tbuckley/cabot-search huggingface dataset:
Adjuvant therapy in non-metastatic melanoma result from a Brazilian cohort.
Authors: Sinara Figueiredo Silva, Monique Celeste Tavares, Milton Jos De Barros E Silva, José Augusto Rinck, Joao Paulo SN Lima, Daniel Garcia, Vinicius Fernando Calsavara
Journal: Journal of Clinical Oncology (2020)

e22095 Background: The PD-1–blocking antibodies, combination of target therapy and anti-CTLA4 have shown a favorable safety profile with better efficacy than high-dose interferon in the adjuvant setting. However, in Brazil only a minority of patients in private institutions have access to new therapies in adjuvants. Here, we describe the evolution of patients with non metastatic melanoma who received anti-PD1 or target therapy adjuvant or only followed. Methods: This is an observational, descriptive, retrospective cohort, which included patients diagnosed with cutaneous, mucous or acral melanoma (operated stage III or stage IVa) submitted or not they undergoing adjuvant chemotherapy between January 2013 and December 2019 at AC, São Paulo, Brazil. Results: We evaluated 82 patients with a median age of 54 years, 62.2% of the patients were male, the majority, 81.1%, white. In 29.3% had primary ulceration and presence of satellites was observed in 18.3% and the average Breslow value of the cases was 3,3mm. We found that 18.3% of patients were classified as stage IIIA, 4.9% IIIB, 22% IIIC, 8.5% IIID and 9.8% stage IV operated. The 44.6% of patients completed 1 year of adjuvant treatment. Related to the presence of ulceration, we observed a progression-free survival of 36.3 months for cases with ulceration versus 47.1 months for cases with absent ulceration, ( p= 0.449). Patients with satellite presence had a progression-free survival of 29.9 months versus 49.1 months for cases of missing satellite, ( p= 0.118). Patients who underwent lymph node dissection had a progression-free survival of 50.3 versus 36.4 months, those who did not undergo ( p= 0.201). Patients who completed 1 year of adjuvant therapy achieved a recurrence-free survival of 66.1 versus 27.9 months who did not complete, ( p= 0.003). Considering the tumor staging, patients classified T1a-T2a had a progression-free survival of 59.8 months, T2b-T3b of 42 months and those grouped as T4a, T4b, of 29.9 months, ( p = 0.021). The median progression-free survival was 44 months, 40.6 months for patients who received adjuvant treatment versus 27.2 months for those who did not ( p = 0.271) with a reduced risk of progression in the order of 33% for patients who received adjuvant. Conclusions: The presence of ulceration, satellites and advanced T staging were associated with a worse outcome with a greater chance of recurrence. Emptying of the lymph node chain, receiving adjuvant treatment and completing 1 year of adjuvant treatment were directly associated with improved survival
Abstract 11217: Copeptin: A Novel Biomarker in Pediatric Heart Failure Due to Cardiomyopathies
Authors: Karan B Karki, Jeffrey A Towbin, Ranjit R Philip, Camden Harrell, Sachin Tadphale, Samir Shah, Arun Saini
Journal: Circulation (2019)

Introduction: Cardiomyopathies are common causes of Pediatric Heart Failure (HF). Biomarkers are often used to assess the severity of HF. B-type natriuretic peptide (BNP) is the only commonly used ...
Rising incidence of clostridium difficile infection and associated clinical outcomes in hospitalized cancer patients: A national perspective.
Authors: Shivani Dalal, Krunalkumar Patel, Dhruvil Radadiya, Kirtenkumar Patel
Journal: Journal of Clinical Oncology (2020)

e19095 Background: Cancer patients are more prone to Clostridium difficile infection (CDI). Several factors such as increased exposure to antibiotics (either in the form of prophylaxis or treatment), being on chemotherapy, and frequent exposure to healthcare settings are responsible for this. Rate of CDI in these patients ranges from 10-20%. Here, we performed a retrospective analysis using the national inpatient sample to study the trend and to see whether CDI leads to poor outcomes in these patients. Methods: We have used National Inpatient Sample database from the year 2009 to 2015 to identify hospitalized adult patients with cancer using ICD-9 CM codes. Similarly, We also identified patients with concurrent CDI amongst all cancer patients. Our primary aims were to study the trend of CDI and associated outcomes in from of mortality, cost of hospitalization and length of stay. Incidence of CDI per 10,000 discharges in those patients over the study period was assessed. Outcomes related to CDI in cancer patients were compared with those without CDI. Categorical and continuous variables were compared between matched cohorts using Chi-square and Student’s t-test, respectively. Statistical significance level was set at &lt; 0.05. All analyses were performed with the use of SAS (version 9.4). Results: Total of 6,035,966 cancer patients was identified over the study period. Out of which, 57,167 (0.9%) had concurrent CDI. Age, sex and race were comparable in both the groups. Incidence of CDI increased from 89 cases to 101 cases per 10,000 cancer patients (p-trend: &lt; 0.05). Inpatient mortality was significantly higher in cancer patients with CDI compared to without CDI(12.1% vs 4.7%, p &lt; 0.0001). Cost of hospitalization was almost 3 times higher ($36,243 vs $12,910, p &lt; 0.0001).Median length of stay was almost four-fold longer (16 days vs 4 days, p &lt; 0.0001). Patients with Medicare and Medicaid had higher percentages of CDI cases while patients with private insurance had lower percentages. Conclusions: Incidence of CDI in cancer patients is on the rise. CDI lead to higher mortality, cost of hospitalization, and length of stay in cancer patients. Preventive strategies in form of judicious use of antibiotics and prompt identification with treatment may help with reducing mortality and associated healthcare burden.
An integrative molecular framework to predict homologous recombination deficiency.
Authors: Joshua SK Bell, Aarti Venkat, Jerod Parsons, Catherine Igartua, Benjamin D. Leibowitz, Robert Tell, Kevin White
Journal: Journal of Clinical Oncology (2020)

e15664 Background: Homologous recombination deficiency (HRD) is the primary biomarker for sensitivity to PARP inhibitors, but identifying the genetic and transcriptomic characteristics that fully capture all HRD patients has remained difficult. For example, DNA-based approaches are limited to patients with pathogenic mutations and loss of heterozygosity (LOH) events, and can fail to properly classify patients with variants of unknown significance. To capture more dynamic cellular processes that arise immediately upon induction of HRD through silencing or loss of BRCA 1/2, a more integrated approach that includes both RNA and DNA based models is necessary. Methods: Using DNA sequencing we developed a genome-wide LOH score that combines pathogenic mutation status and LOH at the BRCA1/2 loci, and the proportion of bases sequenced in the Tempus xT panel that undergo LOH. We also developed three independent RNA-based models to predict BRCA deficiency: 1) An elastic net transcriptome model to predict DNA-based HRD scores derived from exome and SNP array data for each tumor type represented in TCGA; 2) A logistic model to detect BRCA1 promoter hypermethylation from the transcriptome in TCGA data; 3) A model that leveraged the mSigDB annotated gene sets to conduct single sample gene set enrichment analysis (ssGSEA) on Tempus-sequenced patients, selecting over a hundred gene sets that were predictive of BRCA-deficiency. These 4 features were combined to develop a stacked, linear-regression model to distinguish BRCA-intact from BRCA-deficient patients. Results: We found that the genome-wide LOH score alone is predictive of BRCA deficiency. However, our integrated model was highly accurate at distinguishing between BRCA-intact and BRCA-deficient patients and outperformed any single RNA- or DNA-based model. Using this model, we identified many patients that are likely to respond to PARP inhibitors that would have been overlooked using RNA or DNA-based inferences alone. Conclusions: Our approach highlights the strength of integrating diverse molecular features to refine diagnosis and enable oncologists to deliver the most effective therapies to patients.
Safety and efficacy of chimeric antigen receptor T cells modified to target mesothelin and express PD-1 antibodies in patients with relapsed/refractory solid cancers in a phase I trial.
Authors: Juemin Fang, Yan Sun, Xianling Guo, Bailu Xie, Hui Wang, Wei Mao, Zhongzheng Zhu, Zhuqing Liu, Fei Hu, Min Yuan, Song Gao, Zhicai Lin, Zhiwei Zhang, Huimei Li, Wenqi Chu, Xinru Pang, Qijun Qian, Huanlong Qing, Qing Xu
Journal: Journal of Clinical Oncology (2020)

3039 Background: The limitations of chimeric antigen receptor T cells (CAR-T) in solid tumors are immunosuppressive tumor microenvironment and difficult infiltration to tumor. In order to reduce on-target off-tumor toxicities and circumvent the immune-suppressive tumor microenvironment(TME), we modified autologous CAR-T to be specific for mesothelin (MSLN) on cancer cells and secrete PD-1 antibodies (aPD1-MSLN-CAR T cells). Here, we report the safety and efficacy of aPD1-MSLN-CAR T cells in 10 patients with relapsed/refractory solid cancers in this single-arm, open-label, first-in-human phase I pilot study (ClinicalTrial.gov: NCT03615313). Methods: aPD1-MSLN-CAR T cells were prepared from peripheral blood mononuclear cells and engineered using PiggyBac Transposon System to target MSLN and secrete PD-1 antibodies. 10 patients with mesothelin positive relapsed/refractory solid cancers after failure to standard therapies were treated with aPD1-MSLN-CAR T cells for two or more cycles until disease progression or intolerable toxicity. The dose escalation of CAR T cells was designed to be 5×10 6 /kg, 5×10 7 /kg, and 1×10 8 /kg, respectively. Adverse events were evaluated according to CTCAE-V4.03 and clinical response was assessed by RECIST 1.1. CAR expression was analyzed using quantitative real-time polymerase chain reaction. PD-1 antibodies were detected by ELISA. Serum IL-2, IL-4, IL-6, IL-10, IFN-γ and TNF-α were measured using flow cytometry. Results: The most common adverse events were mild fatigue and fever. Abdominal pain was also observed in 1 patient. Grade 1 and 2 cytokine release syndromes were observed without neurologic symptoms in 10 patients. After aPD1-MSLN-mRNA-CAR T cells treatment, 2 patients (20%) achieved partial response (PR), 4 (40%) remained stable (SD), and the rest 4 (40%) patients developed disease progression (PD). The median PFS was 97 days [95% CI (13, 180)] estimated by Kaplan-Meier method. Conclusions: These findings lend support that the combination of modified CAR T cells targeting MSLN with PD1 inhibition for solid tumors is safe. Modified CAR-T cells expressing PD-1 antibodies maybe an option to improve CAR-T efficacy as a result of refined TME. Clinical trial information: NCT03615313 . [Table: see text]
病与非病
Authors: 曾昭耆
Journal: BMJ (2005)

2004年7月8日,我出干部门诊,见到几个患者. 一位患者男,73岁.妻子2年前去世,患者心情不佳,体重下降约5 kg,同事和医生很关心.患者自己怀疑为消化系统和前列腺肿瘤,经做肠镜及查前列腺特异性抗原(PSA)已除外.曾有医生说他有3次查血压为140/80 mm Hg(1 mm Hg=0.133 kPa),且有右侧面瘫,是脑中风前兆.患者自述常于睡眠时有右口角流涎.故十分紧张。
Lipid measures for prediction of insulin resistance
Authors: Jing Guan, Ying Yang, Xian-cheng Liu, Cai-xia He
Journal: BMJ (2008)

A cross-section study was designed to investigate clinical utility of lipid measures for prediction of insulin resistance(IR).A total of 793 healthy volunteers were divided to IR group or non-IR group based on the value of HOMA-IR.Area under receiver operating characteristic curve(ROC)found that TG/HDL-C was more related with IR in comparison with other lipid ratios,and could be used as a measure in predicting IR.

Key words: 
Insulin resistance; Forecasting
Renal calculi treated with extracorporeal shockwave lithotripsy in children: a report of 27 cases
Authors: Wei Lin, Hai-peng Huang, Hui Huang, Dong-liang Meng, Jie-qing He
Journal: BMJ (2010)

Clinical data of 27 children with renal calculi (11 cases on the right side and 16 on left)who were treated with extracorporeal shockwave lithotripsy (ESWL) using HB-ESWL-VG lithotripter from April 2006 to October 2008 were retrospectively reviewed.The size of stones ranged from 5 mm to 17 mm in diameter (mean 11 mm).In 22 out of 27 cases (82%) stones were crushed completely after the first course.Eleven of 27 ESWL cases were stone-free in 7 days,8 patients in a month after treatment;the stonefree rate was 96% when patients were followed up for 1 year.The results suggest that ESWL is a safe and effective method for treatment of renal calculi in children.

Key words: 
Lithotripsy;  Child
A highly effective and practical desensitization regimen: Results in comparable clinical outcomes for multiple myeloma patients with skin rash after immunomodulatory drugs.
Authors: Amin Firoozmand, Naveed Ali, Nausheen Ahmed, Pingfu Fu, Shufen Cao, George Brown, Hannah Schmikla, James Joseph Driscoll, Timothy O' Brien, Paolo Fabrizio Caimi, Marcos J.G. De Lima, Ehsan Malek
Journal: Journal of Clinical Oncology (2020)

12104 Background: Immunomodulatory drugs (IMiDs) are backbone of myeloma therapy for patients with Multiple Myeloma (MM). The incidence of IMiD-associated rash is up to 27% in some reports impeding maximal benefit of this agent. The optimal management of IMiDs-associated skin is unclear. The concurrent weekly Dexamethasone (Dex) does not diminish the incidence of skin eruptions with IMiDs (Sviggum, et al. 2006), therefore we designed a low dose daily and tapering corticosteroid regimen to tame this immune response upon restarting IMiDs and allow desensitization and reinstitution of the same IMiD. Furthermore, we assessed the impact of this desensitization regimen on clinical outcome. Methods: A total of 160 patients were evaluated. The incidence of rash was found to be 13% (n = 21). A cohort of age- and gender-matched without rash (n = 39) was randomly selected. The effects of rash on overall and progression free survival (OS and PFS) were further estimated using Cox regression controlling the effects of age and gender. Results: Median time to development of rash after IMiD initiation was 28 days (range, 2-232). Rashes were graded as low (I-II) in 89% (n = 17) and high (III-IV) in 19% of pts. All pts were managed by temporary treatment interruption and upon clearance of rash, re-institution of the same IMiD concomitantly with a standardized 3-week steroid rash prophylaxis protocol (prednisone at 10 mg daily for 10 days, followed by 5 mg daily for 10 days, followed by 5 mg on alternate days for 10 days). As a result, all patients were able to restart the same IMiD with none re-experiencing any dermatologic adverse effect afterward. Comparing to no-rash controls, there was no significant difference in PFS (0.13) or OS (p = 0.12) in multivariate regression model. Conclusions: Proposed 3-week corticosteroid regimen showed 100% success rate in reinstituting IMiDs in our cohort. It may provide a highly effective and practical short term immunosuppression required to enable patients to restart IMiDs and enjoy comparable outcome to pts without skin rash.
以胸闷、心悸伴喘息为症状的脑干炎症一例
Authors: 牛姝媛, 阮颖, 张振声, 张密, 李秀玉, 宋新梅
Journal: BMJ (2007)

患者女,44岁,以突发胸闷、心悸伴喘息1 d,于2006年12月18日15:00急诊收入内科病房.当时无眩晕、恶心及呕吐,无复视和走路不稳,无吞咽困难和饮水呛咳,无胸痛和咯血,无意识障碍和言语障碍,无肢体无力和大小便失禁。
Analysis for risk factors related to non-alcoholic fatty liver in people undergone physical examinations in Beijing
Authors: An-nan Liu, Ling Zhu, Tie-mei Zhang, Lan-jun Ma, Yan-yan Zhao
Journal: BMJ (2009)

To explore relationship of body mass index (BMI), waist circumference (WC), blood lipid level with non-alcoholic fatty liver (NAFL) to provide evidence for its early intervention. Methods Data of 13 532 people living in Beijing undergone regular physical examinations at Beijing Hospital, including liver-ultrasonic scanning, measurements of blood lipid, height, weight, waist circumference and BMI during January to December 2007 were statistically analyzed. Results Totally, 4 807 people were diagnosed as NAFL by B-type ultrasonic scanning, with a mean age of (54 ± 14) years and median age of 53 years. Prevalence of NAFL significantly increased with changes in body building (normal weight, overweight and obesity) and age groups (X2 = 1640.394, P<0.01 ). There was statistical significance in prevalence of NAFL between groups with normal weight and overweight at varied ages ( X2 = 172.618 and 31.928, respectively, P < 0.01 ), with the highest at ages of 51 - 60 years. No statistical difference in prevalence of NAFL between varied age groups was found in those with obesity (X2 = 6.194, P =0.402). Mean of WC, BMI, serum levels of triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) were significantly higher in NAFL group than those in those without NAFL, but mean serum level of high-density lipoprotein cholesterol (HDL-C) was significantly higher in the former than that in the latter ( P < 0.05 ). Prevalence of dyslipidemia was significantly higher in NAFL group than that in those without NAFL ( X2 = 112. 974 - 895. 500, respectively, P < 0. 01 ), with the highest of hypertriglyceridemia, accounting for 54. 36 percent. Prevalence of NAFL was significantly higher in those with larger WC than that in those with normal WC in the normal weight and overweight group (X2 = 120.982 and 45.327, respectively, P<0.01). Results of logistic regression analysis showed that WC, BMI, TG and LDL-C all were risk factors for NAFL both in men and women, and HDL-C was a protective factor for NAFL only in women. Conclusions Overweight, obesity and dyslipidemia closely correlate with occurrence of NAFL Control of body weight and blood lipid level are essential for decreasing prevalence of NAFL.

Key words: 
Fatty liver;  Risk factors;  Dyslipidemias
妊娠合并特发性血小板减少性紫癜的诊治问题
Authors: 赵永强
Journal: BMJ (2007)

国内外文献报道妊娠合并特发性血小板减少性紫癜(简称妊娠ITP)的发生率为0.1‰～3.0‰.在妊娠期间的各种血小板减少症中,妊娠ITP仅占5%左右,最常见的是妊娠血小板减少症,占70%左右。
Application of abbreviated protocol of magnetic resonance imaging for breast cancer screening in dense breast tissue
Authors: Shuangqing Chen, Chenlu Liu, Yuying Shen, Qing Cai, Chuanxiao Xu
Journal: BMJ (2017)

Objective
To evaluate the application of abbreviated protocol (AP) of magnetic resonance imaging (MRI) in screening of breast cancer with dense breast tissue.


Methods
Total 478 patients with dense breast tissue, who had negative X-ray mammography (MG), underwent dynamic contrast-enhanced MRI (DCE-MRI). The AP MRI, which consisted of first postcontrast subtracted (FAST) and maximum-intensity projection (MIP), and full diagnostic protocol (FDP) MRI images were analyzed by Breast Imaging Reporting and Data System (BI-RADS). Among 478 patients the histopathological diagnosis was available in 39 cases (41 breast lesions) . With pathological diagnosis as gold standard, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of AP and FDP in breast cancer detection were evaluated.


Results
In 41 breast lesions there were 16 malignant lesions and 25 benign lesions. FDP detected all 16 malignant lesions, including 9 cases of ductal carcinoma in situ, 6 cases of invasive ductal carcinoma and 1 case of mucinous carcinoma; AP detected 15 out of 16 cases of breast cancer. The sensitivity of FDP and AP in detection of breast malignant lesions was 16/16 and 15/16, respectively (χ2=0.725, P=0.224). The specificity of FDP and AP was 92%(23/25) and 76%(19/25), respectively (χ2=6.327, P=0.012).


Conclusion
For women with dense breast tissue AP of MRI can be used in early screening of breast cancer.


Key words: 
Breast screening; Magnetic resonance imaging; First postcontrast subtracted; Maximum-intensity projection
Risk factors for symptomatic steno-occlusive carotid disease
Authors: Yao Li
Journal: BMJ (2010)

One hundred and fifty patients with 70 percent or more of carotid steno-ocelusion confirmed by digital subtraction angiography were selected to analyze risk factors for its clinical symptoms.Results of analysis showed that risk for clinical symptom increased with severity of unilateral carotid stenosis (OR = 3.546,95% CI 1.515-8.300,P = 0.004).Whereas presence of functional complete circle of Willis was a protective factor for it (OR = 0.208,95 % CI 0.045-0.962,P = 0.045).

Key words: 
Carotid stenosis;  Factor analysis,statistical
Health and cancer concerns among siblings of childhood cancer survivors: A report from the Childhood Cancer Survivor Study (CCSS).
Authors: Sonia Morales, Sedigheh Mirzaei Salehabadi, Deokumar Srivastava, Todd M. Gibson, Wendy M. Leisenring, Anne Lown, Lonnie K. Zeltzer, Gregory T. Armstrong, Kevin R. Krull, David Kyle Buchbinder
Journal: Journal of Clinical Oncology (2020)

12117 Background: Siblings of long-term survivors of childhood cancer can be at risk for persistent concerns regarding their future health and risk for cancer. We examined self-perceived future health and cancer risk concerns among such siblings. Methods: 3,969 siblings (median age 29 [range 18–56] years) of 5+ year matched pair cancer survivors (n= 3,969; age 25 [6–48] years; time since diagnosis 19.6 [9.6-33.8] years) in the CCSS self-reported physical/psychosocial problems, including concerns regarding future health and cancer risk (dichotomized as concerned vs not concerned). Chronic health conditions (CHC) were graded using the Common Terminology Criteria for Adverse Events system: mild (grade 1), moderate (grade 2), severe/disabling (grade 3),or life-threatening (grade 4). Sibling demographics, their matched survivor’s diagnosis, era and treatment components, complications (death, relapse, disfigurement) as well as self-reported health status and CHCs for siblings and survivors were examined as potential risk factors for concern using multivariable logistic regression. Adjusted odds ratios (OR) and 95% confidence intervals (CI) are reported. Results: The prevalence of siblings reporting concerns regarding health and cancer risk decreased based on decades of matched survivor diagnosis: 1970-79 (73.3%; 63.9%), 1980-89 (67.2%; 62.6%), 1990-99 (45.7%; 52.3%). Risk factors for concerns included sibling poor/fair current health (future health OR 3.65, 95% CI 2.37-5.62; cancer risk OR 1.54, 1.12-2.13) compared to good/very good/excellent health. Sibling grade 2 (future health OR 1.46, 1.23-1.74; cancer risk OR 1.20, 1.01-1.42) or grade 3-4 CHCs (future health OR 1.37, 1.09-1.71; cancer risk OR 1.28, 1.03-1.58) were associated with greater concerns compared to those with less than grade 2 CHCs. Survivor treatment with chemotherapy/radiation was associated with elevated cancer risk concerns (OR 1.51, 1.13-2.02) compared to surgery/no therapy. Siblings of survivors with grade 3-4 CHCs (OR 1.35, 1.12-1.63) had greater future health concerns compared to those with less than grade 2 CHCs. Sibling bereavement was a risk factor for future health (OR 1.45, 1.04-2.03) and cancer risk (OR 1.44, 1.05-1.99) concerns. Conclusions: The prevalence of sibling concerns regarding future health and cancer have diminished in more recent decades. Subgroups of siblings are at-risk for concerns over future health and cancer risk, partially determined by medical characteristics of their survivor and their own health status.