tbuckley/cabot-search huggingface dataset:
Growth and development status of offspring infants born by women with intrahepatic cholestasis of pregnancy after treatment
Authors: Xufen Jiang, Dexue Zu, Xuejun Dai
Journal: BMJ (2016)

Ninety six offspring infants (48 males, 48 females) born by hospitalized patients with intrahepatic cholestasis of pregnancy from January 2010 to February 2013 (study group) and 108 cases of offspring infants (54 males, 54 females) born by hospitalized healthy pregnant woman (control group) were enrolled in the study. All offspring infants were followed up for 2 years after birth, physical and neuropsychological development parameters were investigated at 1 month, 1 year and 2 years after birth. There were no significant difference in body weight [(11.94±0.89) vs.(13.99±0.78)kg], length[(86.2±2.0) vs. (87.0±3.1) cm], sitting height, [(51.8±2.1) vs. (51.8±1.9) cm], head circumference[(47.9±1.3) vs. (48.1±1.1) cm], development of intelligence quotient index[(99.4±12.9) vs. (100.0±12.0)] at 2 years after birth between two groups (P>0.05). Two-year follow up reveals that ursodeoxycholic acid and S-adenosine methionine treatment for women with intrahepatic cholestasis of pregnant has no significant adverse effect on the growth and development of their offspring.


Key words: 
Cholestasis, intrahepatic; Pregnancy; Children; Growth and development; Mental retardation
Vascular maps with dynamic contrast-enhanced MRI for diagnosis of breast cancer
Authors: Bo Yin, Li Liu, Dao-ying Geng, Yadi Li
Journal: BMJ (2009)

Total 52 patients with breast lesions underwent dynamic contrast-enhanced breast MRI; and the breast vascularization was scored on the MRI vascular maps with a range of 0 to 3. The mean number of vessels per ipsilateral breast in malignant cases was higher than that of benign cases (3.8±2.0 vs. 1.3± 1.0; P=0.000). When the breast vascularity score 0-1 was defined as benign and 2-3 was defined as malignant, the sensitivity and specificity was 79% and 83%, respectively. Results indicate that dynamic contrast-enhanced breast MRI is of value in diagnosis of malignant breast lesions.

Key words: 
Breast neoplasms;  Magnetic resonance angiography
Intracranial activity of selpercatinib (LOXO-292) in RET fusion-positive non-small cell lung cancer (NSCLC) patients on the LIBRETTO-001 trial.
Authors: Vivek Subbiah, Justin F. Gainor, Geoffrey R. Oxnard, Daniel Shao-Weng Tan, Dwight Hall Owen, Byoung Chul Cho, Herbert H. F. Loong, Caroline Elizabeth McCoach, Jared Weiss, YuJung Kim, Lyudmila Bazhenova, Keunchil Park, Haruko Daga, Benjamin Besse, Oliver Gautschi, Sarah Ng, Xin Huang, Alexander E. Drilon
Journal: Journal of Clinical Oncology (2020)

9516 Background: Patients with RET fusion-positive NSCLC have an ~50% lifetime prevalence of developing central nervous system (CNS) metastases. Selpercatinib is a highly selective oral RET inhibitor with CNS penetration. Its intracranial antitumor activity was previously demonstrated in an orthotopic RET fusion-positive preclinical model. The activity of selpercatinib in RET fusion-positive NSCLC patients with CNS metastases was evaluated as a prespecified subgroup analysis in LIBRETTO-001, a registrational phase 1/2 trial (NCT03157128). Methods: This global (89 sites, 16 countries) trial enrolled patients with advanced RET-altered solid tumors, including patients with RET fusion-positive advanced NSCLC with baseline CNS metastases. The selpercatinib recommended phase 2 dose was 160 mg twice daily, dosed orally in 28-day cycles. CNS metastases were assessed by MRI/CT scan at baseline, then every 8 weeks for 1 year, and every 12 weeks thereafter. The primary endpoint for this analysis was intracranial objective response rate (ORR, confirmed; RECIST v1.1) as assessed by independent review committee (IRC). Secondary endpoints included intracranial duration of response (DoR) by IRC. To be included in the efficacy analysis, patients were required to have adequate follow-up time (opportunity for ≥6 months follow-up from the first dose). Analyses were based on 17Jun2019 data cutoff date. Results: 79 patients with RET fusion-positive NSCLC and baseline CNS metastases were enrolled. Per IRC, 22 of 79 patients had measurable (≥10 mm) CNS disease; 14 of the 22 patients had adequate follow-up time for analysis. This efficacy-evaluable population had a median age of 64 yrs (range 43-80), ECOG PS 0/1 = 21% / 79%, and all had prior systemic therapy. 5 of the 14 patients received prior intracranial radiotherapy; all radiotherapy was completed &gt; 2 months prior to selpercatinib. The intracranial ORR in the 14 patients was 93% (n = 13; 95% CI = 66.1 – 99.8), including 2 complete responses (14%) and 11 partial responses (79%). The median intracranial DoR was 10.1 months (95% CI = 6.7 – NE), with CNS progression events (n = 5) or death (n = 1) reported in 6 of 13 responders. The remaining responders (n = 7) were ongoing and censored. Presentation will include updated IRC data as of 16Dec2019. Conclusions: Selpercatinib had marked intracranial anti-tumor activity in RET fusion-positive NSCLC patients with CNS metastases. Tumor responses were durable, independently-confirmed, and observed in patients with prior systemic chemotherapy. Clinical trial information: NCT03157128 .
Phase I trial of D2C7 immunotoxin (D2C7-IT) administered intratumorally via convection-enhanced delivery (CED) for recurrent malignant glioma (MG).
Authors: Annick Desjardins, Dina Randazzo, Vidyalakshmi Chandramohan, Katherine B. Peters, Margaret O Johnson, Stevie Threatt, Chevelle A Bullock, James Emmett Herndon, Patrick Healy, Eric S Lipp, John H. Sampson, Allan H. Friedman, Henry S. Friedman, David M. Ashley, Darell D. Bigner
Journal: Journal of Clinical Oncology (2020)

2566 Background: D2C7-IT is a recombinant immunotoxin comprised of a dual-specific antibody fragment targeting EGFRwt and EGFRvIII and a genetically engineered form of the Pseudomonas exotoxin, PE38-KDEL. We report the results of a phase I trial evaluating D2C7-IT delivered intratumorally by CED. Methods: Eligible patients were adults with recurrent supratentorial WHO grade III or IV MG; solitary tumor; ≥4 weeks after chemotherapy, bevacizumab or study drug; adequate organ function; and KPS&gt;70%. Two patients per dose level (DL) were to enroll in the dose escalation portion (dose range: 40ng/mL to 23,354ng/mL). Results: From May 2015 to May 2018, 43 patients enrolled on study. Observed dose limiting toxicities include: grade 4 seizure (n=1) on DL3, grade 3 confusion and pyramidal tract syndrome (n=1) on DL13, and grade 4 cerebral edema (n=1) and grade 3 dysphasia (n=1) on DL17. Grade 3 or higher adverse events possibly related to D2C7-IT include: seizure (grade 4, n=2; grade 3, n=3), cerebral edema (grade 4, n=1), hydrocephalus (grade 3, n=5), headache (grade 3, n=4), hemiparesis (grade 3, n=4), dysphasia (grade 3, n=3), lymphopenia (grade 3, n=4), thromboembolic event (grade 3, n=3); and one each of grade 3 elevated ALT, urinary tract infection, fall, wound complication, generalized muscle weakness, confusion, encephalopathy, and somnolence. As of February 2020, four patients remain alive, with three patients demonstrating persistent radiographic partial response more than 54, 34 and 28 months after a single infusion of D2C7-IT. Conclusions: Dose level 13 (6,920ng/mL) was selected as the optimal phase II dose. Accrual in a dose expansion phase II trial is ongoing, and we are initiating a combination trial of D2C7-IT with checkpoint inhibitior. Clinical trial information: NCT02303678 .
Digital life, a theory of minds, and mapping human and machine cultural universals
Authors: Kevin B. Clark
Journal: Behavioral and Brain Sciences (2020)

Abstract Emerging cybertechnologies, such as social digibots, bend epistemological conventions of life and culture already complicated by human and animal relationships. Virtually-augmented niches of machines and organic life promise new free-energy-governed selection of intelligent digital life. These provocative eco-evolutionary contexts demand a theory of (natural and artificial) minds to characterize and validate the immersive social phenomena universally-shaping cultural affordances.
Association between homologous recombination deficiency and tumor mutational burden in lung cancer.
Authors: Yong Jiang, Shiying Dang, Li Yang, Yin Han, Yongshen Zhang, Tianhao Mu, Shifu Chen, Feng-Ming Kong
Journal: Journal of Clinical Oncology (2020)

e21043 Background: Homologous recombination (HR) is an important repair method for DNA double-strand damage. HR is involved with complex signaling pathways and multiple steps, including BRCA1/2. Homologous Recombination Deficiency (HRD) can be caused by the loss of function of BRCA1/2 proteins due to gene mutation. Tumor mutational burden (TMB) was indicated to involved with HRD, which is critical to the guidance of immunotherapy. Methods: Patients available with tumor specimen genomic testing for lung cancer were enrolled in this study. The sequencing library was captured using a 605-gene panel. Homologous recombination (HR)-related gene list included 102 genes. Genomic alterations of HR-related genes were assessed by next-generation sequencing assay, including nonsense, nonstop, frameshift, splice site, damaging missense mutations in somatic variants and pathogenic germline variants. Then, TMB was calculated by dividing the total number of mutations counted by the size of the coding region. Results: A total of 741 patients was enrolled and 182 of them (25.6%) had at least one genomic alteration of the HR genes. The top mutant HR genes included ATM (4.1%), DNMT3A (2.8%), ATR (1.8%), CHEK2 (1.5%), BRCA2 (1.5%), ABL1 (1.4%), FANCA (1.2%), RIF1 (1.1%), FANCI (1.1%), RAD50 (0.9%), BRCA1 (0.9%), and MRE11A (0.9%). The most common mutational type was missense mutation (69.2%), followed by frameshift (15.6%), and nonsense mutation (15.2%). The median age was 62 in the HRD group (age &lt; 45:5.4%, 45-65:59.6%, &gt; 65:34.9%) compared to 60 in the rest of the patients (age &lt; 45:11.3%, 45-65:61.3%, &gt; 65:27.4%). There were overall 57.5% males and 42.5% females in terms of gender. HRD group had a significantly higher rate than Non-HRD group in males (72.1% vs 52.8%, p &lt; 0.01). The occurrence of HRD mutations was significantly correlated with a high level of TMB (p &lt; 0.01). The median TMB of HRD group (7.9 muts/Mb, 95%CI:7.1-9.2 muts/Mb) was significantly higher than that of Non-HRD group (3.8 muts/Mb, 95%CI:3.3-4.2 muts/Mb). In addition, the upper quantile value (7.5 muts/Mb) was used to identify patients with high TMB. HRD group had a significantly higher rate of TMB-high patients than Non-HRD group (51.1% vs 17.0%, p &lt; 0.01). Conclusions: Our study demonstrated genomic alterations of the HR genes in about one fourth’s lung cancer. Besides, there was a significant positive correlation between HRD mutations and TMB level. The significance of HRD genomic mutation on predicting the efficacy of immunotherapy deserves further study.
Long-term Outcomes After Thrombolytic Therapy for Acute Ischemic Stroke
Authors: Christopher C. Muth
Journal: JAMA (2020)

The role of intravenous thrombolytic therapy in the management of acute ischemic stroke is well established,1 and faster administration of intravenous tissue plasminogen activator (tPA) has been associated with better short-term outcomes in clinical practice.2
Association between vitamin D and vascular endothelial injury in hypertensive patients
Authors: Jian Jia, Yayu Tang, Ning Zhang, Haixia Ding, Yiyang Zhan
Journal: BMJ (2018)

Objective
To evaluate the association between vitamin D (VD) and vascular endothelial injury in hypertensive patients.


Methods
Ninety nine patients with hypertension and 126 healthy subjects (control group) from the same community in Nanjing were recruited in the study. The serum levels of fasting blood glucose (GLU), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) were measured. Serum 25-hydroxy vitamin D (25-OH-D) and nitric oxide (NO) levels were determined by enzyme-linked immunosorbent assay. The level of plasma endothelial microparticles was measured by flow cytometry. The data were statistically analyzed with SPSS version 19.0.


Results
The serum 25-(OH)-D[(55.22±11.92)nmol/L vs. (64.17±21.52) nmol/L, t=-3.71], vitamin D binding protein (VDBP)[(257.32±141.31) ng/ml vs. (314.21±124.13) ng/ml, t=-3.21], NO levels [(39.35±13.33) μmol/L vs. (43.42±11.83) μmol/L, t=-2.42]in hypertension group were significantly lower than those in control group. And the circulating endothelial cell particles(4.95±1.78 vs. 2.84±2.07, t=8.05)in hypertension group was significantly higher than that in control group. In hypertensive patients, the circulating endothelial cell particles in VD deficiency group was significantly higher than that in low VD group and normal VD group [(6.42±1.25)% vs. (4.6±1.68)%, (3.15±0.90)%, F=15.08]. And the serum NO level in VD deficiency group was significantly lower than that in other two groups[(36.57±10.52) μmol/L vs. (39.77±13.01) μmol/L, (46.26±25.90) mol/L, F=1.20]. Multiple linear regression analysis showed that low serum 25 (OH) D(B=-0.189, SE=0.033, β=0.509, t=-5.72)and gender (B=-0.682, SE=0.351, β=-0.182, t=-2.054)were the risk factors of vascular endothelial injury.


Conclusion
The serum vitamin D levels in hypertensive patients is decreased, and vitamin D deficiency may be a risk factor for endothelial injury in hypertension.


Key words: 
Vitamin D; Hypertension; Vascular endothelial cells injury
Obstructive sleep apnea hypopnea syndrome and atrial fibrillation
Authors: 刘丹, 张海澄
Journal: BMJ (2010)

心房颤动(房颤)发病率的增加与多种因素有关,其中一个重要的原因是肥胖率逐年增加,近年来发现阻塞性睡眠呼吸暂停低通气综合征(obstructive sleep apnea hypopnea syndrome,OSAHS)是房颤重要的临床相关因素.超重但未达到肥胖标准的西方中年成人OSAHS发病率约为有嗜睡症状人群的4～5倍~([1])。
胃食管反流性疾病及反流性食管炎
Authors: 刘宾, 刘岚
Journal: BMJ (2010)

刘宾:今天我们来复习一下胃食管反流性疾病(GERD)及反流性食管炎(RE)的相关知识.先来看一个病例,男性,70岁,反复胸骨后疼痛2个月,疼痛为阵发性,多于活动后、弯腰起坐、餐后及夜间明显,持续数分钟至1h不等,常伴有胃部灼热,偶有反酸,有时进食水能缓解.平常无其他不适及症状,有高血压病史,长期服降压药,无特殊嗜好.体检:一般情况好,血压140/90 mm Hg(18.6/12.0 kPa),心率70次/min,呼吸18次/min.双肺无异常,心律齐,无杂音,心界正常,腹软,肝脾未及肿大,全腹无压痛,未扪及包块,肠鸣音正常,腹水征(-)。
Ibrutinib-based combination therapy exhibited therapeutic benefit in newly diagnosed primary central nervous system lymphoma.
Authors: Feili Chen, Diwen Pang, Hanguo Guo, Qiuxiang Ou, Xue Wu, Xinmiao Jiang, Xiaojuan Wei, Sichu Liu, Ling Huang, Zhanli Liang, Wenyu Li
Journal: Journal of Clinical Oncology (2020)

2556 Background: Ibrutinib has shown single-agent activity in relapse/refractory (R/R) primary central nervous system lymphoma (PCNSL), and the high dose methotrexate (HD-MTX) has been the backbone of treatment of de-novo PCNSLs. Combination therapy of HD-MTX and ibrutinib has recently shown activity in R/R PCNSLs. Methods: Eleven newly diagnosed PCNSL patients who underwent combination therapy of HD-MTX and ibrutinib were analyzed for treatment response and safety profile. HD-MTX was given at 3.5 g/m2 every 2 weeks for a total of 8 doses. Ibrutinib was held on days of HD-MTX infusion until HD-MTX clearance. Single-agent daily ibrutinib was administered continuously after completion of induction therapy until disease progression, intolerable toxicity, or death. Patients’ clinicopathologic characteristics were retrospectively reviewed and genomic traits were further analyzed. Results: Nine out of 11 patients have completed the induction phase of ibrutinib-based combination therapy and received ibrutinib maintenance in addition to two patients whose disease progressed during the therapy. An objective response rate (ORR) of 82% (9/11) was observed, including 7 patients with complete response (CR, 64%) and 2 patients with partial response (PR, 18%). The median progression-free survival (PFS) was 7.4 months while the median overall survival (OS) was not reached. The combination therapy of HD-MTX and ibrutinib was well tolerated and has acceptable safety. In addition, the presence of ctDNA in cerebrospinal fluid (CSF) samples closely correlated with tumor response. Sustained tumor responses were associated with the clearance of ctDNA from the CSF. Conclusions: Combination of ibrutinib and HD-MTX has acceptable safety and has demonstrated anti-tumor activity in newly diagnosed de-novo PCNSL patients. The detection of ctDNA in CSF is feasible for monitoring tumor burden in PCNSL patients.
Hypocalcemia with immune checkpoint inhibitors: The disparity among various reports.
Authors: swarna sri nalluru, Paramarajan Piranavan, Ying Ning, Haritha Ackula, Ahmad Daniyal Siddiqui, Nitin Trivedi
Journal: Journal of Clinical Oncology (2020)

e15153 Background: Immune-related adverse events affecting parathyroid function are rarely reported with immune checkpoint inhibitors (ICPI). Activating calcium-sensing receptor antibodies causing autoimmune hypoparathyroidism with nivolumab was recently published by Piranavan et al. KEYNOTE-189 and CHECKMATE-067 trials reported a 21-29% hypocalcemia event rate. The purpose of our study is to identify the hypocalcemia incidence in patients receiving ICPI at a single institution with multiple sites. Also, we aimed to investigate hypoparathyroidism as the etiology in these patients, if hypocalcemia was detected. Methods: A chart review to study patients receiving ICPI from 2015 to 2018 at multiple sites affiliated with Saint Vincent Hospital. The study population was divided into two groups based on the presence or absence of calcium altering conditions or medications. True hypocalcemia incidence was calculated after correcting calcium for albumin from the initiation of ICPI to their last follow-up. Results: Group 1 (N = 83) includes patients with no calcium altering conditions or medications. Group 2 (N = 98) includes patients on calcium supplements (N = 17), vitamin D (N = 44), bisphosphonates (N = 24), &gt; stage IIIB CKD (N = 5), and bone metastasis (N = 38). Hypocalcemia events in Group 1 vs. Group 2 were 8.4% and 19.3%, respectively. Our entire study demonstrated 26.8% vs. 1.1% of Grade I vs. II hypocalcemia events. However, after correcting the calcium for albumin, hypocalcemia incidence was 0.56% (N = 1). No further workup was done to investigate the etiology as that patient passed away. Conclusions: Our data suggest that the true hypocalcemia incidence after using albumin-corrected calcium values is very low in patients receiving IPCI, even in the presence of calcium altering factors. The percentage of patients with hypocalcemia is much higher and similar to the KEYNOTE-189 and CHECKMATE-067 trials when serum calcium values without albumin correction are used. Thus, the higher reported incidence of hypocalcemia in these trials is likely due to the reporting of serum calcium without albumin correction.
Extracting humanistic thoughts from traditional Chinese medicine
Authors: Xiaochun Liang
Journal: BMJ (2016)

医学是具有人文属性的科学。中医学蕴含丰富的人文精神，奉行天人合一的思想，崇尚生命至重的理念，坚守医乃仁术的德行，强调医贵乎精的信念，恪守贵义贱利的准则，遵守尊重同行的行规，这些都是医学人文思想的具体体现。
Trends in overall mortality among US veterans with intermediate (Int)/high-risk primary myelofibrosis (PMF).
Authors: Gustavo Rivero, Jingbo Yu, Shivani Pandya, Christopher Dieyi, Shreekant Parasuraman
Journal: Journal of Clinical Oncology (2020)

e19534 Background: PMF is a heterogeneous disorder with variable outcomes and differential effects on overall survival (OS) based on risk. Data on the OS of veterans with MF are limited and represent a unique opportunity given the stability of longitudinal retrospective follow up in patients (pts) with multiple comorbid conditions. In phase 3 trials, ruxolitinib (RUX; Janus kinase [JAK]1/JAK2 inhibitor) improved OS in pts with MF [int2/high DIPSS] leading to FDA-approval in 2011. In this study, we investigated mortality trends among US veterans with PMF pre- and post-RUX approval. Methods: De-identified PMF pt-level data obtained from Veterans Integrated Service Networks using PMF diagnosis codes (ICD-9: 238.76, ICD-10: D47.1) were collected from 2 Veterans Health Administration (VHA) data periods (01JAN2006–31DEC2010 and 01JAN2014–30SEP2018) reflecting years pre- and post-RUX approval. The first PMF diagnosis in the identification periods (pre-RUX, 01JAN2007–31DEC2010; post-RUX, 01JAN2015–30SEP2018) was the index date. Pts were required to be continuously enrolled in the VHA plan from 1 calendar year prior to 6 mo after the index date. Pts also must have had int/high-risk PMF defined as ≥1 risk factor at diagnosis (age &gt; 65 y, hemoglobin [Hb] &lt; 10 g/dL, white blood cells [WBCs] &gt; 25 × 10 9 /L). Demographic and clinical characteristics were recorded. All-cause 1-y, 2-y, and overall mortality rates and time to death from index until end of data availability were estimated using Kaplan-Meier (KM) methodology; univariate Cox regression was used to examine the hazard ratio (HR) for all-cause mortality for the pre- and post-RUX cohorts. Results: 244 and 1005 pts with PMF were included in the pre-and post-RUX cohorts, respectively. Most pts were age ≥65 y (84% vs 95%), male (99% vs 99%), and white (64% vs 77%). 64% vs 32% of pts had Hb &lt; 10 g/dL at PMF diagnosis and 20% vs 14% had WBCs &gt; 25 × 10 9 /L for pre- and post-RUX cohorts, respectively. Based on KM analysis, the 1-y, 2-y, and overall mortality rates for pre- vs post-RUX periods were 45%, 63%, and 89% vs 27%, 37%, and 57%, respectively. Time from index PMF diagnosis to death was significantly longer for the post- vs pre-RUX cohort (median [95% CI], 1091 [989‒NR] vs 430 [347‒568] d; P&lt; 0.001), and risk of death was 47% lower in the post- vs pre-RUX period (HR, 0.53; P&lt; 0.001). Conclusions: In this retrospective analysis, patients with PMF had a high mortality rate; a 47% lower risk of mortality was observed post-RUX approval. Multiple factors may have influenced the lower mortality observed, which will be further explored.
有关甘露醇应用问题的答疑
Authors: 龚涛
Journal: BMJ (2009)

众所周知,大脑病变导致死亡的最主要原因之一就是颅高压导致脑疝.因此,寻求有效的降低颅内压力的药物是所有神经科医师关心的问题,也是难题.在目前所用的药物中,公认降低颅内压力最好的脱水药物就是浓度为20%的甘露醇;针对脑出血急性期的脱水降颅压治疗,首选药物也是甘露醇.但在甘露醇脱水降低颅内压力的机制、应用时机、治疗疗程以及用量用法方面还存在较多争议.下面就上述问题作一简单的阐述,希望对基层医生有些帮助。
清开灵静脉滴注致急性喉头水肿一例
Authors: 邹艳, 全星, 钟敏
Journal: BMJ (2006)

患者男,24岁,因咳嗽、发热4 d就诊.既往体健,否认药物过敏史.体格检查:体温37.8℃,呼吸18次/min,血压120/80 mm Hg(1 mm Hg=0.133 kPa),脉搏80次/min,咽充血明显,双侧扁桃体未见肿大,心肺腹部检查未见异常,血常规:白细胞9.4×109/L,中性粒细胞分类0.82。