tbuckley/cabot-search huggingface dataset:
Phase II study of antidisialoganglioside antibody, dinutuximab, in combination with GM-CSF in patients with recurrent osteosarcoma (AOST1421): A report from the Children’s Oncology Group.
Authors: Pooja Hingorani, Mark D. Krailo, Allen Buxton, Paul R. Hutson, Justin Davis, Katherine A. Janeway, Richard Greg Gorlick, Michael Isakoff
Journal: Journal of Clinical Oncology (2020)

10508 Background: Treatment of patients with recurrent osteosarcoma (OS) is challenging and novel effective therapies are urgently needed. This study evaluated disease control rate (DCR) in patients with recurrent pulmonary OS, when treated with dinutuximab plus cytokine therapy as compared to a historical benchmark. The rationale for dinutuximab was the ubiquitous ( &gt; 95%) GD2 positivity in OS tumors and cell lines. Methods: AOST1421 was a single-arm phase 2 study. Patients with recurrent pulmonary OS in complete surgical remission were eligible. Patients received five cycles of dinutuximab 70mg/m 2 /cycle with GM-CSF. Two different dinutuximab infusion schedules were used - 35mg/m 2 /day over 20 hours (2-day) and 17.5mg/m 2 /day over 10 hours (4-day) schedule. Primary end point was DCR, defined as proportion of patients event-free at 12 months from enrollment. Events were progressive disease or death within 12 months attributed to treatment or progression. The historical benchmark was AOST0221 with a 12-month DCR of 20% (95% CI 10-34%). Success was defined as ≥16/ 39 patients ( &gt; 40%) event-free at 12 months from enrollment. Secondary objectives included toxicity evaluation and dinutuximab pharmacokinetics (PK). Results: Forty-one patients were enrolled from Nov 2015 - Jan 2018. Thirty nine were eligible and evaluable (age 7-26 yr; median 15 yr). Data current to December 31, 2019 was used for analysis. Accrual rate was higher than expected (22.1 vs. 19.2 patients/ yr.) despite a concurrently open competing study. One of 136 administered therapy cycles met criteria for unacceptable toxicity when one patient receiving the 2-day schedule died after cycle 2 due to an unknown cause, attributed as probably related to protocol therapy. The protocol was revised to allow only the 4-day schedule. Other ≥ Grade 3 toxicities occurring in &gt; 10 % participants were expected dinutuximab toxicities such as pain, diarrhea, hypoxia and hypotension. Dinutuximab did not demonstrate sufficient evidence of efficacy as 27/ 39 patients experienced an event for a DCR of 30.7% (95% CI 17- 47%). PK studies are pending and will be reported. Conclusions: Dinutuximab toxicity in adolescent and young adult OS patients was similar to younger patients. While GD2 remains a relevant target in OS, combination of dinutuximab with GM-CSF did not meet the targeted successful DCR in patients with completely resected tumor. Other strategies for targeting GD2 or dinituximab combination therapy may still be warranted. Clinical trial information: NCT02484443.
Malignant MIXED mullerian tumors and serous endometrial cancer: Molecular targets the need of the hour.
Authors: Manan Shah, Sanjay R Jain, Gabriela Oprea, Saba Shafi
Journal: Journal of Clinical Oncology (2020)

e18106 Background: Malignant Mixed Mullerian Tumors (carcinosarcomas) and serous variants are rare but aggressive endometrial cancers which constitute less than 5 percent of uterine tumors. Our aim was to understand the clinical and molecular features of these variants which could aid us in further management. Methods: We retrospectively reviewed cases of carcinosarcomas and serous endometrial cancers at our institution over a period of 5 years. A total number of 28 cases were identified. Baseline clinical characteristics, treatment parameters including adjuvant chemo-radiotherapy and disease status at one year follow up were noted. Molecular markers included hormone receptor status (ER/PR), p16, p53, Her-2/neu, and the MMR gene panel (MLH1, PMS2, MSH2, MSH6). Results: The mean age for carcinosarcomas was 66 ± 12 years and for serous tumors 71± 8 years. The mean BMI of patients with carcinosarcoma was 32±7 kg/m 2 and serous tumors was 32±4 kg/m 2 . African American and Hispanic females were the predominant race. FIGO stage 1 at presentation constituted 75% in patients with carcinosarcomas while FIGO stage 3 and 4 constituted 62 % in serous variants. All our patients underwent surgery (TAH/BSO or debulking) followed by adjuvant chemotherapy/radiation or both. At 1 year follow up post treatment only 33% patients with carcinosarcomas and 12% with serous tumors had stable disease. Remaining patients showed progression or new metastasis to lung, peritoneum, retroperitoneum and vaginal vault. Molecular studies revealed ER+ in 41% and PR + in 33% with carcinosarcomas and 43% and 31% with serous tumors respectively. All patients with carcinosarcomas were Her-2/neu negative while 25 % were positive in serous tumors. 88% cases were strongly positive for both p53 and p16 in the serous variant. All patients showed an intact MMR gene panel. An interesting observation was that all patients with stable disease at 1 year follow up were ER/PR+ and Her-2/neu negative. Conclusions: Overall survival of these variants remains poor. Biomarkers such as p16, p53, Her-2, MMR panel and hormone receptors have become indices for individualization of treatment and further studies using targeted agents are warranted.
Early administration of ritonavir-boosted lopinavir could prevent severe COVID-19
Authors: Elise Klement-Frutos, Sonia Burrel, Gilles Peytavin, Stéphane Marot, Minh P. Lê, Nagisa Godefroy, Vincent Calvez, Anne-Geneviève Marcelin, Eric Caumes, Valérie Pourcher, David Boutolleau
Journal: Journal of Infection (2020)
Tumor growth rate (TGR) as an early predictor of outcomes in advanced non-small cell lung cancer treated with PD-1 axis inhibitor.
Authors: Li-na He, Xuanye Zhang, Haifeng Li, Tao Chen, Li Zhang, Shaodong Hong
Journal: Journal of Clinical Oncology (2020)

e21560 Background: Tumor growth rate (TGR) signifies percentage change in tumor size per month (%/m). We investigated the association of TGR with outcomes in patients with advanced non-small cell lung cancer (aNSCLC) undergoing anti-PD-1/PD-L1 monotherapy. Methods: We retrospectively reviewed 172 aNSCLC patients treated with anti-PD-1/PD-L1 monotherapy in Sun Yat-Sen University Cancer Center between August 2016 and June 2018. Computed tomography images were reviewed to calculate TGR before treatment (“TGR 0 ”) and upon early treatment (from treatment initiation to the first evaluation; “TGR 1 ”). X-tile software was used to determine cut-off values that maximumly differentiate overall survival (OS). Log-rank tests and Cox regression models were performed for survival analysis. Results: 73 patients with paired TGR 0 and TGR 1 were included in the testing cohort. The optimal cut-off values of TGR 0 and TGR 1 were 46.6 %/m and 10.9 %/m, respectively. Patients with higher TGR 1 significantly experienced inferior OS versus those with lower TGR 1 (HR 2.74, 95% CI 1.34-5.61, P = 0.006). Patients with higher TGR 0 tended to have poorer OS, though not statistically significant (HR 1.79, 95% CI 0.84-3.79, P = 0.131). In multivariate analyses, TGR 1 remained an independent predictor of OS (HR 2.33, 95% CI 1.12-4.83, P = 0.024). In an external validation cohort (n = 69) enrolling patients with available TGR 1 but lacking TGR 0 data, TGR 1 was also significantly associated with OS (HR 2.73, 95% CI 1.33-5.60, P = 0.006). Conclusions: Higher TGR 1 was correlated with inferior outcomes in aNSCLC patients who received anti-PD-1/PD-L1 monotherapy. Larger prospective studies are warranted to identify its added value to RECIST as an early radiological biomarker to predict long-term survival of patients undergoing immunotherapy. [Table: see text]
美式脊椎矫正手法配合松解注射液治疗椎动脉型颈椎病
Authors: 孙肖雷, 颜凡生, 胡明珠, 彭广宇, 刘茜
Journal: BMJ (2006)

对80例门诊患者采用美式脊椎矫正手法配合松解注射液治疗.3个疗程,治愈50例,治愈率为63%,好转24例,好转率为30%,无效6例,总有效率93%.美式脊椎矫正手法配合松解注射液治疗椎动脉型颈椎病临床疗效较好。
Color Doppler ultrasonic diagnosis of thyroid microcarcinoma and analysis of misdiagnostic reasons
Authors: Guangju Liang
Journal: BMJ (2015)

The misdiagnostic reason and sonographic features were retrospectively analyzed for 58 pathologically confirmed cases of thyroid microcarcinoma (TMC) at our hospital from January 2006 to January 2013. The ultrasonographic features of TMC included hypoechogenecity, distinct margin, irregular shape, ratio of anteroposterior axis and rectilinear axia ≥1, visible microcalcifications, posterior attenuation, blood flow signals with high resistance index on color Doppler and visible lymph node involvement in central neck area. And a coexistence of benign and malignant lesions should raise an alert for multiple thyroid nodules.


Key words: 
Thyroid neoplasms; Ultrasonography
Ixabepilone efficacy and tolerability in metastatic breast cancer (MBC) patients in a real-world setting.
Authors: Tara Hyder, Margaret Q. Rosenzweig, Adam Brufsky
Journal: Journal of Clinical Oncology (2020)

e13067 Background: Ixabepilone is a microtubule stabilizing agent that was approved as monotherapy and in combination with capecitabine for the treatment of refractory metastatic or locally advanced breast cancer. With limited options for refractory MBC, especially in triple negative breast cancer (TNBC), ixabepilone has demonstrated an increase in progression free survival (PFS) in randomized control trials. We assess the effectiveness and safety of the drug in a real-world setting. Methods: A large, ongoing clinical database of over 1800 women (1999 to present) was used to identify 91 patients who had received ixabepilone during their treatment course. Clinical outcomes were retrospectively analyzed utilizing descriptive and comparative statistics. Results: Treatment was late in the disease course; median line of treatment was 5.3. At the time of receiving ixabepilone, the patients PFS was 3.5 months with n = 4 patients attaining a PFS &gt; 12 months. Overall survival (OS) was 11.3 months. A subset of patients that had triple negative breast cancer (N = 37) had similar PFS, 3.6 months, and OS, 10.2 months, as the total population. Most common adverse events of any grade were fatigue (37%), nausea (32%), and peripheral sensory neuropathy (28%). Grade 3 or higher anemia was present in 10% of the patients. Conclusions: Ixabepilone has demonstrated efficacy in the treatment of patients with MBC, including the challenging population of TNBC patients in this real-world example. It is also well tolerated. These findings make ixabepilone a reasonable chemotherapeutic agent for refractory MBC and TNBC patients. [Table: see text]
Reliable detection of the presence of pulmonary carcinoma on whole-slide images by a deep learning model.
Authors: Gouji Toyokawa, Fahdi Kanavati, Seiya Momosaki, Michael Rambeau, Yuka Kozuma, Fumihiro Shoji, Koji Yamazaki, Sadanori Takeo, Osamu Iizuka, Masayuki Tsuneki
Journal: Journal of Clinical Oncology (2020)

9025 Background: Lung cancer is one of the leading causes of cancer-related death worldwide, and its histopathological diagnosis is crucial for deciding on optimum treatment strategies. Recently, artificial intelligence (AI) models have been widely shown to be useful in various medical fields, particularly image and pathological diagnoses; however, AI models for the pathological diagnosis of pulmonary lesions that have been validated in large-scale test sets are yet to be seen. Methods: We trained a convolution neural network based on the Efficient Net B3 architecture to classify carcinoma from whole slide images (WSIs) using a training dataset of 3640 images. WSI diagnoses were available. We used a transfer learning approach, in which the starting weights were obtained from a pre-trained model on ImageNet. The model was then trained on our dataset using multiple instance learning, a semi-supervised learning approach. To classify a WSI, the model was applied in a sliding window fashion with an input tile size of 512x512 and a stride of 256. The maximum probability was then used as a WSI diagnosis. Results: We evaluated our model on a total of 2680 WSIs originating from five independent sources (two hospitals in Japan and three public datasets from around the world). The model achieved a Receiver Operator Curve Area Under the Curves (ROC AUCs) of 0.974, 0.974, 0.996, 0.988, and 0.981, respectively. Conclusions: We successfully established a reliable AI model for differentiating between lung carcinoma and non-neoplasm with a high ROC AUC on five independent test sets. If used in clinical practice, our model could help reduce the burden on pathologists and be useful for diagnosing pulmonary lesions in areas in which there are shortages of pathologists. Further prospective multicenter studies are warranted in order to validate the results obtained in the current study.
询问病史(二)
Authors: 吴东, 朱峰, 陈嘉林
Journal: BMJ (2010)

一、当你评估患者时,患者也在评估你(when you evaluate patients,patients also evaluate you) 病史采集是一个医患互动的过程.表面上看,似乎是医生在询问患者,患者回答医生的问题,医生一边了解病史,一边思考诊断.而事实上,当医生评估病情时,患者也在观察医生的言谈举止,在心里评估医生:这个医生关心我的病情吗?他(她)的专业水平怎么样? 我能不能完全信任他(她)?人们常说第一印象极为重要(the first impression tells all),如果医生对自己的仪表和言行很不注意,不能给患者留下良好的第一印象,则很难获得患者的信任,为日后的工作增加难度。
The efficacy of first-line chemotherapy in endocrine-resistant hormone receptor-positive (HR+), human epidermal growth factor receptor 2- negative (HER2-) metastatic breast cancer (MBC).
Authors: Sudpreeda Chainitikun, James Long, Ruben Rodriguez-Bautista, Toshiaki Iwase, Debu Tripathy, Takeo Fujii, Naoto T. Ueno
Journal: Journal of Clinical Oncology (2020)

1056 Background: Combinations of endocrine therapy (ET) and targeted therapy (CDK4/6 or mTOR inhibitors) are standard of care for HR+/HER2- MBC. When ET is not effective, chemotherapy is commonly used. However, clinical outcomes of chemotherapy in the endocrine-resistant setting are limited. We hypothesized that clinicopathological baseline and prior ET factors determine chemotherapy’s efficacy. We sought to identify predictive factors and the compare efficacies of chemotherapy agents in endocrine-resistant MBC. Methods: We conducted a retrospective study of patients with HR+/HER2- MBC who received chemotherapy after progression on ET with or without targeted therapy at MD Anderson Cancer Center from 1999-2017. We collected baseline clinicopathological and all treatment data. The primary endpoint was time to treatment failure (TTF) of first-line chemotherapy for MBC. We performed univariate and multivariate analyses using the Cox proportional hazard model. Kaplan-Meier methods were used to analyze TTF. Results: In the 1,258 patients analyzed, the mean age was 55.3 years (range 21-91). Forty-five patients (3.6%) had inflammatory breast cancer (IBC). Three hundred ninety patients (31%) received previous targeted therapy: 264 with CDK4/6 inhibitor, 205 with mTOR inhibitor, and 79 with both. The most frequent chemotherapy agents were capecitabine (48.9%) and taxanes (paclitaxel, nab-paclitaxel, or docetaxel; 28.6%). After adjustment for all factors in a multivariate model, IBC and prior exposure to a CDK4/6 inhibitor were significantly associated with shorter TTF. Previous treatment with a CDK4/6 inhibitor had the strongest negative effect on chemotherapy TTF regardless of ET duration (adjusted hazard ratio [HR] 1.84; 95%CI 1.49-2.27; p &lt; 0.001). Capecitabine had significantly longer median TTF than taxanes regardless of whether patients had prior exposure to taxanes in (neo)adjuvant setting (6.1 vs 4.9 months; HR 0.64; 95%CI 0.55-0.75; p &lt; 0.001). Conversely, the median TTF for taxanes was shorter in patients who received prior (neo)adjuvant taxanes than in those who did not (4.5 vs 5.1 months). Conclusions: Previous exposure to CDK4/6 inhibitor had a negative predictive effect for the efficacy of chemotherapy. Capecitabine had the best efficacy against endocrine-resistant breast cancer.
Simple virilizing with 21-hydroxylase deficiency: a report of 5 cases and literature review
Authors: 周桂兰, 王芳, 毛拓华, 李竞
Journal: BMJ (2010)

The clinical manifestations, laboratory tests and treatment of 5 cases of simple virilizing with 211-hydroxylase deficiency were analyzed. The average age was 17 at the first hospital visit. The manifestation included abnormal external genitalia at birth, no secondary sexual characteristics developed during adolescence and no menstrual cycles, and their near-adult height (NAH) was affected. The chromosome karyotype of the patients was 46 XX. The CT scans showed bilateral adrenal hyperplasia. The testosterone levels were (665 ± 334 ) μg/L, which were reduced to (81 ± 25 ) μg/L after dexamethasone suppression. The levels of adrenocorticotropic hormone were 123 (57 - 563) ng/L and ＜ 5 ng/L respectively before and after dexamethasone suppression test. Early diagnosis and early treatment is particularly important for improvement of the disease outcomes.

Key words: 
Congenital adrenal hyperplasia ;  21-hydroxylase ;
Indonesian children fecal microbiome from birth until weaning was different from microbiomes of their mothers
Authors: Wei Wei Thwe Khine, Endang Sutriswati Rahayu, Ting Yi See, Sherwin Kuah, Seppo Salminen, Jiro Nakayama, Yuan-Kun Lee
Journal: Gut Microbes (2020)

Gastrointestinal (GI) microbiota play an important role in human health and wellbeing and the first wave of gut microbes arrives mostly through vertical transmission from mother to child. This study has undertaken to understand the microbiota profile of healthy Southeast Asian mother-infant pairs. Here, we examined the fecal, vaginal and breast milk microbiota of Indonesian mothers and the fecal microbiota of their children from less than 1 month to 48 months old. To determine the immune status of children and the effect of diet at different ages, we examined the level of cytokines, bile acids in the fecal water and weaning food frequency. The fecal microbiota of the children before weaning contained mainly Bacteroides and Bifidobacterium, which presented at low abundance in the samples of mothers. After weaning, the fecal microbiome of children was mainly of the Prevotella type, with decreasing levels of Bifidobacterium, thus becoming more like the fecal microbiome of the mother. The abundance of infant fecal commensals generally correlated inversely with potential pathogens before weaning. The fecal Bifidobacterium in children correlated inversely with the consumption of complex carbohydrates and fruits after weaning. The specific cytokines related to the proliferation and maturation of immunity were found to increase after weaning. A decreasing level of primary bile acids and an increase of secondary bile acids were observed after weaning. This study highlights the change in the GI microbiota of infants to adult-type microbiota after weaning and identifies diet as a major contributing factor.
MARC1 variant rs2642438 increases hepatic phosphatidylcholines and decreases severity of non-alcoholic fatty liver disease in humans
Authors: Panu K. Luukkonen, Anne Juuti, Henna Sammalkorpi, Anne K. Penttilä, Matej Orešič, Tuulia Hyötyläinen, Johanna Arola, Marju Orho-Melander, Hannele Yki-Järvinen
Journal: Journal of Hepatology (2020)
抓住机遇 继往开来
Authors: 刘伟竹, 姜民慧
Journal: BMJ (2011)

2011年7月1日,国务院颁布了《国务院关于建立全科医生制度的指导意见》,为全科医学的发展带来了新的机遇与挑战.7月15日中华医学会、中国医师协会共同提出贯彻《国务院关于建立全科医生制度的指导意见》倡议书.值此大好时机,2011年9月15日,《中华全科医师杂志》第三届编辑委员会(编委会)第一次工作会议在西安召开,中华医学会、杂志社有关领导及来自全国各地(包括澳门、台湾地区)的编委与会.本次会议进行了编委会换届工作,在对第二届编委会的杂志工作进行总结的基础上,并对第三届编委会的工作做出计划安排。
Analysis of the management of immunotherapy-derived toxicity in the Stockholm region.
Authors: Lisa Elena Esther Villabona, Oona Huopaniemi
Journal: Journal of Clinical Oncology (2020)

e15069 Background: The debut of immune-checkpoint inhibitors (ICPis) has changed the prognosis of many cancer patients. The immune-related adverse events (irAEs) caused by these monoclonal antibodies are common and can affect nearly any organ system. International guidelines on management of irAEs have been published in recent years. The aim was to investigate the identification and management of irAEs in the Stockholm region, as well as how the patients respond to the management they received. Methods: All adult patients who had received ICPis at the Karolinska University Hospital in 2018 were included. Patients who had enrolled in another study on ICPis were excluded. 62 eligible patients enrolled. Data was collected from the patients’ medical records. In addition to the irAEs documented by clinicians, irAEs were also identified retrospectively. Variables recorded were grade of irAE, management, date of first documentation and date of re-challenge, among others. Management was compared to the guidelines. Descriptive statistics as well as linear correlation analysis and Kaplan-Meier analysis were then performed. Results: 62 patients proved eligible. 121 irAEs were recorded. Nurses at Advanced Home Health Care (AHHC) were first to document grade 3-4 irAEs in 58% of the cases. Kaplan-Meier analysis (p-value 0.043) showed that patients whose irAEs were managed according to the guidelines reached re-challenge sooner. A negative correlation (p-value 0.003) was observed between management according to guidelines and identification by a clinician. Conclusions: Increased knowledge at AHHC and at oncological clinic is necessary to improve the identification and management of irAEs.
Unknown primary tumor high-risk melanoma as a unique patient population with distinct prognosis in the adjuvant setting: An ECOG-ACRIN E1609 study analysis.
Authors: Ahmad A. Tarhini, Sandra J. Lee, F. Stephen Hodi, Gary Irvin Cohen, Uma Rao, Vernon K. Sondak, John M. Kirkwood
Journal: Journal of Clinical Oncology (2020)

e22090 Background: E1609 enrolled 1670 adult patients (pts) with resected AJCC7 stages IIIB, IIIC, M1a, M1b melanoma and compared adjuvant ipilimumab at 3 or 10 mg/kg (ipi3 and ipi10) to high dose interferon-alfa (HDI). With over 5 years of follow up, the risk of relapse and death by primary tumor status and by stage group is expected to inform the design of future adjuvant trials and ultimately, clinical practice. Methods: Unknown primary melanoma status was defined as initial presentation with cutaneous, nodal or lung metastasis that was completely resected without a history of known primary melanoma. We evaluated the pt distribution by the initial site of metastasis. Further, we evaluated the risk of relapse and death by primary tumor status and by stage group. Five-year relapse-free survival (RFS) and overall survival (OS) rates and 95% CIs were estimated by Kaplan-Meier method. Stratified (by stage) log-rank test was used to compare RFS and OS by primary tumor status. Two-sided p-values were derived. Results: Unknown primary melanoma represented 12.8% of the total study population including 11.7% on the ipi arms and 14.7% on HDI. Site of metastasis at initial presentation among unknown primary cases included cutaneous and nodal (97%) and lung (3%). Among the overall study population, M1a stage group included the highest proportion of pts with unknown primary (42.2%). Stratifying by stage, RFS (p = 0.001) and OS (p = 0.009) were significantly better for pts with unknown primary compared to known primary. Including only ipi3 and ipi10 pts, RFS (p = 0.005) and OS (p = 0.023) were consistently significantly better in favor of unknown primary. Five-year RFS and OS rates by primary tumor status and stage group among pts treated with ipi (ipi3 and ipi10) are summarized in Table. Conclusions: Unknown primary status represents a unique population among high-risk melanoma pts treated with ipi with improved RFS and OS outcomes that support their separate assessment in future immunotherapy adjuvant trials. In-depth analyses of the tumor biology and host immunology are ongoing. Outcome analyses by the overall study stage groups and the HDI arm will be reported at the meeting. Clinical trial information: NCT01274338. [Table: see text]