tbuckley/cabot-search huggingface dataset:
GENE-02. ESTABLISHING PERSONALIZED TREATMENT OPTIONS FOR RECURRENT HIGH-GRADE GLIOMAS
Authors: Ann-Christin Hau, Linsey Houben, Eliane Klein, Anais Oudin, Daniel Stieber, Ben Flies, Tony Kaoma, Fransisco Azuaje, Sabrina Fritah, Rolf Bjerkvig, Michel Mittelbronn, Frank Hertel, Anna Golebiewska, Simone Niclou
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND High grade glioma (HGG) patients develop resistance to standard treatment leading to disease progression and limited life expectancy. Recent advances in the molecular characterisation of treatment-naïve HGGs based on next generation sequencing and DNA methylation analyses have led to a better delineation of HGG-subtypes and identification of distinct genomic abnormalities opening opportunities for personalized treatment strategies. METHODS We collected 300 fresh glioma specimen with approximately 100 longitudinal samples of initial and recurrent tumors from 43 matched patients. We succeeded in generating a live-biobank of HGG patient-derived orthotopic xenografts (PDOX) and 3D tumor organoids that neatly recapitulates the mutational spectrum including structural DNA variations and methylation-based subtypes of gliomas. A highlight is the generation of 19 PDOXs of paired initial and relapse HGGs from 9 glioma patients, enabling high-throughput drug screens. We performed comprehensive molecular profiling using arrayCGH, DNA-methylation and targeted DNA sequencing on patient specimen and their derivatives, 3D tumor organoids and PDOXs. RESULTS Detailed analysis of the paired longitudinal samples indicated that PDOXs closely recapitulate the evolutionary trajectory of the parental tumors. Furthermore, targeted genomic sequencing of paired HGGs suggests that relapse tumors also accumulate somatic mutations in epigenetic effectors. Based on patient-derived material we carried out drug response screening on 3D tumor organoids using a compound library matching the majority of genes that were assessed with targeted sequencing. Differential drug responses between initial and recurrent tumors were observed and the prevailing primary drug response profiles were essentially recapitulad in the relapse setting. CONCLUSIONS Response assessment of treatment-naïve gliomas and their recurrences provides crucial information on the differential sensitivity between initial and relapsed HGGs and offers novel personalized therapeutic options for the relapse setting. Furthermore, in depth correlation of the profiled somatic molecular landscape with drug response will enable pharmacogenomic predictions of potential inhibitors in the clinical setting.
VPS4A mutations Cause a Syndrome with Dyserythropoiesis, Hemolytic Anemia, and Neurodevelopmental Delay
Authors: Katie Giger Seu, Lisa Trump, Sana Emberesh, Robert B. Lorsbach, Clarissa E. Johnson, Jessica Meznarich, Hunter Underhill, Haripriya Sakthivel, Omar Niss, Shannon Nortman, Lionel Blanc, Wenying Zhang, Carolyn Lutzko, Theodosia A. Kalfa
Journal: Blood (2019)
NCIC CTG, IND-205: A phase II study of PX-866 in patients with recurrent or metastatic castration-resistant prostate cancer (CRPC).
Authors: Sebastien J. Hotte, Elizabeth A. Eisenhauer, Anthony Michael Joshua, Vikaash Kumar, Susan Ellard, Richard William Gregg, Robyn Jane Macfarlane, Eric Winquist, Vamsee Torri, Joseph D. Ruether, Naveen S. Basappa, Ankineedu Saranya Kakumanu, Scott A. North, Christian K. Kollmannsberger, Anna Tinker, Deepu Mirchandani, Aurelie Tassignon, Diana Felice Hausman, Alison L Allan, Kim N. Chi
Journal: Journal of Clinical Oncology (2013)

5042 Background: PX-866 is an irreversible, pan-isoform inhibitor of Class I PI-3K. Mutations in PIK3CA and loss of PTEN activity lead to activation of AKT signaling; alterations in these genes occur frequently in prostate cancers while activation of the PI-3K/AKT signaling pathway is implicated in prostate cancer progression and treatment resistance. Hence, novel inhibitors of the pathway such as PX-866 are of interest. Methods: In this multicenter, two-stage, phase II study, docetaxel-naïve CRPC pts received PX-866, 8mg daily on a 6-week cycle. Primary endpoint was lack of progression at 12 weeks (PCWG2 criteria). Secondary endpoints included PSA and objective response rates and change in circulating tumor cells (CTC) during treatment. If ≤5 of the first 20 pts were progression free at 12 weeks, the study would stop. Otherwise, 40 pts would be accrued and PX-866 deemed worthy of further study if ≥16 pts were progression free at 12 weeks. Results: 43 pts were accrued after the criteria to progress to stage 2 were met. Median age was 70, ECOG PS was 0/1/2 in 27/15/1 pts, 23 pts had measurable disease, 24 patients had CTC ≥5. Median number of cycles was 2 (range 1–8). Most common adverse events (AE) were diarrhea (27 pts), nausea (25), fatigue (15), vomiting (13), anorexia (15) and grade 1 hypomagnesemia (11); 7 pts discontinued because of toxicity (3 GI, 3 LFTs, 1 fatigue). Grade 3 AEs were diarrhea (5 pts), AST/ALT elevation (4), fatigue (3). 11 patients were progression free at 12 weeks. 16 of the 24 pts with measurable disease were evaluable for response; there were no objective responses but 10 pts had stable disease (2.6-13.9m). One pt had a confirmed PSA response. CTC favorable conversion (from 5 at baseline to &lt;5) was observed in 6/24 evaluable patients (25%). Correlative studies are ongoing. Conclusions: PX-866 is well tolerated and showed modest activity in CRPC but did not meet a priori benchmarks for further development as a single agent in unselected patients. As androgen receptor inhibition promotes PI3K activity in PTEN-loss PC models, the addition of PX-866 in pts whose PSA is rising on abiraterone may reverse resistance and phase B of the study is underway to test this hypothesis clinically. Clinical trial information: NCT01331083.
Redesigning Primary Care to Improve Diabetes Outcomes (the UNITED Study)
Authors: Kevin A. Peterson, Caroline Carlin, Leif I. Solberg, Rachel Jacobsen, Toni Kriel, Milton Eder
Journal: Diabetes Care (2019)

The effective redesign of primary care delivery systems to improve diabetes care requires an understanding of which particular components of delivery consistently lead to better clinical outcomes. We identified associations between common systems of care management (SysCMs) and the frequency of meeting standardized performance targets for Optimal Diabetes Care (NQF#0729) in primary care practices.A validated survey of 585 eligible family or general internal medicine practices seeing ≥30 adult patients with diabetes in or near Minnesota during 2017 evaluated the presence of 62 SysCMs. From 419 (72%) practices completing the survey, NQF#0729 was determined in 396 (95%) from electronic health records, including 215,842 patients with type 1 or type 2 diabetes.Three SysCMs were associated with higher rates of meeting performance targets across all practices: 1) a systematic process for shared decision making with patients (P = 0.001), 2) checklists of tests or interventions needed for prevention or monitoring of diabetes (P = 0.002), and 3) physician reminders of guideline-based age-appropriate risk assessments due at the patient visit (P = 0.002). When all three were in place, an additional 10.8% of the population achieved recommended performance measures. In subgroup analysis, 15 additional SysCMs were associated with better care in particular types of practices.Diabetes care outcomes are better in primary care settings that use a patient-centered approach to systematically engage patients in decision making, remind physicians of age-appropriate risk assessments, and provide checklists for recommended diabetes interventions. Practice size and location are important considerations when redesigning delivery systems to improve performance.
Serum hepatocyte growth factor and interleukin-6 as prognostic markers for stage III non-small cell lung cancer.
Authors: Hideki Ujiie, Mikio Tomida, Hirohiko Akiyama, Daisuke Okada, Yuki Nakajima, Hiroshi Sakai, Yuichi Takiguchi, Hideki Tanzawa
Journal: Journal of Clinical Oncology (2012)

10542 Background: We surveyed prognostic biomarkers for resectable non-small cell lung cancer (NSCLC). Methods: We obtained preoperative serum from 109 patients admitted to our facility, and measured the levels of hepatocyte growth factor (HGF), interleukin-6 (IL-6), and nicotinamide N–methytransferase (NNMT) in the sera by the ELISA method. We also examined the clinical backgrounds of the patients. Results: The median HGF and IL-6 contents in sera from 109 patients were 860 pg/ml and 2.7 pg/ml, respectively. Analysis of survival curves indicated that HGF or IL-6 levels higher than the median were associated with poor overall survival (HGF, P = 0.019; IL-6, P = 0.002). On the other hand, carcinoembryonic antigen (CEA), a known tumor marker, and NNMT, which we found to be a candidate tumor marker, exhibited no correlation with the prognosis. The tumor status (pT factor) and stage were strong prognostic indicators (P &lt; 0.001). In addition, we analyzed stage III lung cancer alone. Higher HGF or IL-6 levels were associated with poor overall survival (HGF, P = 0.016; IL-6, P = 0.013). Disease-free survival was also affected by these cytokine contents, but not statistically significantly. The prognosis of patients with adenocarcinomas (ADC) was better than that of patients with other histological types. However, the pT factor and nodal status (pN factor) were not associated with the survival of stage III patients. Conclusions: The levels of HGF and IL-6 in serum could be useful prognostic indicator of the survival of stage III NSCLC patients undergoing surgery and chemotherapy.
Phase II trial: Concurrent chemotherapy and radiotherapy with nitroglycerin in locally advanced non-small cell lung cancer patients.
Authors: Dolores De la Mata, Monika Blake, Jesus Zamora Moreno, Omar Pena, Diana Flores-Estrada, Jenny Turcott, Oscar Arrieta
Journal: Journal of Clinical Oncology (2012)

7068 Background: The treatment of choice for locally advanced non small cell lung cancer (NSCLC) is concurrent chemoradiation (CRT). However, efforts to improve treatment results include targeted therapy and the use of radiosensitizers. Nitroglycerin (NTG), a nitric oxide (NO) donor agent, reduces expression of Hypoxia-Induced Factor, which is associated to both chemo and radio resistance. Methods: This is phase II trial in patients with locally advanced NSCLC treated with chemotherapy (CT) based on cisplatin and vinorelbin with NTG concurrent with radiation therapy. A 25 mg NTG patch was administered to the patients during the first 5 days of each induction treatment cycle and during chemo-radiotherapy. Blood samples of VEGF were taken before any treatment and after two cycles of CT. The protocol is registered with ClinicalTrials.gov, number NCT00886405. Results: 35 patients were enrolled in this trial. Median Follow up was 16.6 months (SD ±13.6). Mean age was of 59.9 years (±10.8), 68.6% of the patients were smokers. ECOG status was 0 in 22.9%, 1 in 65.7% and 2 in 11.5%, respectively. Histopathology was adenocarcinoma in 68.6%, epidermoid in 17.1% and undifferentiated in 14.3%. Stage distribution was: IIIa, 57.6% and IIIb, 42.5%. All patients completed CRT treatment and four underwent surgical treatment. Toxicity profile related to NTG was grade 1 and 2 headache in 17.1%. Grade 3 and 4 toxicities were esophagitis (17.1%), neutropenia (62.9%), and nausea (5.7%). Sixty-four per cent of patients achieved partial response after CT and 75.8% after CRT. PFS was 11.8 months (95%, IC 7.8-15.6) and OS was 42.9 months (95%IC 31.3-52.1). After two cycles of CT, plasma VEGF levels were significantly lower (Median 132±79 vs. 53±78 pg/ml, p&lt;0.001). No differences on PFS and OS were found between patients with a reduction ≥ 93 pg/ml (median of differences between VEGFR before and after chemotherapy). Conclusions: The addition of NTG to induction CT, and concurrent CRT on locally advanced NSCLC patients seems to increase the response rate, PFS and OS with an acceptable toxicity profile. A prospective trial is warranted to confirm these findings.
사례보고 : 자연파열을 동반한 간의 원발 상피모양혈관내피종 1예
Authors: 김금하 ( Geum Ha Kim ), 김연수 ( Yun Soo Kim ), 김현옥 ( Hyun Ok Kim ), 김길현 ( Kil Hyun Kim ), 정영걸 ( Young Kul Hung ), 정동해 ( Dong Hae Jung ), 김정호 ( Jeong Ho Kim ), 권오상 ( Oh Sang Kwon ), 최덕주 ( Duck Joo Choi ), 김주현 ( Ju Hyun Kim )
Journal: Clinical and Molecular Hepatology (2009)

간의 상피모양혈관내피종은 혈관 내피에서 기원하는 악성 종양이다. 임상증상은 무증상인 경우가 많고 복통, 체중감소, 피로감 등 비특이적이다. 다수의 간내 종괴를 형성하며 간혈관종과 유사한 조영소견을 보이고 복강 내로 자발 파열은 매우 드물다고 보고되고 있다. 저자들은 복통과 간내 다수의 종괴로 전원된 65세 남성에서 간의 상피모양혈관 내피종을 진단하고 간과 비장종괴가 파열되어 혈성 복수를 형성한 1예를 경험하였기에 문헌고찰과 함께 보고한다.
Pain perception and depression in patients with hidradenitis suppurativa
Authors: R.M. Nielsen, P. Lindsø Andersen, V. Sigsgaard, P.T. Riis, G.B. Jemec
Journal: British Journal of Dermatology (2020)

Hidradenitis suppurativa (HS) is a chronic skin disease. It causes painful boils in specific body areas such as the armpits and the groins. This disease affects about 1% of people in the U.K. It is more common in women. HS causes pain, but few studies have looked at this aspect. Depression and anxiety affects how pain is experienced. The patient's age and sex can also influence the experience of pain. The authors aimed to study pain in patients with HS. They handed out questionnaires in a HS specialist clinic in Roskilde, Denmark (Oct 2017 – Mar 2018). Patients described their pain and difficulty of HS, and reported any symptom of depression and anxiety. Pain was described with different words. The most common words were ‘shooting’ (83%), ‘itchy’ (79%) and ‘blinding’ (75%). The study revealed that pain in HS relates to severity of HS and to symptoms of anxiety and depression. The authors found that the pain experience of HS patients can be divided into two different pain qualities: the so‐called nociceptive and neuropathic pain. These two pain types are usually treated with different medications: anti‐inflammatory drugs (e.g. aspirin) and antidepressants. In general, HS patients are more often depressed than other people. HS patients are likely to benefit from different pain relievers including both anti‐inflammatory drugs and antidepressants to treat their pain. However, more studies are needed to make definite recommendations on treatment of HS pain. This summary relates to the study: Pain perception in patients with hidradenitis suppurativa
Surgical Safety of Radical Cystectomy and Pelvic Lymph Node Dissection Following Neoadjuvant Pembrolizumab in Patients with Bladder Cancer: Prospective Assessment of Perioperative Outcomes from the PURE-01 Trial
Authors: Alberto Briganti, Giorgio Gandaglia, Simone Scuderi, Andrea Gallina, Renzo Colombo, Nicola Fossati, Francesco Barletta, Antony Pellegrino, Luigi Nocera, Francesco Montorsi, Andrea Necchi
Journal: European Urology (2020)
A phase II trial of induction gefitinib monotherapy followed by cisplatin-docetaxel and concurrent thoracic irradiation in patients with EGFR-mutant locally advanced non-small-cell lung cancer (LA-NSCLC): LOGIK0902/OLCSG0905 intergroup trial.
Authors: Akiko Hisamoto, Jiichiro Sasaki, Nagio Takigawa, Yoshiyuki Shioyama, Junji Kishimoto, Mitsuhiro Takemoto, Katsuyuki Hotta, Mitsune Tanimoto, Yukito Ichinose, Katsuyuki Kiura
Journal: Journal of Clinical Oncology (2012)

7045 Background: We previously reported efficacy and safety of cisplatin-docetaxel and concurrent thoracic radiotherapy (TRT) for LA-NSCLC (Segawa Y and Kiura K. JCO 2010). However, its cure rate remains unsatisfied, and further improvement in the treatment outcome is strongly warranted. Recently, systemic chemotherapy has been individualized by intensive anti-cancer researches through the discovery of certain molecular targets in the metastatic NSCLC. Especially, gefitinib, EGFR tyrosine kinase inhibitor, is quite active and now one of the standard chemotherapy for untreated metastatic EGFR-mutant NSCLC (Maemondo M and Inoue A. NEJM 2010). Even in the locally advanced setting, approximately 30% of Japanese NSCLC patients possess EGFR-mutant tumors. Given all of these backgrounds, investigation on the role of adding gefitinib monotherapy to the standard concurrent chemoradiotherapy might cause a new paradigm shift in this setting. Methods: Patients have to meet the following eligibility criteria: LA-NSCLC; active tumor EGFR mutations (exons 19 and 21) but without 790M; measurable lesions; performance status (PS) of 0 or 1; age &lt; 75 years; and V20 ≤ 35%. The primary endpoint is set as 2-year progression-free survival (PFS) rate; assuming that 75% in eligible patients would indicate potential usefulness, whereas 60% would be the lower limit of interest (α = 0.05, ß = 0.20), the estimated accrual number is 46 patients. The secondary endpoint includes toxicity, response rate and overall survival. Patients will receive the induction treatment, specified as gefitinib monotherapy (250 mg/body) for 8 weeks. Patients who have not progressed during the induction therapy will receive cisplatin and docetaxel (40 mg/m 2 ; days 1, 8, 29, 36, each) and concurrent three-dimensional conformal TRT (2-Gy, single, daily fractions for 5 consecutive days each week to provide a total dose of 60 Gy). Enrollment began in 2010, and will complete by 2015. UMIN registration number of 000005086.
Alk fusion genes in the pathogenesis of a nonhematopoietic malignancy - inflammatory myofibroblastic tumor (imt)
Authors: Z. Ma, A. Hill, M. Collins, O. P. Witte, J. Bridge, M. Ladanyi, J. R. Cook, L. P. Dehner, C. Coffin, S. W. Morris
Journal: Blood (2000)
Interpreting the Benefit of Simvastatin-Ezetimibe in Patients 75 Years or Older
Authors: Oliver Weingärtner, Eric J. G. Sijbrands, Dieter Lütjohann
Journal: JAMA Cardiology (2020)

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Quality and Safety in Healthcare, Part LXI
Authors: Jay A. Harolds
Journal: Clinical Nuclear Medicine (2019)

Abstract Some of the causes for resident burnout and other impairments of wellness are the same as for other physicians, but some are quite different. For example, residents have much less autonomy and control, are under more pressure to learn a huge amount of information quickly, are more frequently evaluated, have stress from taking more examinations, and have more financial pressure than a typical physician who has graduated from formal training. Residency education also involves oversight from the Accreditation Council of Graduate Medical Education, which seeks to decrease some of the pressures of residency, but an unintended consequence of their limitation of work hours has been, in some programs, the phenomenon of “work compression.”
WIDEN: A tool for medical imaging management in oncology clinical trials.
Authors: Stephane Chauvie, Alberto Biggi, Alexandru Stancu, Piergiorgio Cerello, Andrea Gallamini
Journal: Journal of Clinical Oncology (2012)

e13093 Background: Recently a novel clinical trial generation based on a therapeutic strategy driven by early treatment response assessment to therapy by functional imaging was conceived and a central review of the images became necessary. We describe hear the application of a new web-based tool for imaging exchange and online review of PET scan (WIDEN) conceived for the prospective multicenter clinical trial HD0607. Methods: In the HD 0607 clinical trial 367 patients affected by advanced-stage Hodgkin Lymphoma (HL), are treated with 2 ABVD courses and a PET scan performed afterwards (PET-2). PET-2 positive patients shift to an aggressive treatment, PET-2 negative patients continue with ABVD. PET-2 along with the baseline scan (PET-0) is uploaded to a dedicated web site thanks to WIDEN and hence distributed to six expert reviewers. The latter report the scans within 72 hours from the upload and determine the choice whether intensify or not the treatment intensity (NCT identifier 00795613). Results: The average (median) time per scan upload and download were 6’39” (1’35”) and 3’26” (1’53”) respectively. The average (median) PET scan size were 133.8 MB (121.5 MB), with a minimum size of 51.2 MB and a maximum size of 469.8 MB. The average (median) time frame between the case files upload by the submitting centre and the case review reporting was 48h 45‘ (40h 31’). 7% of the cases were reviewed among the forth and the fifth days. 3% cases were reviewed after the fifth days. In all cases of a review time spanning over more than three days the delay depended on the presence of a week-end of other holiday time. Concordance rate among reviewers measured with Krippendorff,s alpha was 0.799. Conclusions: WIDEN proved to be an effective tool for medical imaging exchange and review. Data security, simplicity, low cost, feasibility and prompt scan review were demonstrated. Its applicability in any clinical trial in which imaging is decisional for treatment modulation is warranted
Best of JAMA Neurology 2019
Authors: Hooman Kamel, Dena B. Dubal
Journal: JAMA Neurology (2020)

Studies published in JAMA Neurology in 2019 featured a breadth of diverse and highly influential investigations. Here, we highlight a few of many exciting studies from the past year that illustrate major strides in neurology across fields from a lens of varied experimental approaches.