tbuckley/cabot-search huggingface dataset:
Association of serum osteoprotegerin levels with bone mineral density and bone turnover markers in patients with hyperthyroidism before and after methimazole treatment
Authors: Shen-tian Wang, Liang Li, Chun-yuan Zhang, Wen Rong
Journal: BMJ (2011)

Serum bone alkaline phosphatase (BAP) , osteocalcin (OC) , C-telopeptides of type-1 collagen (CTx) , osteoprotegerin (OPG) levels, and bone mineral density (BMD) were evaluated in 62 hyperthyroid patients and 60 healthy subjects matched for sex and age. In hyperthyroid patients, the biochemical evaluations and bone density were performed before and after 6 months of methimazole ( MMI) treatment. Results showed that the BMD in lumbar spine L2 - L4, neck of femur, Ward's triangle and greater trochanter of patients before treatment were all significantly lower than those in healthy controls, and improved markedly after MMI treatment. The serum bone turnover parameters BAP, OC and CTx in patients before treatment were all significantly higher than those in control group, and were decreased markedly after treatment. The serum OPG level in patients with hyperthyroidism was significantly higher than that in healthy controls, and decreased markedly after treatment. The serum OPG levels were significantly correlated with bone turnover parameters ( BAP, OC, CTx) and BMD, which indicates that serum OPG level can reflect the abnormality of bone metabolism in patients with hyperthyroidism.

Key words: 
Hyperthyroidism;  Osteoprotegerin
Machine learning algorithms to predict financial toxicity associated with breast cancer treatment.
Authors: Chris Sidey-Gibbons, Malke Asaad, André Pfob, Stefanos Boukovalas, Yu-Li Lin, Anaeze Offodile
Journal: Journal of Clinical Oncology (2020)

2047 Background: Financial burden caused by cancer treatment is associated with material loss, distress, and poorer outcomes. Financial resources exist to support patients but objective identification of individuals in need is difficult. Accurate predictions of an individual’s risk of financial toxicity prior to initiation of breast cancer treatment may facilitate informed clinical decision making, reduce financial burden, and improve patient outcomes. Methods: We retrospectively surveyed 611 patients who had undergone breast cancer therapy at MD Anderson Cancer Center to assess the financial impact of their care. All patients were over 18 and received either a lumpectomy or a mastectomy. We collected data using the FACT-COST patient-reported outcome measures alongside other financial indicators including income and insurance status. We extracted clinical and perioperative data from the electronic health record. Missing data were imputed using multiple imputation. We used this data to train and validate a neural network, LASSO-regularized linear model, and support vector machines. Data were randomly partitioned into training and validation samples (3:1 ratio). Analyses were informed by international PROBAST recommendations for developing multivariate predictors. We combined algorithms into a voting ensemble and assessed predictive performance using area under the receiver operating characteristics curve (AUROC), accuracy, sensitivity, and specificity. Results: In our validation sample, 48 of 203 (23.6%) women reported FACT-COST scores commensurate with significant financial burden. The algorithm predicted significant financial burden relating to cancer treatment with high accuracy (Accuracy = .83, AUROC = .82, sensitivity = .81, specificity = .82). Key clinical predictors of financial burden from linear models were neo-adjuvant therapy (β regularized 0.12) and autologous, rather than implant-based, reconstruction (β regularized 0.10). Conclusions: Machine learning models were able to accurately predict the occurrence of financial toxicity related to breast cancer treatment. These predictions may be used to inform decision making and care planning to avoid financial distress during cancer treatment or to enable targeted financial support for individuals. Further research is warranted to further improve this tool and assess applicability for other types of cancer.
Clinical outcomes and markers of treatment response in a randomized phase II study of androgen deprivation therapy with or without palbociclib in RB-intact metastatic hormone-sensitive prostate cancer (mHSPC).
Authors: Phillip Lee Palmbos, Scott A. Tomlins, Stephanie Daignault, Neeraj Agarwal, Przemyslaw Twardowski, Alicia K. Morgans, William Kevin Kelly, Vivek Arora, Emmanuel S. Antonarakis, Javed Siddiqui, Dan Robinson, Karen E. Knudsen, Arul Chinnaiyan, Maha H. A. Hussain
Journal: Journal of Clinical Oncology (2020)

5573 Background: Targeted therapies based on tumor molecular markers are not currently used in mHSPC. Palbociclib, a CDK4/6 inhibitor, blocked proliferation and promoted G1 arrest in a Rb-and Cyclin D-dependent manner in preclinical models of HSPC. We hypothesized that co-targeting AR (ADT) and cell cycle (palbociclib) would improve outcomes in mHSPC pts. Methods: mHSPC pts with Rb intact tumors based on IHC of metastatic tumor biopsy were stratified and randomized (1:2) to Arm A: ADT or Arm B: ADT+ palbociclib (125mg 3 weeks on, 1 week off). Primary endpoint was confirmed PSA RR (≤ 4 ng/mL) after 28 weeks of therapy. Secondary endpoints included safety/tolerability, PFS, PSA and radiographic RR. Metastatic biopsy and primary tumors were subjected to whole exome and transcriptomic sequencing where available. CTC’s were enumerated at various time points. Results: 72 eligible pts (median age 67 years, PSA 73ng/mL) with newly diagnosed mHSPC were registered and underwent biopsy. 97% retained RB expression (IHC). 62 pts were stratified by disease extent and early initiation of ADT, and randomized. 60 pts initiated therapy (Arm A: 20; Arm B: 40). Adverse events were reported previously. 80% of pts (Arm A: 16/20, Arm B: 32/40; p = 0.87) on both arms met primary PSA endpoint (≤4ng/mL at 28 weeks). PSA undetectable rate at 28 weeks was Arm A: 50% (10/20) and Arm B: 43% (17/40; p = 0.5). Measurable disease RR: Arm A: 89% and Arm B: 89%. 12-month biochemical PFS was Arm A 69% (95%CI: 44-85%), Arm B 74% (95%CI: 57-85%). 41 patients on trial underwent sequencing of metastatic biopsy and 10 patients had matched primary prostate tumor sequencing results. CCND1 amp, 8q gain, PTEN and KMT2C mutations were each observed in metastatic, but not paired prostate primary tumors. TP53, PIK3 pathway (PIK3CA, AKT1, PTEN) mutations and 8q gains were associated with reduced PSA PFS [HR (95%CI): 3.0 (1.2-7.2), p = 0.018; 3.2(1.03-10),p = 0.044; 4.96 (1.8-12), p = 0.001, respectively]. Pretreatment CTCs were associated with lower PSA CR (p = 0.04) and shorter PFS (12-month PFS: 58% vs. 86%, p = 0.031). Conclusions: A tissue based biomarker preselected trial is feasible in mHSPC. ADT + palbociclib did not impact outcomes. Pretreatment CTC counts, TP53 and PIK3 pathway mutations, and 8q gain may offer prognostic value in mHSPC. Support: Movember-PCF Challenge Award, Pfizer. Clinical trial information: NCT02059213 .
The clinical impact of MicroRNA-21 in low rectal cancers treated with curative radiotherapy in the organ preserving setting.
Authors: Torben Hansen, Caroline Brenner Thomsen, Rikke Fredslund Andersen, Lars Henrik Jensen, Anders Kristian Moeller Jakobsen
Journal: Journal of Clinical Oncology (2020)

e16120 Background: Neoadjuvant chemoradiotherapy (CRT) in curatively intended doses may result in clinical complete response (cCR) in selected patients, allowing for non-surgical management (NSM) of patients with low rectal cancers. MicroRNA-21-5p (miR-21), ubiquitous upregulated in cancer, has been associated with treatment response in rectal cancers treated with standard preoperative CRT. The aim of the present study was to investigate this association in low rectal cancers treated in the NSM setting. Methods: Forty eight patients from our single-arm phase II trial (NCT00952926) were available for analyses. All patients had resectable, T2 or T3, N0–N1, low adenocarcinomas and received 65Gy (intensity-modulated radiotherapy plus brachytherapy boost) and oral tegafur-uracil. Patients with cCR 6 weeks after treatment (clinical examination, magnetic-resonance imaging and biopsy) were referred to observation and followed closely. The miR expression, in the diagnostic biopsies, was measured by qPCR in 20 µl reactions using TaqMan MicroRNA Assays. The protocol using custom RT and preamplification pools was followed. The miR-193a-5p, -27a and –let7g were used for normalization based on previous recommendations from our group. The relationship between miR-21 expression and cCR was assessed using the Wilcoxon rank-sum tests. Results: Thirty-eight patients achieved cCR after treatment and were followed in observation while 10 patients proceeded to surgery due to a non-cCR. MicroRNA-21 was successfully analyzed in all samples. The median tumor expression of miR-21 in patients proceeding to surgery was significantly higher compared to patients achieving cCR, 24.3 (95% confidence interval (CI) 17.1-36.8) and 16.6 (95% CI 13.9-21.1), p = 0.02, respectively. Conclusions: The present results support a clinical impact of miR-21 in rectal cancer treated with CRT, comparable with results seen in patients treated in the standard preoperative setting, and may assist in the selection of patients for an organ preserving approach.
Results of surgical skill assessment in general practitioners in Beijing
Authors: Ya-jun Wang, Hua Kang, Zhi Qiu, Jia-ling Niu
Journal: BMJ (2010)

Nine hundred and forty nine general physicians in Beijing urban area received surgical skill assessment in 2008.The assessment results of five surgical skills (taking out stitches,changing dressings,skin suture,knot with gloves and wearing isolation gown) were analyzed with the relations of different gender,age,educational background,professional title,specialty,hospital grade,length of service and times of test taking.The average score of the total assessment was 71.The score was lower in the practitioners who were male,older than 50 years,higher educational background,lower professional tide,more than 2 times of test taking,and who were specialized in traditional Chinese medicine,ophthalmology and otorhinolaryngology and emergency medicine.Results suggest that the levels of surgical skills in general practitioners are generally low and periodical training is needed.

Key words: 
Surgical procedures;  Community health services
Using digital-image analysis of tumor-infiltrating lymphocytes to predict survival outcomes in primary melanoma.
Authors: Margaret Chou, Irineu Illa-Bochaca, Ben Minxi, Keith M. Giles, Farbod Darvishian, George Jour, Una Moran, Richard L. Shapiro, Russell S. Berman, Iman Osman, Hua Zhong
Journal: Journal of Clinical Oncology (2020)

10066 Background: Inclusion of tumor-infiltrating lymphocytes (TIL) into AJCC staging criteria has been proposed due to evidence suggesting its prognostic significance. However, subjective inter-observer discordance prevents adoption of semi-quantitative TIL grading (e.g. absent, non-brisk, brisk) into clinical practice. We hypothesize that digital-image analysis (DIA) of TIL can provide a standardized, quantitative scoring system that more accurately predicts survival compared to currently used semi-quantitative grading methods. Methods: Clinical data and tumor specimens were analyzed from prospectively enrolled primary melanoma patients in the New York University Interdisciplinary Melanoma Cooperative Group with median follow-up of 5 years. H&amp;E-stained slides were digitized using an Aperio ScanScope at 20X magnification. QuPath software was used for automated TIL quantification. Cox regression analysis was used to assess the improved prognostic value of TIL on recurrence-free (RFS) and overall survival (OS). Patients were separated into high- and low-TIL groups using a score threshold determined by the Youden Index. Results: 453 patients (18% stage I, 42% stage II, 40% stage III) were scored using automated TIL assessment and scores were significantly correlated with better RFS and OS per 10% increase in TIL (stage adjusted hazard ratio [aHR] = 0.92 [0.84-1.00] for RFS and aHR = 0.90 [0.83-0.99] for OS). A model combining TIL score with stage increased prognostic ability for both RFS (0.68 to 0.70, P = 0.02) and OS (0.62 to 0.64, P = 0.01), as assessed by concordance indices (C-index). Kaplan-Meier curves of high- ( &gt; 16.6%) versus low-TIL (≤16.6%) patients showed clear separation in RFS and OS (median RFS = 155 vs 48 months, P &lt; 0.001; median OS = 155 vs 89 months, P = 0.002). For comparison, a subset of the cohort (n = 250) was semi-quantitatively graded (absent, non-brisk, brisk) by an attending melanoma pathologist; however, this did not significantly differentiate RFS between groups (P &gt; 0.05). Conclusions: A standardized, quantitative TIL scoring system significantly improved prediction of RFS and OS in primary melanoma patients compared with semi-quantitative TIL grading. Incorporation of quantitative TIL scoring into prognostic algorithms, such as AJCC criteria, should be considered.
Granularity of <i>SERPINA1</i> alleles by DNA sequencing in CanCOLD
Authors: Nisha Gupta, Nathalie Gaudreault, Sébastien Thériault, Pei Zhi Li, Cyndi Henry, Miranda Kirby, François Maltais, Wan Tan, Jean Bourbeau, Yohan Bossé
Journal: European Respiratory Journal (2020)

DNA sequencing of the SERPINA1 gene to detect α 1 -antitrypsin (AAT) deficiency (AATD) may provide a better appreciation of the individual and cumulative impact of genetic variants on AAT serum levels and COPD phenotypes. AAT serum level and DNA sequencing of the coding regions of SERPINA1 were performed in 1359 participants of the Canadian Cohort Obstructive Lung Disease (CanCOLD) study. Clinical assessment for COPD included questionnaires, pulmonary function testing and computed tomography (CT) imaging. Phenotypes were tested for association with SERPINA1 genotypes collated into four groups: normal (MM), mild (MS and MI), intermediate (heterozygote MZ, non-S/non-Z/non-I, compound IS, and homozygote SS) and severe (ZZ and SZ) deficiency. Smoking strata and MZ-only analyses were also performed. 34 genetic variants were identified including 25 missense mutations. Overall, 8.1% of alleles in this Canadian cohort were deficient and 15.5% of 1359 individuals were carriers of at least one deficient allele. Four AATD subjects were identified and had statistically lower diffusion capacity and greater CT-based emphysema. No COPD phenotypes were associated with mild and intermediate AATD in the overall cohort or stratified by smoking status. MZ heterozygotes had similar CT-based emphysema, but lowered diffusion capacity compared with normal and mild deficiency. In this Canadian population-based cohort, comprehensive genetic testing for AATD reveals a variety of deficient alleles affecting 15.5% of subjects. COPD phenotype was demonstrated in severe deficiency and MZ heterozygotes. This study shows the feasibility of implementing a diagnostic test for AATD using DNA sequencing in a large cohort.
International Classification of Diseases (ICD)-based diagnosis of retinal detachment and surgical modalities of vitrectomy
Authors: Weihong Li, Lili Zhao
Journal: BMJ (2015)

Objective
To diagnose retinal detachment with International Classification of Diseases-10 (ICD-10) and to analyze the surgical modalities of vitrectomy for the disease.


Methods
The clinical data of 1 648 hospitalized patients with retinal detachment undergoing vitrectomy in our hospital in 2013 were retrospectively analyzed.


Results
The ICD etiological classification showed that primary retinal detachment accounted for 50.18% (827/1 648), tractional retinal detachment accounted for 32.52% (536/1 648), exudative retinal detachment accounted for 0.61%(10/1 648)and other types accounted for 16.69% (275/1 648). The top 5 common etiological diagnoses were simple rhegmatogenous retinal detachment (25.73%, 424/1 648), diabetic tractional retinal detachment (12.62%, 208/1 648), traumatic retinal detachment (12.08%, 199/1 648), other primary retinal detachment (11.23%, 185/1 648) and retinal detachment after intraocular surgery (10.62%, 175/1 648). The top 4 modalities of vitrectomy were combined silicone oil implanting surgery (54.73%, 902/1 648), basic vitrectomy (21.97%, 362/1 648), combined silicone oil and lenticular surgery (14.38%, 237/1 648) and combined lenticular surgery (5.58%, 92/1 648).


Conclusions
Modern vitrectomy is used mainly for the treatment of primary retinal detachment and the treatment of retinal detachment related to diabetes, ocular trauma and intraocular surgeries.The complexity of various retinal detachment diseases requires different surgical modalities of vitrectomy for treatment.


Key words: 
Vitrectomy; Retinal detachment; International Classification of Diseases
Preclinical evaluation of XPO1 inhibition in Wilms tumors.
Authors: Michael Vincent Ortiz, Armaan Siddiquee, Daoqi You, Prabhjot Singh Mundi, Lianna Marks, Kristina Guillan, Daniel Diolaiti, Mahalaxmi Aburi, Andrea Califano, Filemon S. Dela Cruz, Andrew Kung
Journal: Journal of Clinical Oncology (2020)

3580 Background: XPO1 is a nuclear export protein that selectively transports tumor and growth regulatory proteins out of the nucleus, thereby effectively inhibiting their function. We previously utilized the Virtual Inference of Protein-activity by Enriched Regulon analysis (VIPER) algorithm to discover that malignant rhabdoid tumors were dependent upon XPO1 inhibition and then evaluated a preclinical cohort using selinexor (KPT-330), the first-in-class selective inhibitor of nuclear export, to demonstrate that XPO1 inhibition was sufficient to cause cell cycle arrest, apoptosis, and disease control in multiple cell line and patient derived xenograft (PDXs) models. Our subsequent analysis revealed that the most common childhood kidney tumor, Wilms tumor, has even high higher inferred activity of XPO1 than rhabdoid tumors leading to our hypothesis that XPO1 inhibition is an effective therapeutic strategy to treat Wilms tumors. Methods: A panel of 9 Wilms tumor cell lines and 3 Wilms tumor PDXs were genomically characterized and tested to evaluate the pre-clinical efficacy of XPO1 inhibition in Wilms tumors. Results: Proliferation rate, increased XPO1 protein expression, and loss of function mutations in TP53 correlated with in vitro Wilms tumor cell line sensitivity to selinexor. Evaluation of co-segregation of all single nucleotide variant changes using with inferred activity of XPO1 on VIPER in all TGCA tumors demonstrates a strong association with TP53 alterations. XPO1 inhibition was effective in all Wilms tumor models tested, most significantly in MSKREN-57196, a favorable histology Wilms tumor PDX with somatic 1q gain as well as WTX and MYCN mutations, as well as in MSKREN-31827, a diffusely anaplastic TP53 mutant Wilms tumor PDX. Eltanexor (KPT-8602) is an XPO1 inhibitor with decreased CNS penetration and an improved toxicity profile; this drug was tested in these in vivo models and found to be at least as effective as selinexor. Conclusions: Somatic 1q gain in favorable histology Wilms tumors and TP53 mutations in diffusely anaplastic Wilms tumors have a particularly poor prognosis in the relapsed setting. Our study demonstrates that XPO1 inhibition may provide a rational therapeutic option to treat such high-risk Wilms tumors. Future clinical trials evaluating XPO1 inhibitors should evaluate its efficacy in children with relapsed Wilms tumors.
Abnormal glucose metabolism in subjects with high-risk for diabetes and analysis for its risk factors in Changfeng community, Shanghai
Authors: 江孙芳, 高鑫, 盛建华, 陈旭昇, 吴琳, 李湘, 张斌, 赵耐青
Journal: BMJ (2007)

目的 了解社区糖尿病高危人群中糖代谢异常情况及相关危险因素.方法 对40～80岁符合糖尿病高危人群招募条件的1197位上海市长风社区居民,进行问卷调查、体检和生化检测,确定是否有糖尿病高危因素.同时予75 g口服葡萄糖耐量试验.结果 根据检测结果,982人符合糖尿病高危人群定义(高危组),215人不符合糖尿病高危人群定义(非高危组).高危组中糖代谢异常占47.9%(470/982),新诊断糖尿病占11.5%(113/982),糖调节受损占36.4%(357/982),其中单纯空腹血糖受损(IFG)占14.8%(145/982),单纯糖耐量异常(IGT)占10.7%(105/982),IFG合并IGT占10.9%(107/982),明显高于非高危组[分别为17.2%(37/215),0.9%(2/215),16.3%(35/215),9.3%(20/215),5.1%(11/215),1.9%(4/215)](P均＜0.05).Logistic回归分析显示,年龄、糖尿病家族史、体重指数、收缩压、甘油三酯与糖代谢异常呈正相关,高密度脂蛋白胆固醇与糖代谢异常呈负相关.结论 采用糖尿病高危人群筛查模式能提高糖代谢异常的筛查效率.增龄、糖尿病家族史、超重或肥胖、高血压、脂代谢紊乱是糖代谢异常的主要危险因素。
Application of bronchoscopy in the therapy of pediatric status asthmaticus
Authors: Yun-gang Yang, You-fen Chen
Journal: BMJ (2013)

Objective
To explore the therapeutic value of bronchoscopy in pediatric status asthmaticus.


Methods
A total of 16 children with status asthmaticus received standard medical therapies (therapy group) from January 2008 to August 2010 in pediatric intensive care unit (PICU) at First Hospital, Xiamen University. However, 10 of them underwent fiberoptic bronchoscopy and bronchoalveolar lavage (BAL) (bronchoscopy group) along with standard medical therapies from September 2010 to July 2012. The values of oxygenation index (PaO2/FiO2), arterial partial pressure of carbon dioxide (PaCO2), blood oxygen saturation (SaO2), heart rate (HR), respiratory rate (RR) within 1 hour before bronchoscopy procedure, within 6 hour post procedure and within 24 hour post procedure were observed. The extinction time of wheezing sound, PICU length of stay and admission length of stay were observed between therapy and bronchoscopy groups.


Results
Bronchoscopies revealed a lot of thick mucus plugs and secretions. Large airways were lavaged for clearance of obstructive secretions with normal saline. Within BAL fluid counts of the bronchoscopy group, there were neutrophilia (n=8), eosinophilia (n=4) and neutrophilia/eosinophilia (n=3). Within BAL fluid cultivation of the bronchoscopy group, 4 patients had positive results for Streptococcus pneumoniae (n=2), Pseudomonas aeruginosa (n=1) and Staphylococcus aureus (n=1). In bronchoscopy group, the values of PaO2/FiO2, PaCO2, SaO2, HR and RR were 319±19,(40±4) mm Hg (1 mm Hg=0.133 kPa), (92.6±1.5)%, (128±12) rates/min and (35±4) breaths/min within 6 hour post procedure versus 255±24, (54±5) mm Hg, (89.2±2.6)%, (148±10) rates/min and (50±6) breaths/min within 1 hour before procedure (P<0.01). At 24 hour post procedure, the values of PaO2/FiO2, PaCO2, SaO2, HR, RR for bronchoscopy group were 354±21,(40±3) mm Hg, (93.4±1.1)%, (125±9) rates/min and (34±3) breaths/min versus 317±21, (46±4) mm Hg, (90.1±2.5)%, (138±8) rates/min and (43±3) breaths/min respectively for therapy group (P<0.01). The extinction time of wheezing sound was (67±22) hours for bronchoscopy group vs. (98±23) hours for therapy group (P<0.01). The mean PICU length of stay was (1.6±0.7) days for bronchoscopy group vs. (2.6±0.7) days for therapy group (P<0.01). The mean admission length of stay was (5.0±0.7) days for bronchoscopy group vs. (6.6±1.2) days for therapy group (P<0.01). All patients for bronchoscopy group tolerated the procedure without any complications.


Conclusion
As a safe adjunctive therapy in pediatric status asthmaticus, flexible bronchoscopy with bronchial lavage may reduce the admission and PICU length of stay and alleviate clinical symptoms.


Key words: 
Status asthmaticus; Bronchoscopy; Bronchoalveolar lavage
2型糖尿病患者正常血清γ-谷氨酰转移酶与代谢综合征相关性研究
Authors: 刘佳, 朱梦瑜, 张雅静, 姜春艳, 温寅林, 张宏
Journal: BMJ (2011)

血清γ-谷氨酰转移酶(gamma-glutamyltransferase，GGT)是代谢综合征的预测因子，可预测非糖尿病人群代谢综合征的发生[1]，而对于糖尿病人群的研究较少。本研究回顾分析2008至2010年我院收住的血清GGT正常2型糖尿病患者253例（排除肝病及有大量饮酒史者）临床资料，探讨2型糖尿病患者血清GGT与代谢综合征的相关性。 关键词：γ-谷氨酰转移酶