tbuckley/cabot-search huggingface dataset:
Association of driver genes with high-tumor mutation burden and outcome in patients with head and neck cancer: Implications for immunotherapy.
Authors: Yu Chen, Chuan-ben Chen, Xiao-bin Zheng, Xuan Gao, Liu Jun, Jia-ni Xiong, Jin Lin, Yaping Xu, Yan-Fang Guan, Yi Li, Yingying Huang, Xuefeng Xia
Journal: Journal of Clinical Oncology (2020)

e18533 Background: While the immune checkpoint blockades had demonstrated promising benefits in head and neck cancer (HNSC), its clinical efficacy is limited to a selected subset of less than 20% HNSC patients. Tumor mutation burden (TMB) has been reported as a predictor for ICBs in multiple tumors, including HNSC. However, the association of driver genes with TMB and outcomes in patients with HNSC has not yet been established. Methods: Somatic mutation landscape was characterized by interactively analyzed the sequencing data of 495 HNSC samples obtained from The Cancer Genome Atlas (TCGA) database and 185 samples from a Chinese cohort (Geneplus-database). Hybrid capture of a 1021 gene panel with potential clinical relevance was performed on tumor and paired Peripheral blood lymphocytes (PBLs) from 185 HNSC samples in a Chinese cohort. Results: In the Chinese cohort, patients harboring ≥5 muts/Mb (the top quartile of tTMB distribution) were classified as the TMB-H group; while ≥4.7 muts/Mb were classified as the TMB-M group. TMB -H was associated with better OS in the TCGA cohort. The rest were classified as TMB-L patients. Thirteen aberrant genes were significant correlation with TMB-H, including TSC2, POLE, CDK4, TSC1, MLH1, PTCH1, NF1, MSH3, RAD50, MSH2, CDH1, TNFRSF14, TERC. Among them,10 were further verified in the TCGA Head and Neck Cancer cohort, including TNFRSF14, MSH3, NF1, TSC2, RAD50, MSH2, PTCH1, POLE, MLH1, TSC1. Moreover, aberrant genes such as CDH1, MSH2 and RAD50 implicated better DFS (DFS:HR = .296, p = .034; HR = 0.128, p = .016; HR = .0422, p = .043) in HNSC of the TCGA cohort. Transcriptomic analysis in the TCGA Head and Neck Cancer cohort showed various degrees of immune upregulation in the tumor microenvironment (TME) in CDH1, MSH2, and RAD50 mutated population. Conclusions: These findings indicated that CDH1, MSH2, and RAD50 mutations may be associated with TMB-H, immuno-upregulation in TME and better survival outcomes. Combined with TMB, genes mentioned above may give us some insights into how ICB therapeutic strategies assist natural host immune responses against HNSC in Chinese population.
Prevalence and influencing factors of generalized anxiety disorder among disabled people in Shanghai Jing′an district
Authors: Yanyan Zhou, Yahong Bi, Yao Liu, Limin Lao
Journal: BMJ (2018)

Objective
To survey the status of generalized anxiety disorder (GAD) among disabled people in Shanghai Jing′an district and to investigate the influencing factors.


Methods
A cross-sectional study was conducted in January to March 2016 among the disabled residents in Shanghai Jing′an district. The general information was collected with questionnaire; the GAD status was rated with the Chinese version of 7-item Generalized Anxiety Disorder Scale; the influencing factors related to GAD was examined with Logistic regression analysis.


Results
Among 1 417 participants there were 713 males (50.3%) and 704 females (49.7%). The highest proportion of disability was disabled limb (n=742, 52.4%). The grade 4 disability (mild) accounted for 45.9% (650/1 417) , and the grade 1 and 2 disability (severe) accounted for 13.6% (190/1 417) and 15.2% (212/1 417), respectively. There were 347 participants positive for GAD screening (GAD≥5) with a positive rate of 24.5%: 24.3% for males and 24.1% for females (χ2=0.007, P=0.960). The rates of mild, moderate and severe GAD were 19.1%, 3.5% and 1.1%, respectively. Multi-factor analysis showed that subjects with severe disability (vs. mild disability,β=0.575, P=0.003) , those unable activities of daily living (ADL) (vs. normal ADL, β=0.034, P=0.000) were more likely to lead to GAD. There was a lower risk of GAD for people with high school or junior college education than those with bachelor degree or above (P<0.05). The frequency of GAD in the disables aged 18-40 years was lower (P<0.05).


Conclusion
The GAD positive rate of disabled people in Shanghai Jing'an district is relatively high. Severe disability, ADL disorder, educational level and age are the factors affecting the prevalence of GAD.


Key words: 
Disabled person; Questionnaires; Generalized anxiety disorder
Effect of community management of diabetic patients with hypertension
Authors: Yujie Lyu, Wencui Niu, Ziquan Han, Ying Qi, Fei Sun, Hanjing Fu, Shenyuan Yuan
Journal: BMJ (2016)

Objective
To evaluate the effect of community management of diabetic patients with hypertension in Beijing Cuigezhuang community in last three years.


Methods
A community diabetic management program was started from 2007 in Beijing Cuigezhuang community. Three hundred and seventy six patients who participated in the program for more than 3 years were enrolled in the study, including 196 with type 2 diabetes mellitus (T2DM) only (DM group) and 180 with T2DM and hypertension (DMH). The control rate of blood glucose, blood pressure, lipids and the comprehensive control rate were compared between two groups after 3-year intervention.


Results
There were no significant differences in age, gender ratio, course of diabetes, education background, monthly income and the history of stoke between two groups; while prevalence of dyslipidemia in DMH group was significantly higher than that in DM group [41.7%(75/180) vs. 24.5%(48 196), χ2=11.938, P=0.001]. Compared with the baseline data, the types of antidiabetic drugs used were not significantly changed in two groups after 3-year intervention (DM group: 1.32±0.81 vs.1.31±0.93, t=-0.155, P=0.877, DMH group: 1.43±0.72 vs. 1.48±0.82, t=0, 831, P=0.407). The types of antihypertensive drug in DMH group were significantly decrease. (1.12±0.77 vs. 1.25±0.45, t=2.484, P=0.014), while the rate of statins usage in DM group was significantly increased [13.3%(26/196) vs. 5.1%(10/196), χ2=7.830, P=0.005]. The hemoglobin A1c (HbA1c) levels in DM group was decreased [(7.4±1.5)% vs. (7.8± 2.1)%, t=2.586, P=0.011]. The systolic pressure [(129±12) mmHg (1 mmHg=0.133 kPa) vs. (133±16) mmHg, t=3.503, P=0.001] and the diastolic pressure [(80±8) mmHg ratio (82±10) mmHg, t=2.436, P=0.016] in DMH group were significantly declined. The average LDL-C level [DM group: (3.0±0.9) mmol/L vs. (3.2±1.0) mmol/L, t=2.165, P=0.032; DMH group (2.9±1.0) mmol/L vs. (3.2±1.1) mmol/L, t=3.210, P=0.002] were also significantly decrease. Compared with the baseline, the comprehensive control rates of blood glucose, blood pressure and lipid level were increased in both groups [DM group: 9.7% (19/196) vs. 6.1%(12/196), χ2=1.716, P=0.190, DMH group 13.9% (25/180) vs. 5.0%(9/180), χ2=8.315, P=0.004].


Conclusions
The community management program is effective for improvement of comprehensive control rates of blood glucose, blood pressure and blood lipids in diabetic patients with hypertension in Beijing Cuigezhuang community.


Key words: 
Community health services; Diabetes mellitus, type 2; Hypertension; Disease management
局麻下善愈补片腹膜前修补腹股沟疝的探讨
Authors: 王明刚, 陈杰, 申英末, 刘素君, 包少瑜, 朱大伟
Journal: BMJ (2008)

目前国内开展的开放式无张力腹股沟疝修补术术式常见的有5种:平片修补法、疝环充填式无张力修补法、复合平塞修补法、普里灵三合一无张力疝修补法(PHS)、腹膜前铺网法.善愈补片是一款适用于腹股沟疝腹膜前间隙修补的国产疝成形补片.2007年8月至2008年5月,我科采用此补片进行无张力疝修补术117例,取得较满意效果,现报告如下.
声音嘶哑
Authors: 周仲华
Journal: BMJ (2006)

全科医师在工作中经常会遇到声音嘶哑的病人,他们可表现为声音粗哑、异样或者刺耳.急性声音嘶哑常发生于上呼吸道感染,因病人还常常合并其他上呼吸道感染的症状和体征,所以比较容易识别;还常见于一些象歌唱家、老师等特殊的职业,由于过度使用声带而发生声音嘶哑.通常情况下,病毒感染所引起的声音嘶哑即使不用任何药物也会在几天内自然痊愈.如果声音嘶哑持续的时间超过了3周,就变成了慢性,这时医生需要考虑下列可能的原因:①过度使用声音,如唱歌或者讲课;②打鼾;③真菌性口腔炎(如接受激素吸入治疗者);④甲状腺功能低下; ⑤喉癌或者肺癌(喉返神经麻痹); ⑥声带疾病.无法解释的声音嘶哑持续超过3～4周,原则上就应该转诊至专科医生,对上述可能的情况进行进一步的评估。
Pharmacokinetically-guided 5-FU dose optimization within the preoperative FOLFOXIRI regimen in resectable pancreatic cancer patients.
Authors: Anna Vilalta, Amaia Urrizola Martínez, Azucena Aldaz, Pablo Sala Elarre, Mariano Ponz-Sarvisé, Fernando Rotellar, Fernando Pardo, Jose Carlos Subtil, Ana Chopitea, Javier Rodriguez
Journal: Journal of Clinical Oncology (2020)

4636 Background: Neoadjuvant therapy is an increasingly used approach in patients with resectable pancreatic cancer (PC). A positive link between chemotherapy dose intensity and patients’ outcome has been suggested in PC. The aim of this study was to rule out whether 5-FU pharmacokinetic (PK) parameters correlate with outcome in resectable PC patients treated with preoperative FOLFOXIRI. Methods: Patients with resectable and borderline resectable PC treated with Oxaliplatin (85mg/m 2 ), Leucovorin (400mg/m 2 ), Irinotecan (150 mg/m 2 ) and 5-FU (initial dose of 3200 mg/m 2 in 46h infusion and subsequent doses based on PK-guided dose adjustements targeting an AUC of 25-30 mcg*h/ml) were included. 5-FU PK analysis was performed taking two plasma samples during 5-FU infusion in at least two cycles. Drug concentrations were analysed by High-Perfomanced Liquid Chromatography. After induction polychemotherapy (IPCT), patients with no progressive disease received chemoradiation (CRT) (50.4 Gy with concurrent Capecitabine and Oxaliplatin) followed by surgical resection 4 to 6 weeks after the completion of CRT. Subsequent follow-up until disease progression was remained. An exploratory analysis with Log-Rank test was performed to assess progression free survival (PFS) based on 5-FU AUC values. Results: From November 2012 to October 2018, 29 patients were retrospectively assessed: median age 63 (46-75); M/F rate 20/9; R0 resection rate of 90% in the intention-to-treat analysis. The pathological response according to CAP classification was 0, 1, 2 and 3 in 14, 58, 19.5 and 8.5%, respectively; and median number of resected lymph nodes was 11 (2-22), with lymph node infiltration (ypN1) in 14% of patients. Grade 3-4 IPCT related toxicities and grade 3 CRT related toxicities were reported in 40 and 30% of patients, respectively. Median PFS was 723 days (24 months) and median 5-FU AUC 28.5 mcg*h/ml (23-53). Median PFS for patients with 5-FU AUC ≥27 mcg*h/ml was 29 months versus 15 months in patients with 5-FU AUC &lt; 27 mcg*h/ml (adjusted hazard ratio for disease progression 0.223; 95% CI = 0.059-0.848; p = 0.028; in a model controlled by age, sex and irinotecan dose intensity). Conclusions: 5-FU pharmacokinetic parameters achieving a target of AUC ≥ 27 mcg*h/ml seem to correlate with longer PFS in this subset of patients.
Practice and exploration of a standardized training program for general practitioner assistant (3+ 2 mode) in Shanghai Jiading District
Authors: Kun Zhu, Yingmin Chen, Jianye Qin, Yi Zhai, Chunmei Wang
Journal: BMJ (2018)

A 3+ 2 standardized training program of assistant general practitioner was launched in Shanghai Jiading District in 2012 in order to train new medical talent in suburb area. The program was developed through the jointed efforts among the government, medical school and train bases. The model was designed as training assistant general practitioners with distinctive sequential education process in different levels and stages. After five years of practice, the 3+ 2 standardized training program of assistant general practitioner has accomplished its goal, which provides a reference for training assistant general practitioners in Shanghai Municipality.


Key words: 
General practitioner; Standardized training
Diagnosis and treatment of blunt diaphragmatic rupture
Authors: Wen-feng Zhang, Qin Fang, Yu Li, Dong-yi Chen, Shun Xu
Journal: BMJ (2008)

A retrospective analysis was carried out in 36 patients with blunt diaphragmatic rupture during March 1991 and March 2006. Twenty-two diagnoses were confirmed preoperatively, and the rest 14were confirmed perioperatively. Three patients underwent surgical treatment after no response to conservative therapy. Thoracotomy was performed in 21 patients, laparotomy in 9, thoracotomy plus laparotomy in 5 and combined thoraco-laparotomy in 1. Most diaphragmatic rupture may be caused by blunt collision and could lead to thoracoabdominal injury. In spite of high mortality rate, the condition is usually under diagnosed. Definite diagnosis and timely operation are important to increase survival rate and reduce mortality. 

Key words: 
Wound and injuries; Diaphragm
DWI in differential diagnosis between dysembryoplastic neuroepithelial tumors and low-grade glioma
Authors: Lei Han, Huixian Shi, Song′an Shang, Jing Ye, Qingrun Li, Hongri Chen, Hongying Zhang
Journal: BMJ (2019)

Clinical and imaging data of 11 patients with dysembryoplastic neuroepithelial tumors (DNET) and 15 patients with low-grade glioma (LGG) admitted in Northern Jiangsu People′s Hospital were analyzed retrospectively. Routine MRI scan, diffusion weighted imaging (DWI) and enhanced scan were performed. The workstation automatically generated apparent diffusion coefficient (ADC) maps and then to obtain ADC values of the tumor parenchymal area and the contralateral normal reference area. Relative tumor/reference ADC values (rADC) were also calculated. The ADC values of parenchymal regions of tumor and contralateral normal reference areas and the rADC between DNET and LGG were compared. There was significant difference in age distribution between the two groups [(16.6±13.1) vs. (43.0±19.2) years, t=3.938, P 0.05). The ADC values of tumor parenchymal regions in both groups were significantly higher than those in contralateral reference regions (both P<0.01), the rADC of DNET was significantly higher than that of LGG (P<0.01). It is difficult to identify DNET and LGG by conventional image morphology, however the rADC value of DNET in DWI is significantly higher than that of LGG, and can provide important reference for differential diagnosis between them.


Key words: 
Neuroectodermal tumors, primitive; Glioma; Diffusion magnetic resonance imaging; Apparent diffusion coefficient
Phase III randomized study of adjuvant treatment with the ANTI-PD-L1 antibody avelumab for high-risk triple negative breast cancer patients: The A-BRAVE trial.
Authors: Pier Franco Conte, Maria Vittoria Dieci, Giancarlo Bisagni, Michelino De Laurentiis, Carlo Alberto Tondini, Peter Schmid, Gian Luca De Salvo, Giacomo Moratello, Valentina Guarneri
Journal: Journal of Clinical Oncology (2020)

TPS598 Background: Chemotherapy represents, today, the only treatment option for triple negative breast cancer (TNBC) and still a considerable proportion of pts with primary TNBC experience disease relapse. The risk is particularly high in the presence of poor prognostic features, such as more advanced stage and, for pts treated with neoadjuvant chemotherapy, failure to achieve a pCR. Recent evidence suggest that immunotherapy can play a major role in TNBC pts. Methods: The A-BRAVE trial is an investigator-driven trial sponsored by the University of Padova (Dept. of Surgery, Oncology and Gastroenterology). This is a phase III, multicentric, randomized adjuvant study that compares 1 year of treatment with the anti PD-L1 avelumab vs observation for pts who completed treatment with radical intent for primary TNBC including surgery and chemotherapy. The study enrolls pts in two strata: -Stratum A: primary TNBC pts who completed surgery followed by adjuvant, defined according to one of the following stage categories: if pN2, any pT; if pN1, pT &gt; 2 cm; if pN0, pT &gt; 5 cm. -Stratum B: primary TNBC pts who completed neoadjuvant chemotherapy followed by surgery who did not achieve pCR. Pts who also received additional adjuvant chemotherapy for no more than 6 months are eligible in Stratum B, after the completion of the adjuvant chemotherapy. Pts are randomized (1:1, balanced for strata A and B) to receive Avelumab 10 mg/kg I.V. q2w for 1 year or to observation. The first and second co-primary endpoints are disease-free survival (DFS) in all pts and DFS in Stratum B pts. With a planned sample size of n = 474 pts the trial has 90% power to detect a HR = 0.60 for the first co-primary endpoint (n = 172 events required). Taking into account that the percentage of patients enrolled in the stratum B could range from 70 to 80%, there will be 70-79% power to detect a HR = 0.60 at alpha allocated in this patient subgroup (second co-primary endpoint). Secondary objectives include: DFS in PD-L1 positive pts, overall survival, safety, biomarkers. Tumor tissue, plasma samples and fecal samples are collected for biomarker analysis. The study is currently recruiting across 73 sites in Italy and UK. As of February 2020, n = 349 pts have been enrolled. EUDRACT 2016‐000189‐45. The authors present the A-BRAVE trial in progress on behalf of Italian and UK investigators. Clinical trial information: NCT02926196 .
Prevalence of germline mutations in <i>BRCA</i>1/2 in patients from northeastern Brazil.
Authors: Clarissa Gondim Picanço-Albuquerque, Isabelle Joyce de Lima Silva-Fernandes, Maria Júlia Barbosa Bezerra, Maria Claudia dos Santos Luciano, Rosane Oliveira Sant'Ana, Paulo Goberlanio de Barros Silva, Marcos Venício Alves Lima
Journal: Journal of Clinical Oncology (2020)

e13603 Background: Identifying carriers of hereditary cancer predisposition syndromes (HCPS) improves prevention and treatment. However, due to the elevated cost of genetic testing, information on the prevalence and incidence of HCPS is scarce, depriving patients of assertive treatment―a scenario observed worldwide, especially in regions like Northeastern Brazil. In this study, we determined the prevalence of hereditary breast and ovarian cancer (HBOC) in patients from Ceará (Brazil) based on NCCN criteria. Methods: The patients (n = 267) were evaluated using NGS gene panels, while retrospective data were analyzed statistically with the chi-squared test, Fisher’s test and multinomial logistic regressions ( p&lt; 0.05; SPSS 20.0). Results: BRCA1/2 was detected in 21.3% (57/267) of the sample, but BRCA1 was more prevalent than BRCA2 (70%; 40/57 vs 30%; 17/57) ( p&lt; 0.001). Having two or more primary tumors ( p= 0.031) or primary ovarian cancer ( p= 0.029) was associated with the pathogenic mutation BRCA1/2. The latter was detected in patients with bilateral tumors (40%) and male breast cancer (45%), and in patients under 45 years (67%), with familial breast cancer (27%) and familial ovarian cancer (41%). In the multivariate analysis, the triple-negative phenotype was strongly associated with mutated BRCA1/2 ( p= 0.003). Conclusions: The prevalence of HBOC in our sample is compatible with rates reported worldwide. The study variables (bilaterality, male sex, age &lt; 45 years, family history of breast or ovarian cancer, and triple-negative phenotype) reinforce the diagnostic criteria published by the NCCN.
Effect of health management in risk behavior control of chronic diseases
Authors: Qiu-hua Wu, Yu-mei Shen, Guo-qin Zhang, Li Yang, Jian Liu
Journal: BMJ (2008)

Three hundred and ninety-five administrative staffs were randomly selected and provided health management to evaluate its effects in risk factors control of chronic diseases. At 1 year, the rate of people health knowledge and attitude were increased from 14.2% to 39.2%, 7.1% to 25.1%, P≤0.01 ; risk behavior exposure, including incorrect dietary intake, sedentary habit, alcohol consumption or smoking, reduced to some extent (P<0.05).

Key words: 
Health services administration;  Risk factors
Expanding the definition of covid-19 deaths will show the true effect of the pandemic
Authors: Peter L Labib, Somaiah Aroori
Journal: BMJ (2020)

Appleby asks what is happening to non-covid deaths.1 The covid-19 pandemic has significantly affected our hepatopancreaticobiliary unit. Because of the need to ring fence critical care facilities, our theatre lists have been reduced, and surgery is only proceeding in cases likely to become inoperable before normal service resumes. Unfortunately, many patients will develop inoperable disease before theatre capacity is reinstated. Although many …
Clinical features and left ventricular (LV) dysfunction in heart failure patients with normal ejection fraction
Authors: 林少华, 姜领, 鞠衍松, 唐子东
Journal: BMJ (2011)

100 inpatients with heart failure were divided into two groups: 50 with preserved LVEF and 50 with reduced LVEF. Another 50 age-matched healthy subjects served as the control group. The severity and etiology of heart failure, tissue Doppler imaging indexes (Sm;Ea;Aa;E/Ea) and plasma BNP concentrations were compared among the three groups. There was no difference in terms of NYHA classification between groups of preserved LVEF and reduced LVEF. Hypertension and DM are more common in the group of preserved LVEF. The index of Sm decreased most significantly in the group of reduced LVEF, and was negatively correlated with the BNP concentration (r = -0. 35, P ＜ 0. 05 ). The ratio of E/Ea increased gradually among the three groups, and was positively correlated with the BNP concentration ( r = 0. 728, P ＜ 0. 05 ). The LV filling index E/Ea and the BNP concentration may be helpful in the diagnosis of heart failure patients with preserved LVEF.

Key words: 
Heart failure ;  Ventricular function,Left ;  Echocardiography ;
Efficacy and safety of pegylated recombinant human granulocyte colony-stimulating factor in the primary and secondary prevention of chemotherapy-induced neutropenia in patients with lymphoma.
Authors: Meifeng Tu, Jun Zhu, Yuqin Song
Journal: Journal of Clinical Oncology (2020)

e20061 Background: To evaluate the efficacy and safety of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF, brand name: Jinyouli) in the primary and secondary prevention of chemotherapy-induced neutropenia in patients with lymphoma. Methods: This single-center, one-arm and open-label clinical study enrolled 119 patients with lymphoma in Peking University Cancer Hospital &amp; Institute from May 2016 to December 2018. Patients ≥45 kg received a single dose of PEG-rhG-CSF for 6mg, &lt; 45kg for 3mg, subcutaneous injection once in 24-48 h after chemotherapy. Results: 119 lymphoma patients, including 60 primary and 59 secondary prevention patients, underwent a total of 427 cycles of chemotherapy. The overall incidence of febrile neutropenia (FN) was 6.32% (27/427), with rates of 5.39% and 7.17% in the primary and secondary prevention groups, respectively. There was no significant difference between two groups ( P&gt; 0.05).The incidence of FN was significantly lower in the second cycle than in the first cycle in both the primary and secondary prevention groups ( In the primary group: cycle 1 vs. cycle 2: 15.00% vs. 2.22%, respectively, P= 0.027; In the secondary group: cycle 1 vs. cycle 2: 16.95% vs. 5.08%, respectively, P= 0.040). The overall incidence of grade Ⅳ neutropenia was 13.58% (58/427), with rates of 8.82% and 17.94% in the primary and secondary prevention groups, respectively. There was a significant difference between two groups ( P= 0.006). The incidence of grade Ⅳ neutropenia was significantly lower in the second cycle than in the first cycle (In the primary group: cycle 1 vs. cycle 2: 25.00% vs. 4.44%, respectively, P= 0.005; In the secondary group: cycle 1 vs. cycle 2: 47.46% vs. 11.86%, respectively, P&lt; 0.001). The main treatment-related adverse event was bone pain, with an incidence of 2.52% (3/119). Conclusions: PEG-rhG-CSF can effectively reduce the incidence of FN and neutropenia with good safety in patients with lymphoma after chemotherapy. Primary prevention can significantly reduce the risk of grade IV neutropenia in all chemotherapy cycles compared with the secondary prevention. Clinical trial information: NCT02905916 .