tbuckley/cabot-search huggingface dataset:
Analysis on risk factors for ischemic stroke in people aged 80 years and over
Authors: Yu-hui Chen, Tao Gong
Journal: BMJ (2010)

A total of 94 patients aged 80 years or over diagnosed as acute ischemic stroke based on their clinical features and CT or MRI and 64 elderly people without stroke as controls were enrolled in this study. They were admitted in Beijing Hospital from September 2003 to July 2008. Blood pressure measurement, electrocardiogram (ECG) and color doppler ultrasonography in carotid arteries were performed for all of them, as well as blood glucose, lipid and fibrinogen were measured and history of hypertension,diabetes, coronary heart disease, hyperlipidemia, smoking and alcohol drinking were recorded. Univariate analysis showed that more hypertension, hyperfibrinogenemia, atrial fibrillation and carotid atherosclerosis were found in the elderly patients with ischemic stroke than in those without it ( P ＜ 0. 05 ). And, multivariate logistic regression analysis showed that hyperfibrinogenemia ( OR = 16. 23, P = 0. 009 ), atrial fibrillation ( OR = 3.47, P = 0. 080) and isolated systolic hypertension ( OR = 1.05, P ＜ 0. 01 ) all were independent risk factors for ischemic stroke in the elderly.

Key words: 
Cerebrovascular accident;  aged, 80 and over
Amivantamab (JNJ-61186372), an anti-EGFR-MET bispecific antibody, in patients with EGFR exon 20 insertion (exon20ins)-mutated non-small cell lung cancer (NSCLC).
Authors: Keunchil Park, Thomas John, Sang-We Kim, Jong Seok Lee, Catherine A. Shu, Dong-Wan Kim, Santiago Viteri Ramirez, Alexander I. Spira, Joshua K. Sabari, Ji-Youn Han, Jose Manuel Trigo, Chee Khoon Lee, Ki Hyeong Lee, Nicolas Girard, Patricia A Lorenzini, John Xie, Amy Roshak, Meena Thayu, Roland Elmar Knoblauch, Byoung Chul Cho
Journal: Journal of Clinical Oncology (2020)

9512 Background: EGFR exon20ins-mutated NSCLC is generally refractory to EGFR tyrosine kinase inhibitors (TKIs) and is associated with poor prognosis. Amivantamab (JNJ-61186372) is a novel, fully human anti-EGFR-MET bispecific antibody whose mechanism of action can target both EGFR- and MET-driven disease and has shown monotherapy activity in patients (pts) with diverse EGFR mutant disease characterized by EGFR C797S, T790M, exon20ins, and MET amplification. We present preliminary results of pts with advanced NSCLC harboring exon20ins mutations from CHRYSALIS, an ongoing phase 1 study of amivantamab (NCT02609776). Methods: This study comprises a dose escalation phase in pts with advanced NSCLC and a dose expansion phase in pts with EGFR- and MET-mutated disease. This analysis includes all enrolled pts with exon20ins disease who received the recommended phase 2 dose (RP2D) of 1050 mg (1400 mg, pts ≥80 kg) amivantamab. Response was assessed by investigator per RECIST v1.1. Results: As of 30 Oct 2019, 50 pts with exon20ins mutations had received amivantamab at the RP2D. 39/50 pts were response-evaluable and had ≥2 disease assessments or had discontinued therapy prior to the assessment period; among these pts, 29 had prior platinum-based chemotherapy (PBCT). Median age for response-evaluable pts was 61 y (40–78), 51% were female, and median prior lines was 1 (0–7). In the 50 pts harboring exon20ins mutations treated at the RP2D, the most common adverse events (AEs) reported were rash (72%), infusion related reaction (60%), and paronychia (34%). Additional EGFR-related AEs included stomatitis (16%), pruritus (14%), and diarrhea (6%). Grade ≥3 AEs were reported in 36% of pts; 6% were treatment-related. One grade 3 diarrhea and no grade ≥3 rash was reported. Among the 39 response-evaluable pts, with a median follow-up of 4 months (1–26), the overall response rate (≥partial response [PR]) was 36% (95% CI, 21–53), and 41% (95% CI, 24–61) for the 29 pts who had prior PBCT. The clinical benefit rate (≥PR or stable disease ≥11 weeks) was 67% for response-evaluable pts and 72% for pts who had prior PBCT. Among all 14 responders, median duration of response was 10 months (1–16), with ongoing responses in 9 pts at data cutoff. Median progression-free survival was 8.3 months (95% CI, 3.0–14.8) for response-evaluable pts and 8.6 months (95% CI, 3.7–14.8) for pts who had prior PBCT. Conclusions: Amivantamab demonstrates robust and durable antitumor activity in pts with exon20ins disease, with a manageable safety profile. Clinical trial information: NCT02609776 .
Effect of percutaneous coronary intervention on sleep quality of coronary heart disease patients with obstructive sleep apnea syndrome
Authors: Zhiqiang Pei, Xin Su, Lijun Wu, Baoping Jia, Chen Wang, Jingbo Mu, Jing Bai, Dengfeng Ma
Journal: BMJ (2020)

One hundred and nine consecutive coronary heart disease (CHD) patients with obstructive sleep apnea (OSA) undergoing percutaneous coronary intervention (PCI) during February 2016 to August 2018 were enrolled in the study. After treatment the quality of sleep was improved in 35 cases (observation group) and was not improved in 74 patients (control group). The basic characteristics, coronary lesions of patients were compared between two groups. Compared with the control group, patients in observation group had significant higher proportion of males [80.0%(28/35) vs. 59.5%(44/74), χ2=4.471, P=0.035], smoking history [85.7% (30/35) vs. 63.5% (47/74), χ2=5.647, P=0.018], lower body mass index [(25.8±3.1) kg/m2vs. (27.4±3.2) kg/m2, t=2.461, P=0.033]. Compared with control group, the observation group had lower coronary Gensini score[(35.4±5.7) vs. (38.7±6.5), t=2.571, P=0.011], less number of stent[ (1.4±0.4) vs. (1.6±0.4), t=2.427, P=0.016]. And the lesions were mostly distributed in the right coronary artery in observation group (61.9%, 26/35) (χ2=11.759, P=0.003).


Conclusion
The improvement of sleep quality by PCI depends on the clinical features and coronary artery lesions of CHD patients with OSA.


Key words: 
Sleep apnea, obstructive; Coronary disease; Percutaneous coronary intervention; Sleep
Differential expression of micro-RNAs in breast cancer with relapsed disease: A clinical data base study.
Authors: Yadav Pandey, Zhongning Chen, Issam Makhoul
Journal: Journal of Clinical Oncology (2020)

e12514 Background: Micro-RNAs (miRNAs) are small, noncoding RNA molecules that play important role in RNA silencing and post-transcriptional regulation of gene expression that are dysregulated in cancer. miRNAs are divided into oncogenic and tumor suppressor miRNAs. Both of these subtypes are known to regulate breast cancer development and progression. We studied the expression of these miRNAs before and after treatment in patients with breast cancer with relapsed disease. Methods: Data was obtained from the TCGA database. 11 patients with biopsy proven diagnosis of invasive ductal adenocarcinoma of the breast receiving adjuvant chemotherapy with relapsed disease who had tissue biopsy post-treatment were included in the study. miRNA expression was assessed in the pre- and post-treatment tissue samples. A total of 178 miRNA were analyzed after filtering out miRNA expression counts &lt; 10. A pair-wise comparison of the differential expression of miRNA before and after treatment with adjuvant chemotherapy was analyzed using a quasi-likelihood F test implemented by bioconductor package, edgeR. This package is well documented for analyzing RNA-seq data due to adjustment for biological variations and measuring error using a negative binomial distribution. The expression of miRNA |Log2FC| &gt; 1 and P value &lt; 0.05 were obtained. Results: Out of 11 female patients, 10 were Caucasian. 9 out of 11 patients’ tumors were Estrogen Receptor positive; 8 patients had progesterone Receptor positive and 1 patient had Human epidermal growth factor receptor2 positive cancer. Of the 178 miRNAs of interest, we found 14 miRNA that are differentially expressed. The miRNA that are up-regulated post-treatment were hsa-miR-148a, hsa-miR-126, hsa-miR-142, hsa-miR-210, hsa-miR-374a, hsa-miR-192. The miRNA that were down-regulated were hsa-miR-197, hsa-miR-155, hsa-miR-149, hsa-miR-365a, hsa-miR-365b, hsa-miR-484, hsa-miR-339 and hsa-miR-3653. Among the miRNA up-regulated post-treatment, miR-148 and miR-126 are known major tumor suppresser miRNA whereas miR-210 and miR-374a are major oncogenic miRNA in breast cancer. Among the miRNA down-regulated post treatment, miR-155 is major oncogenic miRNA whereas miR-365 is major tumor suppressor miRNA in breast cancer. Conclusions: There is mixed expression profile of tumor suppressor miRNA and oncogenic miRNA molecules between before and after treatment in patients with breast cancer with relapsed disease. Further studying these miRNA molecules can help us better understand about the tumor progression and disease relapse.
转移性膀胱癌三例临床分析
Authors: 何炜, 刘军, 陈兵, 刘云峰, 李旭东
Journal: BMJ (2008)

膀胱癌是我国泌尿系最常见的恶性肿瘤,对于原发于膀胱的恶性肿瘤,治疗方法有经尿道膀胱肿瘤电切术(TURBT),膀胱部分切除和根治性膀胱切除术3类[1].而转移性膀胱癌症状重,恶性度较高,均为晚期,需要考虑患者的身体情况,预期寿命以及原发病等予综合治疗.现对我科收治的3例患者资料进行分析,并结合文献讨论。
Genetic polymorphisms associated with clostridium difficile infection in multiple myeloma patients undergoing autologous stem cell transplantation.
Authors: Issam Hamadeh, Zainab Shahid, Manisha Bhutani, Jai Narendra Patel, Nury Steuerwald, Alicia Hamilton, Shebli Atrash, Reed N. Friend, Barry Paul, Peter Michael Voorhees, Saad Zafar Usmani, Jiaxian He
Journal: Journal of Clinical Oncology (2020)

8522 Background: CDI is the primary cause of infectious diarrhea in immunocompromised patients including those undergoing autologous stem cell transplant (SCT). Given the key role of gut microbiome and its interaction with host immune system, we investigated whether polymorphisms in innate immunity genes (identified through Ingenuity Pathway Analysis) were associated with CDI. Methods: We queried our database to identify MM patients who underwent an autologous SCT between April 2015-June 2019. Patients who had their buccal swabs collected through an IRB approved specimen collection protocol were included herein. Data were collected on age, conditioning regimen, CDI diagnosis, time from admission until CDI diagnosis, absolute neutrophil count (ANC) at time of CDI diagnosis, and antibiotic prophylaxis. Genomic DNA was extracted from buccal swabs and genotyped for 62 single nucleotide polymorphisms (SNPs) in ASPH , RLBP1L1, ATP7B, IL-8, FAK, TNFRSF14, CTH, TLR and IL-4. Univariate and multivariate logistic regression analyses were performed to assess association between CDI and presence of SNPs in these genes. Results: A total of 83 patients were identified (25 cases and 58 controls). Baseline characteristics were comparable between two groups. Median age was 67 years (range: 50-79). All patients received high dose melphalan as conditioning, and the same antibiotic prophylaxis during peri-transplant period. Median time from hospitalization until CDI diagnosis was 10 days (IQR:9 days), and median ANC was 0.7/mL (IQR:1.6/mL). Two SNPs (rs2227307 T &gt; G in IL-8 and rs2234167 G &gt; A in TNFRSF14) were significantly associated with CDI risk in both univariate and multivariate logistic regression analyses (Table). Conclusions: Our findings suggest that rs227307G (in IL-8) and rs2234167A (in TNFRSF14) alleles are potential risk factors for CDI after autologous SCT. Our findings, if validated in a larger cohort, would support genetic testing as a screening tool to identify patients who might benefit from prophylaxis against CDI. [Table: see text]
Role of adjuvant imatinib dose in radically resected GIST harboring KIT exon 9 mutations.
Authors: Bruno Vincenzi, Andrea Napolitano, Margherita Nannini, Elena Fumagalli, Giovanni Grignani, Javier Martin Broto, Nadia Hindi, Antoine Italiano, Piotr Rutkowski, Peter Hohenberger, Antonella Brunello, Silvia Gasperoni, Heikki Joensuu, Giuseppe Badalamenti, Spyridon Gennatas, Tommaso Martino De Pas, Alessandro Gronchi, Angelo Paolo Dei Tos, Robin Lewis Jones, Sebastian Bauer
Journal: Journal of Clinical Oncology (2020)

11533 Background: Gastrointestinal stromal tumors (GIST) with a driver mutation in KIT exon 9 (Ex9) represent about 10% of all newly diagnosed cases. In the metastatic setting, Ex9-mutated GIST patients benefit from higher doses of imatinib (800 mg/day vs standard 400 mg/day). The additional therapeutic benefit from a higher dose of imatinib in the adjuvant setting in this molecular subgroup has not been confirmed. Methods: We retrospectively identified 105 patients (pts) with resected Ex9-mutated GIST treated with adjuvant imatinib (800 mg/day or 400 mg/day) in 15 different European centers. Disease-Free Survival (DFS) and Imatinib Failure-Free Survival (IFFS) were calculated and analyzed according to the daily dose of imatinib and relevant clinical and pathological variables. Kaplan–Meier curves were used to estimate survival in univariate analyses, and the log-rank test was used to compare the groups. Hazard Ratios (HR) with 95% confidence intervals (CI) were calculated using a univariable Cox model. A multivariate Cox regression model was also performed. Results: Of the 105 pts who met the inclusion criteria, 69 (65.7%) were treated with 400 mg/day and 36 (34.3%) with 800 mg/day. The risk score (AFIP-Miettinen criteria) between the two dose groups was not statistically different (P = 0.29). Median DFS was 73.0 months (mo) in the 400 mg/day group and 61.9 mo in the 800 mg/day group (HR = 0.82, 95% CI: 0.47-1.47; P = 0.50). Median IFFS was 156.8 mo in the 400/day mg group and 117.4 mo in the 800 mg/day group (HR = 0.66, 95% CI: 0.34-1.29; P = 0.19). In a multivariable analysis, the variables statistically associated with DFS were mitotic count, the longest tumor diameter and the duration of adjuvant therapy. Mitotic count and the duration of adjuvant therapy were also associated with IFFS. Importantly, the daily imatinib dose was not associated with survival in either analysis (Table). Conclusions: This is the largest reported cohort of pts with Ex9-mutated GIST treated with either the 400 mg/day or the 800 mg/day dose of adjuvant imatinib. Although retrospective in nature, the data confirm the prognostic value of mitotic count and suggest that patients with Ex9-mutated GIST derive no additional survival benefit from the 800 mg/day dose. [Table: see text]
Survey on perception of general practice and career intention among undergraduates in Harbin Medical University
Authors: Pengpeng Wang, Wen Ren, Bing Han, Kun Wang, Yongchen Wang
Journal: BMJ (2019)

A questionnaire survey on the perception of general practice and career intention was conducted among 365 undergraduates in Harbin Medical University in May 2018. Among all participants 71 (19.45%) had studied the course of  to General Medicine, and 289 did not (79.18%). Twenty one students well knew general practice (5.78%), 189 knew (51.78%) and 155 students did not know (42.47%); 164 (44.93%) would pursue a master degree study in general practice after graduation, 216 people (59.18%) were willing to attend standardized residency training after graduation, and 147 (40.27%) choose to be a general practitioner after graduation. The proportion of students willing to pursue a master degree study in general medicine and to receive standardized resident training of general practice in students who had studied Introduction to General/Family Medicine was lower than that in hose did not studied (χ2=7.46, 7.14, both P<0.05). The top three reasons for becoming a general practitioner were more chance for career development (70.15%, 109/147), loving the subject (52.38%, 77/147), and difficulty to be employed for other specialties (27.21%, 40/147). The first three reasons for not being a general practitioner were less chance for career development (52.17%, 133/138), less interesting specialty (47.10%, 65/138), unfamiliar with grassroots work (39.86%, 55/138). The survey indicates that medical colleges should continue to strengthen the education of general practice, and constantly improve its curriculum system to attract more medical students to join the team of general practitioners after their graduation.


Key words: 
General practice; Education, medical, undergraduate; Cognitive; Career intention
A novel multiple-catheter implantation method for advanced head and neck cancer.
Authors: Masatoshi Ohmae, Itsuro Kato, Yusei Fujita, Noritoshi Meshii, Ayako Motoki, Mitsuhiro Nakazawa, Narikazu Uzawa
Journal: Journal of Clinical Oncology (2020)

6582 Background: We previously developed a super-selective intra-arterial chemotherapy (iaCT) approach for head and neck cancer (HNC), by which, an intra-arterial catheter is retrogradely inserted via either the superficial temporal artery (STA) or occipital artery (OA) and connected to a subcutaneous reservoir. As a result, since this approach overcomes the need for frequent fluoroscopy sessions, the infusion frequency can be increased and the therapeutic effectiveness improved. However, since the anticancer effect is limited to the region supplied by the selected blood vessel, it is often difficult to control an advanced HNC by single-catheter iaCT. Subsequently, a novel multiple-catheter implantation method (MCIM) for super-selective iaCT has been developed using, both, the STA and OA. Methods: A total of 21 patients with stage III or IV HNC were enrolled in this study and treated via MCIM for iaCT between 2009 and 2017. The catheters were super-selectively placed in the tumor-feeding arteries after having entered the STA or OA. The first catheter was introduced into one of the target branches. Next, a second catheter was introduced into another target branch. If a third catheter was required, the procedure was repeated. The extra-arterial portions of the catheters were subcutaneously connected to an implanted juxta-mastoidal infusion reservoir. Results: The response rate was 100%; particularly, 20 cases of complete response and 1 of partial response were confirmed. Although the partial responder underwent salvage surgery and two complete responders ultimately died (due to either delayed recurrence or brain metastases), the other 18 patients have been living cancer-free for 2-9 years. Conclusions: The MCIM method allows to expand the infusion region while maintaining the main advantages of super-selective iaCT. As a consequence, due to the lack of need for patient confinement in the catheter room and for frequent fluoroscopy sessions, patients’ mental and physical distress, medical expenses, and treatment time are all ultimately reduced.
Corticosteriod tapering in patients (Pts) with relapsed or refractory multiple myeloma (RRMM) receiving subcutaneous daratumumab (DARA SC): Part 3 of the open-label, multicenter, phase Ib PAVO Study.
Authors: Hareth Nahi, Saad Zafar Usmani, Maria-Victoria Mateos, Niels W.C.J. van de Donk, Philippe Moreau, Albert Oriol, Torben Plesner, Shiyi Yang, Peter Hellemans, Brenda J. Tromp, Man (Melody) Luo, Donna Zemlickis, Andrew Farnsworth, Ajai Chari
Journal: Journal of Clinical Oncology (2020)

8537 Background: Intravenous DARA (DARA IV) is approved for the treatment of MM. In Part 2 of PAVO, DARA SC, a concentrated, pre-mixed SC co-formulation of DARA and recombinant human hyaluronidase PH20 (rHuPH20), was well tolerated, with a low infusion-related reaction (IRR) rate, and showed consistent serum concentrations and similar efficacy to DARA IV in RRMM pts. In PAVO Part 3, we evaluated the safety of pre- and post-dose corticosteroid tapering during DARA SC administration. Methods: RRMM pts with ≥2 prior lines of treatment, including a proteasome inhibitor (PI) and immunomodulatory drug (IMiD), received DARA SC (DARA 1,800 mg + rHuPH20 30,000 U in 15 mL) by manual SC injection per approved IV monotherapy dosing schedule. Pts received a 3-week (wk) tapering schedule (corticosteroid-free by Cycle [C] 1 Day [D] 22), with methylprednisolone (MP) given PO/IV pre-dose (C1D1, 100 mg; C1D8, 60 mg; C1D15, 30 mg) and PO post-dose (C1D1, 20 mg for 2 days; C1D8, 20 mg for 1 day; C1D15, 20 mg for 1 day), or a 2-wk tapering schedule (corticosteroid-free by C1D15), with MP given PO/IV pre-dose (C1D1, 100 mg; C1D8, 60 mg) and PO post-dose (C1D1, 20 mg for 2 days; C1D8, 20 mg for 1 day). Results: Pts (3-wk group, n = 15; 2-wk group, n = 15) received a median of 2 (range: 2-7) prior lines of therapy, with 37% refractory to a PI and an IMiD. The 3-wk and 2-wk groups received a median (range) of 14 (2-19+) and 8 (2-16+) DARA SC doses without corticosteroids, respectively. No IRRs were reported in the 3-wk group. 3 pts (20%) in the 2-wk group experienced IRRs on C1D1 (grade 3 hypertension, grade 2 chills, grade 1 pyrexia, grade 1 oropharyngeal pain, and grade 1 tachycardia). IRRs occurred within 2 h of the first DARA SC administration; no IRRs were reported at later administrations. Most common (≥25%) treatment emergent adverse events (TEAEs) were upper respiratory tract infection (40%) and fatigue and nausea (27% each). Most common (≥5%) grade 3/4 TEAEs were anaemia, lymphopenia, neutropenia, and hypertension (7% each). At median follow-up of 6.8 mo (3-wk group) and 2.4 mo (2-wk group), the overall response rates were 40% (95% CI, 16-68%) and 27% (95% CI, 8-55%) and ≥very good partial response rates were 13% (95% CI, 2-40%) and 7% (95% CI, 0-32%), respectively. Conclusions: Rapid corticosteroid tapering over 2 wks is safe in RRMM pts receiving DARA SC. These data help guide future DARA SC combinations (ie, T-cell redirectors, CAR-T, or checkpoint inhibitors), where limiting concurrent corticosteroids may be preferred. Clinical trial information: NCT02519452 .
Positive Public Health Ethics: Toward Flourishing and Resilient Communities and Individuals
Authors: Jennifer Prah Ruger
Journal: The American Journal of Bioethics (2020)

The COVID-19 pandemic is a global contagion of unprecedented proportions and health, economic, and social consequences. As with many health problems, its impact is uneven. This article argues the COVID-19 pandemic is a global health injustice due to moral failures of national governments and international organizations to prepare for, prevent and control it. Global and national health communities had a moral obligation to act in accordance with the current state of knowledge of pandemic preparedness. This obligation—a positive duty to develop and implement systems to reduce threats to and safeguard individuals' and, communities' abilities to flourish—stems from theories of global health justice and governance. The COVID-19 pandemic revealed and amplified the fragility and deficiencies in our global and domestic health institutions and systems. Moving forward, positive public health ethics is needed to set ethical standards for building and operating robust public health systems for resilient individuals and communities.