ABP 798 and rituximab RP in subjects with CD20-positive NHL. *At the time of this submission, ABP 798 had not been approved by the FDA or any relevant regulatory agency and the indications are yet undetermined. Please consult ABP 798’s later approved label in the relevant country for information regarding the approved uses for ABP 798.
Studies on the criteria of two-way referral between hospital and community health-care service centerfor patients with cerebral hemorrhage: an analysis of 91 cases
Authors: Jing Li
Journal: BMJ (2012)

This study aimed to study the criteria of two-way referral between tertiary-care hospital and community health-care service center for patients with cerebral hemorrhage and a protocol of implementation to promote its treatment and rehabilitation.The criteria of two-way referral between tertiarycare hospital and community health-care service center for patients with cerebral hemorrhage after surgical operation were formulated on a trial basis with mutual consultation by the department of neurosurgery,Shenzhou hospital affiliated to Shenyang Medical College and Hunhewan Community Health-Care Service Center,Heping district,Shenyang. Totally,91 patients of cerebral hemorrhage admitted to the hospital during October 2007 to September 2010 were recruited for the study,46 in the intervention group with two-way referral and 45 in the control group by self-referral determined by their family members.All the patients of the two groups were followed-up for three years.During the follow-up in the intervention group,40 of 46 (95％) patients could comply with taking medication ordered by physicians,ability of daily living remarkably improved by Barthel index in 21 (50％),physical function recovered well in 33 (79％),34 (81％) could insist in self-monitoring and 32 (76％) could visit physicians for regular consultation,all these being significantly better than those in the control group (64％,31％,28％,25％ and 25％,respectively) (P ＜0.01 ).Medical and rehabilitative cost for patients with cerebral hemorrhage accounted for 575 RMB yuan per month in intervention group,as compared to 2246 RMB yuan for those in control group.Two-way referral for patients with cerebral hemorrhage can reduce their medical cost and promote their better rehabilitation.

Key words: 
Cerebral hemorrhage; Referral and consultation
Association of HLA class I genotype with outcomes of gastrointestinal cancer patients with immunotherapy.
Authors: Zhihao Lu, Lin Shen, Henghui Zhang, Xi Jiao, Yujiao Wang, Lei Zhang, Juanjuan Qian, Huan Chen, Ying Yang, Lijia Wu, Chang Liu, Jifang Gong, Jian Li, Xiaotian Zhang, Xicheng Wang, Zhi Peng, Changsong QI, Zhenghang Wang, Yanyan Li
Journal: Journal of Clinical Oncology (2020)

e16551 Background: Chowell et al. showed that HLA (human leukocyte antigen) class I (HLA-I) heterozygosity may avail to survival benefit from immune checkpoint blockade (ICB) in advanced cancer patients. Among their cohorts of melanoma patients, patients with the HLA-B44 supertype had improved survival, while the individuals with HLA-B62 supertype had worse outcome. However, these observations were not supported by another study of NSCLC patients treated with immune checkpoint inhibitors (ICIs). Now whether HLA-I genotype can serve as predictive marker for ICB treatment of other malignancies such as gastrointestinal cancer remains unclear. Methods: Tumor tissue samples before immunotherapy as well as related clinical data were collected from 91 Chinese gastrointestinal cancer patients receiving anti-PD-1/PD-L1 inhibitors and/or anti-CTLA-4 antibodies. Genomic features of tumor specimens were characterized by whole exome sequencing (WES) and HLA-I genotyping of normal DNA from peripheral blood cells were performed using WES data. Tumor immune microenvironment signatures were examined by RNA-sequencing targeting 395 immune related genes. Results: We observed that the individuals with HLA-B62 supertype (n = 15) had a significantly shorter PFS (median PFS, 1.83 months versus 3.53 months; HR, 2.3; 95% CI, 1.03-5.0; p= 0.009) than that of those without HLA-B62 supertype (n = 35) in a subgroup of patients with microsatellite stability (MSS, n = 50) and it was not so in other patients with microsatellite instability-high (MSI-H, n = 17) or unknown MSI status (n = 24). Moreover, the patients with B62 supertype and TP53 mutations (n = 15) exhibited more markedly shortened PFS (mPFS, 1.8 months versus 5.57 months; HR, 3.9; 95% CI, 1.5-9.6; p&lt; 0.0001) and OS (mOS, 4.2 months versus 17.3 months; HR, 4.5; 95% CI, 1.5-13.2; p&lt; 0.0001) compared to those patients with non-B62 supertype and TP53 wildtype (n = 26). Furthermore, gene expression levels of certain immune activation related pathways or markers (IFN-γ signature, cytolytic marker, etc.) in the patients with B62 supertype and without B44 supertype (n = 23) were statistically lower ( p&lt; 0.05) than in those patients without B62 supertype (n = 62). Chi-square test revealed no correlation between HLA-B62 supertype and TP53 mutation, MSI status, tumor mutation burden (TMB) or PD-L1 expression. Conclusions: HLA-B62 supertype in combination with TP53 mutations may define a subset of gastrointestinal cancer patients who probably fail to benefit from ICIs, especially in MSS patients.
Association of prior immune checkpoint blockade (ICB) with longer progression-free survival (PFS) in patients treated with intermittent versus continuous dabrafenib and trametinib: A post-hoc analysis of S1320.
Authors: Alain Patrick Algazi, Megan Othus, Adil Daud, Janice M. Mehnert, Thach-Giao Truong, Robert Martin Conry, Kari Lynn Kendra, Gary C. Doolittle, Joseph I Clark, Michael J. Messino, Dennis Frederic Moore, Christopher D. Lao, Bryan A. Faller, Rangaswamy Govindarajan, Amy K. Harker-Murray, Luke P. Dreisbach, James Moon, Kenneth F. Grossmann, Roger Lo, Antoni Ribas
Journal: Journal of Clinical Oncology (2020)

10039 Background: S1320 is a phase 2 randomized clinical trial presented at the 2020 AACR Annual Meeting in April demonstrating that continuous dosing of dabrafenib and trametinib yields longer PFS than intermittent dosing of these agents in patients with BRAF V600E/K melanoma. Here we look at the association between prior exposure to ICB and PFS in patients randomized to either intermittent or continuous dosing on S1320. Methods: Patients without disease progression after 8 weeks of dabrafenib and trametinib were randomized 1:1 to proceed with intermittent therapy (3-week-off, 5-week-on) or to stay on the continuous daily dosing schedule. The design called for 206 randomized patients with the primary outcome of PFS. Response assessments were made using RECIST v1.1 at 8-week intervals. A post-hoc analysis assessed differences in PFS in the pool of all randomized patients based on prior exposure to anti-PD1 antibodies, a randomization stratification factor. Kaplan-Meier estimates and multivariable Cox regression models (controlling for pre-randomization age, Zubrod performance status, LDH, unknown primary, M-Stage) were used to evaluate the association between this stratification factor and PFS. Results: Of 242 patients treated on study, 105 were randomized to continuous dosing, 101 to intermittent dosing, and 36 were not randomized due to disease progression at 8 weeks or other factors. 37% of the 242 enrolled and 37% of the 206 randomized patients had previously been treated with ICB. Among all randomized patients, there were no differences in baseline characteristics comparing patients with and without prior immune checkpoint inhibitor exposure: age median 62 vs 59, LDH elevation 37% vs 39%,, stage IVB/C 73% vs 64%, Zubrod performance status 0, 57% vs 58%. PFS was longer in patients with prior ICB exposure (hazard ratio = 0.60, 95% confidence interval 0.41,-0.98, median = 6 vs 9 months from randomization, 8 vs 11 months from starting treatment). There was no difference in the association between prior ICB exposure and PFS between arms (interaction p-value = 0.62). Conclusions: In patients without early progression on dabrafenib and trametinib, PFS was longer with prior to exposure to ICB . Although the groups had similar baseline characteristics and rates of randomization, these results could still be influenced by non-controlled factors influencing clinicians’ decisions to start a patient on immune versus targeted therapy. Clinical trial information: NCT02196181.
Predictors of immune-related adverse events associated with checkpoint inhibitors.
Authors: Alhareth Alsayed, Ashish Manne, Daisy E Escobar, Gaurav Sharma, Pranitha Prodduturvar, Omar Alkharabsheh
Journal: Journal of Clinical Oncology (2020)

e15159 Background: Immune-related adverse events (irAE) remain a significant challenge with the expansion of checkpoint inhibitors (ICI) indications. Unlike previous studies published, we investigated risk factors for irAE development, including lymphocytes and neutrophils counts in lung cancer and melanoma treated with all available ICIs in current clinical practice. Methods: This is a retrospective study conducted at the University of South Alabama Mitchell Cancer Institute. Between 2015-2019. A total of 160 patients with a diagnosis of melanoma (N = 54) or lung cancer (N = 106) who received at least two doses of ICI including ipilimumab (15%), nivolumab (32%), pembrolizumab (35%), dual nivolumab/ipilimumab (5%), durvalumab (9%) and atezolizumab (4%). The patient's baseline characteristics were extracted with irAE (grade 3/4) details and survival outcomes. Descriptive statistics were used, Fisher exact test to compare categorical variables, and Wilcoxon rank sum test for continuous variables using JMP software. Results: The median age at diagnosis was 64 years (range 17-93), with 51% females. Race distribution with 76% Caucasians and 26% African Americans. Around 30% of the cohort was treated for recurrence, and 39% did receive prior systemic chemotherapy. Median overall survival (OS) was 13.5 months (m) for melanoma and 16 m for lung cancer with CI 95% [16-24] and [15-23], respectively. Twenty-nine (29%) percent of the cohort (N = 46) had grade 3/4 irAEs. Median of baseline hematological parameters including total white blood count (WBC), absolute neutrophil count (ANC), absolute lymphocyte count (ALC), ANC to ALC ratio, and platelet to ALC ratio of these patients were not statistically different from the cohort without grade 3/4 irAEs. Interestingly, if a patient has baseline ALC &lt; 1K/μL, the risk of irAE recurrence is low when ICI is re-initiated, p = .0143 (after symptomatic recovery from irAEs). Conclusions: Irrespective of ICI used, baseline lymphocyte count, and its relation to other blood counts have no clear impact on irAE. Larger cohorts or prospective studies are needed to make stronger conclusions about the relationship between the immune system and the occurrence of irAEs
An intergroup collaboration for advanced stage classical Hodgkin lymphoma (cHL) in adolescents and young adults (AYA): SWOG S1826.
Authors: Sharon M. Castellino, Michael Leo LeBlanc, Alex Francisco Herrera, Susan K. Parsons, Angela Punnett, David C. Hodgson, Sarah C. Rutherford, Nadia Khan, Louis S. Constine, Kelly Davison, Anca A. Prica, Jonathan W. Friedberg, Kara M. Kelly
Journal: Journal of Clinical Oncology (2020)

TPS8067 Background: Treatment for pediatric cHL varies considerably from that in adult cHL. Hence there are gaps in risk prediction and optimal therapy for de-novo advanced stage disease across the adolescent and young adult (AYA) age spectrum. Early access to novel agents for AYA could be facilitated via collaboration with adult research groups through the U.S. National Cancer Institute’s National Clinical Trials Network (NCTN). The PD-1 inhibitor Nivolumab (Nivo) has safety and efficacy in relapsed and refractory disease in children and adults, but has not been evaluated in de-novo disease to date. Methods: North American cooperative group lymphoma chairs, Cancer Therapy Evaluation Program (CTEP) representatives and patient advocates met to establish consensus on the comparison arms and study design, based on recent historical approaches across adult and pediatric groups. Study champions were identified across North American cooperative groups and include expertise in imaging, radiation oncology, biology and patient-reported outcomes. A therapeutic study was designed with the primary aim being to compare progression-free survival with novel targeted agents in advanced stage cHL. S1826 (NCT03907488), led by SWOG Cancer Research Network, opened to accrual in July 2019. Eligibility criteria include age &gt; 12 years, and Stage III or IV cHL. Patients are randomized (1:1) to 6 cycles of either Nivo-Adriamycin, Vinblastine, Dacarbazine (AVD) or Brentuximab vedotin (Bv)-AVD. Enrollment is stratified by age, baseline International Prognostic Score, and provider intent to use involved site radiation therapy (ISRT). Protocol-prescribed ISRT is response-adapted, based on end of therapy imaging. The primary endpoint is a comparison of progression-free survival between arms. Secondary clinical endpoints include comparison of: overall survival, metabolic response at the end of therapy, physician-reported adverse events, patient-reported adverse events, and health-related quality of life (overall, and specific to fatigue and neuropathy). This unique intergroup collaboration demonstrates the process and the feasibility of consensus study designs toward early adoption of targeted therapies and harmonization of treatment approaches for AYA populations. Clinical trial information: NCT03907488 .
舒必利致严重锥体外系不良反应一例
Authors: 王彩花, 谢传高, 钱可大, 高志强
Journal: BMJ (2007)

患者女,49岁,因反复上腹痛10年入院.体格检查:呼吸18次/min,血压120/75 mm Hg(1 mm Hg=0.133kPa).神清,皮肤巩膜无黄染,心肺无异常,腹软,无压痛,肝脾未及。
Safety and efficacy of pemigatinib plus pembrolizumab combination therapy in patients (pts) with advanced malignancies: Results from FIGHT-101, an open-label phase I/II study.
Authors: Martin Gutierrez, Vivek Subbiah, John J. Nemunaitis, Niharika B. Mettu, Kyriakos P. Papadopoulos, Minal A. Barve, Luis Féliz, Christine Francis Lihou, Chenwei Tian, Tao Ji, Ian M. Silverman, Rashmi Chugh, Mansoor N. Saleh
Journal: Journal of Clinical Oncology (2020)

3606 Background: Pemigatinib (INCB054828) is a selective fibroblast growth factor receptor (FGFR) 1–3 inhibitor with demonstrated efficacy as monotherapy in phase 1/2 (FIGHT-101) and phase 2 (FIGHT-201, -202, -203) trials in pts with advanced cancer. Here, we present preliminary safety, efficacy, and pharmacokinetic (PK) data for pemigatinib (PEMI) combined with pembrolizumab (PEMBRO), a programmed cell death protein-1 (PD-1) inhibitor, in pts with refractory advanced malignancies enrolled in the ongoing FIGHT-101 trial (NCT02393248). Methods: FIGHT-101 includes monotherapy (part 1 and 2) and combination therapy (part 3) cohorts. This analysis is based on pts enrolled in the PEMI + PEMBRO combination dose finding (3a) and dose expansion (3b) cohorts. Eligible adults had advanced malignancies who had progressed after prior therapy and for whom PEMBRO treatment was relevant; pts in part 3b had FGF/FGFR alterations. Pts received oral PEMI at 9 mg or 13.5 mg QD on an intermittent dosing (ID) schedule (21-day cycle, 14-day on/7-day off), or 13.5 mg QD on a continuous dosing (CD) schedule, plus PEMBRO 200 mg IV on day 1 of each 21-day cycle. Results: At data cutoff (August 30, 2019), 23 pts had received PEMI + PEMBRO; 22 (96%) had discontinued therapy (disease progression, 70%). Most frequent tumors were NSCLC (n = 3), bladder (n = 3), pancreatic, testicular, and sarcoma (each n = 2). Of 19 enrolled pts with baseline FGF/FGFR data; 5 had FGFR mutations or rearrangements. No dose-limiting toxicities occurred with PEMI + PEMBRO. The recommended PEMI dose combined with PEMBRO was 13.5 mg QD. Most frequent all-cause, all-grade (Gr) adverse events for ID (n = 17) were hyperphosphatemia (n = 14 [82%]; Gr ≥3, n = 0), anemia (n = 9 [53%]; Gr ≥3, n = 3 [18%]), and decreased appetite (n = 9 [53%]; Gr ≥3, n = 0); for CD (n = 6), hyperphosphatemia (n = 5 [83%]; Gr ≥3, n = 0), and dry mouth (n = 4 [67%]; Gr ≥3, n = 0). One pt discontinued, 2 reduced dose, and 13 interrupted dose due to AEs (none for hyperphosphatemia; dose interruption mainly for gastrointestinal AEs [n = 5]). One fatal AE occurred (suicide, not treatment-related). PK parameters for PEMI in the PEMI + PEMBRO combination were comparable with those for PEMI monotherapy. Five pts had partial response (3 had FGFR rearrangements or mutations); 5 pts had stable disease. Conclusions: PEMI + PEMBRO combination therapy was tolerable with no new safety signals, and demonstrated preliminary antitumor activity in pts with advanced malignancies including those with FGF/FGFR alterations. Clinical trial information: NCT02393248 .
Large gastric hyperplastic polyps: to resect or not to resect, that is the question!
Authors: Amol Bapaye
Journal: Endoscopy (2020)

See also:Gastric hyperplastic polyps (hyperplasiogenic polyps): a constant debate!Endoscopy 2021; 53(01): 100-100DOI: 10.1055/a-1217-0521
Association between human leukocyte antigen DQB1 gene polymorphisms and bronchial asthma among Mongolia and Han nationalities
Authors: Li-ying Cui, Ying Nian, Jie Tan, Hong Suo, Xiu-yun L, Tian-ji Zhu, Hui Ren
Journal: BMJ (2010)

Objective To investigate association between human leukocyte antigen DQB1 (HLADQB1 ) gene polymorphisms and bronchial asthma among Mongolian and Han nationalities. Methods Sequence-specific primer polymerase chain reaction (PCR-SSP) was used to detect frequencies of HLA DQB1 genotypes and alleles in 50 cases of Han and 68 Mongolian asthmatic patients, and 50 Han and 54 Mongolian healthy controls, respectively. Difference in gene frequencies between the two nationalities was estimated by odds ratio (OR) and chi-square test. Results Frequency of the HLA-DQB1 0602 allele was significantly higher in Han patients with bronchial asthma than that in healthy Han nationality (OR = 6.163,P ＜0.01 ). Frequency of the HLA-DQB1 0603/0608 allele decreased in Mongolian asthmatic patients, as compared to that in healthy Mongolians ( OR = 0.199, P ＜ 0.05 ). Frequency of the HLA-DQB1 0301/4 allele was significantly higher in Mongolian asthmatic patients as compared to that in healthy Mongolians ( OR =2.074,P ＜0.05). Frequency of the HLA-DQB1 0301/4 allele was significantly higher in Mongolian than that in Han asthmatic patients ( OR = 2.482 ,P =0.05). Frequency of the HLA- DQB1 0602 allele was significantly higher in healthy Mongolians than that in healthy Han nationality ( OR = 3.341, P ＜ 0.05 ), in contrast, frequency of the HLA-DQB1 0402 allele was significantly lower in healthy Mongolians than that in healthy Han nationality ( OR = 0.209, P ＜ 0.05 ). Conclusions The HLA-DQB1 0603/0608 allele is possibly a protective gene and the HLA-DQB1 0301/4 allele a susceptible gene for bronchial asthma in Mongolians, and the HLA-DQB1 0602 allele is possibly a susceptible gene for bronchial asthma in Han nationlity.

Key words: 
Asthma;  HLA antigens;  Mongolian nationality;  Han nationality
Evaluation of osteoporosis self-assessment tool for Asians in screening of osteoporosis for postmenopausal women in community
Authors: Yan'ge Sun, Xueping Du, Kai Huang
Journal: BMJ (2014)

Objective
To evaluate the application of osteoporosis self-assessment tool for Asians(OSTA)in screening of osteoporosis for postmenopausal women in community.


Methods
Total 793 postmenopausal women were included.OSTA were calculated and bone mineral density(BMD)was measured by dual energy X-ray absorptiometry (DXA). The correlation of OSTA index with DXA results was analyzed.


Results
The prevalence of osteoporosis and osteopenia was 18.3% (145/793)and 47.7%(378/793)respectively, the remaining 270 women had normal bone mass (34.0%). According to OSTA index the rate of low-risk, medium-risk, high-risk osteoporosis groups were 61.9%(491/793), 29.5%(234/793)and 8.6%(68/793), respectively.The BMD measured by DXA was positively correlated with OSTA index(r=0.559, P=0.000). The area under receiver operating characteristic curve(ROC) of OSTA for diagnosing osteoporosis was 0.736.Taking -1 as cut off value, the sensitivity and specificity of OSTA in diagnosis of osteoporosis was 73.1%(106/145)and 69.8%(452/648), respectively.


Conclusion
OSTA can be used as an effective index for screening of osteoporosis in postmenopausal women in community.


Key words: 
Osteoporosis, postmenopausal; Osteoporosis self-assessment tool for Asians; Screening
Characteristics of Ongoing Clinical Trials for Alcohol Use Disorder Registered on ClinicalTrials.gov
Authors: Joshua D. Wallach, John H. Krystal, Joseph S. Ross, Stephanie S. O’Malley
Journal: JAMA Psychiatry (2020)

This cross-sectional study evaluates the characteristics of ongoing clinical trials for alcohol use disorder medications registered on ClinicalTrials.gov, including the medications, populations, and end points currently being studied.
Longitudinal Toxicity over Time (ToxT) analysis to evaluate tolerability: a case study of lenalidomide in the CALGB 50401 (Alliance) trial
Authors: Gita Thanarajasingam, John P Leonard, Thomas E Witzig, Thomas M Habermann, Kristie A Blum, Nancy L Bartlett, Christopher R Flowers, Brandelyn N Pitcher, Sin-Ho Jung, Pamela J Atherton, Angelina Tan, Paul J Novotny, Amylou C Dueck
Journal: The Lancet Haematology (2020)