tbuckley/cabot-search huggingface dataset:
Comparative efficacy of primary treatment approaches in anaplastic thyroid carcinoma (ATC): An updated network meta-analysis.
Authors: Kevin M. Gallagher, Philip A. Haddad, Dalia A. Hammoud
Journal: Journal of Clinical Oncology (2020)

e18566 Background: ATC is a rare tumor accounting for around 5% of all thyroid cancers. With survival measured in months, ATC is often fatal despite combined therapeutic approaches. Several studies reported on ATC treatment modalities indicating different outcomes and occasionally conflicting results. This analysis was conducted to update and expand our existing knowledge of the relative efficacy of the available therapeutic modalities in this rare disease. Methods: A review of the medical literature was conducted using online databases. Inclusion criteria consisted of (i) English language, (ii) diagnosis of ATC, (iii) treatment with complete resection (SX), radiotherapy (RT), surgery and radiotherapy (SRT), chemoradiotherapy (CRT), and combined surgery, radiation, and chemotherapy (COMB), and (iv) comparative studies reporting survival rates. A frequentists network meta-analysis was conducted using netmeta package and random-effects model. Results: Six studies comprising a total of 476 participants were included. SX, RT, CRT, SRT, and COMB approaches demonstrated significant survival advantage over no treatment and/or palliative care. Using odds ratio for analysis, COMB ranked highest followed by SRT, SX, CRT, and RT in a decreasing order. Inconsistency analysis did not reveal any significant differences between direct and indirect estimates. Conclusions: This network meta-analysis is the first to compare and rank commonly used treatment modalities in ATC. It indicates that SX and RT remain the backbone for any treatment approach that significantly impacts survival in ATC.
An epidemiologic study on hyperuricaemia and gout in residents of coastal areas of Haiyang City in Shandong
Authors: 张学顺, 于文广, 于丽霞, 张鲁阳, 于瑛
Journal: BMJ (2006)

目的 对山东省海阳市沿海5个社区年龄≥20岁居民的高尿酸血症与痛风的发病情况进行调查,并分析其影响因素.方法采用统一的调查表对5 372名居民进行调查,调查内容包括职业、性别、年龄、食用海产品情况、饮酒史、血尿酸值.对高尿酸血症者测量身高、体重、血压,对痛风患者进行血脂、血糖、肾功能及泌尿系统B超检查.结果高尿酸血症患病率男性为16.85%(424/2 517),女性为 7.88%(225/2 855),男女合计为12.08%(649/ 5 372).发现痛风患者23例,男性21例,患病率为0.83%(21/2 517);女性2例,患病率为0.07%(2/2 855);男女合计为0.43%(23/5 372).相关因素分析显示,男性、女性高尿酸血症组与在性别和年龄上相匹配的健康对照组比较,体重指数、高血压患病率、食用海产品史、男性饮酒史差异均有统计学意义(P《0.01或0.05).结论沿海社区居民高尿酸血症和痛风患病率较高,体重指数、高血压、饮酒和食用含高嘌呤海产品等为高尿酸血症相关危险因素。
下肢动脉硬化闭塞症的诊断治疗和预防
Authors: 吴庆华, 姜民慧
Journal: BMJ (2010)

吴庆华:动脉硬化闭塞症(arteriosclerosis obliterans,ASO)是指动脉壁因粥样硬化引起的慢性动脉闭塞性疾病,以下肢最常见,由于ASO是人体全身动脉病变的局部表现,故本病多见于中老年男性,发病率呈逐渐增高趋势.
Peripheral endothelial function changes during HER2-directed therapy differ based on whether or not a patient receives anthracycline.
Authors: Antonious Ziad Hazim, Lara F. Nhola, Hector R. Villarraga, Shruti R Patel, Nicole Sandhu, Amir Lerman, Charles L. Loprinzi, Kathryn Jean Ruddy, Joerg Herrmann
Journal: Journal of Clinical Oncology (2020)

1044 Background: Trastuzumab is well-demonstrated to be associated with cardiotoxicity (typically reduced ejection fraction), most commonly in patients who also receive anthracycline. The vascular effects of trastuzumab and anthracycline are understudied; we aimed to compare change in endothelial function during and after trastuzumab and to assess how anthracycline receipt affects this. Methods: This is an observational prospective study of women with newly diagnosed HER2-positive breast cancer. All participants underwent baseline evaluation of endothelial function testing by use of the EndoPAT2000 device approximately every three months over the subsequent 18 months after the initiation of HER2-directed therapy +/- anthracycline. The primary endpoint was change in endothelial function over time using the reactive hyperemia index (RHI). Framingham Risk Score (FRS) and lower RHI are both known to be independent predictors of future cardiovascular events in the general population. RHI deterioration was defined as a 20% reduction from baseline RHI to any available follow-up RHI assessment. Univariate analyses assessed if age, FRS, baseline RHI, and RHI deterioration differed between recipients and non-recipients of anthracycline using the Wilcoxon test. A multivariate logistic model evaluated FRS, age, and anthracycline receipt as possible independent predictors of RHI deterioration. Results: Among 38 eligible patients who consented and completed baseline assessments in addition to at least one follow-up assessment, 17 (45%) subsequently received anthracycline. 145 total follow-up RHI assessments were available overall (5 per patient on average). There were no differences between recipients and non-recipients of anthracyclines with regard to age [mean 49 years (SD 12) vs 53 years (SD 11); p=0.25], baseline FRS [mean 1.0 (SD 1.0) vs 1.5 (SD 1.4); p= 0.28] or baseline RHI [mean 2.4 (SD 0.6) vs 2.1 (SD 0.7); p=0.09]. RHI deterioration was more common for anthracycline recipients (mean 43% vs 21%; p=0.004), and in the multivariate model, anthracycline use was the only independent predictor of RHI deterioration (odds ratio: 2.8; 95% confidence interval: 1.35-6.07; p=0.006). Conclusions: This study suggests that endothelial dysfunction is more common after combined anthracycline and HER2-directed therapy than after HER2-directed therapy alone. RHI should be further studied as a possible early biomarker of cardiovascular toxicity in patients receiving treatment for breast cancer.
Phase I study of CRISPR-engineered CAR-T cells with PD-1 inactivation in treating mesothelin-positive solid tumors.
Authors: Zhenguang Wang, Meixia Chen, Yan Zhang, Yang Liu, Qingming Yang, Jing Nie, Lianjun Shen, Pengfei Jiang, Jiaping He, Xun Ye, Wei Cao, Haoyi Wang, Weidong Han
Journal: Journal of Clinical Oncology (2020)

3038 Background: Our previous phase I study with MPTK-CAR-T (mesothelin-directed 28ζ CAR-T cells with PD-1 and TCR disruption by CRISPR-Cas9 system) demonstrated feasibility and safety of CRISPR-mediated PD-1 inactivation in CAR-T cells, and suggested the natural TCR is beneficial for the proliferation of CAR-T cells in solid tumors. Based on these observations, we initiated a pilot dose escalation study to investigate mesothelin-directed CAR-T cells with only PD-1 disruption by CRISPR (termed as GC008t) in patients with mesothelin-positive advanced solid tumors (NCT03747965). Methods: On the data cut-off date (Jan 20, 2020), nine patients (6 pancreatic cancers, 2 ovarian cancers, 1 colorectal cancer) were treated (5 received ≥12 numbers of therapy), three in cohort 1 (0.1-0.2×10 7 /kg), four in cohort 2 (0.5-1.0×10 7 /kg), two in cohort 3 (2.5-5×10 7 /kg). Eight of the 9 patients received lymphodepletion regimen of cyclophosphamide and nab-paclitaxel with or without gemcitabine. Four of the 9 patients received repeat infusions of GC008t per protocol. Results: Comparable proliferation capacity was observed in vitro between the MPTK-CAR-T and the GC008t products. The mean PD-1 surface expression in cell products was 0.5% (range, 0.2%-0.9%). GC008t infusions were well tolerated with no observed on-target/off-tumor toxicity, autoimmune activity. Only two patients in cohort 3 developed grade 1 CRS with fever and rash. Circulating GC008t expanded with a peak at day 7-14 and became undetectable by qPCR beyond 1 month. The mean peak levels of circulating CAR-T cells between GC008t and MPTK-CAR-T at similar dose level were not statistically significant. Failure of GC008t engraftment after repeat infusion was observed in 2 out of 4 patients. The best response of the 7 evaluable patients was stable disease in 4 and partial response in 2 patients (dosed ≥ 1×10 7 /kg) with PFS of 80 and 160 days. Conclusions: Phase I trial of GC008t further establishes that genetic inactivation of PD-1 in CAR-T cells by CRISPR is feasible and safe. The expansion and persistence of CAR-T cells with PD-1 disruption is not improved significantly even in the setting of natural TCR and lymphodepletion. Future endeavors are needed to improve the clinical efficacy of CAR-T therapy in the treatment of solid tumor. Clinical trial information: NCT03747965 .
Influencing factors for medical school graduates to choice general practice in Shanghai
Authors: Huiling Xia, Zhigang Pan, Tianhao Wang, Jian Wang, Jie Gu
Journal: BMJ (2018)

Objective
To investigate the influencing factors and their weights of professional choice among medical school  in Shanghai.


Methods
Base on literature review and interviews with medicine students in a university of Shanghai, a questionnaire of employment intention for general practice in medical graduates was developed. A questionnaire survey on influencing factors of general practice among five year medical students was conducted in the medical college of a university in Shanghai during May to June 2016. The weights of each factor were calculated with analytic hierarchy process (AHP).


Results
The valid questionnaires were retrieved from 14 male and 26 female students. The results showed that 53.8% (21/40) preferred Beijing, Shanghai, Guangzhou and other economically developed cities as future working place, and 38.5% (15/40) chose to go home town; for general practice 22.5% (9/40) chose very  , 70% (28/40) chose like and 7.5% (3/40) chose   ; only 10% (4/40) were willing to be a general practitioner, 55.0% (22/40) were depended on the working conditions of community health center, and 35% (14/40) were not ready to be a GP. AHP analysis showed that the weights of influencing factors were: the salary (0.380 2), the doctor-patient relationship (0.262 3), professional interest and occupation development prospects (0.220 4), social status and family contribution (0.137 1). Weight analysis for the affecting factors on professional interest and occupation development showed that the guidance of mentors in theoretical study and clinical practice were the major factors (comprehensive weight was 0.067 3 and 0.062 1, respectively), and the attitude GPs to general practice in community learning was more important (comprehensive weight was 0.042 5 and 0.019 6).


Conclusion
The willingness to be a general practitioner is not strong in the medical school  in Shanghai. It is important to improve the status and working conditions of general practitioners, and to strengthen education and guidance of the general practice in theoretical study and clinical practice for medical students.


Key words: 
Career choice; Questionnaires; General practice
Real-world patterns of treatment and recurrence by frailty status among older women with HR-positive, HER2-negative early breast cancer.
Authors: Gregory Sampang Calip, Colin Hubbard, Nadia Azmi Nabulsi, Alemseged Ayele Asfaw, Inyoung Lee, Jifang Zhou, Jenilee Cueto, Debanjali Mitra, Ernest H Law
Journal: Journal of Clinical Oncology (2020)

535 Background: Frail health status impacts clinical decision making for older cancer patients and their families, and frailty is independently associated with increased risks of mortality. Our objective was to describe differences in treatment and rates of recurrence by frailty status among older women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative early breast cancer. Methods: We performed a large, population-based retrospective cohort study of women aged 65 years and older diagnosed with first primary stage I-III HR+/HER2-breast cancer using the Surveillance, Epidemiology, and End Results Medicare-linked database between 2007 and 2015. Using administrative health claims, we ascertained information on breast cancer treatment and utilized validated claims-based algorithms to determine frailty status (robust, pre-frail, and frail) and identify subsequent invasive breast cancer recurrences. Relative hazards of recurrence were determined using Fine and Gray competing risks regression models with estimated subdistribution hazard ratios (SHR) and robust 95% confidence intervals (CI). Results: From an overall cohort of 46,027 women, most women (56%) were classified as robust at breast cancer diagnosis, whereas 37% and 7% were identified as pre-frail and frail, respectively. Compared to robust patients, frail patients were more likely to have stage III disease (10% vs. 7%) and receive mastectomy (27% vs. 18%), and less likely to receive radiation (35% vs. 57%) or chemotherapy (5% vs. 9%). Five-year cumulative incidences of recurrence were 15%, 18% and 22% among robust, pre-frail, and frail women, respectively. In multivariable competing risks models adjusted for age, race, stage, and treatment, frail (SHR 1.28, 95%CI 1.17-1.41) and pre-frail (SHR 1.15, 95%CI 1.09-1.21) women had a significantly increased risk of breast cancer recurrence. Conclusions: Independent of differences in treatment, frailty was associated with increased breast cancer recurrence risk in this population-based cohort of older women. However, the vast majority of older women living with HR+/HER2- early breast cancer were not identified as frail. These study results suggest that age alone is not an adequate indicator of physical resilience and underscores the need to consider additional factors when assessing the benefits and risks of treatments for the prevention of recurrence among HR+/HER2- early breast cancer patients.
TROPiCS–03: A phase II open-label study of sacituzumab govitecan (SG) in patients with metastatic solid tumors.
Authors: Ashish Saxena, Loren S. Michel, Quan Hong, Karrie Hilsinger, Charu Kanwal, Cabilia Pichardo, Trishna Goswami, Alessandro Santin
Journal: Journal of Clinical Oncology (2020)

TPS3648 Background: Trophoblast cell surface antigen (Trop-2) is highly expressed in many epithelial cancers (non–small-cell lung cancer [NSCLC], endometrial cancer, urothelial carcinoma [UC], and triple-negative breast cancer [TNBC]) and has been linked to aggressive disease and poor prognosis. SG is a Trop-2–directed antibody drug conjugate containing SN-38 (active metabolite of irinotecan) with a 7.5:1 drug-to-antibody ratio and unique hydrolyzable linker that allows for extracellular bystander effect. The phase 1/2 IMMU-132-01 basket study reported clinical activity with SG in patients with multiple tumor types not selected for Trop-2 expression including NSCLC (objective response rate [ORR]: 17%), TNBC (ORR: 33%), and UC (ORR: 31%).1-3 Results from the overall safety population (N=420) from this study found that SG was tolerable, with a predictable and manageable safety profile, and low discontinuation rates due to AEs. Methods: To test a biomarker-enrichment strategy with Trop-2, the TROPiCS-03 (TROP-2 Investigations in Cancer with SG) study was initiated. TROPiCS-03 (NCT03964727) is a multi-cohort, open-label, phase 2 study in patients with metastatic solid tumors - presently NSCLC (adenocarcinoma and squamous cell carcinoma), head and neck squamous cell carcinoma, and endometrial cancer - selected based on elevated Trop-2 expression by a validated IHC assay. Patients receive SG (10 mg/kg IV, days 1 and 8 every 21 days) and continue treatment until lack of clinical benefit or unacceptable toxicity. The primary endpoint is objective response rate (local assessment) and additional endpoints include clinical benefit rate, duration of response, progression-free survival, and safety. Females or males ≥18 years old who are histologically documented to have locally advanced or metastatic (M1, stage 4) solid tumors of the above types are eligible. Patients must have ECOG 0 or 1 and adequate clinical laboratory results to be enrolled. All subjects will have progressed after prior platinum-based chemotherapy and programmed death-ligand 1 (PD-L1) or programmed cell death protein 1 (PD-1) directed therapy. Patients who have previously received topoisomerase I inhibitors and those with known active CNS metastases are excluded. Approximately 160 patients will be enrolled in the trial overall; enrollment in the NSCLC cohort is currently in progress. References: Heist RS et al. J Clin Oncol. 2017;35:2790-7, Bardia A et al., NEJM. 2019;380:741-51.,Tagawa ST et al., Oral presentation; ASCO-GU 2019, San Francisco, CA. Clinical trial information: NCT03964727 .
Pathological Comparisons of Paraseptal and Centrilobular Emphysema in Chronic Obstructive Pulmonary Disease
Authors: Naoya Tanabe, Dragoş M. Vasilescu, Cameron J. Hague, Kohei Ikezoe, Darra T. Murphy, Miranda Kirby, Christopher S. Stevenson, Stijn E. Verleden, Bart M. Vanaudenaerde, Ghislaine Gayan-Ramirez, Wim Janssens, Harvey O. Coxson, Peter D. Paré, James C. Hogg
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

Rationale: Although centrilobular emphysema (CLE) and paraseptal emphysema (PSE) are commonly identified on multidetector computed tomography (MDCT), little is known about the pathology associated with PSE compared with that of CLE.Objectives: To assess the pathological differences between PSE and CLE in chronic obstructive pulmonary disease (COPD).Methods: Air-inflated frozen lung specimens (n = 6) obtained from patients with severe COPD treated by lung transplantation were scanned with MDCT. Frozen tissue cores were taken from central (n = 8) and peripheral (n = 8) regions of each lung, scanned with micro-computed tomography (microCT), and processed for histology. The core locations were registered to the MDCT, and a percentage of PSE or CLE was assigned by radiologists to each of the regions. MicroCT scans were used to measure number and structural change of terminal bronchioles. Furthermore, microCT-based volume fractions of CLE and PSE allowed classifying cores into mild emphysema, CLE-dominant, and PSE-dominant.Measurements and Main Results: The percentages of PSE measured on MDCT and microCT were positively associated (P = 0.015). The number of terminal bronchioles per milliliter of lung and cross-sectional lumen area were significantly lower and wall area percentage was significantly higher in CLE-dominant regions compared with mild emphysema and PSE-dominant regions (all P < 0.05), whereas no difference was found between PSE-dominant and mild emphysema samples (all P > 0.5). Immunohistochemistry showed significantly higher infiltration of neutrophils (P = 0.002), but not of macrophages, CD4, CD8, or B cells, in PSE compared with CLE regions.Conclusions: The terminal bronchioles are relatively preserved, whereas neutrophilic inflammation is increased in PSE-dominant regions compared with CLE-dominant regions in patients with COPD.
Artificial intelligence to accurately identify breast cancer patients with a pathologic complete response for omission of surgery after neoadjuvant systemic therapy: An international multicenter analysis.
Authors: André Pfob, Chris Sidey-Gibbons, Marios Konstantinos Tasoulis, Han-Byoel Lee, Vivian Koelbel, Henry Mark Kuerer, Joerg Heil
Journal: Journal of Clinical Oncology (2020)

565 Background: Neoadjuvant systemic treatment elicits a pathologic complete response (pCR) in up to 80% of women with breast cancer. In such cases, breast surgery, the gold standard for confirming pCR in the breast, may be considered overtreatment. So far, no approach alone – e.g. imaging, vacuum-assisted biopsy (VAB) – has accurately detected and excluded residual disease without surgery in multicenter prospective trials. We evaluated the ability of Artificial Intelligence algorithms to securely identify patients with residual tumor in the breast to safely select patients who might be spared from surgery. Methods: We collected multicenter, international data from 570 women who were included in prospective trials with initial stage I-III breast cancer of all biological subtypes and at least partial response on imaging, undergoing VAB before guideline-adherent surgery. We trained an ensemble of algorithms (including Regularized Regression, Support Vector Machines, and Neural Network) using 27 patient, tumor and VAB variables. Data were randomly partitioned into training and test sample with a 3:1 ratio and developed with 10-fold cross-validation. Primary endpoint was the sensitivity to diagnose residual disease by algorithm compared to surgery. Diagnostic performance of the algorithm was further evaluated on an external, independent dataset. Results: The algorithm was able to reliably identify women with residual disease before surgery (see table): Sensitivity for the internal test set was 96.9% (94 of 97; 95%CI 91.2-99.4%) and for the external, independent dataset 96.2% (26 of 27; 95%CI 80.4-99.9%). Most informative predictor of residual disease were tumor cells diagnosed in the VAB specimen, DCIS in the initial diagnostic biopsy, grading, and largest diameter on imaging after neoadjuvant treatment. Conclusions: Safely selected patients without residual disease as assessed by our algorithm may be spared by breast surgery in future trials. [Table: see text]
A chemogenomic approach to identify personalized therapy for patients with relapse or refractory acute myeloid leukemia: results of a prospective feasibility study
Authors: A. Collignon, M. A. Hospital, C. Montersino, F. Courtier, A. Charbonnier, C. Saillard, E. D’Incan, B. Mohty, A. Guille, J. Adelaïde, N. Carbuccia, S. Garnier, M. J. Mozziconacci, C. Zemmour, J. Pakradouni, A. Restouin, R. Castellano, M. Chaffanet, D. Birnbaum, Y. Collette, N. Vey
Journal: Blood Cancer Journal (2020)

Targeted next-generation sequencing (tNGS) and ex vivo drug sensitivity/resistance profiling (DSRP) have laid foundations defining the functional genomic landscape of acute myeloid leukemia (AML) and premises of personalized medicine to guide treatment options for patients with aggressive and/or chemorefractory hematological malignancies. Here, we have assessed the feasibility of a tailored treatment strategy (TTS) guided by systematic parallel ex vivo DSRP and tNGS for patients with relapsed/refractory AML (number NCT02619071). A TTS issued by an institutional personalized committee could be achieved for 47/55 included patients (85%), 5 based on tNGS only, 6 on DSRP only, while 36 could be proposed on the basis of both, yielding more options and a better rationale. The TSS was available in <21 days for 28 patients (58.3%). On average, 3 to 4 potentially active drugs were selected per patient with only five patient samples being resistant to the entire drug panel. Seventeen patients received a TTS-guided treatment, resulting in four complete remissions, one partial remission, and five decreased peripheral blast counts. Our results show that chemogenomic combining tNGS with DSRP to determine a TTS is a promising approach to propose patient-specific treatment options within 21 days.
Emphysematous pyelonephritis: case report and literature review
Authors: Shao-zhong Xian, Bo Song
Journal: BMJ (2013)

To explore the diagnosis and treatment of emphysematous pyelonephritis so as to improve its diagnosis and reduce its mortality. The clinical data were retrospectively analyzed for 2 diabetic patients with emphysematous pyelonephritis. Their symptoms included high fever, chills and lumbago. Computed tomography (CT) scans were performed to reach a definite diagnosis of emphysematous pyelonephritis with gas within renal parenchyma and/or perirenal tissue. Both received intravenous antibiotics. One patient underwent open abscess drainage while another percutaneous puncture under ultrasonic guidance. Their conditions improved and healed. CT scan is an efficient imaging modality for early diagnosis. The combination of antibiotics and early drainage may offer a better outcome.


Key words: 
Emphysema; Pyelonephritis
治疗脑血管病常用中成药的合理使用
Authors: 张孟仁
Journal: BMJ (2009)

脑血管病是一组老年常见病,因其发病率、致残率和病死率高而给个人、家庭和社会带来巨大的精神压力和沉重的经济负担.随着我国人群预期寿命的延长和人口老龄化速度的加快,脑血管病发病率和患病率有逐年增高的趋势[1].中国目前共有500万脑血管病患者,每年约有160万例死于脑血管病,有新发患者250万左右.因此,脑血管病的治疗非常重要。