tbuckley/cabot-search huggingface dataset:
Ultrasound monitoring of cervical canal length combined with measurement of fibronectin in cervical secretion for predicting preterm delivery
Authors: Ji-hua Zhang, Xing-qin Wang, Hong Ma, Su-ping Zhang, Jing-wei Yang, Li Liu, Dong-xia Ma, Li-hong Yan
Journal: BMJ (2013)

The length of cervical canal was monitored by perineal ultrasonography in 377 pregnant women with 22 to 36 weeks of gestation, at the same time the contents of fibronectin (fFN) in cervical secretions were measured. The rate of cervical canal length shortening from the time of first visit to the appearance of preterm signs was calculated. When the cervical length shortening rate was 16%~60%, fFN (+) was correlated with higher preterm birth rate (P  60% there was no significant difference in preterm delivery rate between fFN (+) and fFN (-) groups (P>0.05). The results indicate that the monitoring of cervical canal length combined with fiberonectin measurement in cervical secretion may better predict preterm birth.


Key words: 
Fibrin; Preterm birth
Pharmacodynamic, safety, and efficacy results of a phase I/II trial of intratumoral INT230-6 alone (IT-01) or in combination with pembrolizumab (PEM) (Keynote A10) in patients with advanced solid tumors.
Authors: Jacob Stephen Thomas, Anthony B. El-Khoueiry, Ian B. Walters, Nilofer Saba Azad, Lewis H. Bender, Diana L. Hanna, Giles Francis Whalen, Anthony J. Olszanski, Lillian L. Siu
Journal: Journal of Clinical Oncology (2020)

3016 Background: INT230-6 is comprised of cisplatin (CIS), vinblastine (VIN) and an amphiphilic penetration enhancer which facilitates dispersion throughout tumors and diffusion into cancer cells when given IT. Preclinical experiments show strong synergy with a PD1 antibody. Methods: Solid tumors pts that progressed on standard treatment were enrolled. INT230-6 dose was set by tumor volume, injected Q2weeks x 5. Escalation occurred by increasing number of tumors injected, loading per tumor, and total dose. In another arm, PEM (200mg IV Q3weeks) was combined with INT230-6. Patients were monitored for safety weekly while on INT230-6. Blood and tumors were assessed for PK and PD. Results: 46 pts (17 unique cancer types) were enrolled in the monotherapy arm and 4 pts in the PEM combo arm with a median of 3 prior treatments. Doses from 0.3 ml up to-160 ml of INT230-6 (80 mg CIS and 16mg of VIN) were injected. PK results indicate 95% of the drugs are retained in the tumor when compared to historical IV dosing. No dose limiting toxicity was reported. Two pts experienced drug-related SAE’s of tumor pain. The most frequent treatment-related AEs were: pain at injected site (48%), fatigue (40%) and nausea (33%). Most AE’s were grade 1 and 2, 17% were grade 3, and none ≥ grade 4. Several injected and non-injected tumors had &gt; 30% decreases in diameter. Assessments revealed substantial reductions in tumor volume ( &gt; 50%). Stable pts had a median increase of 50% in circulating CD4 and CD8 T-cells, while PD subjects showed decreases in circulating T-cells (p &lt; 0.05). Dose-response suggests that monotherapy subjects receiving &gt; 50% of tumors injected at dose/tumor volume ratio of &gt; 1:4 (target dosing), predicts for prolonged SD with 88%(7/8) having SD ≥ 4mo, correlating with reduced tumor viability on IHC, and increase in tumor-infiltrating lymphocytes (TIL’s). Conclusions: Proof of concept was demonstrated that INT230-6 delivers high drug doses into the tumor without systemic exposure and typical cytotoxic AEs. Systemic and local immune activation was observed. INT230-6 was safe and well tolerated in &gt; 175 deep tumor injections with tumor burden reduction in injected and non-injected tumors (an abscopal effect). Patients who received target dosing often had prolonged disease control post treatment. Updated safety, response and biomarker data from the monotherapy and PEM combo arm will be presented. Clinical trial information: 03058289 .
Naloxegol for patients with cancer pain diagnosed with opioid induced constipation (OIC): NACASY observational study.
Authors: Andrew Davies, Jan Tack, Ana Fernandez, Jonathan Chambers, Juan Luis Sanz
Journal: Journal of Clinical Oncology (2020)

e19350 Background: Opioids have been the cornerstone of analgesic treatment for severe chronic pain. OIC is the most commonly reported adverse effect associated with opioids, and compromises patient satisfaction and adherence to analgesic treatment and also quality of life. Naloxegol is a PEGylated derivative of the µ-opioid receptor antagonist naloxone indicated for the treatment of opioid-induced constipation (OIC) in adult patients who have had an inadequate response to laxatives. This real-world (RW) study (NCT03638440) aims to evaluate safety and efficacy of Naloxegol in patients with cancer pain diagnosed with OIC. Methods: This is a single-arm, multinational, prospective, RW observational study in adult subjects receiving treatment with opioids for at least 4 weeks, diagnosed with OIC that receive naloxegol in routine clinical practice. This study will recruit patients from 25 European hospitals. Data for efficacy are collected through the patient's diary during a 4-week period. Results: One hundred fifty-two patients, median age 66 years, 54% women, have been included in this analysis. Main cancer locations were lung (26%), breast (21%), prostate (10%), pancreas (9%) and head and neck (9%), and 67% had metastasis, mainly in bone (37%). Most frequent opioid treatments were fentanyl (29%), oxycodone (22%), and morphine (15%). Most frequent previous laxatives were osmotic (61%) and stimulant (27%) laxatives. Over 109 patients with at least one BFI score available after baseline, change in BFI score was ≥12 points in 61% of patients and 33% had BFI score &lt;30 points after 4 weeks of treatment. There were statistically significant differences between baseline and final visit in BFI overall score as well as in the score of each of the three questions. Most common adverse reactions to naloxegol were abdominal pain (7.9%), diarrhea (2.6%), flatulence (1.3%) and nausea (1.3%), most of them grade 1-2. Eight patients had adverse reactions leading to study discontinuation: abdominal pain (5), diarrhea (2), intestinal perforation (1) and fatigue (1). Only one patient died due to an adverse reaction: intestinal perforation. Conclusions: Preliminary results show a promising efficacy of naloxegol in this RW treatment study. Toxicity profile was as expected. RW evidence seems to be a useful methodology to assess the real-life use of naloxegol and its efficacy in cancer patients.
Examination of binocular disparity information of normal vision children
Authors: Juanjuan Cheng, Guohong Zhao, Wei Lu, Li Yan
Journal: BMJ (2014)

To explore the binocular disparity information for children with a normal vision based on computer-assisted evaluation system. We examined the random dot zero-order disparity, line zero-order disparity, 2nd-order disparity and random dot motion parallax for 97 children with normal vision. And 94 children reached 100＂vision disparity both in random dot zero-order disparity and line zero-order disparity (pass rate of 96.9%); all 94 cases passed the 2nd-order disparity and random dot motion parallax. Thus children with a normal vision develop their stereopsis.


Key words: 
Vision disparity; Vision, binocular
The values of exercise rehabilitation treatment in patients with pulmonary embolism-deep vein thrombosis
Authors: 严文文, 王乐民
Journal: BMJ (2006)

近年来国际康复医学界进行了大量的研究及临床工作,科系统康复治疗逐步走上循证医学发展之路,科学的个体化运动康复治疗可显著地改善患者生活质量.已有一些临床对照试验及大规模前瞻性研究[1]证实了心肺病合并肺栓塞-深静脉血栓形成(pulmonary embolism-deep vein thrombosis,PE-DVT)患者的早期运动康复是安全、有益的,以心肺运动试验(cardiopulmonary exercise test,CPET)作为心脏和肺脏储备功能的运动康复评估及运动处方的标准,已写入2003年美国胸科协会(American Thoracic Society,ATS)及美国胸科医师协会(American College of Chest Physicians,ACCP)对CPET的阐述中[2]。
股浅静脉瓣窦包窄术治疗下肢原发性深静脉瓣膜功能不全136例
Authors: 李建军, 陈泽忠, 刘亚松, 刘小平, 梁发启
Journal: BMJ (2006)

下肢原发性深静脉瓣膜功能不全(primary deep venous insufficiency,PDVI)是引起下肢静脉倒流性疾病和浅静脉曲张的主要原因[1].自1997年4月至2002年10月山东宁阳第一人民医院应用自体大隐静脉行股浅静脉瓣窦包窄术治疗下肢PDVI患者136例,现报告如下。
Outcome analyses in patients with metastatic gastroenteropancreatic neuroendocrine tumors receiving peptide receptor radionuclide therapy with <sup>177</sup>Lu-DOTATATE – Impact of treatment order and combination on mortality.
Authors: Alexander Rheinhard Siebenhuener, Dominique Pretot, Valerie Treyer
Journal: Journal of Clinical Oncology (2020)

4606 Background: Neuroendocrine tumors of the gastroenteropancreatic tract present heterogeneous with several systemic treatment options in the advanced setting. PRRT with 177 Lu-DOTATATE targeting the SSTR-2 receptor of these tumors showed effective responses in the NETTER-1 trial in the short as well as long term follow-up of patients. The aim of our study was to determine the HRQoL and outcome of GEP-NET patients. Methods: 41 GEP-NET patients who received 177 Lu-DOTATATE (mean: 3 cycles) between 2012 and 2017 at University Hospital Zurich (USZ) were included in this retrospective analysis. HRQoL parameters (fatigue, insomnia, loss of appetite, abdominal pain, nausea, emesis, diarrhea, weight loss) were assessed before and after treatment. At least 3 weeks after the last PRRT cycle, data on blood parameters, HRQoL, and overall survival data were extracted from patient records. To determine factors influencing the success of PRRT therapy and survival, we recorded pre- and post-PRRT treatments (e.g. selective internal radiation therapy/SIRT, somatostatin analogue therapy/SSA, TKI or chemotherapy) and the time-point of PRRT in the therapeutic sequence was analyzed. Results: Baseline rates of HRQoL and ECOG performance status were assessed (baseline mean: ECOG 0). PRRT was well tolerated, with most patients reporting no significant deterioration in HRQoL after treatment. Blood parameters (hemoglobin, leucocyte and platelet counts, creatinine) and glomerular filtration rate were not significantly affected by PRRT therapy. The number of previous treatments did not influence survival after PRRT; neither did the length of the time period between first diagnosis and PRRT. Patients with a SIRT treatment prior to PRRT had an elevated mortality odds ratio of 4.083. If SIRT was applied to patients with a pancreatic tumor, the mortality odds ratio was 1.33 compared to patients without a pancreatic tumor. Post-PRRT SSA increased the odds for survival, with a mortality odds ratio of 2.33 for patients without SSA after PRRT. Conclusions: Patients with advanced GEP-NETs may benefit from PRRT with 177 Lu-DOTATATE, as this treatment appears to be well tolerated and does not significantly impair the HRQoL or symptom load. SIRT before PRRT seems to lower the chances of response and reduces survival instead using this sequence vice versa. This trend was also seen if SSA was not used after PRRT. But these trends have to be proven in prospective trials.
C反应蛋白水平与脑梗死的关系
Authors: 姜悦, 周敦荣
Journal: BMJ (2007)

对92例脑梗死患者进行神经功能缺损标准评分,测定发病后24 h内及3、7、14 d血清C反应蛋白(CRP)水平,观察脑梗死灶不同面积CRP变化,并以96例正常体检者为对照.脑梗死发病后24 h内CRP水平即升高并达到峰值,随着病情好转而逐渐下降;脑梗死患者血清CRP水平明显高于对照组(P＜0.05),其变化与梗死灶大小关系密切.提示血清CRP水平可作为临床评价脑梗死严重程度的生物学指标。
Family cancer patterns and variation by race and ethnicity among individuals with pathogenic variants in multi-gene cancer predisposition panels at a large urban comprehensive cancer center.
Authors: Sushma Tatineni, Kristen Purrington, Hadeel Assad, Nadine Abdallah, Meri Tarockoff, Malini Surapaneni, Nancie Petrucelli, Rachel Reagle, Michael S. Simon
Journal: Journal of Clinical Oncology (2020)

e13540 Background: The identification of pathogenic variants and variants of unknown significance (VUS) in multi-gene cancer predisposition testing raises new questions regarding cancer risk and management. We evaluated the personal and family cancer patterns and variation by race and ethnicity, among individuals positive for pathogenic variants in non-BRCA1/ 2 cancer predisposing genes. Methods: The Karmanos Cancer Institute (KCI) Cancer Genetics database was queried from May 13, 2013 through December 31, 2018. There were 3,544 unrelated individuals evaluated for hereditary cancer predisposition of whom 1,868 had 18-gene panel testing at 6 sites across Michigan. Data was collected on personal and family cancer history including ages at diagnosis utilizing a 3-generation pedigree, self-identified race and ethnicity and results of genetic testing. We describe the prevalence of pathogenic variants by proband cancer diagnosis, family history, race, and ethnicity. Results: The race/ethnic distribution of the tested cohort included 67.5% non-Hispanic White (NHW), 24.4% African American (AA), 2.1% Arab, 1.8% Ashkenazi Jewish (AJ), 1.0% Hispanic, and 3.4% other. The distribution of cancer diagnoses included 40.6% breast, 5.5% ovarian, 4.1% colon, 3.5% endometrial, 2.0% pancreas and 39.7% unaffected. Pathogenic variants were seen in 151 (8.1%) individuals and VUS in 309 (16.5%). The five most common pathogenic variants were CHEK2 (40), MUTYH (22), ATM (20), and PALB2 (18). The most common pathogenic variants by race and ethnicity were CHEK2 (NHW), RAD51C (AA), PALB2 (Arab), CHEK2, MSH6 (AJ), and none in Hispanics. Variants associated with the four most common cancer types were breast ( CHEK2 ), ovarian ( CHEK2, MUTYH, BRIP1), colon ( ATM), and endometrial ( MSH6, PALB2). Of 40 individuals with CHEK2 variants, 92.5% were NHW, and 34 (85%), 31 (78%), 10 (25%), 1 (2.5%) had family history of breast cancer, breast cancer before age 50, ovarian, and colon cancer, respectively. Of 20 with ATM variants, 95% were NHW, 13 had family history data and 10 (76.9%), 8 (61.5%), 2 (15.4%), 1 (7.7%) had family history of breast, breast cancer before age 50, ovarian, and colon cancer, respectively. Conclusions: Pathogenic variants seen using multigene panel testing differ by race, ethnicity and personal/family history of cancer. This data will inform genetic counseling strategies in regards to cancer risk and management. Data on additional genes updated through 2019 will be presented.
Comparative effectiveness of proton versus photon chemoradiotherapy for patients with private insurance.
Authors: Brian Christopher Baumann, Nandita Mitra, Joanna Harton, Ying Xiao, Andrzej Wojcieszynski, Peter Edward Gabriel, Haoyu Zhong, Huaizhi Geng, Abigail Doucette, Jenny J. Wei, Peter J. O'Dwyer, Justin E. Bekelman, James M. Metz
Journal: Journal of Clinical Oncology (2020)

7049 Background: Proton therapy may increase the tolerability/efficacy of concurrent chemoradiotherapy (CRT) but is controversial &amp; generally not covered by private insurers. There is little data on the comparative effectiveness (CE) of proton vs photon CRT among private insurance pts to guide payers on proton coverage policies. Methods: We conducted a CE study of adult non-metastatic cancer pts with private insurance treated with curative-intent proton vs photon CRT from 2011-2016 at Penn. The choice of radiation modality was heavily influenced by the insurer’s proton coverage policy. Data on adverse events (AEs) &amp; survival were gathered prospectively using standardized templates. Primary endpoint was 90-day AEs associated with unplanned hospitalizations (CTCAEv4 grade ≥3 AEs). Secondary endpoints included 90-day grade ≥2 AEs, decline in ECOG performance status (PS) during treatment, disease-free survival (DFS) &amp; overall survival (OS). Modified Poisson regression models with inverse propensity score weighting were used for adverse event outcomes. Weighted Cox proportional hazards models were used for survival outcomes. Propensity scores were estimated using an ensemble machine-learning approach. P&lt;0.01 was significant. Results: 920 pts were included (178 proton/742 photon), with H&amp;N(25 proton/296 photon); CNS(44/128); lung(41/120); upper GI(34/78) &amp; lower GI/GYN(34/120). Median age was 57. Race, comorbidity score, BMI, baseline AEs &amp; baseline PS were similar (p&gt;0.05 for all). 11.2% of proton pts had grade ≥3 AE’s vs 26.8% of photon pts. On propensity score weighted-analyses, proton CRT was associated with significantly lower relative risk (RR) of 90-day grade ≥3 AEs (RR 0.51, 95%CI 0.32-0.81, p&lt;0.01). 90-day grade ≥2 AE’s (RR 0.91, 95%CI 0.83-0.99, p=0.03); decline in PS (RR 0.85, 95%CI 0.70-1.04, p=0.11); DFS (HR 0.64, 95%CI 0.27-1.52, p=0.31) &amp; OS (HR 0.53, 95%CI 0.18-1.52, p=0.24) favored protons. Sensitivity analysis showed that a substantial imbalance in an unmeasured confounder would be needed to alter the significance of the primary outcome. Proton accepting insurance status was not associated with a difference in 90-day grade ≥3 AE’s (RR 1.02, 95%CI 0.95-1.10, p=0.54) for pts treated with photon CRT (608 with non-proton accepting insurance &amp; 134 with proton-accepting insurance). Conclusions: In adults with private insurance, proton CRT was associated with significantly reduced acute grade ≥3 AE’s with similar DFS &amp; OS. Proton-accepting insurance status was not associated with better health outcomes when adjusting for RT modality.
Bariatric Surgeons Should Operate on Patients With Obesity Who Are Receiving Dialysis
Authors: Melina R. Kibbe, David A. Gerber
Journal: JAMA Surgery (2020)

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Consistency between symptoms and colorectoanal function tests in elderly patients with functional constipation
Authors: Wenjuan Fan, Zhifeng Wang, Xiaoping Xie, Jin Wang, Shi Liu, Jun Zhang, Xiucai Fang
Journal: BMJ (2018)

Objective
To analyze the consistency between constipated symptoms and the parameters of gastrointestinal transit time (GITT), anorectal manometry (ARM) in elderly patients with functional constipation.


Methods
Total 111 patients (54 males and 57 females) with an average age of (70.2±6.5) years, who met Rome Ⅲ criteria of functional constipation were enrolled from June 2010 to October 2012. After enrollment, patients took two-week diary, recording the spontaneous bowel movements per week, stool type of Bristol Stool Form, the frequency and severity of defecation straining, sensation of anorectal obstruction, manual maneuvers and sensation of incomplete evacuation. The GITT and ARM tests were performed, and the consistency between symptoms and test results were analyzed.


Results
Patients with symptoms of slow transit, defecation disorder and mixed symptoms were 19.8% (22/111), 16.2% (18/111) and 59.5% (66/111) respectively; and 4.5% (5/111) patients had scattered symptoms. Based on results of GITT, slow transit subtype, defecation disorder subtype and mixed subtype were 54.1% (59/109), 1.8% (2/109) and 29.4% (32/109) respectively; and 14.7% (16/109) patients were with normal transit time. ARM results showed that 38.0% (41/109) of patients had dyssynergic defecation. The percentage of slow transit in GITT test showed no significant difference between patients with slow transit symptoms and mixed symptoms[50.0% (11/22) vs. 57.9% (33/57) , χ2=0.401, P=0.527]. The consistency of predominant symptom with GITT subtype was low (к=-0.013). The percentage of dyssynergic defecation detected with ARM showed no significant difference between patients with defecation disorder-predominant symptom and with mixed symptom [23.1% (6/24) vs. 38.2% (21/55) , χ2=1.813, P=0.178]. The consistency of defecation disorder-predominant symptom with dyssynergic defecation in ARM was low (к=-0.019).


Conclusion
The mixed subtype symptoms are the most common presentations of elderly patients with functional constipation, and the consistency of predominant constipated symptoms with GITT, ARM test results is poor.


Key words: 
Aged; Constipation; Gastrointestinal transit; Anorectal manometry
Using sequential next-generation sequencing assays to identify germline cancer predisposition variants.
Authors: Ira Lignugaris Kraft, Amy M. Trottier, George F. Steinhardt, Nifang Niu, Pankhuri Wanjari, Wenjun Chen, Jeremy Segal, Lucy A. Godley
Journal: Journal of Clinical Oncology (2020)

1581 Background: Next-generation sequencing (NGS) increasingly guides clinical care in hematological malignancies by identifying DNA mutations that change dynamically over time. Clinical samples contain variable numbers of malignant and non-malignant cells. So, careful interpretation is required to determine if a particular variant is somatic, germline, or clonal hematopoietic in origin. Methods: The University of Chicago uses a targeted NGS assay of ~1200 genes, reporting 150 as a clinical test. We aimed to identify individuals with hereditary predisposition by detecting persistent variants on sequential assays regardless of disease state. Results: 943 NGS assays from July 2017 – Feb. 2020 on 711 patients [ages 1 mo – 95 yrs, median 65 yrs] were included. 2,320 variants in 33 genes were identified with 144 patients having the same variant identified on more than one assay. Single nucleotide variants (SNVs) with variant allele frequency (VAF) ≥ 0.3 were prioritized. The first candidate gene identified with potential germline SNVs was CSF3R. 28 unique SNVs in CSF3R were found, 14 were confirmed as germline, 6 somatic, and 8 were unconfirmed due to lack of available tissue. At least 2 confirmed germline CSF3R variants were likely deleterious based on functional testing. Sequential SNVs were quantified using the coefficient of variation, characterizing each by change in VAF over time. Using a worst-case-scenario analysis, in which unconfirmed variants were not counted as germline, a computer algorithm was designed to identify potential germline variants (specificity 0.89, PPV 0.75). Via an iterative method, the algorithm compares new assays to a pool of previously reported tests, flagging patients with potential germline mutations so that biopsies may be studied in the lab, records reviewed, and referrals placed to genetic counselors. To date, 61 patients with 89 likely germline variants have been identified. Known hereditary hematological malignancy genes, such as ATM, ASXL1, CHEK2, DDX41, TSC1, and RUNX1, had the most variants identified. Limitations include the challenge in distinguishing variants that do not change over time, reliance on a targeted NGS panel, and normalizing VAF data prior to analysis. Conclusions: These data highlight the utility of NGS of bone marrow and peripheral blood samples to identify patients suspected of having germline DNA variants. In addition to identifying known predisposition syndromes, one may discover new inherited cancer syndromes and help guide clinical practice in real time.