tbuckley/cabot-search huggingface dataset:
Lean NAFLD: A Distinct Entity Shaped by Differential Metabolic Adaptation
Authors: Fei Chen, Saeed Esmaili, Geraint B. Rogers, Elisabetta Bugianesi, Salvatore Petta, Giulio Marchesini, Ali Bayoumi, Mayada Metwally, Mahmoud Karimi Azardaryany, Sally Coulter, Jocelyn M. Choo, Ramy Younes, Chiara Rosso, Christopher Liddle, Leon A. Adams, Antonio Craxì, Jacob George, Mohammed Eslam
Journal: Hepatology (2019)

Nonalcoholic fatty liver disease (NAFLD) affects a quarter of the adult population. A significant subset of patients are lean, but their underlying pathophysiology is not well understood.We investigated the role of bile acids (BAs) and the gut microbiome in the pathogenesis of lean NAFLD. BA and fibroblast growth factor (FGF) 19 levels (a surrogate for intestinal farnesoid X receptor [FXR] activity), patatin-like phospholipase domain containing 3 (PNPLA3), and transmembrane 6 superfamily member 2 (TM6SF2) variants, and gut microbiota profiles in lean and nonlean NAFLD were investigated in a cohort of Caucasian patients with biopsy-proven NAFLD (n = 538), lean healthy controls (n = 30), and experimental murine models. Patients with lean NAFLD had a more favorable metabolic and histological profile compared with those with nonlean NAFLD (P < 0.05 for all). BA levels were significantly higher in NAFLD with advanced compared with earlier stages of liver fibrosis. Patients with lean NAFLD had higher serum secondary BA and FGF19 levels and reduced 7-alpha-hydroxy-4-cholesten-3-one (C4) levels (P < 0.05 for all). These differences were more profound in early compared with advanced stages of fibrosis (P < 0.05 for both). Lean patients demonstrated an altered gut microbiota profile. Similar findings were demonstrated in lean and nonlean murine models of NAFLD. Treating mice with an apical sodium-dependent BA transporter inhibitor (SC-435) resulted in marked increases in fgf15, a shift in the BA and microbiota profiles, and improved steatohepatitis in the lean model.Differences in metabolic adaptation between patients with lean and nonlean NAFLD, at least in part, explain the pathophysiology and provide options for therapy.
Measurement of Serum microRNAs in US Veterans with Monoclonal Gammopathy of Undetermined Significance
Authors: Weixin Wang, Youn K Shim, Joel E Michalek, Emily Barber, Layla M Saleh, Byeong Yeob Choi, Chen-Pin Wang, Norma Ketchum, Rene Costello, Gerald E Marti, Robert Vogt, Ola Landgren, Katherine R. Calvo
Journal: Blood (2018)
Results of the dose-finding phase of ARST 1321 from the Children's Oncology Group and NRG Oncology: Neoadjuvant chemoradiation or radiation therapy +/- pazopanib in non-rhabdomyosarcoma soft tissue sarcomas.
Authors: Yen-Lin Chen, Aaron R. Weiss, Thomas Scharschmidt, Yueh-Yun Chi, Jennifer M. Black, Edwin Choy, Simon C. Kao, Mark Kayton, Scott H. Okuno, Andrew Ostrenga, R Randall, Stephanie Alicia Terezakis, Eduardo Zambrano, Sheri L. Spunt, Douglas S. Hawkins, Dian Wang
Journal: Journal of Clinical Oncology (2019)

11070 Background: Pazopanib is a tyrosine kinase inhibitor approved globally for advanced soft tissue sarcomas. The dose finding phase of this cooperative group trial assessed the dose limiting toxicities (DLT) and the maximally tolerated dose (MTD) of adding pazopanib to neoadjuvant chemoradiation or radiation therapy in children and adults with unresected intermediate/high-risk trunk and extremity non-rhabdomyosarcoma soft tissue sarcomas (NRSTS). Methods: ARST1321, a jointly designed intergroup study lead by Children's Oncology Group and NRG Oncology opened for enrollment in July 2014. Eligible adult and pediatric patients with newly diagnosed, unresected trunk/extremity NRSTS with plans for primary tumor resection were enrolled into either the Chemotherapy Cohort (those with chemosensitive NRSTS &gt; 5 cm, grade 3, including all synovial sarcoma) or the Non-Chemotherapy Cohort (those with chemotherapy insensitive NRSTS of any size, grade 2/3, or any chemosensitive NRSTS for whom no chemotherapy was planned per discretion of patients and treatment teams). In the Chemotherapy Cohort, pazopanib was given with ifosfamide (7.5 grams/m 2 ) and doxorubicin (75 mg/m 2 ) plus 45 Gy preoperative RT starting after cycle 2. Primary tumor was resected at week 13, followed by chemotherapy and pazopanib to week 25. In the Non-Chemotherapy Cohort, pazopanib was given with 50 Gy preoperative RT, primary tumor was resected at week 10, and pazopanib continued to week 25. Feasibility was assessed through week 6 of therapy to determine pazopanib dose escalation/de-escalation based on DLT, total doses of pazopanib, and overall adverse event profile. Results: In the Chemotherapy Cohort, MTD was reached at Dose Level 1 (350 mg/m 2 peds; 600 mg adults) with two DLTs (1 grade 3 ALT rise, 1 intolerability to therapy) in 10 patients. In the Non-Chemotherapy Cohort, 11 patients enrolled at Dose Level 1 (350 mg/m 2 peds; 600 mg adults) without any observed DLTs and all received ≥75% of prescribed total pazopanib dose; MTD was reached at Dose Level 2 (450 mg/m 2 peds; 800 mg adults) with 2 DLTs in ten patients enrolled (1 grade 3 dermatitis and 1 intolerability to therapy) and 9/10 receiving ≥75% of full dose. Conclusions: Pazopanib in combination with chemoradiation or radiation therapy alone was found to be safe in children and adults with NRSTS. Following this finding, ARST1321 opened in both arms using the newly determined pazopanib MTDs. Clinical trial information: NCT02180867.
A 17-cm endoscopic submucosal tunnel dissection for esophageal cancer and insertion of polyglycolic acid-coated stent
Authors: In Kyung Yoo, Min Kang Seo, Sung Pyo Hong, Hyojung Lee, Joo Young Cho
Journal: Endoscopy (2019)

A 58-year-old man was referred to our hospital because of the large extent of his esophageal cancer. Gastroendoscopy with iodine staining showed a 17-cm long circumferential lesion.
Phoma (Peyronellaea) spp.: a phytopathogen as a cause of cystic phaeohyphomycosis in a diabetic patient
Authors: R.P. Nolêto, I.S. Santos, T.G. Amaro, D. Diebold, G. Vettorato, T.C. Daboit
Journal: Clinical Microbiology and Infection (2019)

A 63-year-old man with type 2 diabetes, resident on the north coast, Rio Grande do Sul, Brazil, was referred to the dermatology health service at Santa Casa de Porto Alegre due to a nodular subcutaneous lesion on the left ankle (Fig. 1a) in May 2012. He underwent direct and cultural mycological examinations, and in the former, septate hyphae were detected (Fig. 1b). In the latter, material from the ankle injury was inoculated on Mycosel and Sabouraud agar with chloramphenicol and incubated for 15 days at 35°C. This showed the growth of a filamentous fungus with initial hyaline aspect, but becoming dematiaceous over time (Fig. 1c). The colonies obtained were submitted to the microculture technique, through which fruiting structures with the presence of pycnidia and hyphae were observed (Fig. 1d). Sequencing of ITS1-5.8S rDNA-ITS2 was performed using universal primers. Sequences were analysed using MEGA 7.0 and indicated a phaeohyphomycosis caused by Phoma (Peyronellaea) spp. With this diagnosis, treatment with itraconazole 200 mg/day was initiated, together with the application of hot compresses on the injury site. During the 4 months of therapy there was a progressive regression of the disease. Surgical removal of the cyst was not performed because the patient was diabetic and the anatomical location was not favourable. Phaeohyphomycosis is a term used to describe a group of heterogeneous mycotic diseases caused by several dematiaceous fungal microorganisms. Being an uncommon condition, the disease is under-diagnosed, affecting directly the success of the treatment with a high rate of mortality when dissemination occurs. Phoma spp. form a group of ubiquitous phytopathogens found in soil and organic matter. These pathogens have been identified as a cause of opportunistic infections in humans and animals. Until now, there have been 32 reports in the literature of human phaeohyphomycosis caused by Phoma spp. [[1]Bennett A. Ponder M.M. Garcia-Diaz J. Phoma infections: classification, potential food sources, and their clinical impact.Microorganisms. 2018; 58: 1-12Google Scholar]. There was no external funding for this study.
Biologic markers guiding the treatment of non-small cell lung cancer: RRM-1, class III ß tubulin, and ERCC-1.
Authors: Esat Namal, Mustafa Bozkurt, Akin Ozturk, Kezban Nur Planci, Nuray Bassullu, Ozgul Pamukcu, Gulen Bulbul Dogusoy, Sezer Saglam, Zafer Akcali, Gokhan Demir
Journal: Journal of Clinical Oncology (2013)

e19127 Background: Lung cancer is the most common cause of cancer deaths in the world. Despite the developments in diagnosis and treatment, the high mortality rate in metastatic non small cell lung cancer (NSCLC) is still an important problem. Recent non-targeted standard therapy for NSCLC is the dual therapy regimens which involve platins. Our former knowledge whether these therapies can be effective or not would save the patient from the redundant toxicity and provide us to use more effective drugs formerly. Understanding the biology of NSCLC can allow choosing the effective and appropriate therapy in terms of life quality, survival rate and relapses. There are ongoing studies upon prognostic and predictive values of ERCC1, RRM1 and β tubulin in NSCLC patients. In this study we aimed to investigate the role of β tubulin, ERCC1 and RRM1 expressions as predictive biomarkers. Methods: 47 patients who are on follow up by Bilim University, Medical Oncology Department, were taken to the study. ß tubulin, ERCC1 and RRM1 over expressions were investigated in the biopsy materials of these patients by Pathology Department. Retrospectively, it was evaluated whether there is correlation between these biological markers and patients’ survial rates and responses to antineoplastic therapies. Results: In the literature, there are some studies which show that β tubulin score is a predictive marker for the good response to taxan therapy. On the other hand, it was shown that taxans enhance the platin sensitivity decreasing the β tubulin expressions. Our study was also correlated with these studies in the literature. Furthermore, there was relationship between the β tubulin score and age. 15 patients (%32) were 65 or under 65 and these were accepted as ‘young patient population’; 32 patients were over 65 and were accepted as ‘old patient population’. Most of the patients whose β tubulin score was high (n=29), were young (n=19); and most of the patients whose β tubulin score was low (n=18) were old patients (n=12) (p=0.032). Conclusions: Detecting the levels of β tubulin, ERCC1 and RRM1 before treatment in NSCLC patients, can be predictive to organize the treatment. Unquestionably, it must be supported by the studies involve more patients.
Which Biopsy to Diagnose Interstitial Lung Disease? A Call for Evidence and Unity
Authors: Luca Richeldi, Vincent Cottin, Kevin K. Brown, Kevin R. Flaherty, Kerri A. Johannson, William D. Travis, Harold R. Collard
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

In clinical practice, TBLC is here to stay.In our experience, most patients prefer TBLC to SLB (or indeed any "surgical" procedure) despite the lower diagnostic accuracy of TBLC.In the clinic, and in the proper clinical and radiological context, TBLC is likely to provide far more diagnostic information to the clinician than what is being projected by this study.TBLC may have been projected to be "down" by this study, but certainly it is not out.
Patients with advanced-stage germ cell tumors have a high risk of thromboembolic events.
Authors: Anna Lina-Karin Gordy, Mary J. Brames, Lawrence H. Einhorn, Naveen Manchanda
Journal: Journal of Clinical Oncology (2013)

e15621 Background: Thromboembolism (TE) accounts for significant morbidity and mortality in cancer patients. Rates of TE have been reported from 0.9%-28.0%, depending on the population. Patients with germ cell tumors have a 4.0-8.4% risk of TE following platin chemotherapy. Our patients are high-risk, many with advanced disease receiving high-dose chemotherapy and peripheral blood stem cell rescue. We sought to more completely understand TE events in advanced germ cell tumor patients. Methods: Forty-four consecutive patients visiting our germ cell tumor clinic between 11/05/2012 and 1/22/2013 were selected. Data were collected by retrospective chart review from tumor diagnosis until TE (ranging from TE on diagnosis to 20 years later). A logistic regression model was fitted to determine variables that predispose patients to TE. Results: In our patient series, seven (15.9%) had venous TE and none had arterial events. Five patients (11.4%) had TE within 16 weeks of chemotherapy, and 2 at 10 and 19 years after diagnosis, respectively. Two had bilateral pulmonary emboli (PE) (4.5%), 3 had upper or lower extremity DVTs, or both, and 1 had bilateral PE and DVTs. Five patients with TE had nonseminomatous tumors, 2 had non-testis primaries, 4 had relapsed disease, 2 with late relapse (&gt;7 years), 6 had metastatic disease, 3 had retroperitoneal lymph node dissection, and all 7 received platin chemotherapy. In logistic regression analysis, significant risk factors for TE included relapse (P= .016), bulky retroperitoneal lymphadenopathy (P= .006), alpha-fetoprotein &gt;10,000 (P= .047) beta-HCG &gt; 1,000 (P= .020), chemotherapy (P= .031), platin-refractory disease (P= .055), and poor risk disease compared to good risk disease (P=.020). Conclusions: Germ cell tumor patients have a high risk of venous TE. Those with relapsed disease, bulky retroperitoneal lymphadenopathy, platin chemotherapy, platin-refractory, or poor risk disease are at increased risk. Our estimates are higher than previously reported and in contrast to earlier studies, do not include arterial TE. To confirm our findings, we will extend this study to 100 patients. If confirmed, this pattern of TE events may be a consequence of advanced stage disease in our patients.
A role for neutrophil gelatinase-associated lipocalin in regulating tumor angiogenesis
Authors: Jiang Yang, Marsha Moses
Journal: Cancer Research (2008)

438  Neutrophil gelatinase-associated lipocalin (NGAL, lipocalin 2) is a member of the lipocalin family. Lipocalins are small extracellular proteins that share the highly conserved structure of an 8-stranded anti-parallel barrel and have been shown to transport and present ligands, to bind to cell-surface receptors, and to form macromolecular complexes. Increased NGAL expression has been reported in a variety of human cancers including breast, colon, ovarian, pancreatic, liver and lung cancer, however, the function of NGAL in cancer development and progression remains unknown. In this study, we asked whether NGAL might play a role in tumor angiogenesis. Stable clones expressing NGAL were established from the human breast cancer cell line MCF-7. We found that vascular endothelial growth factor (VEGF) was significantly induced in NGAL-expressing cells at both the mRNA and protein levels compared to parental MCF-7 cells. We next examined the expression of hypoxia-inducible factor-1 α (HIF-1α), one of the most important regulators of VEGF transcription, and found that HIF-1α protein levels were also increased in NGAL-expressing cells. Interestingly, the levels of HIF-1α transcripts remained the same between NGAL-expressing cells and parental MCF-7 cells, suggesting that HIF-1α was regulated by NGAL only at the translational level. Next, NGAL was silenced using specific siRNA constructs in another breast cancer cell line, MDA-MB-231, which expresses high levels of NGAL. Both VEGF and HIF-1α levels were reduced in MDA-MB-231 cells with NGAL silencing thereby supporting our findings with MCF-7 cells that NGAL may regulate HIF-1α and VEGF. Finally, we asked whether NGAL affected tumor angiogenesis in vivo. NGAL-expressing cells and parental MCF-7 cells were grown subcutaneously in female nude mice and increased tumor angiogenesis was observed in NGAL-expressing tumors compared to tumors formed with parental MCF-7 cells. In conclusion, these data suggest that NGAL may promote breast cancer angiogenesis, at least in part, by inducing VEGF expression. (This work is supported by NIH R01 CA118764 and the JoAnn Webb Fund for Angiogenesis Research.)
The relationship between HER-2 and TOPO-2A gene expression and clinicopathologic results in gastric cancer.
Authors: Metin Ozkan, Esra Ermis Turak, Halit Karaca, Mevlude Inanc, Veli Berk, Kemal Deniz, Celalettin Eroglu
Journal: Journal of Clinical Oncology (2012)

e14670 Background: HER-2 and Topo-2A genes are settled on a chromosome 17 and their co-amplification rates are high. In this study, early gastric cancer patients who received adjuvant chemo-radiotherapy and chemotherapy were evaluated with HER-2 and Topo-2A expression in association with clinical and histopathologic findings. Methods: A total of 103 gastric cancer patients were included the study. The HER-2 and Topo-2A levels were measured by immunohistochemistry in postoperative tumor materials. A standard evaluation method was admitted for HER-2 positivity, while Topo-2A nuclear staining 3+ and 4+ were considered as overexpression. Those with level 2+ or 3+ of HER-2, the FISH test were attempted. Results: The median follow-up was 19 months (ranges 2–70 months). Forty-six patients (44%) relapsed during follow-up whereas 60 patients (58%) had died. The median overall survival (mOS) was 23 months. Histopathologies of HER-2 positive patients were intestinal type in 7 (87.5%) and diffuse type in one (12.5%) patient. In the follow-up period 4 patients (50%) were died (mOS was 17 months in this group). Median overall survival was 23 months in HER-2 negative group (p=0.6). Histopathologies of Topo-2A positive patients were intestinal type in 9 (64.2%) and diffuse type in 5 (35.8%) patient. In the follow-up period 8 patients (57%) were died (mOS was 22 months in this group). Median overall survival was 23 months in Topo-2A negative group (p=0.8). Three patients (37.5%) who had HER-2 positive histopathologies also had Topo-2A positivity. Conclusions: Overexpression rates of HER-2 in gastric cancer were reported 6.8-34%. Racial differences and different scoring techniques thought to be impact the results. Co-amplification rate of HER-2 and Topo-2A was reported 34% in gastric cancer. In our study HER-2 and Topo-2A overexpression rates were 7.7% and 13.6% respectively and co-amplification of HER-2 with Topo-2A rate was 37.5% is also similar to the other studies. Stages of patients with HER-2 and Topo-2A overexpression were similar to the distribution of the overall patients. While intestinal subtypes showed a higher rate of HER-2 overexpression, the median survival times tend to be shorter in HER-2 positive patients.
Documented Pain Diagnoses in Adults Prescribed Opioids
Authors: John Weiser
Journal: Annals of Internal Medicine (2019)

Letters20 August 2019Documented Pain Diagnoses in Adults Prescribed OpioidsJohn Weiser, MD, MPHJohn Weiser, MD, MPHAtlanta, Georgia (J.W.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L19-0213 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Sherry and colleagues' analysis of data from the NAMCS (1) includes ICD-9 codes but not information about the reason for the visit. As Horton and associates note in their comment, Sherry and colleagues therefore probably underestimated the documentation of pain among patients prescribed an opioid. Not including diagnoses noted in the narrative section of progress notes is another limitation. Electronic health records require the entry of ICD codes to justify billable services, such as ambulatory procedures and diagnostic tests. Entering an ICD code for every diagnosis addressed during an outpatient visit is not necessary. Entries on the ...Reference1. Sherry TB, Sabety A, Maestas N. Documented pain diagnoses in adults prescribed opioids: results from the National Ambulatory Medical Care Survey, 2006-2015. Ann Intern Med. 2018;169:892-4. [PMID: 30208400]. doi:10.7326/M18-0644 LinkGoogle Scholar Author, Article, and Disclosure InformationAffiliations: Atlanta, Georgia (J.W.)Disclosures: The author has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L19-0213. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoDocumented Pain Diagnoses in Adults Prescribed Opioids: Results From the National Ambulatory Medical Care Survey, 2006–2015 Tisamarie B. Sherry , Adrienne Sabety , and Nicole Maestas Documented Pain Diagnoses in Adults Prescribed Opioids Daniel B. Horton , Theresa Juliano , Matthew T. Taylor , and Tobias Gerhard Documented Pain Diagnoses in Adults Prescribed Opioids Tisamarie B. Sherry , Adrienne Sabety , and Nicole Maestas Metrics 20 August 2019Volume 171, Issue 4Page: 307KeywordsArthralgiaDisclosureElectronic medical recordsHypertensionInternational classification of diseases ninth revisionObesityOpioidsOutpatientsRashesSexually transmitted diseases ePublished: 20 August 2019 Issue Published: 20 August 2019 PDF downloadLoading ...
Long-Term Follow-up of Adult Double Unit Cord Blood (CB) Transplantation (dCBT) Recipients Reveals High Rates of Progression-Free Survival after a Novel Cy/ Flu/ Thio/ TBI 400 Intermediate Intensity Conditioning Regimen
Authors: Ioannis Politikos, Sean M. Devlin, Alexandra Jacob, Molly Maloy, Christopher Mazis, Kristine Naputo, Andromachi Scaradavou, Richard O'Reilly, Scott Avecilla, H.R. Castro-Malaspina, Parastoo B. Dahi, Sergio A. Giralt, Boglarka Gyurkocza, Ann A. Jakubowski, Esperanza B. Papadopoulos, Jonathan U. Peled, Miguel-Angel Perales, Craig S. Sauter, Brian C. Shaffer, Gunjan L. Shah, Roni Tamari, Marcel R.M. van den Brink, James W. Young, Doris Ponce, Juliet Barker
Journal: Blood (2017)
The impact of complex karyotype on the overall survival of patients with relapsed chronic lymphocytic leukemia treated with idelalisib plus rituximab
Authors: Karl-Anton Kreuzer, Richard R. Furman, Stephan Stilgenbauer, Ronald L. Dubowy, Yeonhee Kim, Veerendra Munugalavadla, Esther Lilienweiss, Hans Christian Reinhardt, Paula Cramer, Barbara Eichhorst, Peter Hillmen, Susan M. O’Brien, Andrew R. Pettitt, Michael Hallek
Journal: Leukemia (2019)
Response to Correspondence to ‘Time to change the primary outcome of lupus trials’ by Oon <i>et al</i>
Authors: Frederic A Houssiau
Journal: Annals of the Rheumatic Diseases (2019)

Response to 'Steroid sparing effect: an essential element in assessing therapeutic efficacy in SLE: response to 'Time to change the primary outcome of lupus trials' by Houssiau' by Oon et al I read with interest the comment by Oon et al on my editorial 'Time to change the primary outcome of lupus trials', published in a recent issue of the Annals of the Rheumatic Diseases. 1 The authors further fuel my viewpoint by updating their previous meta-analysis on glucocorticoid (GC) spare in phase III lupus trials. 2 They have now included two additional studies, that is, CHABLIS-SC 3 -which triggered the Editorial-and the Asian belimumab trial. 4Quite interestingly, this extended meta-analysis confirmed that significantly more lupus patients receiving a targeted therapy within the frame of a phase III trial could successfully taper GC.Achieving GC spare is well in line with EULAR recommendation 2.2.3 for the management of lupus: 'For chronic maintenance treatment, GC should be minimised to less than 7.5 mg/ day (prednisone equivalent) and, when possible, withdrawn'. 5A similar statement was made-already 5 years ago-by an international task force advocating a treat-to-target approach in recommendation 8: 'Lupus maintenance treatment should aim at the lowest GC dosage needed to control disease, and if possible, GC should be withdrawn completely'.