tbuckley/cabot-search huggingface dataset:
Outpatient treatment with lisocabtagene maraleucel (liso-cel) across a variety of clinical sites from three ongoing clinical studies in relapsed/refractory (R/R) large B-cell lymphoma (LBCL).
Authors: Carlos R. Bachier, John E. Godwin, Charalambos Andreadis, Maria Lia Palomba, Jeremy S. Abramson, Alison R. Sehgal, Gerhard Hildebrandt, Don A. Stevens, Daanish Hoda, Edward J. Licitra, Tanya Siddiqi, Thalia Andrea Farazi, Ana Kostic, Nikolaus S. Trede, Lei Wang, James Lymp, David G. Maloney
Journal: Journal of Clinical Oncology (2020)

8037 Background: Currently approved CAR T cell therapies are generally administered as inpatient (inpt) treatment at university medical centers due to concerns about frequency, onset, severity, and management of AEs, including cytokine release syndrome (CRS) and neurologic events (NEs). We sought to characterize whether patients (pts) could be safely monitored in the outpatient (outpt) setting after receiving liso-cel, an investigational, CD19-directed CAR T cell product administered at equal target doses of CD8+ and CD4+ CAR+ T cells, across university and non-university sites in TRANSCEND NHL 001 (NCT02631044), OUTREACH (NCT03744676), and PILOT (NCT03483103). Methods: Eligible pts had R/R LBCL after systemic chemoimmunotherapy; moderately impaired organ function was allowed. For outpt infusion of liso-cel, pts were required to receive safety monitoring education, have a caregiver and stay within 1 h travel to site of care for 30 d post-treatment. All study sites had a multidisciplinary CAR T cell team and standard operating procedures for toxicity monitoring and management. Results: At data cutoff, 53 pts had received liso-cel on Study Day 1 and were monitored as outpts (university, n = 33; non-university, n = 20), including pts ≥65 y of age (n = 23) and with high tumor burden (SPD ≥50 cm 2 ; n = 16). Any grade CRS and NEs were reported in 18 (34%) and 14 pts (26%), respectively. Severe CRS and/or NEs occurred in only 2 pts (4%) and were reversible. Median (range) time to onset of CRS and NEs was 5 (2–9) and 8.5 (3–22) d, respectively. Tocilizumab and/or corticosteroids for treatment of CRS and/or NEs were required in 8 pts (15%). Overall, 30 pts (57%) required hospitalization post-treatment, with a median (range) time to hospitalization post-treatment of 5.5 (2–22) d; 9 pts (17%) were hospitalized Study Day 4 or earlier. Two pts required ICU-level care. There were no grade 5 treatment-emergent AEs. Safety in pts monitored as outpts was comparable across types of sites. Overall response rate was 81% (95% CI, 68–91). Safety and efficacy were consistent with data from inpts across the 3 studies (N = 270). Conclusions: Pts with R/R LBCL were successfully treated with liso-cel and monitored for CAR T cell-related toxicity in the outpt setting across different types of sites. Incidences of severe CRS, NEs, and early hospitalization were low; 43% of pts did not require hospitalization. A larger dataset will be presented, including comparisons of outpts vs inpts and sites of care. Clinical trial information: NCT02631044 (TRANSCEND NHL 001), NCT03744676 (OUTREACH), NCT03483103 (PILOT) .
小儿蓖麻子中毒并肾积水一例
Authors: 姚莹, 李雪艳
Journal: BMJ (2007)

患儿男,6岁,因误食蓖麻子后腹泻1 d入院.患儿于1 d前上午8:00误食蓖麻子1粒,于11:00开始出现恶心、呕吐、腹痛、腹泻,排黄色稀水样便2次.于家中口服诺氟沙星、黄连素及藿香正气水等药物(具体剂量不详),症状无好转.于当地医院就诊后,给予静脉输液治疗(具体药物及剂量不详),病情无好转,患儿出现精神萎靡,尿少.为明确诊治故来我院.入院时查体:体温36.2℃,心率108次/min,呼吸24次/min,血压90/60 mm Hg(1 mm Hg=0.133 kPa),精神萎靡,嗜睡,轻度脱水貌,皮肤弹性稍差、干燥,咽部充血。
Applicability of the CURB-65 pneumonia severity score for outpatient treatment of COVID-19
Authors: Yann Nguyen, Félix Corre, Vasco Honsel, Sonja Curac, Virginie Zarrouk, Bruno Fantin, Adrien Galy
Journal: Journal of Infection (2020)

The CURB-65 is a severity score to predict mortality secondary to community acquired pneumonia and is widely used to identify patients who can be managed as outpatients. However, whether CURB-65 can be applicable to COVID-19 patients for the decision of outpatient treatment is still unknown.We conducted a retrospective single-centre study assessing the performance of the CURB-65 to predict the risk of poor outcome, defined as the need for mechanical ventilation and/or death, among patients hospitalized for COVID-19. The association between the CURB-65 and the outcome was assessed by a univariable Cox proportional hazard regression model.A total of 279 patients were hospitalized between March 15th and April 14th, 2020. According to the CURB-65, 171 (61.3%) patients were considered at low risk (CURB-65 01), 66 (23.7%) at intermediate risk (CURB-65=2), and 42 (15.1%) had high risk of 30-day mortality (CURB-65 35). During the study period, 88 (31.5%) patients had a poor outcome. The CURB-65 was strongly associated with a poor outcome (Pfor linear trend <0.001). However, among patients with a CURB-65 of 01, thus considered at low risk, 36/171 (21.1%) had a poor outcome.Our study suggests that the applicability of CURB-65 to guide the decision of inpatient or outpatient care is scarce, as it does not safely identify patients who could be managed as outpatients.
Etiologic diagnosis of small bowel ulcer with double balloon enteroscopy
Authors: Liang Zhao, Yijuan Ding, Honggang Yu, Tao Deng, Jun Liu
Journal: BMJ (2017)

Objective
To assess the value of double balloon enteroscopy (DBE) in etiological diagnosis of small bowel ulcer.


Methods
The clinical and endoscopic data of patients undergoing DBE at the Department of Gastroenterology, Renmin Hospital of Wuhan University from January 2010 to January 2016 were reviewed. For patients with small bowel ulcer revealed by DBE, the etiologic diagnosis was retrospectively analyzed.


Results
One hundred and three patients with small bowel ulcer were included in the analysis. The initial diagnosis based on morphology of ulcer was Crohn′s disease (58.3%, 60/103), intestinal tuberculosis (18.4%, 19/103 ), etiology unknown (24.3%, 25/103 ). The final diagnosis comprehensively based on pathology, clinical data and disease outcome was Crohn′s disease (44.7%, 46/103), intestinal tuberculosis (18.4%, 19/103), lymphoma (3.8%, 4/103), eosinophils enteritis (1.9%, 2/103), non-steroidal anti-inflammatory drug enteritis (1.9%, 2/103), adenocarcinoma (1.0%, 1/103), stroma tumor (1.0%, 1/103), ischemic enteritis (1.0%, 1/103 ), vascular malformation (1.0%, 1/103), Henoch-Schonlein purpura (1.0%, 1/103), etiology unknown (24.3, 25/103). The accurate diagnosis rate and misdiagnosis rate for Crohn′s disease by DBE were 73.3%(44/60)and 10.0%(6/60). The accurate diagnosis rate and misdiagnosis rate for intestinal tuberculosis by DBE were 14/18 and 2/18.


Conclusion
There are diversity and complexity in etiologic diagnosis of small bowel ulcer. The diagnosis should be based on the comprehensive analysis of morphology of ulcer, endoscopic and surgical pathology and clinical data. Follow up of small bowel ulcer by DBE may provide important information for etiologic diagnosis.


Key words: 
Diagnosis; Small bowel ulcer; double balloon enteroscopy
A survey on the smart medical service model in Hangzhou: signing behavior and associated factors
Authors: Xiaoyan He, Junfang Chen, Meng Wang, Qiong Zhang
Journal: BMJ (2019)

To analyze  associated factors of signing behavior of  smart medical  model in Hangzhou, 500 residents aged 18 years and older who signed  smart medical  and 500 unsigned residents were randomly selected from 5 urban districts of Hangzhou city from 19 to 26, July 2016. The social-demographic characteristics, chronic disease, health-seeking behavior, kinds of medical insurance were investigated by face-to-face interview. The results showed that there were significant differences in educational level, self-rated health status, chronic disease, seeking behavior and type of medical insurance, while there were no significant differences in gender and age between  signed group and  non-signed group. Logistic regression analysis revealed that residents with higher education level (OR=1.226, 95%CI: 1.118-1.344, P<0.01) and having more chronic diseases (OR=1.854, 95%CI: 1.524-2.257, P<0.01) preferred to sign   contract. The main reasons for unwillingness of signing contract were    was not suitable for me (17.0%, 61/359), I didn′t know  specific content of  service (16.7%,60/359), the signing procedure was complicated (15.0%, 54/359). In conclusion, different communication strategies should be adopted considering residents with different educational level and chronic diseases. And delivery of detailed information, simplification of signing process will promote to popularize this smart medical service.

Key words: 
Community health service; Contracted; Smart medical service; Influence factors
社区居民对糖尿病的知识态度行为调查
Authors: 赵惠珍, 乔磊, 左爱玲, 贾晓佳
Journal: BMJ (2005)

在北京市东城区某社区对居民进行有关糖尿病知识、态度和行为的调查. 1.对象与方法:采用整群抽样方法,对某社区800名20～60岁的居民做问卷式调查,有效调查795人,调查应答率为99.4％.调查内容:糖尿病患病情况,吸烟,饮酒,体育锻炼,高血压,高血脂,肥胖和超重等.调查员由社区卫生服务站具有全科医师资格的人员担任,由区健康教育所负责对调查员进行一天的培训,并对测量仪器进行校准. 超重、肥胖、高血压等指标按世界卫生组织制定的标准判定。
In Vivo-like model of glial tumors: Creation of primary cell lines.
Authors: Sofia V. Timofeeva, Oleg I. Kit, Anastasia O. Sitkovskaya, Irina V. Mezhevova, Svetlana Yu. Filippova, Tatiana V. Shamova, Eduard E. Rostorguev, Sergey N. Ignatov, Natalya S. Kuznetsova, Dmitriy P. Atmachidi, Sergey E. Kavitskiy, Inna A. Novikova
Journal: Journal of Clinical Oncology (2020)

e14515 Background: The choice of cell source for 3D bioprinting of in vivo-like models of glial tumors is crucial and must take into account the ability to proliferation and stable metabolism. Oral administration of 5-aminolevulinic acid (5-ALA) in patients prior to surgery increases the fluorescent contrast between tumor and surrounding tissue, but the effect of contrast agents on cells in vitro is unknown. The aim of the study was obtaining viable glial tumor tissues using 5-ALA, as well as the development of a stable primary cell culture for 3D bioprinting. Methods: Tumor tissue was obtained from patients with glioblastoma during surgery under visual control using the Opmi Pentero Blue E400 microscope and 5-ALA. Material was disaggregated on a BD Machine using Medicons 50 μm (BD). Glioblastoma cells were cultured in DMEM/F12 medium with L-glutamine (Gibco) containing 10% fetal bovine serum (Biolot, Russia), 1% non-essential amino acids (NEAA, Sigma-Aldrich) and 0.5% penicillin-streptomycin (Biolot) at 37C. Glial cell lines were characterized immunohistochemically using antibodies to the glial fibrillary acidic protein (GFAP) and proliferation index (Ki-67). Microsatellite analysis was performed using three dinucleotide repeat markers D2S123, D17S250, D5S346 and five mononucleotide loci BAT25, BAT26, NR21, NR24 and NR27. Results: The positive expression of GFAP on the cell processes of the star-like shape was clearly visualized, indicating a morphological feature of glial tumors. The Ki-67 labeling index was 70%. Changes were observed at the D17S250 locus (148-148/148-152) for the glial tumor primary cells after the sixth passage. Microsatellite instability was not observed in the primary cell culture. Conclusions: The accumulation of porphyrins from 5-ALA in glial tumor cells does not prevent the in vitro creation of a cell culture from tumor tissue. Microsatellite analysis showed that the obtained glioblastoma cell lines remain stable for at least 10 passages. Material obtained during resection using 5-ALA is a reliable source of stable glial tumor cell lines.
Identification of stage IIA melanoma patients at high risk for disease relapse using a clinicopathologic and gene expression model.
Authors: Renske Wever, Félicia Tjien-Fooh, Domenico Bellomo, Enrica Quattrocchi, Sindhuja Sominidi Damodaran, Martin Van Vliet, Jvalini Dwarkasing, Alexander Meves, Alexander M. Eggermont
Journal: Journal of Clinical Oncology (2020)

e22088 Background: In recent years, adjuvant therapy trials in stage III melanoma have been successful and trials have started with the inclusion of stage IIB/C patients. However, stage IIA melanoma patients are currently not eligible for adjuvant therapy, even though a large part of all melanoma related deaths occur in this patient group. Therefore, a strong clinical need has emerged for diagnostic tools that can identify high-risk patients who currently have no access to adjuvant therapy. Here, we sought to assess the ability of a recently introduced clinicopathologic gene expression model (CP-GEP) (Bellomo et al., JCO Precis Oncol. 2020: in press) to select stage IIA patients at high risk for disease relapse, upon design of a stage-specific operating point. Methods: We assessed the prognostic performance of the CP-GEP model in all 141 stage IIA patients from a Mayo Clinic cohort of 837 consecutive melanoma patients who had a sentinel lymph node biopsy (SLNb) performed within 90 days of their diagnosis. The CP-GEP model combines Breslow thickness and patient age, with the expression of 8 genes in the primary tumor. Moreover, it stratifies patients according to their risk of relapse: CP-GEP High Risk or CP-GEP Low Risk, based on an operating point that was specifically developed for stage IIA. This stage-specific operating point was selected to fulfill the following criteria: hazard ratio RFS &gt; 2 with a p-value &lt; 0.05, and risk groups of similar size. The main clinical endpoint was five-year relapse free survival (RFS). Results: The CP-GEP High Risk group corresponds to 45% (63/141) of all stage IIA patients and captures 62% (18/29) of the total relapses in this substage. Moreover, CP-GEP High Risk patients relapse more frequently than CP-GEP Low Risk patients (RFS of 56% versus 78%; HR, 2.23; P &lt; 0.05). The prognosis for stage IIA CP-GEP High Risk patients in our cohort is worse than for stage IIC/IIIA patients with reported RFS ranging from 63% to 77%. Conclusions: The CP-GEP model can be optimized by designing a stage-specific operating point, to identify a subset of stage IIA patients with an increased risk for disease relapse, not very different from IIC/IIIA patients. Therefore, stage IIA CP-GEP High Risk patients may be considered for inclusion in adjuvant trials. Independent validation studies are ongoing for the newly developed operating point. [Table: see text]
Active tuberculosis, sequelae and COVID-19 co-infection: first cohort of 49 cases
Authors: Marina Tadolini, Luigi Ruffo Codecasa, José-María García-García, François-Xavier Blanc, Sergey Borisov, Jan-Willem Alffenaar, Claire Andréjak, Pierre Bachez, Pierre-Alexandre Bart, Evgeny Belilovski, José Cardoso-Landivar, Rosella Centis, Lia D'Ambrosio, María- Luiza De Souza-Galvão, Angel Dominguez-Castellano, Samir Dourmane, Mathilde Fréchet Jachym, Antoine Froissart, Vania Giacomet, Delia Goletti, Soazic Grard, Gina Gualano, Armine Izadifar, Damien Le Du, Margarita Marín Royo, Jesica Mazza-Stalder, Ilaria Motta, Catherine Wei Min Ong, Fabrizio Palmieri, Frédéric Rivière, Teresa Rodrigo, Denise Rossato Silva, Adrián Sánchez-Montalvá, Matteo Saporiti, Paolo Scarpellini, Frédéric Schlemmer, Antonio Spanevello, Elena Sumarokova, Eva Tabernero, Paul Anantharajah Tambyah, Simon Tiberi, Alessandro Torre, Dina Visca, Miguel Zabaleta Murguiondo, Giovanni Sotgiu, Giovanni Battista Migliori
Journal: European Respiratory Journal (2020)

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) pandemic has attracted interest because of its global rapid spread, clinical severity, high mortality rate and capacity to overwhelm healthcare systems [1, 2]. SARS-CoV-2 transmission occurs mainly through droplets, although surface contamination contributes and debate continues on aerosol transmission [3–5]. Diagnostic, treatment and outcome details of 49 COVID-19 patients with concurrent or previous tuberculosis from 8 countries show varied clinical profiles <https://bit.ly/369ZGGu> The article is part of the scientific activities of the Global Tuberculosis Network (GTN); GREPI (Groupe de Recherche et d'Enseignement en Pneumo-Infectiologie), a working group from SPLF (Société de Pneumologie de Langue Française); SEPAR (Sociedad Española de Neumología and Cirugía Torácica); Moscow Society of Phtisiology and of the WHO Collaborating Centre for Tuberculosis and Lung Diseases, Tradate, ITA-80, 2017-2020- GBM/RC/LDA). Delia Goletti is a professor of Pathology at Unicamillus University in Rome, Italy. The authors wish to thank Enrico Girardi (National Institute for Infectious Diseases, L. Spallanzani, IRCCS, Rome, Italy) for the useful comments on the manuscript.
Relationship between <i>CYP2D6</i> genotype, tamoxifen metabolites, and adverse events, tumor biomarkers and breast cancer recurrence in a low-dose phase III trial in noninvasive disease.
Authors: Andrea De Censi, Harriet Ann Johansson, Thomas Helland, Matteo Puntoni, Tania Buttiron Webber, Debora Macis, Valentina Aristarco, Irene Maria Briata, Davide Serrano, Mauro D'Amico, Ersilia Bifulco, Steinar Hustad, Håvard Søiland, Bernardo Bonanni, Gunnar Mellgren
Journal: Journal of Clinical Oncology (2020)

1553 Background: Low dose tamoxifen (T, 5 mg/d) given for 3 years halved recurrence in 500 women with non-invasive disease (DeCensi et al. JCO 2019). Retrospective studies with 20 mg/d have shown an association between low levels of endoxifen (9-16 nM) or Z-4OHtam (3.26 nM) and recurrence, but recent prospective studies have not confirmed these findings. We measured CYP2D6 genotype and 8 metabolite levels to determine their associations with adverse events, tumor biomarkers (IGF-I, SHBG, C-reactive protein, CRP) and breast cancer recurrence. Methods: CYP2D6 genotyping was performed in the T arm (n = 183) as previously described (Johansson H et al. BCRT 2016). T and metabolites were measured at 1 (n = 169) and 3 y (n = 152) as previously described (Helland T et al. BCR 2017). We tested linear relationships between metabolite levels and biomarkers, adjusting for age, BMI, treatment compliance and baseline biomarker levels. Cumulative incidence of recurrence according to endoxifen levels was calculated by the Cox model. Results: Endoxifen concentrations were associated to CYP2D6 metabolizer status (p &lt; 0.001). Median (IQR) endoxifen levels were 8.4 (5.2-11.3) and 8.8 (5.8-11.5) at 1 and 3 y, with only 42% and 47% of subjects reaching 9 nM. Median endoxifen levels were related to pill count (5.5, 7.1 and 9.0 nM/L for medication possession rate &lt; 83.3%, 83.4-99.9%, 100%, respectively). There was no difference in metabolite levels and menopausal symptoms. There was an inverse relationship between endoxifen and endometrial thickness at 3 y (p = 0.04), and between endoxifen or tamoxifen levels and IGF-I levels at 3 y (p = 0.001). T levels were positively associated with SHBG levels in postmenopausal women (p-interaction = 0.04). Endoxifen, T and 4OHtam decreased CRP, with a greater effect in premenopausal women (p-interaction = 0.02). An increase in CRP after 3 years was associated with a HR of 4.37 (95% CI, 1.14-16.73, P = 0.03) of recurrence compared to women with no increase of CRP. Median (IQR) endoxifen levels at year 1 were 8.4 (5.3-11.4) in patients who recurred vs 7.5 (5.1-10.2) in those who did not recur (p = 0.6), although this comparison was underpowered. Conclusions: T levels themselves may contribute to clinical activity by decreasing IGF-I and increasing SHBG. Elevated CRP is a predictive factor for recurrence which is down-regulated by T and metabolites. Endoxifen is below 9 nM in the majority of subjects treated with 5 mg/day, although this threshold was obtained in studies up to 20 years. Clinical trial information: NCT01357772.
Correlative study of disease activity in Langerhans cell histiocytosis.
Authors: Jeffrey Garnet Edwards, Michael Raymond Jeng
Journal: Journal of Clinical Oncology (2020)

e19540 Background: Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasia that primarily affects younger children, most often involving bone, skin, lung, lymph nodes, or liver. Current treatment for LCH includes chemotherapy and biologically targeted therapies. Given its clinical heterogeneity and low prevalence, decision-making regarding intervention relies on subjective evaluation of disease status, which is often dependent on provider experience. Thus, there is a need to identify biomarkers for disease recurrence and activity in patients with LCH. Methods: We conducted a retrospective cohort study including pediatric LCH patients (n = 48) ≤21 years of age with biopsy-proven diagnosis of LCH and ≥1 year of follow-up after diagnosis. Data regarding demographics, symptom history, organ system involvement, and laboratory values at different time points were extracted from the from patient medical records and entered into a REDCap Database. The primary outcome was recurrence status as measured by the end of the study period. Data were analyzed using Stata statistical analysis software. Results: In our cohort, the sample was 64.6% Male and 35.4% Female with a median age of 29 months at diagnosis. 68.1% of patients had single organ involvement while 31.9% exhibited multi-system involvement. 70.8% of our cohort received treatment with chemotherapy with an average initial treatment duration of 12.1 months. 27.1% of the cohort experienced recurrence by the time of chart review. Logistic regression of the demographic factors and lab values at diagnosis revealed a statistically significant association between multi-system involvement (OR: 3.94, p = 0.04), moderate or high central nervous system risk assessment (OR: 7.67, p = 0.03; OR: 5.75, p = 0.03) and likelihood of recurrence. Additionally, logistic regression analysis revealed that alkaline phosphatase level at the time of diagnosis was associated with a slightly decreased likelihood of recurrence (OR: 0.987, p = 0.02). Conclusions: These results reveal that in addition to the traditionally utilized inflammatory markers (Erythrocyte Sedimentation Rate, White Blood Cell and Platelet Count), Alkaline Phosphatase could be used as a predictor of disease activity for patients with LCH, especially for those with bone involvement. Moving forward, an increased sample size might reveal other correlative biomarkers that can predict disease activity, helping to more precisely manage LCH.