tbuckley/cabot-search huggingface dataset:
Incidence of COVID-19 in Pediatric Surgical Patients Among 3 US Children’s Hospitals
Authors: Elaina E. Lin, Todd J. Blumberg, Adam C. Adler, Faris Z. Fazal, Divya Talwar, Kyle Ellingsen, Apurva S. Shah
Journal: JAMA Surgery (2020)

Incidence of COVID-19 in Pediatric Surgical Patients Among 3 US Children's HospitalsThe coronavirus disease 2019 (COVID-19) pandemic continues to spread, with more than 4.6 million confirmed cases worldwide as of May 19, 2020.Children appear less susceptible, with the Chinese Center for Disease Control and Prevention reporting that children constitute only 2.16% of confirmed cases. 1 This may underestimate the true incidence of COVID-19 in children.Children are more likely to be asymptomatic or mildly symptomatic and thus less likely to be tested.The purpose of this study was to determine the incidence of COVID-19 in pediatric patients presenting for surgery at 3 tertiary care children's hospitals across the United States.Methods | After universal preoperative screening for COVID-19 was instituted at the Children's Hospital of Philadelphia in Philadelphia, Pennsylvania, Texas Children's Hospital in Houston, and Seattle Children's Hospital in Seattle, Washington, all children younger than 19 years without known COVID-19 were tested.Data collection across all 3 hospitals began March 26, 2020, and ended April 22, 2020.All 3 hospitals use an in-house laboratory-developed reverse transcriptasepolymerase chain reaction assay to detect the severe acuteTable 1.Demographics and Preoperative RT-PCR Result Stratified by Hospital Characteristic
Use and outcomes in men with metastatic castration-sensitive prostate cancer (mCSPC) treated with docetaxel in addition to androgen deprivation therapy (ADT): Analysis of real-world data in the United States (US).
Authors: Neeraj Agarwal, Suneel Mundle, Lindsay Dearden, Ravi C. Potluri, Sandhya Nair, Maneesha Mehra
Journal: Journal of Clinical Oncology (2020)

e19322 Background: mCSPC patients treated with docetaxel + androgen deprivation therapy (D+ADT) demonstrate increased overall survival (OS) 1,2 . However, limited real-world outcome data is available for such patients. This study assesses the real-world use and outcomes with D+ADT in mCSPC in the US. Methods: Adult (≥18 years old) men with mCSPC (defined as men with metastasis at index diagnosis of prostate cancer [de novo] or those who progressed to mCSPC after prior diagnosis of localized disease) were retrospectively identified from the Optum (2007–2018) and SEER Medicare (2007–2016) databases. Men diagnosed with mCSPC in or after 2014 with exposure to docetaxel and no brain metastasis were included for analysis. Patients were characterized based on age; baseline prostate specific antigen (PSA) level; administration of ADT; prior radiotherapy (RT); prior radical prostatectomy (RP); presence of visceral disease, bone or bone + visceral metastases; and treatment duration of docetaxel. OS and time to metastatic castration-resistant prostate cancer (mCRPC) were measured. Results: Among 4959 men identified with mCSPC during or after 2014, 192 (3.8%) received D+ADT ± Bicalutamide as first line systemic therapy. Baseline characteristics are presented in the Table below. Mean ± SD duration of docetaxel exposure was 115 ± 84.2 days (median 118 days). Median OS among these men was 30.5 (28.1, 36.7) months and median time to mCRPC was 18.3 (14.5, 24.6) months. Only 9% of men received docetaxel for ≥6 cycles (180 days); median OS in these men was NR (19.1- NR) with 74% surviving at 2 years compared to 65% surviving at 2 years in those with docetaxel duration &lt;6 cycles. Conclusions: Use of docetaxel in the real-world mCSPC patient population in the US is limited. Majority of men received less than the recommended dose of 6 cycles. OS with D+ADT in real-world patients with mCSPC appears to be lower than the OS reported in published trials. References:1) Sweeney CJ, et al. N Engl J Med. 2015;373:737–46. 2) James ND, et al. Lancet. 2016;387:1163–77. Funding: Janssen Research &amp; Development, LLC. [Table: see text]
The prevalence of HLA LOH across 10 cancer types in Chinese patients.
Authors: Jian'An Huang, Jie Hu, Xiaorui Fu, Xiuqing Zhang, Fan Tong, Xinhua Du, Ziwen Luo, Yuting Yi, Yan-Fang Guan, Xuefeng Xia
Journal: Journal of Clinical Oncology (2020)

3124 Background: Recognition of tumor neoantigen is the key to generating immune response. The expression and integrity of human leukocyte antigen (HLA) are the prerequisites for neoantigen presentation, and loss of heterozygosity in HLA (HLA LOH) may facilitate immune evasion. However, the incidence of HLA LOH in Chinese cancer patients is unknown. Methods: In this study, 45 samples sequenced with both 1021-gene panel and whole-exome sequencing(WES) were used to evaluate the consistency of HLA LOH in the two testing strategies. The prevalence of HLA LOH analysis was performed in 1546 advanced patients across 10 diverse cancer types and 114 early-stage lung cancer patients who had undergone tumor profiling using 1021-gene panel. Exon 2, exon 3 and bilateral introns of HLA-A/B/C genes were well covered in 1021-gene panel. HLA LOH were analysis using LOHHLA algorithm (McGranahan, et al. 2017). Results: In the HLA LOH analysis of 45 samples, the consistency of 1021-gene panel and WES was 95.6% (43/45). Among the 1660 samples, 1.3% (21) were detected as HLA homozygous at all of the three site. HLA LOH was found in 45.1%(697/1546) of all the advanced patients, range from 24.1% to 59.7%. In colorectal cancer, the HLA LOH ratio of MSS samples was significantly higher than that of MSI-H samples (46.2%, 61/132 vs 16.7%, 3/18 p =0.0214). For NSCLC, the proportion of HLALOH in early-stage (I-IIIa) lung adenocarcinoma and lung squamous cell carcinoma was 25.7% (18/70) and 65.9% (29/44), respectively, consistent with the report. However, advanced (IIIa-IV) lung adenocarcinoma and lung squamous cell carcinoma were 49.4%(168/340) and 58.7%(179/305), respectively. The reason for the difference between early-stage lung adenocarcinoma and advanced lung adenocarcinoma needs further study. In 43.8% of cases (326/744), LOH occurred simultaneously in HLA-A, B and C,suggesting that the Class I locus was often lost together. Conclusions: We can use multi-gene panel for HLA LOH analysis, provided that the relevant regions are well captured. The prevalenceof HLA LOHpresent differences among cancer types.Understanding these distributions may provide more information for immunotherapy research. [Table: see text]
A phase I study of SHR6390, a cyclin-dependent kinase 4/6 inhibitor in patients with advanced breast cancer (ABC).
Authors: Pin Zhang, Binghe Xu, Lin Gui, Wenna Wang, Meng Xiu, Xiao Zhang, Guilan Sun, Xiaoyu Zhu, Jianjun Zou
Journal: Journal of Clinical Oncology (2020)

1095 Background: SHR6390 is a novel inhibitor of cyclin-dependent kinase 4/6 (CDK 4/6). This study was conducted to evaluate the tolerability, pharmacokinetics, safety, and preliminary antitumor activity of SHR6390 in patients (pts) with advanced breast cancer (ABC). Methods: In this open-label, single-arm phase I study, pts who had failed standard therapy were enrolled to receive oral SHR6390 in 3 + 3 dose-escalation pattern at doses of 25−175 mg. Eligible pts were given a single-dose of SHR6390 in week 1, followed by once daily continuous doses for three weeks, and one week off in 28-day cycle. Based on the tolerability, pharmacokinetics, and activity data revealed from the dose-escalation phase, three dose cohorts were selected to expand to 8−10 pts. The primary endpoints were maximum tolerated dose (MTD) and pharmacokinetics. Results: Between Apr 15, 2016 and Dec 21, 2018, 40 pts were enrolled. All pts were diagnosed of hormone receptor positive and HER2-negative ABC. 45.0% of pts had at least three prior chemotherapies and 55.0% had at least two prior endocrine therapies. SHR6390 100 mg, 125 mg, and 150 mg cohorts were expanded to 10 pts, respectively. No dose limiting toxicity was observed and the MTD was not reached. Adverse events (AEs) of grade ≥3 were observed in 22 (55.0%) of 40 pts, being neutropenia (52.5%), leukopenia (35.0%), thrombocytopenia (5.0%), and hypertension (2.5%). No serious AEs were reported. At the doses of 50−175 mg, median time to peak concentration was 2.5−4.0 h, and mean terminal half-life was 40.3−51.4 h with single-dose SHR6390. Following multiple dosing, steady state SHR6390 was observed on day 8. The steady state areas under the concentration and peak concentration increased slightly greater than the increase rate of dose, with steady state C max at day 21 of 41.1, 53.4, 87.0, 115.0, 126.0, and 155.0 ng/mL in 50, 75, 100, 125, 150, and 175 mg cohorts, respectively. The disease control rate was 62.5% (25/40, 95% CI 45.8% to 77.3%). Two pts (5%, one in 125 mg, one in 150 mg cohort) achieved partial response, with responses lasting 169 and 356+ days, respectively. Conclusions: SHR6390 showed acceptable safety profile and dose-dependent plasma exposure in pts with ABC. The recommended phase II dose was 150 mg. Preliminary evidence of clinical activity was observed, warranted further study. Clinical trial information: NCT02684266 .
Circulating tumor cells with small nuclear size: A novel biomarker for survival and clinical outcomes in advanced prostate cancer.
Authors: Jasmine Jiemei Wang, Pai-Chi Teng, Yu Jen Jan, Jie-Fu Chen, Galen Cook-Wiens, Nu Yao, Gina Chia-Yi Chu, Pin-Jung Chen, Hao Ho, Yi-Te Lee, Jiaoti Huang, Ker-Chau Li, Leland WK Chung, Yazhen Zhu, Michael Freeman, Andre Rogatko, Ju Dong Yang, Hsian-Rong Tseng, Edwin Melencio Posadas
Journal: Journal of Clinical Oncology (2020)

e17512 Background: Very-small-nuclear circulating tumor cells (vsnCTCs) as a subset of CTCs with nuclear size &lt; 8.5 μm associated with visceral metastases (VM) in advanced metastatic, castration-resistant prostate cancer (mCRPC). As VM predicts foreshortened survival, we hypothesized that vsnCTCs would be directly associated with poor overall survival (OS). Methods: Clinically annotated, blood samples from patients with mCRPC with survival follow-up within the Translational Oncology Program Blood &amp; Biospecimen Bank were selected for analysis. CTCs were isolated and analyzed using the NanoVelcro assay. The nuclear size from all CTCs from each patient sample was compared to OS and progression-free survival (PFS) from the time of the blood draw. Results: A total of 76 patients had samples suitable for analysis. Sixty-six (87%) had CTCs; 49 (64%) were vsnCTC+ (≥1 vsnCTC). vsnCTCs were more common in mCRPC patients with previous androgen receptor signaling inhibitor (ARSI) therapy and/or 2 or more lines of treatment. OS was significantly shorter for vsnCTC+ than vsnCTC- patients (median 34 vs. 149 weeks; log-rank HR = 2.6; 95% CI = 1.5 to 4.5; P = 0.0006). Fifty patient samples were available for PFS analysis (i.e. drawn within 4 weeks of starting therapy). vsnCTC+ patients experienced more rapid progression than vsnCTC- patients (median 12 vs. 26 weeks, log-rank HR = 2.2, 95% CI = 1.3 to 4.0; P = 0.004). Multivariable Cox regression revealed that vsnCTC status was independently associated with OS and PFS. P-spline plot analysis showed that the HR of OS increased as the minimum CTC nuclear size decreased. The minimum CTC nuclear size was also independently associated with OS and PFS in a multivariable Cox regression analysis. Patients with prior use of androgen receptor signaling inhibitor (ARSI) therapy had significantly smaller minimum CTC nuclear size compared to those without prior use of ARSI. Average and median nuclear size did not strongly associate with OS or PFS. Conclusions: vsnCTC+ patients are at risk for more rapid clinical progression and have greater risk of death than vsnCTC-. We posit that the vsnCTC may be a biomarker of aggressive mCRPC with foreshortened survival. Interestingly, the CTCs with the smallest nuclei appear to best reflect the observed clinical behavior. This has potential importance in optimizing therapeutic choices and may point toward a unique biology relating nuclear size to aggressive molecular features. Our group continues to explore the biology underlying the vsnCTC.
The use of antihypertensive medications in cancer patients on chemo immunotherapy: Protection or not?
Authors: Bohdan Baralo, Samia Hossain, Rithikaa Ellangovan, Ajinkya Kulkarni, Vinay E. Keshava, Rajesh Thirumaran
Journal: Journal of Clinical Oncology (2020)

e19238 Background: Antihypertensive medications is a widely used in the cancer patients due to comorbid hypertension. The following analysis was devoted to find if any particular group can provide nephroprotective effect for patient that is receiving chemo immunotherapy. Methods: A retrospective cohort of the 95 patients, who received chemo immunotherapy in the infusion center of Mercy Fitzgerald Hospital in 2018-2020 were analyzed. We divided patient in 4 groups. Those who were receiving beta-blockers - group 1, angiotensin-converting enzyme/angiotensin receptor blockers – group 2, dihydropyridine calcium channel blocker – group 3, non-dihydropyridine calcium channel blocker – group 4. KDIGO criteria were used to identify patients with Acute Kidney Injury (AKI). Chi-square test was used to estimate if there is association between using specific group of anti-hypertensives medications and AKI. Results: 12 out of 95 patients in the study developed AKI. In group 1 5 had AKI and 23 not, p = .032. Group 2 included 3 patient who developed AKI and 22 who did not, p = 0.91. Group 3 group had 6 patients with AKI and 10 without, p = 0.001. Group 4 had 10 patients and none of them had AKI, p = 0.16. Conclusions: In our study we found that patient who were using the dihydropyridine calcium channel blocker (amlodipine) had a higher incidence of the AKI then patients, who were using other groups of the anti-hypertensive medications. Large prospective studies may be necessary to confirm that use of amlodipine in patients who undergo chemo immunotherapy is associated with higher incidence of the AKI and should be avoided in the treatment of this patients.
The application of the semi-automatic biopsy needle in indolent and minimally invasive muscle biopsy for the patients with psudohypertrophic muscular dystrophy
Authors: Yi-bin Zhang, Xiao-feng Yang, Hong-mei Wang, Yi-feng Xu, Yan-xiang Wu, Nai-wu Lu, Ji-ping Cui, Hong Shan
Journal: BMJ (2011)

Five hundred and twelve patients with psudohypertrophic muscular dystrophy underwent rapidly minimally invasive muscle biopsy with TZ semi-automatic biopsy needle under intravenous anesthesia. Three hundred and seventy nine samples were taken from quadriceps femoris muscle, while other 133 samples were taken from the deltoid muscle. The pathological diagnosis was obtained in all patients and there were no complications after biopsy. The results indicated that this method was simple, safe, effective, indolent, and minimally invasive. The obtained muscle samples can meet the request of histopathological and immunohistochemical examination and the method should be recommended for clinical applicatioa.

Key words: 
Biopsy, needle;  Muscular dystrophies
Corrigendum to ‘Socioeconomic and Administrative Factors Associated with Healthcare Delay and Treatment of Esophageal and Gastric Carcinoma: Experience at a Tertiary Care Centre in a Developing Country’
Authors: S. Hassan, L. D, L. Jacob, S. Babu, L. Kn, R. Ah, R. Lk, S. Saldanha, A. Thottian
Journal: Annals of Oncology (2020)
Efficacies of cryotherapy plus 5-aminolevulinic acid-photodynamic therapy in patients with condyloma acuminatum and nursing experiences
Authors: Ying Duan
Journal: BMJ (2015)

A total of 65 patients of condyloma acuminatum (CA) received cryotherapy plus 5-aminolevulinic acid-photodynamic therapy (ALA-PDT) or ALA-PDT alone. During cryotherapy, handling was gentle with a moderate depth. The nursing of PDT was both meticulous and comprehensive. Patients with adverse reactions received Kangfuxin liquid for wet packing and topical antibiotic ointment. The combination group received cryotherapy for 2 sessions and then PDT for 1-3 sessions while PDT was administered for 1-4 sessions in single PDT group. Then all patients received PDT once for consolidation therapy. For groups 1 and 2, the effective rates were 83% and 70% and the recurrent rates 17% and 30% respectively. Cryotherapy plus ALA-PDT is feasible for CA and it offers better efficacies and lower recurrent rates. And comprehensive, meticulous and comfortable nursing may achieve clinical efficacies, reduce the recurrent rate and minimize discomforts during treatment.


Key words: 
Photochemotherapy, 5 -Aminolevulinate synthetase; Nursing care
Ophthalmology rotation for general practice residency training
Authors: Huiyan Xu, Jingyu Yang
Journal: BMJ (2019)

Ophthalmology rotation is an integral part of standardized training for general practitioners. The duration of ophthalmology training is only half a month in whole 33-month general practice residency training. The main objective of training for general practice residents is to master the basic clinical skills of ophthalmology, to be able to accurately and timely identify eye diseases, especially those requiring urgent treatment, and to prevent the loss of visual function. This article introduces our teaching experience in ophthalmology training for general practice residents accumulated since 2014. We suggest that the trainees should pre-examine patients independently, play a role of standard patients and receive consultation from teachers. We developed a simple patient assessment form for primary care doctors, the patient who got 10 or more points of the form, should be referred to ophthalmological specialists.


Key words: 
General practitioners; Standard training; Ophthalmology; Assessment form
Presence of human papillomavirus DNA in breast cancer patients: SERUM and tissue analysis.
Authors: Sara Ravaioli, Andrea Rocca, Francesca Pirini, Serena De Matteis, Francesca Fanini, Maria Maddalena Tumedei, Roberta Maltoni, Palleschi Michela, Giovanni Martinelli, Sara Bravaccini
Journal: Journal of Clinical Oncology (2020)

e12582 Background: It has been demonstrated an increased risk of breast cancer (BC) incidence in patients with previous cervical dysplasia, suggesting a role of human papillomavirus (HPV) of cervical lesions in the development of BC. Although, the origin of HPV spreading to the mammary gland and its mechanism of dissemination is not clear. Methods: Seven serum samples from healthy donors and 58 from early BC patients collected pre-surgery were analyzed for the presence of HPV DNA. For 49/58 patients HPV DNA was analyzed also on the primary tumor tissue. 17 patients had luminal A BC (4 relapsed, 13 non relapsed), 16 had luminal B BC (5 relapsed, 11 non relapsed), 13 had triple-negative BC (6 relapsed, 7 non relapsed), 12 had HER2-positive BC (4 relapsed, 8 non relapsed). Circulating DNA was extracted from 500 μl of serum by Qiamp DNA Mini kit (Qiagen, Milan, Italy) and tumor DNA was extracted from at least four 10-micron sections by QIAamp DNA FFPE Tissue Kit (Qiagen, Milan, Italy). Circulating HPV DNA was amplified by a multiplex PCR with HPV E6 or E7 gene-specific primers and the sequence was assessed by a high-throughput MALDI-TOF mass spectrometry-based method. Results: HPV DNA was detected in only 5 serum of BC patients and in none of the healthy controls. 4/5 BC cases had high-risk HPV DNA (type 39,45,52,59) and 1 had type 73 low-risk HPV DNA. 4/5 HPV DNA-positive patients had previously low-grade cervical intraepithelial neoplasia (CIN I) detected by Pap smear. These 5 patients with circulating HPV DNA did not show HPV positivity in the BC tissue. 2 out of 49 cases were positive for universal HPV DNA sequence in tissue and only 1 case showed HPV type 51. No relation was found between HPV infection and tumor subtype or prognosis, neither for HPV DNA positivity between serum and tissue. Conclusions: Our data support the feasibility of HPV DNA detection by liquid biopsy in BC. The presence of circulating HPV could be due to a viral spread from other organs. More data are needed to establish the role of circulating HPV DNA and its potential association with HPV infection of the breast and/or of the cervix. [Table: see text]
Common symptoms, identification and diagnosis of depressive disorder
Authors: Wang Huiyao, Li Mingli
Journal: BMJ (2016)

抑郁障碍是临床常见的精神疾病之一，但目前其病因未明，识别率低。通过简要介绍抑郁障碍的基本概念、常见症状及识别和诊断要点，并举例介绍重性抑郁障碍及双相情感障碍鉴别的要点，提示抑郁障碍的诊断仍需要在详尽的病史评估及全面的精神检查基础上，参照诊断标准予以诊断，避免漏诊和误诊。
Outcomes in patients with metastatic non-small cell lung cancer (mNSCLC) with brain metastases treated with pembrolizumab-based therapy.
Authors: Lova Sun, Christiana Davis, Melina Elpi Marmarelis, Seth Jeffries, Lydia Frenzel Sulyok, Wei-Ting Hwang, Aditi Puri Singh, Abigail T. Berman, Steven J. Feigenberg, William C. Levin, Joshua Bauml, Christine Agnes Ciunci, Roger B. Cohen, Corey J. Langer, Charu Aggarwal
Journal: Journal of Clinical Oncology (2020)

9599 Background: Patients (pts) with mNSCLC with active brain metastases (BM) are often excluded from clinical trials; data on efficacy and safety of immunotherapy in this population are limited. We compared outcomes of pts with mNSCLC with and without BM who received pembrolizumab-based therapy. Methods: We conducted a retrospective single-center study of pts with mNSCLC treated with pembrolizumab (P) with or without chemotherapy. Progression-free survival (PFS) and overall survival (OS) were determined by Kaplan-Meier methodology and compared using multivariable Cox regression and log rank testing. Results: We identified 587 consecutive pts with mNSCLC who began P-based therapy between 8/2013 and 12/2018: 306 (52%) female, median age 67 years (range 32-98), 437 (74%) adenocarcinoma, and 508 (87%) former/current smokers. 388 (66%) patients received P in first line therapy, and 334 (57%) received single-agent P. 131 pts (22%) had detectable BM at baseline (start of P-based therapy). Pts with BM were younger (median 65 y vs 68 y, p &lt; 0.01) and more likely to have adenocarcinoma (86% vs. 71%, p &lt; 0.01) and baseline steroid use (22% vs 1%, p &lt; 0.01). Presence of BM did not differ by race, sex, line of therapy, treatment regimen, or PD-L1 status. Of the 131 patients with detectable BM on pre-treatment brain MRI, 55 (42%) had stable BM as a result of prior local therapy, while 76 (58%) had active (new or growing) BM on pre-treatment imaging. Most patients with active BM underwent radiation therapy (RT) in either the 30 days before (n = 46) or 30 days after (n = 17) P start; of the remaining 13 treated with P-based therapy alone, intracranial responses included 2 CR, 2 PR, 3 SD, and 4 PD. As of 1/1/2020, with 15-month median follow up, there was no difference in mPFS (9.2 vs 7.3 months, p = 0.41) or mOS (18.3 vs 18.0 mo, p = 0.67) between pts with and without BM in our P-treated cohort. On multivariable analysis, female sex, ECOG 0-1, adenocarcinoma histology, and P as first line therapy were associated with improved PFS and OS. Presence of BM, baseline steroid use, and timing of local RT (before vs. after P) were not associated with inferior survival. Conclusions: In our single-center experience of pts with mNSCLC treated with P, pts with and without BM had similar PFS and OS. We observed several intracranial responses to P-based therapy alone, but most pts with active BM underwent local RT. mNSCLC pts with BM should be considered for P-based therapy; BM may be treated with RT immediately before or even after P with similar survival outcomes.