tbuckley/cabot-search huggingface dataset:
Clinical characteristics of adult patients with autoinflammatory diseases presenting as recurrent fever of unknown origin
Authors: Di Wu
Journal: BMJ (2018)

Objective
To analyze the clinical characteristics of adult patients with autoinflammatory diseases (AUID) presenting as recurrent fever of unknown origin (FUO).


Methods
The clinical and genetic features of 51 adult patients with recurrent FUO, who were suspected of monogenic AUID admitted in adult AUID center Department of Rheumatology, Peking Union Medical College Hospital from April 2015 to March 2017, were prospectively studied. The clinical phenotypes were compared between patients with pathogenic gene mutations and diagnosed as monogenic AUID (gene-positive group), and those without pathogenic gene mutations (gene-negative group).


Results
Among 51 patients, there were 26 patients with positive monogenic mutations (51.0%); in addition 6 patients were diagnosed as periodic fever-aphthous stomatitis-pharyngitis-adenitis (PFAPA) syndrome. Finally 32 patients (63.0%) were diagnosed as AUID, including 11 cases of familial Mediterranean fever (34.4%), 5 cases of cryopyrin-associated periodic syndrome (15.6%), 5 cases of NLRP12-autoinflammtory disease (15.6%), 2 cases of Blau syndrome (6.3%), 2 cases of Yao syndrome (6.3%), 1 case of tumor necrosis factor-receptor associated periodic syndrome (3.1%), and 6 cases of PFAPA syndrome (18.8%). Among 25 gene-negative patients except 6 cases of PFAPA syndrome, 9 were diagnosed as other diseases, and the diagnosis of AUID was not confirmed in 10 cases (40.0%). Compared with gene-negative group, gene-positive group had more common childhood-onset (30.8% vs. 8.0%, P=0.041), longer disease duration (11.2±10.1 vs. 6.1±5.9, P=0.031), and more common abdominal pain/diarrhea (42.3% vs.12.0%, P=0.015). There were no significant differences in manifestations such as rash, arthralgia/arthritis, thoracic pain, eye inflammation and oral ulcers between two groups. One patient had family history of AUID, and finally diagnosed as Blau syndrome with NOD2 gene mutation.


Conclusion
AUID is one of the main causes of adult patients with recurrent FUO. Childhood-onset, long disease duration, abdominal pain/diarrhea, and family history of AUID are more common in patients with AUID pathogenic gene variations. Recognizing these symptom patterns can provide the clues, leading to the initiation of gene testing for patients with recurrent FUO. Adults patients with recurrent FUO suspected of AUID should be referred to specialist physicians in adult AUID center.


Key words: 
Fever of unknown origin; Autoinflammatory diseases; Disease attributers
Neoplastic fibrocytes play an essential role in bone marrow fibrosis in Jak2V617F-induced primary myelofibrosis mice
Authors: Yoshinori Ozono, Kotaro Shide, Takuro Kameda, Ayako Kamiunten, Yuki Tahira, Masaaki Sekine, Keiichi Akizuki, Kenichi Nakamura, Hisayoshi Iwakiri, Mitsue Sueta, Tomonori Hidaka, Yoko Kubuki, Shojiro Yamamoto, Satoru Hasuike, Akira Sawaguchi, Kenji Nagata, Kazuya Shimoda
Journal: Leukemia (2020)

Abstract Primary myelofibrosis (PMF) is a myeloproliferative neoplasm (MPN) characterized by clonal myeloproliferation, progressive bone marrow (BM) fibrosis, splenomegaly, and anemia. BM fibrosis was previously thought to be a reactive phenomenon induced by mesenchymal stromal cells that are stimulated by the overproduction of cytokines such as transforming growth factor (TGF)-β1. However, the involvement of neoplastic fibrocytes in BM fibrosis was recently reported. In this study, we showed that the vast majority of collagen- and fibronectin-producing cells in the BM and spleens of Jak2V617F-induced myelofibrosis (MF) mice were fibrocytes derived from neoplastic hematopoietic cells. Neoplastic monocyte depletion eliminated collagen- and fibronectin-producing fibrocytes in BM and spleen, and ameliorated most characteristic MF features in Jak2V617F transgenic mice, including BM fibrosis, anemia, and splenomegaly, while had little effect on the elevated numbers of megakaryocytes and stem cells in BM, and leukothrombocytosis in peripheral blood. TGF-β1, which was produced by hematopoietic cells including fibrocytes, promoted the differentiation of neoplastic monocytes to fibrocytes, and elevated plasma TGF-β1 levels were normalized by monocyte depletion. Collectively, our data suggest that neoplastic fibrocytes are the major contributor to BM fibrosis in PMF, and TGF-β1 is required for their differentiation.
儿童呼吸道感染156例中卡他莫拉菌感染分析
Authors: 潘韶霞, 潘韶华, 刘茂林, 刘新风, 汪红
Journal: BMJ (2005)

从156例呼吸道感染的儿童的痰、咽试子标本中培养分离出28株卡他莫拉菌,显示卡他莫拉菌的感染率为17.9%,产β-内酰胺酶为67.8%.提示临床医生在对产β-内酰胺酶的卡他莫拉菌所致的呼吸道感染使用抗生素时应高度重视。
如何实施戒烟过程中的动机访谈
Authors: 胡大一, 俞红霞
Journal: BMJ (2009)

烟草依赖的治疗,不仅仅需要克服生理上尼古丁成瘾,更需要花费一定的精力克服心理依赖及行为习惯.大部分吸烟者在决定戒烟前需要经过很长时间的思考,国外的研究表明,虽然有70%以上的吸烟者有戒烟的愿望,但真正进入戒烟行动的比例并不高,进入戒烟门诊寻求帮助的人更少,大约在2%左右.医生的简单戒烟建议及面对面最小剂量干预(<3 min咨询)对戒烟成功起着积极有效的作用(循证等级为A),临床医生对吸烟者系统的动机访谈(motivational interviewing,MI)有着重要的作用。
Direct inpatient costs and influencing factors for patients with rectal cancer with low anterior resection: a retrospective observational study at a three-tertiary hospital in Beijing, China
Authors: 陈治水, 冷家骅, 高广颖, 张连海, 杨阳
Journal: BMJ (2019)

目的
调查分析在北京地区接受低位前切除术的直肠癌患者直接住院费用及其关联影响因素。


研究设计
一项回顾性观察研究。


研究地点
北京一所三级甲等肿瘤专科医疗机构。


研究对象
回顾性检索北京大学肿瘤医院2015年1月至2016年12月期间主诊断为直肠癌且接受低位前切除术患者的出院记录，共448例。搜集其人口统计学、临床和费用等数据。


结果
次均住院费用中位数为89 064元，由于耗材使用费用差异较大，费用范围介于46 711~191 329元。材料费用占52.19%，在费用构成里占比最高。造口[比值比（OR）4.17；95%可信区间（CI）1.79~9.71]、合并高血压(OR 5.30；95% CI 1.94~14.42)和合并其他部位肿瘤(OR 2.92；95% CI 1.12~7.60)是高额费用的影响因素，而遵循临床路径(OR 0.10；95% CI 0.03~0.35）、医疗保险实时结算(OR 0.26；95% CI 0.10~0.68)与合并心血管疾病(OR 0.09；95% CI 0.02~0.52)则是住院费用的保护性因素。


结论
进一步规范临床路径、优化医疗保险支付方式和控制并发症是减轻癌症患者经济负担的有效手段。今后，应设立纵向序列研究以调查直肠癌患者不同治疗阶段的全成本费用。
Analysis on drug treatment protocols of out-patients with hypertension
Authors: 华焱坤
Journal: BMJ (2011)

The antihypertensive treatment protocols of 4102 patients from the database of Changbai Community Health Service Center of Shanghai Yangpu District were analyzed.Patients with irregular drug treatment were excluded in the study.In 4102 hypertensive patients,45.6% took calcium channel blockers (CCB),16.0% took angiotensin converting enzyme inhibitors ( ACEI),3.6% took AT1-receptor blocker (ARB),9.0% took β-adrenergic receptor blockers,4.7% took diuretics and 21.1% took compound preparation.68% patients were in single-drug protocol,29.3% in two-drug,2.6% in three-drug and 0.1% in four-drug.In patients with two-drug protocol,75.8% was based on CCB; three-drug or four-drug protocols were also based on the combination of CCB.The results indicate that the treatment protocol for hypertensive patients in our community health service center basically meets the requirements of International Society of Hypertension Treatment Guidelines,but the proportion of the single drug use seems to be high,more combination of antihypertensive drug use should by proposed.

Key words: 
Antihypertensive agents; Community health centers
Pharmacokinetics, safety, and early activity of a nanoparticle micellar formulation of docetaxel in women with metastatic breast cancer: Results of two randomized trials (phase I and II).
Authors: Markus Joerger, Helena Bjermo, Per Blom, Nina Anna Heldring
Journal: Journal of Clinical Oncology (2020)

3526 Background: Docetaxel micellar (DM) is a nano-sized particle formulation of docetaxel in which a retinoic acid derivative is used as solubilizer with a high drug to excipient ratio possibly resulting in reduced systemic toxicity or hypersensitivity reactions due to the excipient. DM is given without standard use of premedication, avoiding steroid-associated immunosuppression. Here we present the pharmacokinetics (PK) after a single dose of DM or polysorbate-solubilized docetaxel (D) as well as safety and early activity including overall response rate (ORR) in female patients with metastatic breast cancer. Methods: The PK study was a two-cycle, cross-over study where 30 patients were included and randomized to either DM followed by D or D followed by DM, both given as a 1-hour intravenous infusion at a dose of 100mg/m 2 . The phase II study was a prospective, multicenter, open-label, third-party blinded, randomized, parallel group, active-controlled study including 200 patients to compare the early activity and safety of DM and D, both given as 100 mg/m 2 1-hour intravenous infusion every 21 days (1 cycle) for a total of 6 cycles. Results: Bioequivalence of total docetaxel in plasma, AUC0-last and Cmax, was demonstrated for DM compared to D. The incidence of adverse events was higher in the D arm than in the DM arm for the majority of SOCs and PTs in the phase II study. Overall, Grade 3 or 4 AEs were reported for 82.7% of patients from DM arm and 99.0% of patients from D arm. Twelve (12.2%) patients in the DM arm and 24 (24.0%) patients in the D arm needed at least one dose reduction due to AEs. The primary efficacy endpoint in the phase II study was based on the assessment according to Response Evaluation Criteria in Soldid Tumors (RECIST) 1.1 and non-inferiority was not reached based on the pre-defined non-inferiority margin. A post-hoc analysis investigating the ORR based on tumour assessment at the end of chemotherapy, and non-inferiority of DM as compared to D was shown (ITT population). Conclusions: DM is bioequivalent to D regarding total drug in plasma and provides a docetaxel formulation that spares patients steroid premedication. An improved safety profile for DM compared to D was shown while additional efficacy data is needed for future development of DM. Eudra CT: 2012-005161-12 and 2013-004889-33. Clinical trial information: 2012-005161-12 and 2013-004889-33 .
Subsequent pregnancy and long-term safety from breast cancer patients.
Authors: Yunyeong Kim, Minsun Kang, Jaehun Jung, Eun Kyung Cho, Heung Kyu Park, Yong-Soon Chun
Journal: Journal of Clinical Oncology (2020)

e13575 Background: Long-term safety of pregnancy after breast cancer still remained controversial, especially according to tumor subtypes. Prior results of other studies have limitations of short follow-up periods or small groups. Methods: We analyzed a population-based retrospective cohort data extracted from a random sample of 50% of women aged between 20 and 60 years who were diagnosed with breast cancer from 2002 to 2017 in the Korean National Health Insurance Service database. Propensity score matching analysis for age and Charlson Comorbidity Index (CCI) variables was performed for pregnant groups and non-pregnant groups with the same type of hormone therapy, chemotherapy and surgery. Study population was categorized to 4 biologic subgroups by the combination of hormone therapy, chemotherapy and target therapy. In this observational study, 1,566 patients with pregnancy after breast cancer were matched (1:2) to 2,462 non-pregnant patients of similar characteristics, adjusting for guaranteed bias. The matched patients were followed up to 7 years, or disease and mortality occurrence after the diagnosis of breast cancer. Survival estimates were calculated using the Kaplan-Meier analysis, groups were compared with the log-rank test. Results: Mean time from diagnosis to pregnancy was 3.4 years in study population. At a follow-up of 7 years after pregnancy, no inferiority in disease-free survival and overall survival was observed in pregnant patients factoring in treatment bias. In sub-analysis according to tumor subtypes, no difference in disease-free survival was observed between pregnant and non-pregnant patients in HR-positive and triple negative subgroup ( p= 0.088, p= 0.048, respectively). Likewise, no overall survival difference was observed in ER-positive patients and triple negative patients ( p= 0.05∼0.73, p= 0.03∼0.09, respectively). Conclusions: Our observational data provides reassuring evidence on long-term safety of pregnancy in young breast cancer patients, regardless of tumor subtypes.
Clinical implementation of 2010 reference standards of the U.S.Chinical and Laboratory Standards Institute in antimicrobial susceptibility for Enterobacteriaceae
Authors: Li-yan Ma, Jian-rong Su
Journal: BMJ (2011)

Objective To compare the performance of 2009 and 2010 reference standards of the United States Clinical and Laboratory Standards Institute(CLSI)in antimicrobial susceptibility for Enterobacteriaceae.Methods The breakpoints of susceptibility for ceftriaxone,ceftazidime and aztreonam in CLSI M100-S19(2009)were used to analyze results of antimicrobial susceptibility of Escherichia coli (308 isolates)and Klebsiella pneumoniae(194 isolates),as well as those revised in M100-S20(2010).Results With both the breakpoints in CLSI M100-S19(2009)and CLSI M100-S20(2010),proportions of antimicmbial resistance of ceftriaxone,ceftazidime and aztreonam for isolates of extended-spectrum β-lactamases(ESBLs)-producing E. coli were 84.2 percent vs.98.0 percent and 84.9 percent vs.98.0percent,respectively:those for isolates of ESBLs negative E. coli were 4.2 percent vs.7.7 percent and 5.6percent vs.8.4 percent,respectively;those for isolates of ESBLs positive Klebsiella spp.were 67.2 percent vs.90.2 percent and 67.2 percent vs.90.2 percent,respectively:and those for isolates of ESBLs negative Klebsiella spp.were 9.8 percent vs.10.6 percent and 10.6 percent vs.10.6 percent,respectively.Conclusions Proportions of antimicrobial resistance for ceftriaxone,ceftazidime and aztreonam with the rcference breakpeints of CLSI M100-S20(2010)increase to various extent,8.8 compared to those with the old ones in 2009.Compared with ESBLs negative isolates,ESBLs positive isolates are affected much more by the breakpeints of CLSI M100-S20(2010).Proportion of affected Klebsiella spp.by the revised breakpoints of CLSI M100-S20(2010)for ceftazidime and aztreonam is higher than that of E. coli with ESBLs positive.

Key words: 
Enterobacteriaceae;  Microbial sensitivity tests;  Reference standard
Intra-tumoral microbes and overall survival in colorectal cancer patients.
Authors: Pannaga G. Malalur, Xiaokui Mo, Rebecca Hoyd, David Paul Carbone, Daniel Spakowicz
Journal: Journal of Clinical Oncology (2020)

4083 Background: The presence of certain bacteria among or adjacent to tumor cells may contribute to colorectal cancer (CRC) development. However, the effect of the tumor microbiome on survival in CRC patients undergoing treatment is poorly understood. We hypothesize that intra-tumoral microbes correlate with overall survival (OS) in CRC patients. Methods: We obtained RNA-seq data from CRC tumor biopsies from patients treated at The Ohio State University Comprehensive Cancer Center as part of the Oncology Research Information Exchange Network (ORIEN). Reads were aligned to human and exogenous genomes using TopHat2 and Kraken2/Bracken, respectively. Results: The analyzed cohort included 99 CRC patients with an age range from 31-83 years, 62% female, and 44% with metastatic CRC. Therapies received prior to sample collection were grouped into chemotherapy with or without radiation (37%), antiVEGF/EGFR therapies (33%), no systemic therapy (23%), immunotherapy (3%); 3% were unknown. Overall, eleven bacteria were significantly associated with shorter OS, including a species in the genus Clostridium and Vibrio. Conversely, five other bacteria including several commensal gut microbes, were associated with longer OS. In patients who received chemotherapy with or without radiation (n = 38), several microbes were significantly associated with shorter OS, including a member of the genus Streptomyces. Only three bacteria were significantly associated with longer OS. In the patients who received antiVEGF/EGFR therapies (bevacizumab, cetuximab, panitumumab) (n = 33), several bacterial taxa were associated with shorter OS. In addition, bacteria including a member of the genera Bacillus and Staphylococcus were significantly associated with metastatic CRCs. (p &lt; 0.05 for all, Fisher’s Exact tests). Conclusions: This study suggests that demonstrating the presence or absence of certain microbes in tumor biopsies could have important therapeutic implications for CRC patients. Only bacteria (no fungi, viruses, archaea, etc.) were found to significantly associate with OS across the entire cohort and within treatment subsets. The presence of bacteria was mostly, but not always, associated with worse OS. Antibiotics targeted towards bacterial species associated with negative outcomes could have the potential to improve OS in CRC patients.
Current status and influencing factors of dental anxiety among elders in communities of Hangzhou city
Authors: Chenxi Zhu, Xingong Liu, Fuming He, Hongyi Niu, Xinchi Zhou
Journal: BMJ (2014)

To explore the current status and influencing factors of dental anxiety among the elders in communities of Hangzhou. A total of 600 elders were selected by multi-stage stratified cluster random sampling and examined by Coarh's dental anxiety scale (DAS). The status and influencing factors of dental anxiety among them were analyzed by single and multi-factor analysis methods. A total of 596 questionnaires were answered 99.3%(596/600). And there were 573 valid questionnaires with a validity rate of 96.1%(573/596). The respondents' DAS score was 7.51±3.18. Their prevalence rate of DA was 34.9%. Among them, there was significant difference for the comparison of prevalence rate of DA in gender, age, different pain tolerance and experiences of dental care (χ2=9.45, 18.24, 33.34, 38.66, 12.62, P<0.05). The results of logistic regression model showed that there was a higher risk of DA occurrence among females, age, poor pain tolerance and elders with painful dental experiences. Gender, age, pain tolerance and experiences of dental care are influencing factors of oral health behaviors among the elders in communities of Hangzhou.


Key words: 
Elder; Dental anxiety
A phase Ib study of ribociclib in combination with doxorubicin in advanced soft tissue sarcomas (aSTS).
Authors: Lara E. Davis, Emile Latour, Reid Burch, Byung Park, Jessica L. Davis, Christopher W. Ryan
Journal: Journal of Clinical Oncology (2020)

11548 Background: aSTS are typically treated with single agent doxorubicin (dox). CDK4 inhibitors such as ribociclib (ribo) may have a role in treating STS, which frequently rely on hyperphosphorylation of Rb to evade the Rb checkpoint. We hypothesized that dox efficacy could be increased by inhibiting Rb phosphorylation with a short course of ribo, then removing ribo to permit cell cycle progression prior to dox, thus potentiating the DNA-damaging effects of dox. Methods: Open label, dose-finding study of ribo and dox in dox-naïve patients (pts) with Rb+ aSTS. Rb status determined by IHC. Primary objective to determine the recommended phase 2 dose (RP2D). Secondary objective of anti-tumor activity. Pts received ribo 400-600 mg PO QD x7d followed by 72h rest before dox 60-75 mg/m2 IV, q21d. Pts free from progression of disease after 6 cycles continued on ribo maintenance at 600 mg QD q3/4wk. Dose-limiting toxicity (DLT) period was cycle 1, with target toxicity rate of 30% using a modified toxicity probability interval (mTPI) design. Growth factor support was not allowed during DLT period. Results: 9 screened pts were ineligible by Rb status. 16 pts enrolled with 15 evaluable for dose determination (7 dedifferentiated LPS, 8 other subtypes). 4 of 7 pts treated at starting dose level (400 mg ribo, 75 mg/m2 dox) had a DLT; all febrile neutropenia. 1 of 8 pts treated at dose level -1 (400 mg ribo, 60 mg/m2 dox) had a DLT of gr4 anemia. Febrile neutropenia events occurred during cycle 1, when growth factors were prohibited. Toxicity was similar to historical dox AEs (Table). Two partial responses for overall response rate (ORR) of 13%. Five (33%) were progression-free at 18 wks. Correlative studies ongoing. Conclusions: This study determined a RP2D of ribo 400 mg with dox 60 mg/m2 when used in combination for the treatment of aSTS. Clinical trial information: NCT03009201 . [Table: see text]
Circulating tumor DNA (ctDNA) in patients (pts) with metastatic uveal melanoma (UM) treated with protein kinase C inhibitor (PKCi).
Authors: John J. Park, Russell J. Diefenbach, Natalie Byrne, Richard Kefford, Georgina V. Long, Richard A. Scolyer, Elin Gray, Matteo S. Carlino, Helen Rizos
Journal: Journal of Clinical Oncology (2020)

e22054 Background: UM is the most common primary intraocular malignancy. About 50% of pts with UM will develop metastatic disease and currently there is no effective treatment in metastatic UM. Nearly 95% of UM harbour mutually exclusive activating mutations in GNAQ, GNA11, CYSTLR2 and PLCb4. We sought to evaluate ctDNA in metastatic UM pts receiving experimental early phase clinical trial of LXS196, a PKCi, using digital droplet PCR (ddPCR) and targeted ion torrent next generation sequencing (NGS). Methods: 17 pts with metastatic UM were identified from a single institution. Pt characteristics including mutation status, disease volume using sum of product of disease (SPOD), best response and clinical benefit defined as partial response (PR) or stable disease (SD) &gt; 6 months were assessed. Plasma samples at baseline and early on treatment (EOT) (14 – 30 days on treatment) were analysed for ctDNA using mutation specific ddPCR. A custom made NGS panel covering 95% of UM mutations was used on plasma ctDNA samples at baseline and on treatment. The allele frequency (AF) of activating mutations identified using ion torrent NGS analysis were then validated using ddPCR. Results: Using ddPCR, 16/17 pts had a +ve ctDNA at baseline with baseline ctDNA copies correlating with LDH (n = 17, p = &lt; 0.001, Spearman’s rank r = 0.8015) and SPOD (n = 17, p = 0.005, r = 0.6642). 16/17 pts had paired samples at baseline and EOT and only 4/16 pts were undetectable at EOT. These 4 pts were GNA11 Q209L positive, had below median SPOD (median 5986, range 200 – 16782), and low numbers of liver metastases (median 9, range 1 – 49). Of these 4 pts, one had PR and three had SD (two with SD &gt; 6 months) as best response. A further 8 pts had +ve ctDNA at baseline and showed a reduction in EOT (reduction range 46 – 99%). Of these 8 pts, one had PR, four had SD (two with SD &gt; 6 months) and three had progressive disease (PD) as best response. The remaining 4 pts showed increasing ctDNA from baseline to EOT and all had SD/PD. Using ROC analysis, EOT ctDNA predicted clinical benefit to PKCi (AUC 0.84, [95% confidence interval, 0.65-1.0, p = 0.026]). AF of ion torrent NGS correlated significantly with ddPCR AF (n = 30, p = &lt; 0.001, r = 0.968). Ion torrent NGS was able to detect additional mutations implicated in UM prognosis including SF3B1 mutations in 4 pts. Conclusions: Baseline ctDNA correlates with baseline LDH level and disease volume. EOT ctDNA predicted clinical benefit to PKCi. The ctDNA AF derived from ddPCR and NGS was comparable and targeted ion torrent NGS was useful in detecting driver as well as additional mutations in UM.