tbuckley/cabot-search huggingface dataset:
Characteristics of growth factors in the blood allowing determination of neuroendocrine component in pancreatic diseases.
Authors: Elena M. Frantsiyants, Irina V. Kaplieva, Ekaterina I. Surikova, Irina V. Neskubina, Valeria A. Bandovkina, Lidia K. Trepitaki, Yulia A. Pogorelova, Ludmila A. Nemashkalova, Viacheslav A. Aleynov, Vladimir S. Trifanov, Fedor N. Grechkin, Sergey V. Sanamyants, Oleg I. Kit, Evgeniya M. Nepomnyashchaya, Dmitry S. Petrov, Yuriy A. Fomenko
Journal: Journal of Clinical Oncology (2020)

e16693 Background: Insulin-like growth factors I and II (IGF-I and II), transforming growth factor β (TGFβ) and its receptor (TGFβR2) are involved in cancer pathogenesis. At the same time, the features of these parameters in the blood related to the disease nature have yet to be determined. The purpose of the study was to analyze the dynamics of IGF-I, IGF-II, TGFβ and TGFβR2 in the blood of patients with pancreatic cancer. Methods: The study included male patients with pancreatic adenocarcinoma T 1-3 N 0-1 M 0 (A, n = 18), pancreatic neuroendocrine tumors (NET, n = 12) and pancreatic adenocarcinoma with the neuroendocrine component T 1-3 N 0-1 M 0 (A+NEC, n = 12) before the treatment. Healthy males (n = 21) were controls. Blood levels of IGF-I and IGF-II were measured by ELISA using standard test systems (Meddiagnost, Germany), as well as levels of TGFβ (BenderMedSystem, Austria) and TGFβR2 (RayBiotech, USA). Results: Patients with pancreatic cancer showed increased blood levels of IGF-II: in PA – by 1.9 times (p˂0.05), in NET – by 2.7 times and in A+NEC – by 3.4 times compared to values in healthy donors. TGFβ was elevated only in patients with A by 1.5 times (p˂0.05). TGFβR2 in the blood of patients with NET and A+NEC was increased by 4.8 and 4.5 times respectively, while in patients with A it was similar to control values. The TGFβ/TGFβR2 ratio was calculated; A+NEC was prognosed in patients with its level of 1.32±0.2. Conclusions: High blood levels of IGF-II were registered in patients with pancreatic cancer. The TGFβ/TGFβR2 ratio served as informative laboratory tests to predict the nature of pancreatic disease.
Postoperative acute exacerbation of interstitial lung disease after pneumonectomy: clinical analysis of four cases
Authors: Chuan Huang, Chao Ma, Qingjun Wu, Peng Jiao, Wenxin Tian, Yaoguang Sun
Journal: BMJ (2020)

Objective
To summarize the clinical features, diagnosis and treatment of postoperative acute exacerbation of interstitial lung disease (ILD) after pneumonectomy.


Methods
The clinical data of 4 patients with postoperative acute exacerbation of ILD after pneumonectomy admitted in Beijing Hospital from October 2014 to November 2015 were retrospectively analyzed and related literatures were reviewed.


Results
Four patients were aged 60 to 74 years, including 3 males and 1 female, 2 of whom were idiopathic pulmonary fibrosis and 2 were connective tissue diseases related ILD. Chest high resolution computed tomography (HRCT) showed multiple lobular septal thickening, ground glass opacities, reticular shadow and strip shadow in both lungs. The patients developed acute dyspnea 2 to 3 days after pneumonectomy. In 2 cases, HRCT showed new patchy ground-glass opacities, reticular shadow and strip shadow in both lungs on the basis of preoperative pulmonary fibrosis. The sputum smear and culture showed no pulmonary infection in all 4 cases. Three patients were treated with glucocorticoids and 3 received mechanical ventilation with endotracheal intubation. One patient was successfully treated by early using adequate glucocorticoids, one patient improved after treatment but died after re-exacerbation, and the other two patients died after treatment failed.


Conclusions
Acute exacerbation of ILD after pneumonectomy often occurs in early postoperative period and it is characterized by progressive dyspnea. Chest CT and respiratory pathogen examination are helpful for early diagnosis. Postoperative acute exacerbation of ILD often lacks effective treatment, requires mechanical ventilation, and the prognosis is poor. Although glucocorticoids may be effective, re-exacerbation should be alert during treatment.


Key words: 
Lung diseases, interstitial; Idiopathic pulmonary fibrosis; Pneumonectomy; Acute exacerbation
Pneumatosis Intestinalis in COVID-19
Authors: Seetha Lakshmanan, Nabil Toubia
Journal: Clinical Gastroenterology and Hepatology (2020)

A 72-year-old man with multiple comorbidities presented with diffuse abdominal pain and bleeding per rectum for 1 day. He denied any respiratory symptoms; however, he did test positive for coronavirus disease 2019 (COVID-19) during screening in his nursing home recently. On arrival, he was febrile (104℉) but hemodynamically stable. Physical examination revealed a distended and diffusely tender abdomen without guarding. Computed tomography of abdomen showed descending and sigmoid colon wall thickening and mid-ascending colon pneumatosis without portal venous gas. This was suggestive of COVID-19–induced ischemic colitis with partial bowel obstruction in the absence of other provoking factors. Patient was treated conservatively with bowel rest, adequate hydration, and intravenous antibiotics. Although his gastrointestinal symptoms improved, his condition was subsequently complicated by sepsis, cardiac ischemia, renal insufficiency, and respiratory failure related to severe COVID-19 infection. Pneumatosis intestinalis is an uncommon condition identified by multiple gas-filled cysts in the intestinal submucosa/serosa on imaging. Rupture of these cysts causes pneumoperitoneum, which mandates emergent surgical intervention. The pathophysiology of this condition is still under speculation; however, it has been associated with many gastrointestinal and pulmonary conditions. Because of this patient's absence of initial respiratory symptoms, the hypercoagulability and thromboinflammation associated with COVID-19 may be the culprit leading to bowel ischemia.
The student-centered teaching clinic in general internal medicine is a new model for outpatient education
Authors: Xiao-ming Huang, Yue Sha, Cheng-jin Huang, Yu Wang, Xue-jun Zeng
Journal: BMJ (2010)

International medical community has seen the prevail of outpatient teaching for medical students in recent years. A student-centered and faculty-run teaching clinic was set up based on current outpatient resources in 2008 by Division of General Internal Medicine (DGIM) in Peking Union Medical College Hospital (PUMCH). We concluded that teaching clinic was an effective teaching mode for medical students to improve clinical skills, diagnostic proficiency and health-care professionalism in internal medicine.

Key words: 
Education; medical;  General internal medicine
Atezolizumab + obinutuzumab + venetoclax in patients with relapsed or refractory diffuse large B-cell Lymphomas (R/R DLBCL): Primary analysis of a phase II trial from LYSA.
Authors: Charles Herbaux, Olivier Casasnovas, Pierre Feugier, Gandhi Damaj, Reda Bouabdallah, Stephanie Guidez, Loic Ysebaert, Herve Tilly, Steven Le Gouill, Luc Fornecker, Nicolas Daguindau, Nadine Morineau, Corinne Haioun, Emmanuel Gyan, David Sibon, Rémy Gressin, Roch Houot, Gilles A. Salles, Franck Morschhauser, Guillaume Cartron
Journal: Journal of Clinical Oncology (2020)

8053 Background: R/R DLBCL treatment remains challenging. Atezolizumab (ATE) and obinutuzumab (OBI) are monoclonal antibodies acting respectively to inhibit T-lymphocyte exhaustion or by inducing lymphoma cells cytotoxicity, whereas venetoclax (VEN) is a small molecule inhibiting BCL-2. Combining tumor-targeted therapies with agents that enhance anti-tumor immunity represents an attractive treatment paradigm. This LYSA sponsored multicenter phase 2 trial (NCT03276468) evaluate the combination of ATE, OBI and VEN in R/R B lymphomas, we present here primary efficacy and safety data fromthe DLBCL cohort. Methods: Patients ≥18 years with biopsy-confirmed R/R DLBCL who failed at least one line of therapy were eligible. OBI was given IV at the dose of 1 g on day (D) 1, 8 and 15 of cycle (C) 1 and on D1 from C2 to C8 every 3 weeks. ATE was given IV, 1.2 g every 3 weeks, started at D2 of C1, then administered at D2 of each cycle for 24 cycles. VEN was given orally at 800 mg/D at full dose, started on D8C1 for 24 cycles. The primary endpoint wasthe Overall Metabolic Response Rate (OMRR) by Lugano criteria at the end of induction (EOI) after 8 cycles of ATE, OBI and VEN (M6) or at premature treatment discontinuation. Results: At the time of the primary analysis (03 Jan 2020), 58 pts were enrolled and the median follow-up was 9 months [6.9-11.8]. Baseline characteristics were: median age, 70 years; male, 53.4%; Ann Arbor Stage IV, 84.5%; aaIPI (≥2), 63.2%; &gt; 2 prior lines of therapy, 83.6%; and refractory to last line of prior regimen, 63.6%. The OMRR at EOI was measured at 23.6% [14.58%-34.93%], including 18% of CMR. To date, these responses seem durable with only 3 reported relapses. According to the highest diameter mass, OMRR was 38.5% versus 10.3%, &lt; 5cm and &gt; 5cm respectively; P = 0,02. All three treatments were stopped in 78% of patients, mostly for progressive disease. At the time of analysis, a median of 4 cycles [1-8] has been administered. A total of 48 (84.2%) pts experienced grade 3–4 adverse event (AE) and 6 (10.5%) had an AE that led to discontinuation of any drug.AE of grade 3 or more reported in at least 20% of patients were neutropenia (33.3%) and lymphopenia (35.1%). Of note, a grade 3 autoimmune colitis and a grade 1 hypothyroidism were reported during induction. Conclusions: The ATE, OBI and VEN combinationappears to be well tolerated. The OMRR rate at EOI is comparable with currently available treatment options in this population, with durable responses. The OMRR seems better in patients with a low tumor burden. Clinical trial information: NCT03276468 .
Intralesional steroids and endoscopic dilation for anastomotic strictures after esophagectomy: systematic review and meta-analysis
Authors: Chandra S. Dasari, Ramprasad Jegadeesan, Harsh K. Patel, Madhav Desai, Muhammad Aziz, Viveksandeep Thoguluvachandrasekar, Abhiram Duvvuri, Divyanshoo R. Kohli, Alessandro Repici, Peter D. Siersema, Prateek Sharma
Journal: Endoscopy (2020)

Abstract Background Post-esophagectomy anastomotic strictures are difficult to treat. The impact of adding local steroid injection to endoscopic dilation for the treatment of post-esophagectomy anastomotic strictures is unclear. We conducted a systematic review and meta-analysis to assess the efficacy of performing steroid injection in addition to dilation. Methods A search was conducted in MEDLINE, Cochrane Library, EMBASE, and Web of Science from inception to January 2019. Randomized controlled trials (RCTs) comparing the efficacy of endoscopic dilation plus either local steroid injection (steroid group) or saline injection (placebo group) were included in the analysis. Results Three RCTs were eligible for the final analysis: 72 patients (mean age 61.3 years, 74 % male) in the steroid group and 72 patients (mean age 59.6 years, 71 % male) in the placebo group. The mean number of dilations required to resolve the stricture was significantly lower in the steroid group compared with the placebo group, with a mean weighted difference of –1.62 (95 % confidence interval [CI] –2.73 to –0.50; P = 0.004). After 6 months of follow-up, there was a trend toward more patients in the steroid group remaining dysphagia free compared with the placebo group, with a pooled odds ratio of 2.36 (95 %CI 0.94 to 5.91; P = 0.07, I2 = 24 %). Conclusion This meta-analysis showed that the addition of local steroid injection at the time of dilation for benign anastomotic strictures led to a significant decrease in the number of procedures required to resolve the stricture and may well reduce dysphagia symptoms during follow-up.
Personalized viral-based prime/boost immunotherapy targeting patient-specific or shared neoantigens: Immunogenicity, safety, and efficacy results from two ongoing phase I studies.
Authors: Charles G. Drake, Melissa Lynne Johnson, Alexander I. Spira, Gulam Abbas Manji, David Paul Carbone, Brian S. Henick, Matthew Ingham, Chih-Yi Liao, Sameek Roychowdhury, Chrisann Kyi, Paul Andrew Basciano, Eirini Bournazou, Jesse Abhyankar, Ashish Bezawada, Sonia Kounavouth, Desiree Schenk, Andrew R. Ferguson, Raphael F. Rousseau, Daniel V.T. Catenacci
Journal: Journal of Clinical Oncology (2020)

3137 Background: Neoantigens are key targets of a tumor-specific immune response and CD8 T cells targeting neoantigens drive clinical benefit in patients (pts) treated with checkpoint inhibitors. Methods: Two Phase I studies are being conducted to assess the safety, immunogenicity, and early clinical activity of a viral-based neoantigen-targeting prime/boost immunotherapy aimed at maximizing the CD8 T cell response. Both studies use a chimpanzee adenovirus prime followed by increasing doses of repeat boosts with a self-amplifying mRNA in combination with IV nivolumab +/- SC ipilimumab. In the first study, GO-004, patient-specific neoantigens are predicted using Gritstone's EDGE model and incorporated into both prime/boost vectors. In GO-005, shared neoantigens derived from common driver mutations (including several from KRAS) are encoded in off-the-shelf prime/boost vectors. Results: To date, 12 pts have been treated: 6 pts with GEA, NSCLC, or MSS-CRC (GO-004) and 6 pts with NSCLC, MSS-CRC, or PDA (GO-005) with all pts receiving IV nivolumab and 5 pts also receiving SC ipilimumab. Nine pts continue to receive study treatment. No DLTs have been observed. Treatment-related AEs are reversible and include Grade 1/2 fever (7/12), injection site reactions (4/12), fatigue (3/12), diarrhea (2/12), hypotension (2/12), pruritus (2/12), skin reactions (2/12), anorexia (1/12), dyspnea (1/12), hyponatremia (1/12), infusion-related reactions (1/12), myalgia (1/12), and asymptomatic Grade 3 CK elevation (1/12). At the time of analysis, 8 of 12 pts with ≥ 1 radiographic assessment have a best response of stable disease (SD) (3) and progressive disease (PD) (4), and one pt with no evaluable disease at baseline continues on study &gt; 8 months. In GO-005, 1 pt with SD has a 20% reduction in tumor dimensions that correlates with a decrease in ctDNA. In 4 pts in GO-004 analyzed to date, all pts showed substantial neoantigen-specific CD8 T cell responses to multiple neoantigens after priming which increase further in 2 of 3 pts analyzed after subsequent boosts. In GO-005, 1 of 3 pts showed a robust KRAS G12C-specific CD8 T cell response. Induced T cells express IFNg and granzyme B, consistent with an effector response. Conclusions: Taken together, these early data support the tolerability of a viral-based prime/boost immunotherapy, demonstrate marked immunogenicity, and are consistent with potential clinical activity. Additional pts and data at higher dose levels will be presented. Clinical trial information: NCT03639714, NCT03953235 .
Influence of selective posterior rhizotomy via different operation-sites on lumbar spine stability in children with spastic cerebral palsy
Authors: 张毅, 程钢, 刘小林, 李智勇, 曾瑞曦, 严凤娇, 刘虹
Journal: BMJ (2010)

Objective To investigate variation of lumbar spine stability in children with spastic cerebral palsy (SCP) after two types selective posterior rhizotomy (SPR) at lumbosacral and conical sites.Methods Forty-five cases of SCP have undergone with lumbosacral SPR and 38 with conical SPR. Posteroanterior, lateral, 40°-double-oblique, and dynamic (hyperextension and hyperflexion) position lumbar Xray films were taken for all of them before and three months to seven years ( 19 months in average) after operation to observe postoperative lumbar deformity, lumbosacral angle, lateral Cobb' s angle, arch-vertex distance, lordotic index, Posner's definition, and other stability indicators pre- and post-operation of the two groups. Results ① There was statistically significant difference in lumbosacral angle, lateral Cobb's angle, arch-vertex distance, lordotic index and Posner's definition at the 1 st to 2nd lumbar vertebrae (L1-L2 ), the 4th to 5th lumbar vertebrae ( L4 - L5 ), and the 5th lumbar to the 1st sacral vertebrae ( L5 - S1 ) among those with lumbosacral SPR before and after operation (P ＜0. 05). But, only Posner's definition at the 12th thoracic vertebra to the 2nd lumbar vertebra ( T12 - L2 ) varied significantly ( P ＜ 0. 05 ) among those with conical SPR ② Various lumbar deformity was observed in six cases ( 13% ) with lumbosacral SPR, three of them with instable neurological symptoms; while two cases (5%) did so after conical SPR,one with neurological symptoms, with statistical significance ( P ＜ 0. 05). Conclusions Little variation of lumbar spine stability is found among children with spastic cerebral palsy in mid-short term after SPR, while influence of conical SPR is much less on lumbar stability. Their long-term postoperative influence has to be followed-up further.

Key words: 
Cerebral palsy ;  Rhizotomy ;  Lumbar vertebrae ;
An open-label, multicenter, phase II study of ceritinib in patients with advanced ALK+ non-lung solid tumors and hematological malignancies (ASCEND-10).
Authors: Victor Moreno, Tae Min Kim, Sun Young Rha, Federico Longo, Sith Sathornsumetee, Shirong Zhang, Yulia Hirschberg, Barnali Pramanik, Barbara D Wamil, Igor Kiss
Journal: Journal of Clinical Oncology (2020)

3520 Background: Prior studies have confirmed the efficacy and safety of ceritinib in patients (pts) with advanced ALK+ non-small cell lung cancer (Soria, et al, Lancet 2017; Shaw et al, Lancet Oncol 2017; Cho et al, JTO 2019). Ceritinib also demonstrated antitumor activity in pediatric pts with ALK+ inflammatory myofibroblastic tumor (IMT) and ALCL (Georger et al, ASCO 2015 [abstract#10005]). Long-term clinical benefits of ceritinib treatment were shown in pts with anaplastic large cell lymphoma (ALCL) (Richly et al, Blood 2015). The aim of the current study was to examine ceritinib efficacy and safety in pts with advanced ALK+ non-lung solid tumors and hematological malignancies. Methods: In this open-label, multi-arm, phase 2 (NCT02465528) trial, adult pts with ALK gene abnormalities who had received ≥1 prior systemic therapy were administered oral ceritinib 750 mg/day, under fasted conditions. Primary endpoint: investigator assessed disease control rate (DCR); secondary endpoints: investigator assessed overall response rate (ORR), duration of response (DOR), time to response (TTR), progression-free survival (PFS), and safety. Results: Overall, 22 pts (ALCL [n = 1], IMT [n = 4], glioblastoma multiforme [GBM, n = 12] and others [n = 5]) were enrolled; median (m) age: 52.5 years; male: 50%; Stage ≥IV: 95.4%. Key efficacy results are shown in the Table. mTTR in pts with confirmed complete response (CR) or partial response (PR) [n = 4] was 7.4 (range, 6–25) weeks. mDOR was not reached. mPFS (95% CI) was 2.6 (1.6, 3.7) weeks. Most common adverse events (AEs; ≥30%) were: diarrhea and nausea (59.1% each), vomiting (50.0%) and increased alanine aminotransferase (31.8%). Most common grade ≥3 AEs (≥10%): hyperglycemia (18.2%), increased gamma-glutamyl transferase, thrombocytopenia, and anemia (13.6% each). Clinical trial information: NCT02465528 . Conclusions: Ceritinib 750 mg/day under fasted conditions showed antitumor activity in pts with ALK+ ALCL and IMT; however, data interpretation is limited due to the small sample size. Safety findings were consistent with the known ceritinib safety profile. [Table: see text]
两种封管液对肺源性心脏病血液流变学的影响
Authors: 张燕, 李映红, 杨桂梅, 吴晓群
Journal: BMJ (2005)

对本院1998年2月至2004年10月肺源性心脏病住院患者400例静脉留置针进行分析. 1.对象与方法:400例被确诊为肺源性心脏病的患者,经常规检查确定无凝血机制障碍及肝肾功能不全、应激性溃疡等,病程3～20年.随机分为观察组及对照组,各200例,观察组男151例,女49例,年龄40～92岁;对照组男136例 ,女64例,年龄45～89岁.常规静脉留置针输液毕,观察组用每百毫升1.25万单位肝素的生理盐水5 ml正压封管,对照组用生理盐水 5 ml正压封管。
Baseline radiomics features (RF) in metastatic colorectal cancer (mCRC): Correlation with m site and clinical-pathological characteristics.
Authors: Raffaella Vivolo, Luca Boldrini, Jacopo Lenkowicz, Gianluca Caliolo, Floriana Camarda, Annunziato Anghelone, Brunella Di Stefano, Maria Alessandra Calegari, Carmelo Pozzo, Michele Basso, Carolina Liguori, Anna Maria De Gaetano, Nicola Dinapoli, Riccardo Manfredi, Vincenzo Valentini, Giampaolo Tortora, Lisa Salvatore
Journal: Journal of Clinical Oncology (2020)

e15589 Background: R is an emerging field of research based on the extraction of a large amount of F from biomedical images and on computed analysis algorithms of tumour architecture. Few data regarding mCRC are available, in particular no correlation of baseline RF both with m sites and clinical-pathological characteristics was so far investigated. Methods: Baseline chest-abdomen CT scans of mCRC patients (pts) were retrospectively analysed. RF were extracted from Regions of Interest (ROI) delineated on CT scan from each m sites, including primary tumor, when on site. The association of specific F and disease site (liver, lung, nodes, peritoneum and on-site primary tumor) was investigated. Sites similarity was assessed with Principal Component Analysis, an unsupervised learning technique to identify patterns and clusters. Then RFs were tested individually for correlation with clinical-pathological covariates of interest (gender, CEA level, synchronous disease, RAS/BRAF status, mucinous histology, grading, number of m site, primary tumor site). Wilcoxon-Mann-Whitney test was used for this purpose (significance level set at 0.05). Results: After RF extraction from the different ROIs, the dataset was composed of 433 observations of 236 variables. Observations referred to the number (N) of pts = 89 and the N of ROIs = 18. RF classes were divided in statistical F (grey-level histogram) (N of F = 10); morphological F (N = 14); texture F GLCM (grey level co-occurrence matrix) (N = 100); texture F GLRLM (grey level run length matrix) (N = 66); texture F GLSZM (grey level size zone matrix) (N = 32). Regarding the association of RF with m sites, an homogenous distribution with liver, nodes, peritoneum and primary tumor was detected, while lung metastases showed a different pattern for all the RF classes. A significant correlation of specific RF with clinical-pathologic characteristics was shown, in particular with gender, CEA level, synchronous disease, mucinous histology, RAS/BRAF status. Conclusions: Despite its retrospective nature and the limited number of pts, this is the first experience demonstrating I) a different pattern of RF for lung m versus an homogeneous RF distribution for the other m sites; and II) a significant association of specific RF with few clinical-pathologic characteristics. Our results, if confirmed in a prospective validation set, may represent an hypothesis generator regarding the different behaviour of lung metastases and a possible R signature able to identify different prognostic subgroups of pts.