tbuckley/cabot-search huggingface dataset:
Role of CD8<sup>+</sup> T-cell infiltration in breast tumors of Black women compared to White women.
Authors: Yara Abdou, Kristopher Attwood, Song Yao, Ting-Yuan David Cheng, Elisa Bandera, Gary Zirpoli, Rochelle Payne Ondracek, Leighton Stein, Wiam Bshara, Thaer Khoury, Christine B. Ambrosone, Angela Omilian
Journal: Journal of Clinical Oncology (2020)

e13608 Background: Literature regarding racial differences in tumor immune responses in breast cancer remains sparse. To address this research gap, we assessed CD8 + T-cells in breast tumor samples from the Women’s Circle of Health Study (WCHS) population of predominantly Black breast cancer patients. We characterized and compared the density of CD8 + T cells, their prognostic value and their association with pharmacologic beta-blockers. Prior studies suggest that reducing adrenergic signaling through beta blockers can stimulate CD8 + T-cells. Methods: Tumor-infiltrating CD8 + T-cells were assessed by IHC staining of tissue microarray cores from 688 breast cancer patients, including 550 Blacks and 138 Whites. CD8 + T cells were scored with digital image analysis. Comparisons of demographic and clinical variables (including CD8 + T cell density) were made using the Mann-Whitney U or Kruskal-Wallis and Fisher’s exact tests. Associations with overall survival (OS) and disease-specific (DSS) survival were evaluated using the log-rank test of Cox regression. Analyses were performed in the overall sample and by disease sub-type. Results: Higher CD8 + T cell density was seen in Black women compared to White, with mean values of 756.2/mm 2 and 292.4/mm 2 respectively (p &lt; 0.001). Within the overall population and in black women, CD8 + T cell density was significantly higher in younger patients, patients with high grade, and ER negative tumors. No significant associations were observed between CD8 + T cell density and OS or DSS. However, when stratified by subtype, Black patients with triple negative breast cancer and high CD8 + T cell density showed a trend towards improved OS in comparison to patients with low CD8 + T cell density (p = 0.065). 170 patients with information on beta blocker usage were analyzed. No significant associations were noted between CD8 + T cell density and beta blocker use. Conclusions: We observe a significantly higher CD8 + T cell density in Blacks compared to Whites, but this does not confer a survival advantage. Additionally, beta-blockers did not seem to enhance CD8 + T cell infiltration in tumors from Black patients. Our data raise the possibility that distinct mechanisms of immune cell action may occur in different racial groups. Future studies are needed to determine the functional properties of CD8 + T cells in Black women and to characterize additional immune cell subtypes that may also play a role.
Patterns and predictors of referral among patients with muscle-invasive bladder cancer: A real-world study.
Authors: Jessica Mary Clement, Zengqi Lu, Qi Pan, Helen Swede, Rajni Mehta, Xiaoyan Wang
Journal: Journal of Clinical Oncology (2020)

e17051 Background: The multidisciplinary treatment of muscle-invasive bladder cancer (MIBC) has demonstrated considerable challenges in widespread clinical adoption. Despite guidelines recommending multidisciplinary, utilization of neoadjuvant chemotherapy for bladder cancer treatment remains low in the real-world settings. This study aims to examine the real-world referral patterns from urology to medical oncology and/or radiation oncology and the factors that associated with the referral following a diagnosis of MIBC. Methods: Following approval of involved IRBs, investigators followed a common protocol under the auspices of the Rapid Case Ascertainment at the Yale Cancer Center and performed manual chart review of MIBC patients diagnosed in the state of Connecticut from 2004 – 2015 and treated at investigator-affiliated hospitals. Information on medical history, radical or partial cystectomy, chemotherapy, radiation therapy, initial treating physician, and referrals to additional providers were recorded. This data set was linked to the Surveillance, Epidemiology, and End Results (SEER) database for demographic information. Logistic regression analysis adjusted with demographics (i.e. gender, race) and medical histories (i.e. prior cancers) was conducted to identify factors associated with referral. Results: Of the 665 patients whose initial treating physician was urologist, only 291 (43.8%) were referred to a medical oncologist and/or a radiation oncologist. Independent factors associated with lack of referral included: older age (OR = 0.994 for every incremental year, P-value: 0.0055), and greater Charlson comorbidity score (OR = 1.064. P-value: 0.015). Patients with kidney diseases and diabetes were less likely to be referred. Conclusions: Lack of referral to medical oncology and/or radiation oncology is a critical barrier to the use of optimal multidisciplinary therapy. Referral decision made by urologists is impacted by a patient’s age and overall health condition. [Table: see text]
PARSIFAL: A randomized, multicenter, open-label, phase II trial to evaluate palbociclib in combination with fulvestrant or letrozole in endocrine-sensitive patients with estrogen receptor (ER)[+]/HER2[-] metastatic breast cancer.
Authors: Antonio Llombart-Cussac, José Manuel Pérez-García, Meritxell Bellet, Florence Dalenc, Miguel J. Gil Gil, Manuel Ruiz Borrego, Joaquín Gavilá, Miguel Sampayo-Cordero, Elena Aguirre, Peter Schmid, Frederik Marmé, Serena Di Cosimo, Joseph Gligorov, Andreas Schneeweiss, Joan Albanell, Pilar Zamora, Duncan Wheatley, Eduardo Martínez-De Dueñas, Kepa Amillano, Javier Cortes
Journal: Journal of Clinical Oncology (2020)

1007 Background: The CDK4/6 inhibitor palbociclib (P) in combination with letrozole (L) has become a standard first-line treatment for patients (pts) with luminal metastatic breast cancer (MBC) (PALOMA-1 &amp; 2 trials). Meanwhile, the anti-estrogen fulvestrant (F) showed to be superior to anastrozole in the same population (FALCON trial). We aimed to identify the best endocrine agent to combine with P in this first-line scenario. Methods: A total of 486 pts with ER[+]/HER2[-] MBC with no prior therapy in the advanced setting and endocrine sensitive criteria (relapse &gt; 12 months [mo] after the end of adjuvant endocrine therapy or diagnosed with “de novo” metastatic disease) were randomly assigned (1:1 ratio) to receive P (oral 125 mg/day [d]; 3 wks on/1 wk off) plus F 500 mg/d (I.M Days 0, 14, 28, and then every 28 d) or PL (oral 2.5 mg/d). Pts were stratified by visceral involvement and type of disease presentation (“de novo”/recurrent). Primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints included overall survival (OS), overall response rate (ORR), clinical benefit rate (CBR), and safety. 254 events were needed with 80% power to detect a hazard ratio (HR) ≤0.7 in favor of PF (2-sided α = 0.05). Results: By March 9th, 2020, 256 PFS events occurred. Pts characteristics were well balanced. Median age was 62 years (range: 25–90), 56.6% were ECOG 0, 40.7% had “de novo” metastatic disease, 48% had visceral disease, and 43.6% with ≥3 organ sites involved. At median follow-up of 32 mo, median PFS was 27.9 mo (95% confidence interval [CI], 24.2-33.1) with PF and 32.8 mo (95% CI, 25.8-35.9) with PL (HR: 1.1; 95% CI, 0.9-1.5; P = 0.321). No differences were observed for pts with or without visceral involvement (HR: 1.3 and HR: 0.97 respectively, interaction P = 0.275), and for “de novo” or recurrent metastatic disease (HR: 1.1 and HR: 1.1 respectively, P = 0.979). The 4-year OS rate was 67.6% in PF and 67.5% in PL arm (HR: 1; 95% CI, 0.7-1.5; P = 0.986). No differences were observed in ORR or CBR between arms. Grade ≥3 adverse events were similar in both arms, being neutropenia and leukopenia the most frequent. No treatment-related deaths were reported. Conclusion: This study was not able to identify an improvement in PFS for PF over PL in patients with endocrine-sensitive ER[+]/HER2[-] MBC. As both arms demonstrated comparable 4 years-OS, PF is a reasonable alternative to PL in this setting. Clinical trial information: NCT02491983 .
Clinical application of different kinds of insulin
Authors: Hongmei Li
Journal: BMJ (2019)

自1922年胰岛素首次用于治疗糖尿病以来，胰岛素的发展由最早的动物胰岛素到人胰岛素，再到胰岛素的类似物，剂型多样，为临床个体化的治疗提供了多种选择。在临床中了解不同类型胰岛素的特点并灵活应用，有利于糖尿病患者的血糖控制，降低并发症，提高患者的生命质量。
Treatment of locally advanced or multiple basal cell carcinoma with vismodegib in real world setting.
Authors: Janja Ocvirk, Tanja Mesti, Katja Leskovsek
Journal: Journal of Clinical Oncology (2020)

e22065 Background: Evaluation of efficacy and safety of vismodegib (V) was done in a retrospective analysis of patients (pts) with locally advanced or multiple basal cell carcinoma (laBCC or multiple BCC) and pts with Goltz-Gorlin Syndrom (G-G Syn) in routine clinical practice. Methods: Baseline characteristics, efficacy data and treatment-related adverse events were collected from 30 laBCC or multiple BCC and 6 G-G Syn pts who were treated with V. Results: In 86-month period, 36 pts were diagnosed with laBCC (18 pts), multiple BCC (12 pts) or G-G Syn (6 pts), all inappropriate for surgery or radiotherapy. Baseline characteristics: median age was 72.6 years in laBCC + multiple BCC pts group and 51.3 years in G-G Syn pts group. Sixty percent of pts in laBCC + multiple BCC group were females; majority (70%) of pts were previously treated by surgery (S) and/or radiotherapy (RT); 43% of pts had 1 lesion with predominant localization in central face (eyes, nose, lips or ears in 84% of pts), 20% had 2-3 lesions and 37% more than 3 lesions. Fifty percent of pts in G-G Syn pts group were males; all pts were previously treated with S and/or RT. The overall response rate (ORR) was 76% in laBCC + multiple BCC and 83% in G-G Syn pts group. Disease control rate (DCR) was 93% in laBCC + multiple BCC and 100% in G-G Syn pts group. Median duration of treatment (DoT) was 7.8 months (range: 1.3-29.8) in laBCC + multiple BCC group and 27.1 months (range: 4.8-86.4) in G-G Syn group. At the time of analysis in laBCC or multiple BCC group one patient died due to other reasons than cancer, in 30% of pts treatment has been interrupted during the treatment course [in most cases due to complete response or adverse events (AEs)], 40% of pts are still on treatment. In G-G Syn group treatment has been interrupted in 50% of pts (in most cases due to adverse events), 67% of pts are still on treatment. AEs of any grade were reported in 97% of pts in laBCC or multiple BCC group and 83% in G-G Syn group. Majority of AEs in laBCC or multiple BCC group were grade 1 or 2 (96%)., 4% of AEs were grade 3: muscle cramps in 3 pts, respiratory infection, vomiting and anemia in 1 patient each. Majority of AEs in G-G Syn group were also grade 1 or 2 (87%), 13% of AEs were grade 3: muscle cramps in 2 pts, weight loss and diarrhea in 1 patient each. No grade 4 or 5 AEs were reported. Conclusions: Vismodegib has shown meaningful efficacy with manageable safety profile in pts with laBCC or multiple BCC as well as in pts with G-G Syn in real world setting.
The KRAS mutation status and resistance to cetuximab in patients with squamous cell carcinoma of oral cavity.
Authors: Aza A. Lyanova, Liubov Yu Vladimirova, Marina A. Engibaryan, Natalia A. Abramova, Irina L. Popova, Ludmila A. Ryadinskaya, Natalia M. Tikhanovskaya, Maria A. Teplyakova, Kristina A. Novoselova, Valeriya S Myagkova, Denis S. Kutilin
Journal: Journal of Clinical Oncology (2020)

e15514 Background: The standard treatment of squamous cell carcinoma of the tongue and the mucosa of the bottom of the oral cavity (SCCTOM) is chemotherapy (CT) in combination with cetuximab (mC, anti-EGFR antibody). However, not all patients manage to achieve positive results. A common cause of resistance to anti-EGFR antibodies is the constitutive activation of mediators of the underlying signaling pathways. Therefore, the aim of the study was to analyze mutations in the KRAS using the Digital Droplet PCR method in patients with SCCTOM on the background of CT in combination with targeted therapy or standard CT. Methods: The study used the QX200 system (Bio-Rad) and the ddPCRtm KRAS Screening Multiplex Kit (7 mutations). The study included 60 patients with T3-4N0-1M0 SCCTOM. The main group consisted of 30 patients (cisplatin, 5-fluorouracil+cetuximab). The control group consisted of 30 patients (CT). For research, cfDNA from blood plasma was used. Analysis of the data was performed using QuantaSoft v1.7.4. Results: The frequency of the KRAS mutant type (mtKRAS) is 43% before treatment and 32% after treatment (n = 60). In the group of patients CT+mC the incidence of mtKRAS before treatment was 40%, after treatment - 20%. In the group of patients CT without mC the incidence of mtKRAS before treatment was 47%, after treatment - 43%. Decrease of 20% (p = 0.00089) in the frequency of mtKRAS after CT+mC was found, while it was 23% (p = 0.00009) lower than the frequency of mtKRAS after CT without mC. After treatment, in the CT+mC group of patients, the number of mtKRAS DNA copies increased 1.5 times (p = 0.048). Analysis of clinical response to therapy allowed us to divide the main and control groups of patients into 2: sensitive and resistant to therapy. After treatment, a change in the mtKRAS ratio was not found in the subgroup sensitive to mC compared with the period before treatment, while the frequency of mtKRAS was reduced by 3 times (p = 0.009). In the mC-resistant subgroup, the mtKRAS ratio increased 1.9 times compared to the period before treatment (p = 0.009), while the frequency of mtKRAS increased 3.5 times compared with the mC-sensitive group (p = 0.0045). Conclusions: Prior to treatment, patients resistant to CT+mC were characterized by an increased occurrence of mutations in the KRAS and an apparently large number of tumor cells carrying mutations. The use of mCs caused a change in the direction of the clonal evolution of tumor cells - leading to an increase in the number of cells carrying mtKRAS (conditions were created for the elimination of cells with mutation in EGFR and KRAS wild type).
Influencing factors of delivery modes for pregnant women at a local community of Shanghai
Authors: Wen-qun Cao
Journal: BMJ (2012)

Objective To investigate the selection of dilivery of pregnant women and related factors.Methods The selection of delivery modes for pregnant women was investigated by analyzing the associated factors of the infants registered into a computerized health care managing system from January 1,2008 to December 31,2010 at a local community of Shanghai.The information associated with delivery modes of their mothers was collected and the choice of delivery modes investigated through a standardized questionnaire by interviewing the mothers at two months after birth.Results The cesarean section (C/S)rate of pregnant women residing in this local area was 58.3 ％ (224/384).In the C/S group,the percentages of delivery age ≥24 yr,white-collar workers,education level at high school and above and monthly income ≥ 3000 yuan were 73.2％ ( 164/224 ),38.4％ ( 86/224 ),79.5％ ( 178/224 ) and 80.8％ ( 181/224 )respectively.And they were all higher than those of vaginal delivery (63.1％,n =101; 32.5％,n =52;69.4％,n =111; 70.6％,n =113 ).The choices of C/S depended on the existences of maternal,fetal,social-psychological and others factors during pregnancy.Most pregnant women and families who chose C/S without medical indications were afraid of pain ( 33.9％ ) or a failure of vaginal delivery ( 30.5％ ).Conclusions The social-psychological factors of pregnant women are important in the choices of delivery modes.Unnecessary C/S could be reduced by improving their knowledge of delivery with meticulous prenatal health care consultations.

Key words: 
Parturition; Cesarean section; Community health services
Statin withdrawal syndrome in patients with coronary heart disease
Authors: Manyan Wu, Wenqing Liang
Journal: BMJ (2020)

Statins, as the first-line anti-atherosclerosis drugs, are of significant benefit in reducing the risk for cardiovascular and cerebrovascular events. However, many studies have shown that the patient adherence to statin is poor in clinical practice, and many cardiovascular patients abruptly discontinue therapy. Acute withdrawal of statin therapy may have a rebound effect on patient outcomes, and clinicians should pay attention to statin withdrawal syndrome to avoid its occurence.


Key words: 
Coronary disease; Statins withdrawal syndrome; Mechanisms
Hemodialysis with Cohort Isolation to Prevent Secondary Transmission during a COVID-19 Outbreak in Korea
Authors: Jang-Hee Cho, Seok Hui Kang, Hayne Cho Park, Dong Ki Kim, Sang-Ho Lee, Jun Young Do, Jong Won Park, Seong Nam Kim, Myeong Seong Kim, Kyubok Jin, Gun Woo Kang, Sun-Hee Park, Yong-Lim Kim, Young-Ki Lee
Journal: Journal of the American Society of Nephrology (2020)

Significance Statement Health care–associated infections during previous serious coronavirus epidemics resulted from human-to-human transmission in hemodialysis (HD) facilities. The authors analyzed the effect of a strategy of HD with cohort isolation on the secondary transmission of coronavirus disease 2019 (COVID-19) in HD facilities in Korea, which involves administering an immediate screening test for COVID-19 to all close contacts (patients on HD and health care workers) and strict maintenance of cohort isolation. Epidemiologic investigation and immediate screening tests across 11 HD centers identified 302 close contacts. HD with cohort isolation was maintained for a median of 14 days, and the transmission rate was 0.66% inside HD units. Clinical practice guidelines for HD with cohort isolation during COVID-19 outbreaks may successfully prevent secondary transmission through HD units. Background Health care–associated infections during previous coronavirus epidemics involving severe acute respiratory syndrome and Middle East respiratory syndrome resulted from human-to-human transmission in hemodialysis (HD) facilities. The effect of a strategy of HD with cohort isolation—separate dialysis sessions for close contacts of patients with confirmed coronavirus disease 2019 (COVID-19)—on the prevention of secondary transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in HD units is unknown. Methods Our multicenter cohort study of an HD with cohort isolation strategy enrolled close contacts of patients with confirmed COVID-19, including patients on HD and health care workers in HD units. Close contacts had been identified by epidemiologic investigation and tested negative on an immediate screening test for SARS-CoV-2. Results As of March 14, 11 patients on HD and 7 health care workers from 11 HD centers were diagnosed as having COVID-19. The immediate screening test was performed in 306 people, and among them, 302 close contacts with negative test results were enrolled. HD with cohort isolation was performed among all close contacts for a median of 14 days in seven centers. During cohort isolation, nine patients showed symptoms but tested negative for SARS-CoV-2. Two health care workers in the HD units (0.66% of the total group) were diagnosed at the termination test for SARS-CoV-2. Conclusions The transmission of COVID-19 can be controlled without closure of HD centers by implementing preemptive activities, including early detection with rapid testing, cohort isolation, collaboration between institutions, and continuous monitoring of infection. Our strategy and experience may provide helpful guidance for circumstances involving the rapid spread of infectious diseases such as COVID-19.
OSTPDL1: A phase II study of avelumab, a monoclonal antibody targeting programmed death-ligand 1 (PD-L1) in adolescent and young adult patients with recurrent or progressive osteosarcoma.
Authors: Michael William Bishop, Sue C. Kaste, April Sykes, Haitao Pan, Filemon S. Dela Cruz, Sarah Whittle, Leo Mascarenhas, Paul G Thomas, Ben Youngblood, Jennifer L Harman, Lisa L. Wang, Paul A. Meyers, Alberto S. Pappo
Journal: Journal of Clinical Oncology (2020)

10521 Background: Outcomes for recurrent osteosarcoma are poor and novel therapies are needed. Osteosarcoma has a high mutational burden with overexpression of PD-L1 in metastatic lesions, providing a rationale for testing immune checkpoint inhibitors in this population. We therefore evaluated the activity of the PD-L1 inhibitor avelumab in patients with recurrent or progressive osteosarcoma. Methods: We conducted a single-arm, open-label phase 2 trial at 4 collaborating institutions. Eligible subjects were ages 12 to ≤50 years with recurrent or progressive osteosarcoma and radiographic evidence of measurable disease. Subjects received avelumab 10 mg/kg intravenously every 2 weeks of 28-day cycles until disease progression or unacceptable toxicity. Primary endpoints were objective response rate (CR + PR according to RECIST v.1.1), and progression-free survival (PFS) at 16 weeks. Kaplan-Meier methods were used to estimate PFS. Secondary endpoints included toxicity. Correlative objectives included measurement of subsets of peripheral blood mononuclear cells and serum markers of immune activation, and measures of cell proliferation, co-inhibitory receptor expression on CD8 T cells, T cell repertoire, and epigenetic programming of T cells. Results: Between February 2017 and October 2019, 18 eligible subjects [67% male, median age 16.8 years (12.8-22.9)] were enrolled. Subjects had received median 3 prior systemic therapies (range 1-5). Sites of disease included lung/pleura (94%), bone (56%), and soft tissue (28%). Subjects received a median of 2 cycles (range 1-4) of avelumab. Median PFS was 8 weeks (95% CI 6.7-9.1). No objective responses occurred (17 with progressive disease), and the 16-week PFS was 0%. The most common adverse events (AEs) were alanine aminotransferase (ALT) elevation (17%), aspartate aminotransferase (AST) elevation, dyspnea, hyponatremia, and pain (each 11%). Treatment-related serious AEs (≥Grade 3) included dyspnea (n = 2), ALT/ALT elevation, hyponatremia, pericardial effusion and anemia (n = 1). Immune-related AEs included pneumonitis, Hashimoto thyroiditis, and pericardial effusion (all n = 1). One patient discontinued therapy after 1 dose due to grade 4 ischemic stroke, unrelated to avelumab. One death occurred on study due to rapid disease progression. Conclusions: Avelumab did not demonstrate activity in recurrent osteosarcoma. Correlative biology studies are ongoing to elucidate mechanisms of resistance to this therapy. Clinical trial information: NCT03006848.
Pay more attention to diagnosis, treatment and prevention for suffocative gas poisoning
Authors: 赵金垣
Journal: BMJ (2005)

窒息性气体中毒一直是困扰全球的普遍问题,其最具代表性的化合物是一氧化碳(CO)和硫化氢(H2S).CO中毒和死亡人数在全球急性中毒中迄今仍高居首位.约有10%～ 40%急性CO中毒患者经数日到数周的假愈期后,还可能发生迟发脑病(delayed encephalopathy, DEP),病程长且治疗困难,给社会带来很大负担;而中毒死亡率则以H2S为最高,我国近年的统计资料表明,其平均死亡率可达46%.因此,切实作好窒息性气体防治工作仍是当前医务卫生工作者的重要使命.就此本刊在本期组织了专题讨论,这对提升我国有关窒息性气体中毒的诊治水平、降低死亡率和后遗症发生率,无疑将发挥有力的推动作用.本文拟对窒息性气体中毒临床诊治中的一些常见问题及进展稍作讨论,供今后工作参考。
Investigation on medical compliance in patients with chronic hepatitis B and an analysis of influence factors
Authors: Zhao-xi Qin, Guang-cai Zhang, Li Wang, Su-fang Zhu
Journal: BMJ (2009)

As to evaluating the medical compliance of patients with chronic hepatitis B (CHB) and the influence factors, information of 163 patients with CHB treated with lamivudine were collected by using the self-designed questionnaire, and the medical compliance and influencing factors of the patients were acquired by the research followed, and the prognosis and allocation were also observed. The results showed the medical compliance in 77.3% of patients with CHB was good, and in 22.7% patients was poor. After following-up for 2 years, the negative rates of HBV DNA and HBeAg shown in patients with good medical compliance were 78.6% and 46.0%, respectively,showing a significantly higher rate than in those with poor medical compliance, which having the rate of 37.8% and 21.6%, respectively (P<0.01). We suggested that there should be a correlation between the medical compliance of patients with CHB and the prognosis.

Key words: 
Patient compliance;  Lamivudine