tbuckley/cabot-search huggingface dataset:
Prevalence of metabolic syndrome, its components and hyperuricemia among Kazakh people in Xinjiang Uighur autonomous region
Authors: Ya-lin Wei, Yi-tong Ma, Yi-ning Yang, Zhen-yan Fu, Fen Liu, Xiao Peng, Xiang Xie, Xiang Ma, Xiao-mei Li, Ying Huang
Journal: BMJ (2011)

Objective To study prevalence of metabolic syndrome (MS) , it's components and hyperuricemia (HUA) among Kazakh people in Xinjiang Uighur autonomous region, China. Methods A cross-sectional survey was conducted among Kazakh people aged 35 years and over in seven prefectures of Xinjiang, including Urumqi, Kelamayi (Karamay) , Fukang, Tulufan (Turpan), Hetian (Hotan) , Aletai (Altay) and Yili during October 2007 to March 2010, with a four-stage cluster sampling, the total sample size were 4094. Through the methods of questionnaire survey, physical examination, biochemical examination and so on, to study prevalence of MS in HUA and it's components by blood biochemical examinations. Results A total of 3915 Kazakh adult people, equal number of men and women, were surveyed, with a response rate of 95. 63 percent. Overall prevalence of HUA was 3. 96 percent( 155/3915 ) , 6.02 percent for men and 2. 03 percent for women(114/1894 and 41/2021) , respectively, with statistically significant difference ( P ＜ 0.05 ). Prevalence of MS was 39.47 percent in those with HUA and 22. 53 percent in those without HUA (45/114 and 401/1780), respectively (P ＜ 0.01). Among women, prevalence of MS was 46. 34 percent in those with HUA and 16. 11 percent in those without HUA( 19/41 and 319/1980), respectively (P＜0. 01). Prevalence of high blood pressure, hypertriglyceridemia, lower blood high-density lipoprotein cholesterol (HDL-C) and central obesity were 59.65 percent, 42.11 percent,32.46 percent, 7. 89 percent and 79. 82 percent in those with HUA, respectively, with prevalence of hyperglyceridemia and central obesity significantly higher than in those of non-HUA ( P ＜ 0. 05 ). Among women, prevalence high blood pressure, hypertriglyceridemia, lower blood HDL-C and central obesity were 48.78 percent, 39.02 percent, 41.46 percent, 2.44 percent and 78.05 percent, respectively, in HUA group, with prevalence of hyperglyceridemia, lower blood HDL-cholesterol and central obesity significantly higher than in those of non-HUA ( P ＜ 0. 05 ). Conclusions Prevalence of MS was higher in Kazakh people suffered with HUA than those without HUA, as well as prevalence of components of MS, suggesting that prevention and treatment for HUA is necessary, which can reduce MS and its components in the region.

Key words: 
Hyperuricemia;  Metabolic syndrome;  Kazakh ethnic
NF1 may serve as a novel genetic biomarker of response to treatment and prognosis in glioblastoma (GBM).
Authors: Bin Huang, Ju Yang, Kongcheng Wang, Weitao Chen, Hongbin Ni, Jing Yan
Journal: Journal of Clinical Oncology (2020)

e14539 Background: The intrinsic capacity of glioblastoma (GBM) tumor cells to infiltrate normal brain predictably results in high rates of early recurrence. Little has changed over the last decade in the treatment available for GBM with survival remaining poor and a novel genetic biomarker is necessary found to predict response to treatment and prognosis in GBM. Methods: Biomarker discovery was performed by a genome-wide screen using DNA extracted from tissue and blood samples of GBM patients. The biomarker was then evaluated for its predictability in OS of GBM patients compared with the Chinese Glioma Genome Atlas (CGGA) and revealed the relationship with tumor-associated macrophages (TAMs). Results: Median OS for NF1-deleted/mutated GBM patients (n = 11) treated with surgery and Chemoradiotherapy was 9.1 mon vs 17.2 mon for NF1 wildtype ones(n = 47), HR (95% CI) 1.83 (0.8753,3.817), p = 0.1. In addition, NF1-deleted/mutated GBMs showed reduced tumor purity and more infiltration of tumor-associated macrophages through pathological stainings. Conclusions: These data suggest that NF1-deleted/mutated GBM patients have a poor prognosis and NF1 may play a role in organizing the tumor microenvironment. NF1 in GBM will be further evaluated in a planned randomized ph 2b study in newly diagnosed GBM patients.
Comparison of treatment costs for pembrolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma based on KEYNOTE-040 clinical trial.
Authors: Justin Yeh, Achuta Guddati
Journal: Journal of Clinical Oncology (2020)

e18524 Background: Pembrolizumab has been approved by the FDA for the treatment of recurrent and refractory squamous cell cancer of the Head and Neck. This approval was based on the favorable results noted in the pembrolizumab arm of the KEYNOTE-040 clinical trial which compared pembrolizumab with the standard of care (methotrexate/cetuximab/docetaxel). This study aims to compare the financial aspects of these treatment arms in the setting of their relative clinical advantages in terms of increased overall survival by applying current pricing of the drugs and treatment for side effects. Methods: Data published from the KEYNOTE-040 study was used to generate a model incorporating the cost of each drug in both arms. The incidence of side effects was also extracted from the published data. The cost of treatment of side effects was extracted from previously published data and used for cost estimation in the model. The number of years added in terms of overall survival was calculated for the entire experimental arm and the cost of each such year was calculated. This model assumes that all drugs were supplied at the cost indicated at the retail price advertised by their producers. The cost was adjusted for inflation to the current year. Results: Based on current pricing, 248 patients in the control arm which involved methotrexate /cetuximab /docetaxel incurred an estimated total cost of $2,918,185 over 24 months. The total cost for the pembrolizumab arm based on current pricing was $36,744,819 for 247 patients over 24 months. The cost of management of adverse effects was $383,910 vs. $18,728 (Std. of care vs. Pembrolizumab). The total cost averaged over all patients in both arms was $13,314 vs. $ 148,840. There is an inverse relationship between drug cost and management of adverse side effects in both arms. Conclusions: Treatment with pembrolizumab confers an increase in overall survival but the cost of the incremental gain appears to be high. The model makes several assumptions including the distribution of cost over the patient population in both arms and extrapolates it to the cost in US dollars. It is very likely that the quality of life was superior in the pembrolizumab arm but it was not incorporated into our model. Justification of the continued use of pembrolizumab must be weighed against the long term survival benefits accrued by its usage in the context of a different and possibly better quality of life.
Oral adverse events in cancer patients treated with immune checkpoint inhibitors.
Authors: Yuanming Xu, Stephen T. Sonis, Natalie Wen, Moaiad Salous, Alessandro Villa
Journal: Journal of Clinical Oncology (2020)

e15106 Background: Immune-checkpoint inhibitors (ICIs) are increasingly used to treat a variety of cancers. Immune-related adverse events (irAEs) have been reported. Oral manifestations of irAEs include stomatitis, oral ulcers, and xerostomia. However, the trajectory and frequency of oral irAEs remain unclear. This study aims to evaluate the prevalence, trajectory and nature of oral irAEs and their association with primary cancer diagnosis and other irAEs. Methods: A retrospective electronic chart review using the Partners Research Patient Data was performed for all patients treated with ICIs at Partners Healthcare hospitals and the Dana-Farber Cancer Institute between 12/2011 and 9/2019. Keywords specific to oral irAE such as oral mucositis, stomatitis or mouth sore were used. We collected data on demographics, cancer features, treatments, and characteristics of oral irAEs. Results: 822 of 4683 patients who received ICIs therapy were identified by keyword filtering. Lung cancer, gastrointestinal cancer, and skin cancer (including melanoma) were the most common types of primary malignancies with a frequency of 35.5%, 12.4 % and 11.7%, respectively. Oral irAEs were identified in 106 patients with the median age of 69 (range: 29-92) years and the female to male ratio of 1:1. 57.5% (n = 61) presented with symptomatic oral mucosal lesions. 47.2% (n = 50) had xerostomia and 17.0% (n = 18) had dysgeusia. The median time from the date of ICIs initiation to the date of oral irAE onset was 105 days (range: 2-631 days) in patients presented with oral mucosal lesions, 103 days (2-860 days) in xerostomia patients, and 156 days (range: 5-836 days) in dysgeusia patients. Melanoma was the most common cancer seen in oral irAE patients (30.2%), followed by lung cancer (26.4%) and oral/oropharyngeal cancer (12.3%). 60, 42, and 12 patients received pembrolizumab, nivolumab, and ipilimumab, respectively. 86.8% of oral irAE patients received only one type of ICIs therapy. Concomitant cutaneous, intestinal, and rheumatological irAEs were commonly reported with a frequency of 19.4%, 15.3%, and 12.2%, respectively in those patients. Conclusions: Oral irAEs can present with both acute and chronic onset in patients with ICIs therapy but are not as common as oral AEs associated with conventional cytotoxic regimens. While data relative to capturing oral irAEs is still preliminary, the current provides insight into their nature and course. Prospective studies focused on assessing the impact of ICI on oral irAEs are likely to provide additional insight into the character, course and impact of these conditions.
Profile of cancer patients admitted in a emergency room of a charity hospital in Southeast Brazil.
Authors: Sabina B. Aleixo, Daiana Meneguelli, Nicolly Del Carmen Parra Molina, Jose Zago Pulido
Journal: Journal of Clinical Oncology (2020)

e19307 Background: Given the increase in cancer cases worlwide, there has been a high demand for urgent and emergency care by oncologic patients. Despite the high demand there is still a lack of studies on the oncological population in the context of urgency and emergency especially in the developing countries like Brazil. Methods: Retrospective longitudinal study. Sample consisted of the medical records of cancer patients who were admitted to the service, selected according to the inclusion and exclusion criteria, covering a period of one year. The variables evaluated were: age, gender, comorbidities, primary site, metastasis, intrahospital transfer, discharge type, days of hospitalization, hospitalizations within one year. Results: Identified 388 patients with a total of 1235 consults among them.; 237 (60.9%) were male, with mean age of 66.5 years old; 151 (39.1%) were female with a mean age of 59.77 years old. The most frequent primary site of cancer was intestine/colon/rectum (14.9%), followed up by hematological cancer (13.8%), and breast cancer (11.5%). Metastasis was identified in 93 patients, with liver as the most commom site of metastasis. The most commom complaints were pain(37.3%), dyspnoea (9.7%), weakness (7.6%), and nausea/vomiting (7.6%). Most patients were not transfered for other hospital units, 20.6% of the consults resulted in transfer to the Oncology Nursery, and 2.7% of the consults resulted in transfer to the Intensive Care Unit. Regarding to type of discharge, 85% of the admissions resulted in discharge, 10% resulted in death, 0.89% resulted on evasion, and the rest of the patients were still hospitalized at the end of this research. The minimum of consults in one year was 1, while one patient visited the ER 35 times. Conclusions: We found that the oncology population seek frequently for ER consults, with pain as the most common complaint.The most common cancer on our service was intestine, followed up by hematological cancer and breast cancer. The majority of the consults resulted in discharge. We suggest more research approaching different ways to assess, classify and to treat oncologic pain, considering that most patients have follow up with their attending physician and yet they seek ER to treat this symptom. Also,we suggest that the population must be clarified and educated about the real role of the ER service to avoid excessive consults.
NGSCUP: Phase II trial of site-specific treatment based on gene expression and mutation profiling by next generation sequencing (NGS) for patients (pts) with cancer of unknown primary site (CUP).
Authors: Hidetoshi Hayashi, Yuichi Takiguchi, Hironobu Minami, Kohei Akiyoshi, Yoshihiko Segawa, Hiroki Ueda, Yasuo Iwamoto, Chihiro Nakayama Kondoh, Koji Matsumoto, Shin Takahashi, Hisateru Yasui, Toshiyuki Sawa, Yusuke Onozawa, Yasutaka Chiba, Yosuke Togashi, Kazuko Sakai, Yoshihiko Fujita, Shuta Tomida, Kazuto Nishio, Kazuhiko Nakagawa
Journal: Journal of Clinical Oncology (2020)

e15577 Background: Although gene profiling is a promising diagnostic technique to determine the tissue of origin for pts with CUP, we reported that site-specific treatment based on gene profiling using microarray did not result in an improvement the survival compared with empirical therapy in the previous randomized phase 2 trial (Hayashi, et. al, JCO 2019). Recently, we have established new integrative diagnostic system combined the gene expression from RNA-sequencing and mutation/copy number variation data from targeted genomic-sequencing using NGS. We have performed a single-arm phase 2 study to assess the efficacy of site-specific therapy determined by this system in previously untreated pts with CUP. Methods: Comprehensive gene profiling was performed by NGS, and an established algorithm was applied to predict tumor origin. Pts with CUP was received site-specific chemotherapy determined by the predicted site. The primary endpoint was one-year survival rate. Results: A total of 111 pts was enrolled and all had sufficient biopsy tissue for gene profiling. Efficacy analysis was performed for 97 pts who received site-specific treatment. Cancer types most commonly predicted were lung (21%), liver (15%), kidney (15%), and colorectal cancer (12%). The one-year survival rate, median overall survival (OS), and progression free survival (PFS) was 53.1% (95%CI, 42.6-62.5%), 13.7 months (95% CI, 9.3-19.7 months), and 5.2 months (95% CI, 3.3-7.1 months), respectively. Median OS (15.7 versus 11.0 months, P = .078) and PFS (5.5 versus 2.8 months, P = .019) were better for predicted tumor types categorized as more responsive types than for less responsive ones. Conclusions: Site-specific treatment based on NGS demonstrated promising efficacy. Pts with CUP predicted to have more responsive tumor types had longer survival compared with pts with less responsive tumor types, suggesting that molecular tumor profiling by both DNA and RNA testing contributes to the management of pts with CUP. Clinical trial information: UMIN051180009.
肉眼血尿-腰腹痛
Authors: 吴东, 庄俊玲, 李剑, 赵志强
Journal: BMJ (2008)

患者女,67岁,因肉眼血尿,左侧腰腹痛1 d就诊于我院急诊科.当日早晨患者起床后排鲜红色肉眼血尿,伴左侧腰部及左下腹部阵发性绞痛.恶心,呕吐胃内容物,不发热.自服去痛片疼痛不能缓解。
A novel liquid biopsy aid for identifying clinically significant prostate cancer in at-risk men: Combining artificial intelligence with flow cytometry-based immunophenotyping.
Authors: George Dominguez, Anthony J Campisi, John Roop, Amit Kumar
Journal: Journal of Clinical Oncology (2020)

e17508 Background: Current screening methods for prostate cancer (PCa) result in a large number of false positives making it difficult for clinicians to assess disease status thus warranting advancements in screening and early detection methods. The goal of this study was to design a liquid biopsy assay that uses flow cytometry-based immunophenotyping and artificial intelligence (AI) analysis to detect clinically significant PCa in at-risk men. Methods: Standard multiparametric flow cytometry techniques were used to immunophenotype 27 different MDSC, myeloid, and lymphocyte cell populations found in the peripheral blood of 114 biopsy-confirmed PCa (GS6 = 54; ≥ GS7 = 60) and 58 biopsy-confirmed benign prostatic hyperplasia (BPH) patients. Pattern recognition neural networks (PRNNs), a type of AI, were trained with flow cytometry data from two data sets: patients with confirmed clinically significant PCa (≥ GS7) versus patients with BPH or clinically insignificant PCa (GS6). Predictions were evaluated using the performance of the trained PRNNs on 37 known ≥ GS7 PCa patients and 40 known BPH/ &lt; GS7 PCa patients not used in the PRNN training set (holdout samples). Results: In the holdout data set, 21 out of the 23 patients with clinically significant PCa were identified correctly (Sens = 91.3%, 95%CI = 72.0%-98.9%; PPV = 33.3%, 95%CI = 28.4%-38.7%) while 30 out of the 72 patients at low-risk or no-risk were identified correctly (Spec = 41.7%, 95%CI = 30.2%-53.9%; NPV = 93.8%, 95%CI = 79.5%-98.3%) for an accuracy of 53.7% (95%CI = 43.2%-64.0%). For all patients in this study, our data suggests that approximately 47 out of the 112 patients with BPH or GS6 PCa could have avoided an unnecessary prostate biopsy procedure. Conclusions: Pairing our PRNN with surface biomarker blood-based analyses of various leukocyte populations has enabled the ability to objectively identify patterns indicative for the existence of clinically significant PCa (≥ GS7). In a clinical setting, we believe that this technology, in use with other known clinical factors, would allow for clinicians to have a more informed decision when recommending their patients for a prostate biopsy procedure.
Integrative tumor and immune cell multi-omic analyses to predict melanoma response to immune checkpoint blockade.
Authors: Valsamo Anagnostou, Daniel C. Bruhm, Noushin Niknafs, James R White, John-William Sidhom, Julie E. Stein, Hua-Ling Tsai, Hao Wang, Zineb Belcaid, Joseph Christopher Murray, Petra B. Ross-Macdonald, Megan Wind-Rotolo, Alexander S Baras, Janis M. Taube, Robert B. Scharpf, Catherine Grasso, Antoni Ribas, Drew M. Pardoll, Suzanne Louise Topalian, Victor E. Velculescu
Journal: Journal of Clinical Oncology (2020)

10009 Background: The complex crosstalk between tumor and immune cells during immune checkpoint blockade mandates the development of integrated models to interpret the antitumor immune response and predict clinical outcome. Methods: We performed comprehensive genomic, transcriptomic and T cell repertoire analyses on tumor biopsies from 64 patients with advanced melanoma receiving nivolumab +/- ipilimumab on CheckMate-038 (NCT01621490). Tumor biopsies were obtained at baseline and 2-4 weeks on therapy. Machine learning and Cox proportional hazards regression analyses were employed to integrate multi-omics features in predictive models of response, defined by RECISTv1.1 as complete and partial response, and survival (PFS and OS). Results: Responding patients had a higher tumor mutation burden (TMB) than non-responders. Expressed TMB more accurately predicted overall survival than genomic TMB (log rank p = 0.028 vs 0.078). High tumor aneuploidy was associated with worse prognosis especially for the patients in the nivolumab + ipilimumab group (log rank p = 0.01). TCR sequencing of paired tumors before and on-treatment revealed that responders had a significantly higher number of unique TCR clones at baseline and more clonotypic shifts on-treatment (p = 0.0018). Gene rearrangement analyses using transcriptome data identified a higher number of rearrangements involving immunoglobulin (Ig) genes in baseline tumors from responders. Deconvolution of transcriptomic data confirmed an enrichment in tumor associated B cells in baseline tumors of responders, suggesting that pre-existing B cell infiltration is a predictor of clinical outcome. Random forests were utilized to integrate Ig rearrangements, expressed TMB and tumor aneuploidy, into a predictive model of response that was superior to TMB (AUC = 0.89 and 0.65 respectively). Multivariate Cox proportional hazards analysis incorporating the same features was utilized to generate a risk score for each patient; those with high risk scores had a significantly shorter PFS compared to low risk patients (median PFS 1.45 months vs 29.01 months, log rank p = 3.4e-06, HR = 9.18, 95% CI: 3.14-26.85). Conclusions: Our findings highlight the multi-faceted interactions between the tumor and the immune system and the importance of pre-existing T and B cell immunity in driving clinical response and PFS after immune checkpoint blockade, laying the groundwork for integration of genomic and immune features into predictive models that may ultimately optimize therapeutic decisions.
The challenging management of a series of 43 infants with Netherton syndrome: unexpected complications and novel mutations*
Authors: N. Bellon, S. Hadj‐Rabia, F. Moulin, C. Lambe, G. Lezmi, F. Charbit‐Henrion, C. Alby, L. Le Saché‐de Peufeilhoux, S. Leclerc‐Mercier, A. Hadchouel, J. Steffann, A. Hovnanian, A. Lapillonne, C. Bodemer
Journal: British Journal of Dermatology (2020)

Background Netherton syndrome (NS) is a rare disease caused by SPINK5 mutations, featuring variable skin and hair involvement and, in many cases, allergic manifestations with a risk of lethality, particularly in infants. The clinical management of NS is challenging. Objectives To analyse the clinical manifestations of a cohort of infants with NS managed in a reference centre and to draw up recommendations for management. Methods We conducted a monocentric analysis of patients with NS. The inclusion criteria were management in our reference centre, a histologically or molecularly confirmed diagnosis of NS and available epidemiological, clinical and laboratory data. Results A total of 43 patients with NS were included. Hypernatraemia was reported in 23 cases (54%) and associated with a greater likelihood of enteral and/or parenteral nutritional support (P < 0.001). Moreover, hypernatraemia was more frequent in patients with skin manifestations at birth (P = 0.026) and in patients bearing the c.153delT mutation in SPINK5 exon 3 (P = 0.014). The need for enteral and/or parenteral nutritional support was associated with a history of hypernatraemic dehydration (P < 0.001). Several unexpected extracutaneous complications were recorded, and new mutations were reported. The death rate (9% overall) was higher among the subset of patients bearing the c.153delT deletion. Conclusions Our data emphasize that neonatal NS is a severe and sometimes lethal multisystem disorder. Patients have a high risk of variable metabolic anomalies (i.e. lethal hypernatraemia) and therefore have major nutritional needs. Cases of NS associated with c.153delT are particularly severe. Unexpected clinical manifestations broadened the phenotypic spectrum of NS. We provide recommendations on the management of the life-threatening manifestations of NS in neonates based on our multidisciplinary experience.
Progress of the femoral head preserving procedures in the treatments of osteonecrosis of the femoral head
Authors: 傅德皓, 杨述华
Journal: BMJ (2007)

股骨头坏死是骨科常见的难治性疾病,尤其非创伤性股骨头坏死高发于中青年患者(平均年龄38岁),如不治疗,80%的患者将在4年内出现股骨头塌陷和骨性关节炎[1].尽管人工关节技术日趋成熟,但由于此类患者年龄偏小、活动量较大,人工关节置换术的远期疗效并不理想.因此,股骨头坏死的保头治疗具有特别重要的意义。