tbuckley/cabot-search huggingface dataset:
Percutaneous cryoablation in pediatric solid tumors: A case series.
Authors: Cristiana Hentea, Olaf Kaufman, Christopher Alan Rokes, Wendy Woods-Swafford
Journal: Journal of Clinical Oncology (2020)

e22516 Background: Percutaneous cryoablation is an effective treatment of focal tumors. With a low complication rate it is a useful adjuvant therapy option to chemotherapy and radiation. To date there is no literature on the use of cryoablation in pediatric solid tumors. Methods: We conducted a retrospective analysis of pediatric solid tumor patients who received percutaneous cryoablation for local control of relapsed disease over the past 10 years within our institution. The following information was extracted from EMR: age, diagnosis, number of ablated lesions and tissue involved (lung, liver, bone), complications following procedure, and rate of local relapse. Results: A total of 40 metastatic lesions were treated by percutaneous cryoablation in 7 patients (ages 5-22yo, median 15yo) with a wide range of solid tumor diagnoses (Ewing sarcoma, Wilms tumor, Osteosarcoma, Germ cell tumor). Lesions represented sites of relapse or metastasis, refractory to several lines of therapy. Sites of cryoablated tumor included lung (33%), bone (32%), chest wall (10%) among others. Each patient had 2-5 separate cryoablation procedures (total 22 procedures) over the course of their therapy. 54% of instances patients were monitored overnight for pain control, with no major complications. One patient required ICU-level care due to pulmonary hemorrhage following lung cryoablation in setting of thrombocytopenia. No infectious complications. Three patients progressed and died within two years following first cryoablation intervention (diagnoses of Ewings and Wilms). Of the remaining four patients, control at the ablation site was achieved with median follow-up of 17 months (range 8-43). Conclusions: Percutaneous cryoablation is a safe and durable approach for local control of solid tumors in children. We present the first pediatric case series detailing response to percutaneous cryoablation.
Hybrid Positron Emission Tomography/Magnetic Resonance Imaging in Arrhythmic Mitral Valve Prolapse
Authors: Marc A. Miller, David H. Adams, Dimosthenis Pandis, Philip M. Robson, Amit Pawale, Renata Pyzik, Steve L. Liao, Ahmed El-Eshmawi, Percy Boateng, Jalaj Garg, Stephen Waterford, Menachem M. Weiner, Srinivas R. Dukkipati, Vivek Y. Reddy, Zahi A. Fayad, Maria G. Trivieri
Journal: JAMA Cardiology (2020)

Myocardial replacement fibrosis has been reported to occur in one-third of patients with mitral valve prolapse (MVP) and significant mitral regurgitation (MR). However, it remains unknown whether there are detectable changes in myocardial metabolism suggestive of inflammation or ischemia that accompany the development of fibrosis.To characterize the burden and distribution of fluorine 18-labeled (18F) fluorodeoxyglucose (FDG) uptake and late gadolinium enhancement (LGE) in patients with degenerative MVP and ventricular ectopy.Prospective observational study of 20 patients with MVP and significant primary degenerative MR who were referred for mitral valve repair and underwent hybrid positron emission tomography/magnetic resonance imaging (PET/MRI). Ventricular arrhythmias were categorized as either complex (n = 12) or minor (n = 8). Coregistered hybrid 18F FDG-PET and MRI LGE images were assessed and categorized. Recruitment occurred in the new patient clinic of a mitral valve repair reference center. This study was conducted from January 11, 2018, to June 26, 2019.Simultaneous cardiac 18F FDG-PET and MRI with LGE imaging on a hybrid PET/MRI system and ambulatory rhythm monitoring.Patients were categorized by the presence and pattern of FDG uptake and LGE, the severity of ventricular arrhythmias, and the indication for mitral valve surgery.In the cohort of 20 patients, the median age was 59.5 years (interquartile range, 52.5-63.2 years). Focal, or focal-on-diffuse uptake, of 18F-FDG (PET positive) was detected in 17 of 20 patients (85%). The FDG uptake coexisted with areas of LGE (PET/MRI positive) in 14 patients (70%). Of the 5 asymptomatic patients with normal ventricular indices and absence of any surgical indications, all were PET/MRI positive.In this pilot study, we demonstrate a novel association between degenerative MVP and FDG uptake, a surrogate for myocardial inflammation and/or ischemia. Such evidence of myocardial injury, even in asymptomatic patients, suggests an ongoing subclinical disease process. These findings warrant further investigation into whether imaging for myocardial inflammation, ischemia, and scar has a role in arrhythmic risk stratification and whether it provides incremental prognostic value in patients with chronic severe mitral regurgitation undergoing active surveillance.
Selinexor, daratumumab, and dexamethasone in patients with relapsed/refractory multiple myeloma (MM).
Authors: Cristina Gasparetto, Suzanne Lentzsch, Gary J. Schiller, Natalie Scott Callander, Sascha Tuchman, Nizar J. Bahlis, Darrell White, Christine Chen, Muhamed Baljevic, Heather J Sutherland, Rami Kotb, Michael Sebag, Richard LeBlanc, Christopher P Venner, William Bensinger, Adriana C. Rossi, Heidi Sheehan, Melina Arazy, Kazuharu Kai, Brea Lipe
Journal: Journal of Clinical Oncology (2020)

8510 Background: Selinexor is a first-in-class oral Selective Inhibitor of Nuclear Export (SINE) compound that binds and inactivates exportin 1 (XPO1). Selinexor in combination with low dose dexamethasone (Sel-dex) was approved by the FDA, based on data from the STORM study, wherein Sel-dex induced an overall response rate (ORR) of 26.2% in patients (pts) with relapsed/refractory MM (RRMM). Single agent daratumumab has demonstrated an ORR of 29% in MM reftactory to proteasome inhibitors (PIs)/immunomodulatory drug (IMiDs). We evaluated the safety, tolerability and preliminary efficacy of the combination of Sel-dex and daratumumab (SDd) in pts with MM refractory to PIs/IMiDs. Methods: This is a multicenter, open-label, phase 1b/2 dose escalation and expansion study. Pts were eligible if they had received ≥ 3 prior lines of therapy, including a PI and an IMiD, or whose MM was refractory to a PI and an IMiD. In the expansion phase, pts were required to be anti-CD38 monoclonal antibody-naïve. One dose level was tested at each schedule: selinexor once-weekly (QW at 100 mg) or twice-weekly (BIW at 60 mg) with dexamethasone 40 mg. Daratumumab 16 mg/kg IV was administered per label. Primary objective was to determine the maximum tolerated dose and recommended phase 2 dose (RP2D), and assess safety, tolerability and efficacy of SDd in pts with RRMM. Results: A total of 34 pts were enrolled; 3 in the 60 mg BIW and 31 in the 100 mg QW cohorts. Median age was 69 and median number of prior treatment regimens was 3 (range, 1–10). Out of 34 pts, 62% and 65% were refractory to bortezomib and lenalidomide respectively. Common treatment related adverse events (all grades, grades 3/4) included: thrombocytopenia (71%, 47%), fatigue (62%, 18%), nausea (71%, 9%), anemia (62%, 32%) and neutropenia (50%, 26%). Two dose limiting toxicities (DLTs) were reported in the 60 mg BIW cohort: Grade 3 thrombocytopenia and Grade 2 fatigue requiring dose reduction in selinexor to 100 mg QW. In the 100 mg QW escalation cohort (n = 6), no DLTs occured. 32 patients were evaluable for efficacy. The ORR was 73% (11 VGPR, 11 PR) for 30 daratumumab-naïve pts. Median progression-free survival was 12.5 months in both groups. Conclusions: Based on tolerability and efficacy, the RP2D of SDd is selinexor 100 mg, daratumumab 16 mg/kg and dexamethasone 40 mg, administered QW. In pts with PI and IMiD refractory MM, weekly SDd demonstrated promising activity with an ORR of 73% in daratumumab-naïve pts and a median PFS of 12.5 months. This supports further development of a novel non-PI, non-IMiD backbone in earlier lines of therapy. Clinical trial information: NCT02343042 .
The impact of first-line therapy with novel agents in multiple myeloma patients age 80 and above: A systematic review.
Authors: Sadaf Rahman, Cody Sider, Fadi Bahodi, Selay Lam, Martha Louzada, Chai W. Phua
Journal: Journal of Clinical Oncology (2020)

e20532 Background: Novel therapeutic agents in multiple myeloma (MM) have demonstrated significant improvements in treatment outcomes. However, data remains scarce in newly diagnosed transplant-ineligible patients aged 80 and above as they are less represented in clinical trials. Optimal treatment of this population also proves challenging due to treatment-related adverse events. Methods: MEDLINE and EMBASE search concluded March 4, 2019. We included studies that evaluated first-line treatment of age ≥80 transplant-ineligible MM patients with novel agents. The primary outcomes assessed were OS and PFS. A qualitative analysis was undertaken due to the small number of included articles. Results: Of 1683 articles assessed for eligibility, 134 articles proceeded to full-text review. 6 articles with a total of 819 patients age ≥ 80 (range 80-96) were included for analysis (5 retrospective analyses and 1 phase II, non-randomized trial). Median OS were significantly shorter in age ≥80 in comparison to younger groups (reported median OS ranged from 19.5-31.9mo for age ≥80, 46-54.8mo for age 66-79, and 81-83.8mo or not reached for age ≤65). Shorter survival was associated with poorer performance status, advanced ISS stage, higher Charlson Comorbidity Index, anemia and elevated serum LDH. In one study, attaining a very good partial response or better (≥VGPR) was associated with improved median OS (30.4mo vs 18.8mo, p = 0.001). There was no difference between age groups for OS if ≥ VGPR was attained (53.4mo in age ≥80, vs not reached in age 66-79 or age ≤65; p = 0.184). In 1 of 3 studies that reported median PFS, a significant difference in one study was noted by age [age ≥80 = 19.1mo, age 66-79 = 26.3mo (p = 0.033), ≤65 = 54.3mo (p = 0.0009)]. Early mortality (at 2 or 6 months; in 3 studies) was significantly greater than in patients age &lt; 80 and was primarily due to infection or renal failure, and more often in the frail. One study noted that despite reduced OS, the relative survival rate was higher in patients aged ≥85 at 2 years than in younger age groups. Conclusions: Our review excluded most RCTs as subgroup analyses of patients aged ≥80 were not available. Regardless, included articles are representative of the real-world experience. This systematic review suggests that while MM patients aged ≥80 experience shorter OS and PFS, treatment with a novel agent may offer comparable survival outcomes to younger groups in those able to attain ≥VGPR. Relative survival in elderly patients also favours active treatment in this age group, while balancing the risks of early mortality.
Cardiac Amyloidosis: Evolving Diagnosis and Management: A Scientific Statement From the American Heart Association
Authors: Michelle M. Kittleson, Mathew S. Maurer, Amrut V. Ambardekar, Renee P. Bullock-Palmer, Patricia P. Chang, Howard J. Eisen, Ajith P. Nair, Jose Nativi-Nicolau, Frederick L. Ruberg
Journal: Circulation (2020)

Transthyretin amyloid cardiomyopathy (ATTR-CM) results in a restrictive cardiomyopathy caused by extracellular deposition of transthyretin, normally involved in the transportation of the hormone thyroxine and retinol-binding protein, in the myocardium. Enthusiasm about ATTR-CM has grown as a result of 3 simultaneous areas of advancement: Imaging techniques allow accurate noninvasive diagnosis of ATTR-CM without the need for confirmatory endomyocardial biopsies; observational studies indicate that the diagnosis of ATTR-CM may be underrecognized in a significant proportion of patients with heart failure; and on the basis of elucidation of the mechanisms of amyloid formation, therapies are now approved for treatment of ATTR-CM. Because therapy for ATTR-CM may be most effective when administered before significant cardiac dysfunction, early identification of affected individuals with readily available noninvasive tests is essential. This scientific statement is intended to guide clinical practice and to facilitate management conformity by covering current diagnostic and treatment strategies, as well as unmet needs and areas of active investigation in ATTR-CM.
表皮葡萄球菌所致肺部感染一例
Authors: 薛军, 张羽
Journal: BMJ (2009)

患者男,82岁,因反复咳嗽、咳痰1年余,加重7 h于2007年10月15日入院.患者心脏起搏器安置术后6年,脑梗死后遗症5年,食道癌慢性综合征2年.入院查体:体温37.8℃,脉搏63次/min,呼吸19次/min,血压110/65 mmHg(1 mm Hg=0.133 kPa),精神欠佳,失语,被动体位,平车推入病房,查体合作,口唇略苍白,无明显紫绀,双肺呼吸音粗,均可闻及痰鸣音及喘鸣音,心脏、腹部、双下肢无异常.入院当日实验室检查:pH值7.47,PaO2 47 mm Hg,PaCO2 31mm Hg,血白细胞9.41×109/L,分类中性粒细胞0.907,血红蛋白103 g/L.支气管镜检查:管腔内见较多橘红色分泌物.胸部X线:双肺炎性改变,心影增大,主动脉硬化,考虑为肺部感染。
Reducing treatment strategy for bronchial asthma based on fractional exhaled nitric oxide level and symptom control
Authors: Qiaozhen Wu, Xiaoyun Hu, Lingyun Dong, Jianfeng Zhang
Journal: BMJ (2019)

Objective
To evaluate the application of fractional exhaled nitric oxide (FeNO) in the reducing treatment of bronchial asthma.


Methods
From October 2015 to September 2016, 60 asthmatic patients with FeNO>25 ppb were randomized into FeNO group and control group with 30 cases in each group. Patients in both groups were treated with combined inhaled corticosteroids and long-acting beta 2 agonist (ICS/LABA) starting with low doses; the dosage was adjusted according to the symptom control alone in control group, while in FeNO group the dosage was adjusted according to the symptom control and FeNO level. After 1 year-follow up, the Asthma Control Test (ACT) scores, Asthma Life Questionnaire (mini AQLQ) scores, pulmonary function, FeNO levels, blood eosinophil counts, total IgE, hierarchical control level, cumulative corticosteroid use and cumulative months of leukotriene receptor antagonists (LTRA) use were compared before and after treatment within group, and between two groups. Stratified analysis was carried out in the patients complicated with allergic rhinitis.


Results
After treatment, ACT scores, mini AQLQ scores and FEV1/pred (%) were significantly higher than those before treatmentin both groups (t=10.755, 10.189,8.632 and 13.311,8.102,12.456,respectively, all P 0.05). For patients complicated with allergic rhinitis, the numbers of acute asthma attack were increased and the cumulative dosage of systemic corticosteroid use was higher in control group than those in FeNO group (both P<0.05).


Conclusion
The reducing treatment strategy based on FeNO level and symptom control is of clinical value for patients with bronchial asthma, especially for those complicated with allergic rhinitis.


Key words: 
Nitric oxide; Inflammation; Asthma; Therapeutic uses
Untypical percheron artery infarct: a case report
Authors: Xiangwen Wu, Yinping Xu, Yuhui Chen
Journal: BMJ (2015)

Percheron artery infarct(PAI) is uncommon clinically. One case had an acute onset of coma, impaired left limb activities, verbal incoherence, drinking cough and vertical gaze palsy after regaining consciousness. Magnetic resonance imaging(MRI) showed symmetrical high signal intensity on diffusion-weighted imaging(DWI) in bilateral paramedian thalami and a distinct pattern of V-shaped midbrain hyperintensity on DWI. Magnetic resonance angiography(MRA) showed left-sided embryonal posterior cerebral artery(PCA) from ipsilateral internal carotid artery(ICA). Systemic treatment yielded a poor prognosis.


Key words: 
Basilar artery; Brain infarction
Efficacy of percutaneous laser disc decompression and its correlation with plasma levels of β-endorphine and substance P in patients with protrusion of lumbar intervertebral disc
Authors: Hua-ping Pan, Hui Feng, Jian Wang, Yu-hui Ding
Journal: BMJ (2010)

Objective To observe efficacy of percutaneous laser disc decompression (PLDD) and its correlation with plasma levels of β-endorphine and substance P in patients suffering from protrusion of lumbar intervertebral disc (PLIVD). Methods Seventy-eight patients with PLIVD were randomly divided into two groups, one group (40 patients) treated with PLDD and the other (38 patients) treated with lumbar spine traction and physical therapy as control. Their peripheral plasma levels of β-endorphine and substance P were measured before the procedure and one day, one week and four weeks after it, respectively.Meanwhile, the visual analogue scale (VAS)was applied to assess their pain index. Results Plasma level of substance P was (186±66) ng/L and (419±82) ng/L, and (127 +83) ng/L and (322 +47) ng/L,in treatment and control groups, one day and one week after the procedure, respectively, and that of β-endorphine was (313 ±27) mg/L and (187 ±56) mg/L, and (364 + 18) mg/L and (211 +39) mg/L,one day and one week after it, respectively ( all P ＜ 0. 01 ), with its clinical efficacy of 90% (36/40)and 66% (25/38) one week after it, respectively ( P ＜ 0. 01 ) . Four weeks after it, plasma level of substance P was (64 ±50) ng/L in treatment group as compare to that in controls (93 ±75) ng/L, and that of β-endorphine was (410 ± 21 ) mg/L and (317 ± 42 ) mg/L, respectively, with efficacy of 95% (38/40) and 84% (32/38), respectively. Conclusions Plasma level of substance P can be reduced and that of β-endorphine can be increased by PLDD in patients with PLIVD, thus relieving their pain.Measurements of substance P and β-endorphine can be used as objective indicators to evaluate clinical efficacy of PLDD.

Key words: 
Laser surgery;  Lambar vertebrae;  Intervertebral disk displacement;  Betaendorphin;  Substance P
IDH1 mutation detection in plasma circulating tumor DNA (ctDNA) and association with clinical response in patients with advanced intrahepatic cholangiocarcinoma (IHC) from the phase III ClarIDHy study.
Authors: Elia Aguado, Ghassan K. Abou-Alfa, Andrew X. Zhu, Teresa Macarulla, Bin Fan, Parham Nejad, Sung Choe, Liewen Jiang, Camelia Gliser, Shuchi Sumant Pandya, Bin Wu
Journal: Journal of Clinical Oncology (2020)

4576 Background: Mutations in isocitrate dehydrogenase 1 ( IDH1) are detected in ~13% of IHCs. Ivosidenib (IVO) is a first-in-class, oral inhibitor of the mutant IDH1 (mIDH1) protein. In ClarIDHy, a global, phase 3, double-blind study in previously treated patients with advanced m IDH1 IHC (N = 186), IVO demonstrated an improvement in progression-free survival (PFS) vs placebo (hazard ratio 0.37, p &lt; 0.001) (Abou-Alfa et al., Ann Oncol 2019; NCT02989857). Feasibility of m IDH1 detection in plasma ctDNA from patients with IHC was demonstrated and was highly concordant with mutation status in tumor tissue (Aguado-Fraile et al., Cancer Res 2019). This analysis was extended to the larger patient cohort from ClarIDHy, and longitudinal m IDH1 detection from ctDNA was assessed and correlated with clinical response. Methods: Baseline plasma and tumor tissue samples were obtained before randomization; longitudinal plasma samples were collected on day 1 of each treatment cycle. m IDH1 status in tissue was prospectively and centrally confirmed using Oncomine Focus Assay. A BEAMing digital PCR test was used for quantification of m IDH1 in plasma. IDH1 mutation clearance ( IDH1-MC) was achieved when plasma m IDH1 variant allele frequency was below the assay’s sensitivity (0.02% for R132C/L/S/G; 0.04% for R132H). Results: m IDH1 detection in plasma ctDNA and tissue was concordant in 92% (193/210) of samples screened. As of 31 Jan 2019, median PFS was 2.7 months for IVO vs 1.4 months for placebo. Longitudinal analysis with biomarker data available as of Jan 2020 demonstrated IDH1-MC in plasma from 10 IVO-treated patients with PFS ≥2.7 months (n = 36) vs 0 patients with PFS &lt; 2.7 months (n = 40). No IDH1-MC was observed in patients treated with placebo, irrespective of response (n = 49). Conclusions: These results reinforce the feasibility of IDH1-R132 detection in plasma from patients with IHC, with a 92% concordance with detection in tumor tissue, supporting m IDH1 detection in liquid biopsy as a viable patient selection strategy where tissue exhaustion can limit conventional methods. Plasma IDH1-MC was also observed in a subset of IVO-treated patients who achieved disease control. Clinical trial information: NCT02989857 .
Impairment of left ventricular function in patients with mild-to-moderate chronic obstructive pulmonary disease
Authors: Jin-guo Yu, Min-hua Shi
Journal: BMJ (2012)

Objective To determine whether the extent of airflow obstruction is associated with left ventricular function in mild-to-moderate chronic obstructive pulmonary disease (COPD) patients.Methods Left ventricle end diastolic volume ( LVEDV ),left ventricle end systolic volume ( LVESV ),left ventricle stroke volume( LVSV),left ventricle ejection fraction( LVEF),heart rate ( HR),cardiac output ( CO) and cardiac index (CI) were measured by ultrasonic cardiogram.Thirty-one patients with chronic bronchitis,42 mild-to-moderate COPD patients and 16 controls with normal lung function were recruited.The relations between the extent of airflow obstruction and the impairment of left ventricular function were analyzed.Results There were no significant differences of LVEDV,LVESV,LVSV,HR,CO or CI between the control and chronic bronchitis groups.LVEDV,LVESV,LVSV,CO and CI of chronic bronchitis group were significantly higher than those of mild-to-moderate COPD group while HR was lower.LVEDV,LVESV,LVSV,CO and CI had a positive correlation with forced expiratory volume in 1 second ( FEV1 ),forced vital capacity (FVC) and FEV1/FVC ratio.And HR had a negative correlation with FEV1 and FEV1/FVC.LVEF was positively correlated with FVC,but not with FEV1 and FEV1/FVC.LVEDV,LVESV,LVSV,HR,CO and CI were linearly related with FEV1.Conclusions Left ventricular function is maintained in chronic bronchitis patients. Left ventricular function,especially left ventricular end diastolic filling,deteriorates among the mild-to-moderate COPD patients.The extent of airflow obstruction may reflect the impairment of left ventricular function in COPD patients.

Key words: 
Pulmonary disease, chronic obstructive;  Ventricular function, left;  Airflow obstruction