tbuckley/cabot-search huggingface dataset:
Phase II, open-label, randomized study of first-line zolbetuximab plus gemcitabine and nab-paclitaxel (GN) in Claudin 18.2–positive metastatic pancreatic cancer (mPC).
Authors: Wungki Park, Eileen Mary O'Reilly, Junji Furuse, Futoshi Kunieda, Fei Jie, Hedy L. Kindler
Journal: Journal of Clinical Oncology (2020)

TPS4667 Background: Combinations of folinic acid, fluorouracil (5-FU), irinotecan, and oxaliplatin (FOLFIRINOX) along with GN are standard first-line treatment options for mPC. Despite treatment advances, mPC has a poor prognosis with a 5-year survival rate of &lt; 5%, emphasizing an urgent need for new targeted therapeutics. Claudin 18.2 (CLDN18.2) is a tight junction protein restricted to normal gastric mucosa cells; however, in the context of malignant transformation, CLDN18.2 is frequently expressed in carcinomas derived from organs that do not normally express it, such as pancreatic adenocarcinoma (50-70% express CLDN18.2). Zolbetuximab is a chimeric IgG1 monoclonal antibody that specifically binds to CLDN18.2, designed to mediate cancer cell death through antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. Methods: This phase 2 study (NCT03816163) with a safety lead-in phase will assess safety and antitumor activity of zolbetuximab plus GN in patients (pts) with histologically confirmed mPC with high CLDN18.2 expression (≥75% of tumor cells demonstrate moderate-to-strong IHC staining). The safety lead-in will assess safety/tolerability of zolbetuximab (n = 3 at 1,000 mg/m 2 on Cycle 1 Day 1 then 600 mg/m 2 Q2W then expand/de-escalate using a 3+3 design) plus GN and confirm the recommended phase 2 dose (RP2D). Dose-limiting toxicities (DLTs), defined as a specified toxicity that occurs during the DLT assessment period and is related to zolbetuximab, will be assessed after Cycle 1 (28 days). After determining the RP2D, approximately 129 pts will be randomly assigned 2:1 to receive either zolbetuximab RP2D Q2W on Days 1 and 15 plus GN on Days 1, 8, and 15 of each cycle ( Arm 1), or GN alone on Days 1, 8, and 15 of each cycle ( Arm 2). Randomization will be stratified by ECOG performance status (0 or 1) and liver metastasis (yes or no). Imaging (CT/MRI) will be performed at baseline and every 8 weeks until investigator-assessed disease progression (per RECIST v1.1 criteria) or the start of other systemic anticancer treatment, whichever comes earlier. Primary objectives are to confirm RP2D (safety lead-in), to assess antitumor activity measured by overall survival (randomization phase), and to establish the safety/tolerability profile of zolbetuximab plus GN across the study. Key secondary endpoints in the randomization phase are progression-free survival and objective response rate. As of January 2020, this study is recruiting pts at 74 centers. Clinical trial information: NCT03816163 .
髂骨瓣植入结合外固定器治疗股骨头坏死18例
Authors: 王庆雷, 侯树勋, 李文锋, 张伟佳, 吴克剑
Journal: BMJ (2005)

采用改良Smith-Petersen(S-P)切口,于股骨头颈部开槽,刮除股骨头内坏死骨,填充髂骨泥,用带旋髂深动脉髂骨瓣植入开槽部位,利用功能性髋关节外固定架撑开髋关节间隙,治疗股骨头缺血性坏死18例.结合早期功能锻炼,随访9个月～4年,结果:均术后3～5个月移植骨块愈合.优14髋,良3髋,可1髋.优良率为94.4%.无发生股骨头塌陷病例。
Criteria for trainers of general practitioners in clinical training bases
Authors: Yao Liu, Shanzhu Zhu, Xiangjie Zhang, Hua Yang, Jing Zhou, Qian Chen
Journal: BMJ (2014)

Objective
To develop criteria for trainers of general practitioners in clinical training bases.


Methods
A primary version of criteria was established through literature review and expert interview. Thirty-two experts with middle-level professional title or above, who had 10 years of working experience or more in general practice, teaching and administration, were invited for 3 rounds of Delphi consultation during March and October 2013.


Results
The criteria consisted of 3 first-grade indicators and 12 second-grade indicators were established. The first-grade indicators included professional quality, clinical competence and teaching capability. The weight coefficient of first-grade indicators were 0.332 0, 0.336 0 and 0.332 0, respectively. For 3 rounds of consultation the activity coefficient of experts was all 100%; the authority coefficients of experts were 0.881, 0.897 and 0.883, respectively; and the harmonious coefficient of importance of the evaluation were 0.136, 0.127 and 0.204, respectively (P<0.01).


Conclusion
The established criteria are credible and important for the selection of trainers of general practitioners in clinical bases, which would improve the quality of standardized training for general practitioners.


Key words: 
General practitioner; Teacher training; Delphi technique; Standards
Research progress on association between particulate matter 2.5 and acute coronary syndrome
Authors: Sheng Jiang, Li Yang
Journal: BMJ (2018)

Particulate matter 2.5 μm (PM2.5) is the fine particulate matter with a diameter less than 2.5 μm, the acute coronary syndrome (ACS) is a clinical syndrome caused by acute myocardial ischemia. Recent studies have shown that there is an association between particulate matter 2.5 μm and ACS. This review focuses on the mechanisms of ACS caused by PM2.5 and its prevention.


Key words: 
Acute coronary syndrome; Particulate matter
Effect of telmisartan on insulin resistance in elderly patients undergoing maintenance hemodialysis
Authors: Rui Wang, Guo-hua Ding, Hong-yan Liu
Journal: BMJ (2009)

Eleven elderly patients undergoing maintenance hemodialysis without ARB or ACEI within 4 weeks were enrolled. Anti-hypertensive agents were replaced by telmisartan gradually to maintain stable blood pressure. Before and after 6 or 12 weeks of treatment, blood biochemical profiles, fasting blood glucose, fasting plasma insulin, insulin resistance index(HOMA-IR), blood pressure, and body weight were recorded. Our results showed that telmisartan did not affect body weight, high-density lipoprotein (HDL), triglyceride (TG), SCr, BUN, Alb, K+ , and PTH, although led to a significant decrease in TC and low-density lipoprotein (LDL). Following telmisartan treatment, FPG did not change significantly, but fasting insulin decreased from 13.9±3.6 mU/ml to 9.9±2.7 or 9.1±2.3 mU/ml at 6 and 12 week (P<0.01), and HOMA-IR decreased from 3.5±1.4 to 2.4±0.8 or 2.2±0.8 at 6 and 12 week (P<0.05). These results suggest that insulin resistance in elderly patients with MHD may be improved by telmisartan.

Key words: 
Hemodialysis; Telmisartan
Right timing of mechanical ventilation in patients with bronchial asthma in emergency room
Authors: Xiaowei Liu, Lulu Li
Journal: BMJ (2014)

Objective
To explore the right timing of mechanical ventilation in patients with bronchial asthma in emergency room.


Methods
A total of 67 patients with bronchial asthma undergoing mechanical ventilation were admitted into our Emergency Intensive Care Unit (EICU) from January 2010 to December 2012. According to PaCO2 before intubation, they were divided into 3 groups of low levels of PaCO2[PaCO2≤35 mmHg (1 mmHg=0.133 kPa)](n=19), normal PaCO2 (35 mmHg<PaCO2<45 mmHg)(n=21)and high PaCO2 (PaCO2 ≥45 mmHg)(n=27). Their clinical data were retrospectively analyzed.


Results
The in-hospital mortality of three groups were 5.3%(1/19), 9.5%(2/21) and 14.8%(4/27) and the difference was not statistically significant (χ2=1.16, P>0.05). However the average duration of mechanical ventilation of three groups were (5.6±1.7), (8.3±2.1) and (13.5±3.6) days and the difference was statistically significant (F=3.36, P=0.042). The average ICU treatment time was (7.4±2.1), (11.5±3.3) and (16.4±3.5) days and the difference was statistically significant (F=3.23, P=0.047). PaCO2 levels before intubation was positively correlated with the duration of mechanical ventilation and the ICU treatment time (r2=0.366, 0.316, P=0.031, 0.029).


Conclusion
The patients with bronchial asthma undergoing intubation in right time in emergency room will affect the duration of mechanical ventilation and ICU treatment time.


Key words: 
Bronchial asthma; Mechanical ventilation; Prognosis
Changes in intravenous immunoglobulin (IVIG) usage for hypogammaglobulinemia (HG) after implementation of a stewardship program.
Authors: Benjamin Avi Derman, Zachary Schlei, Kate M. Mullane, Sandeep Parsad, Randall W Knoebel
Journal: Journal of Clinical Oncology (2020)

e19225 Background: IVIG is used to replenish immunoglobulins in HG due to hematologic malignancies (HM) or their treatment (stem cell transplantation (ASCT) and chimeric antigen receptor T-cell therapy (CAR-T)), in an effort to reduce the risk of infections. There is limited high-level evidence to support this use, and IVIG supplies are limited with a recent shortage leading to restricted allotments. We report the results of a stewardship program designed to safely reduce IVIG usage. Methods: An IVIG stewardship plan (ISP) was implemented with the following requirements for IVIG administration: IgG level &lt; 400 mg/dL (corrected for paraprotein) for post-ASCT and post-CAR-T patients, or IgG &lt; 400 mg/dL with evidence of a bacterial infection within the last 3 months that required hospitalization or an emergency department encounter for those with HM. We evaluated the amount of IVIG administered, the incidence of infections, and antibiotic administration before and after implementation of an ISP. Results: In the 3 months pre-ISP, HG accounted for 38% (72/188) of total IVIG orders. 86 pts received IVIG for HG in the 3 months pre-ISP. The amount of IVIG given decreased from 1907 g/month pre-ISP to 670 g/month post-ISP; estimated cost savings in IVIG was $57,561/month. The pre-ISP median IgG level prior to dosing of IVIG was 550 (range 40-1189) mg/dL. Compared to pre-ISP, pts who stopped receiving IVIG post-ISP had lower median pre-dose IgG (444, range 93-819 mg/dL, p&lt;0.05), infections/patient-months (14/141 vs 56/255, p&lt;0.001), antibiotic usage (12/47 vs 44/86, p&lt;0.05), and hospitalization rate for infection (4/55 vs 21/86, p&lt;0.05); no deaths occurred. For those receiving IVIG post-ISP, adherence to guidelines was 64%. Compared to pre-ISP, median pre-dose IgG was lower (328, range 51-1011 mg/dL, p&lt;0001), infections/patient-months decreased (27/163 vs 56/255, p&lt;0.001), and antibiotic usage, hospitalization rate for infection, and deaths from infection all remained stable. Conclusions: An ISP for HG led to a dramatic and sustainable decrease in IVIG usage, primarily by selecting out patients who are low risk for infection after discontinuation of IVIG. Such an ISP is replicable and warrants adoption.
Antibiotics treatment for peritoneal dialysis-related peritonitis: an analysis of 196 cases
Authors: Liehui Li
Journal: BMJ (2017)

回顾性分析2006年1月至2015年12月本中心治疗的腹膜透析相关性腹膜炎(简称腹膜炎)患者的致病菌分布、药物治疗效果及预后。2010年12月以前的85例次为Ⅰ组，2011年1月以后的111例次为Ⅱ组，Ⅰ、Ⅱ组应用第1＋第3代头孢菌素治愈55例次(64.7%)和32例次(28.8%)，万古霉素＋美罗培南治愈19例次(22.4%)和67例次(60.4%)。提示万古霉素＋美罗培南治疗腹膜炎具有起效快、治愈率高、远期预后好等优点，适合作为腹膜炎的初始治疗。
Practice and outcome of training models for chief doctors and nurses from primary hospitals in Henan province
Authors: Ju-yu Cai
Journal: BMJ (2012)

To advance the medical service system and strengthen the medical staff construction at primary hospitals,our hospital pioneered the training class for doctors and nurses from primary hospitals in Henan province in 2011.We offered the training fee and set rewards for them.The training classes included pre-job training,demonstration lessons,lectures,simulation training,discussion of intractable cases and clinical instructor training.The systematic training based on Henan provincial conditions plays a radiation role of big public hospitals and helps implement the grading medical services.

Key words: 
Education; medical; continuing
<i>RAS-</i>mutated sporadic medullary thyroid cancer: A single-center experience.
Authors: Spandana Brown, Stephen K. Gruschkus, Steven G. Waguespack, Ramona Dadu, Mark Zafereo, Maria E. Cabanillas, Elizabeth Gardner Grubbs, Steven I. Sherman, Mimi I-Nan Hu
Journal: Journal of Clinical Oncology (2020)

6584 Background: Activating RAS mutations are recognized as important drivers in sporadic medullary thyroid cancer (sMTC), with a reported prevalence between 0-43%. However, few studies have looked at correlations between RAS-mutated sMTC and clinicopathologic features. Methods: Patients with sMTC diagnosed between 1992 – 2019 with NGS testing for RET and RAS mutations seen at a tertiary cancer center were retrospectively evaluated. The objective was to analyze demographic and clinical features among patients with RAS-mutated sMTC and to evaluate associations between these features and overall survival (OS). Analyses were performed to correlate patient demographics and pathologic staging with treatment characteristics, disease course, and OS. Results: We identified 42 patients (50% female) with RAS-mutated sMTC out of 218 pts with sMTC. Median age at diagnosis was 50 years (range 24-78 years). 26 (62%) patients had stage IV disease at time of diagnosis. 28 (67%) of patients had HRAS mutations and 14 (33%) had KRAS mutations. HRAS Q61R was the most common HRAS mutation type (n = 19, 45%). Median follow-up time was 64 months (range 23-274 months) during which 11 (26%) patients died. The median OS was 16.2 years, with 5- and 10- year OS of 88% and 73% respectively. Of the 20 (48%) patients who received systemic therapy, 79% had stage IV disease and tended to be older (median age 54). Median time from diagnosis to initiation of systemic therapy was 33 months. Factors associated with worse OS included distant metastases at diagnosis, shorter time interval between diagnosis and treatment, and Ctn/CEA doubling times &lt; 6 months. HRAS Q61R mutations were associated with a better prognosis, with 100% 10-year OS compared with 10-year OS of 39% and 51% (p = 0.02) for other HRAS and KRAS mutations respectively. Conclusions: At a tertiary cancer center, patients with RAS-mutated sMTC had a 10-year OS rate of 73%, with significantly worse OS in patients with HRAS/KRAS mutations other than HRAS Q61R. In comparison, prior studies have reported 10-year OS rates between ~71-90% in sMTC and 10-year OS rates as low as 56% for more aggressive RET M918T sMTC mutations. The findings here are consistent with other studies that have suggested patients with RAS-mutated sMTC are at intermediate risk for aggressive disease, though there are limited data on OS rates in RAS or RAS-/RET- sMTC. Future research comparing outcomes between various RAS mutations and in comparison to RET+ and RAS-/RET- patients is needed, especially as systemic therapy use in RAS-mutated sMTC evolves.
GO39775: A multicenter phase I trial evaluating the safety, pharmacokinetics, and activity of BFCR4350A, a FcRH5/CD3 T-cell dependent bispecific antibody, in patients with relapsed or refractory multiple myeloma.
Authors: Adam D. Cohen, Suzanne Trudel, Peter A. Forsberg, Rafael Fonseca, Amrita Y. Krishnan, Andrew Spencer, Jesus G. Berdeja, Sarah M. Hamirani, Mengsong Li, James Cooper, Simon J. Harrison
Journal: Journal of Clinical Oncology (2020)

TPS8551 Background: Multiple myeloma (MM) remains an incurable disease, with estimated median survival of 8–9 months in patients with relapsed or refractory (R/R) disease (Kumar et al. 2014; Usmani et al. 2016). There is no uniform standard of care for R/R MM, and combinations used in later lines have diminishing responses, especially after re-exposure to previously received classes of therapy (Gandhi et al. 2019). New targets and treatment modalities are needed. Fragment crystallizable receptor-like 5 (FcRH5) is expressed on myeloma cells across lines of therapy, and is overexpressed by myeloma cells with 1q21 gain; expression in healthy tissue is restricted to the B-cell lineage, and is retained in plasma cells (Li et al. 2017). BFCR4350A is an IgG-based T-cell-dependent bispecific antibody that was specifically engineered to target the most membrane-proximal domain of FcRH5 on myeloma cells and cluster of differentiation 3 (CD3) on T cells, with dual binding resulting in efficient immune synapse formation and T-cell killing of myeloma cells. BFCR4350A demonstrates potent killing of plasma cells and patient-derived myeloma cells (including those with low levels of FcRH5 expression) in vitro, and complete depletion of bone marrow plasma cells in primates, without severe or prolonged cytokine release (Li et al. 2017). GO39775 (NCT03275103) is an open-label, multicenter Phase I dose-escalation and dose-expansion trial evaluating the safety, pharmacokinetics (PK), and activity of BFCR4350A monotherapy in patients with R/R MM. Methods: Patients must be aged ≥18 years and must have R/R MM for which no established therapies are available or appropriate, or be intolerant to those therapies. Patients with prior CAR-T therapy and/or prior BCMA-directed therapy are not excluded. BFCR4350A is administered by intravenous infusion, and q3w dosing with Cycle 1 single-step or multi-step dosing is being investigated in dose-escalation (Arms A and B, respectively). Enrolment into both arms is ongoing, with patients receiving up to 17 cycles of treatment until disease progression or unacceptable toxicity. Primary objectives are to evaluate safety (including the maximum tolerated dose and dose-limiting toxicities) and to identify a recommended Phase II dose. Secondary objectives include assessment of PK, activity, immunogenicity, and pharmacodynamic biomarkers. Clinical trial information: NCT03275103 .
The impact of poly ADP ribose polymerase (PARP) inhibitors on clonal hematopoiesis.
Authors: Kelly L Bolton, Lea Anne Moukarzel, Ryan Ptashkin, Teng Gao, Minal Patel, Nicole Caltabellotta, Lior Zvi Braunstein, Carol Aghajanian, David Michael Hyman, Michael F. Berger, Luis A. Diaz, Bob T. Li, Wassim Abida, Alison M. Schram, Britta Weigelt, Claire Frances Friedman, Ahmet Zehir, Elli Papaemmanuil, Karen Anne Cadoo, Ross L. Levine
Journal: Journal of Clinical Oncology (2020)

1513 Background: Poly (ADP-ribose) polymerase (PARP) inhibitors are an important new class of anti-cancer therapies. Therapy-related myeloid neoplasia (tMN) has been reported following PARPi therapy, and is associated with adverse outcomes. Further insight is required into the risk of tMN conferred by PARPi therapy, independent of germline genetic background and prior therapy. We have shown that oncologic therapy selects for acquired mutations in the blood (clonal hematopoiesis; CH) particularly those in the DNA damage response pathway (DDR) including PPM1D, TP53 and CHEK2 and that CH confers an increased risk of tMN. We hypothesized that characterization of the relationship between CH and PARPi therapy provides insight into its potential for leukemogenesis and may offer opportunities for tMN prevention. Methods: We assessed for CH in the blood of 10,156 cancer patients, including 54 who received PARPi therapy, 5942 who received another systematic therapy or radiation therapy and 4160 untreated prior to blood draw. Results: Patients exposed to PARPi therapy were more likely to have CH (33%) compared to those exposed to other systemic therapies or radiation (18%) or untreated patients (16%). This was particularly pronounced for DDR CH; 25% of PARPi treated patients had DDR CH compared to 2% of untreated patients. In a multivariable model accounting for demographics, exposure to chemotherapeutic agents, radiation therapy and germline BRCA mutation status, exposure to PARPi conferred an increased risk of DDR CH (OR = 3.6, 95% CI 1.5-8.5, p = 0.004). This effect was attenuated after accounting for cumulative exposure to therapy (OR = 2.8, 95% CI 0.97-8.2, p = 0.06) suggesting a multifactorial contribution to the enrichment of CH following PARPi therapy. To characterize this further we performed a prospective collection of patients with CH over a median follow-up time of 58 months. During the follow-up period, 17 patients received PARPi, 360 received cytotoxic therapies or radiation and 232 were untreated or received targeted therapies. The growth rate of DDR CH was significantly higher among those who were exposed to PARPi (median, +2.8% increase in VAF per year) compared to untreated patients (+0.08% per year, p = 0.02) and those exposed to other cytotoxic therapies (+1% per year, p = 0.04). Conclusions: Taken together our data suggests that PARPi therapy promotes the expansion of DDR CH. Future studies should examine the potential of CH to identify individuals at high risk of tMN following PARPi therapy and to develop therapies aimed to prevent tMN in patients with CH.
Significance of PDL1 positive in TNBC.
Authors: Seiichi Imanishi, Hirotaka Morishima, Naofumi Oda, Junichi Hasegawa
Journal: Journal of Clinical Oncology (2020)

e12557 Background: Atezolizumab was approved for PD-L1-positive advanced recurrent triple negative breast cancer. However, it is controversial about when and when to measure PD-L1. Here we retrospectively reaearched how PD-L1 positivity rates in biopsy, surgical, and recurrent specimens for triple-negative breast cancer (TNBC) treated with neo adjuvant chemotherapy (NAC). We also investigated the relationship between androgen receptor (AR) and PD-L1, and researched the significance of PD-L1 positivity on TNBC. Methods: 28 TNBC biopsy samples before NAC, 16 surgical specimens with residual tumor after NAC, and 5 cases reccurence specimens were obtained subjected to stain for PDL1 using the SP142 antibody. AR staining was also performed on biopsy specimens. PD-L1 score determination was performed according to the Ventana OptiView PD-L1 (SP142) inspection guide, and AR positive cuttoff was setted 1% or more. Results: The PD-L1 positivity rates of the biopsy samples were IC0: 46.4%, IC1: 25.0%, IC2: 21.4%, IC3: 7.1%, TC0: 28.6%, TC1: 28.6%, TC2: 42.9%, TC: 0%. In the surgical specimens after NAC, PD-L1 showed almost no change in IC ( P = 0.38), but the score significantly decreased in TC ( P &lt; 0.001). The recurrence specimesn that could be collected were IC0: 60%, IC1: 20%, IC2: 20%, IC3: 0%, TC0: 60%, TC1: 20%, TC2: 20%. There were four AR-positive cases, one of which showed TC2, but the others were negative.In terms of prognosis, both the DFS and OS in the PD-L1 strongly positive group (IC≥2 and TC≥2) and other groups Poor in PD-L1 strongly positive group ( P &lt; 0.01, P = 0.041, respectively). Conclusions: TC was affected by NAC, the score decreased markedly, and the positive rate at the site of recurrence also tended to decrease. The PD-L1 strong positive had a significantly worse prognosis than the others. It was suggested that PD-L1 immunostaining may be effective in predicting prognosis by considering TC as well as IC.