tbuckley/cabot-search huggingface dataset:
Postoperative adjuvant therapy with tamoxifen, tegafur-uracil (UFT), or both in women with node-negative breast cancer: A pooled analysis of six randomized controlled trials (relapse-free survival data)
Authors: S. Nakamura, O. Abe
Journal: Journal of Clinical Oncology (2006)

633 Background: In Japan, 6 randomized controlled trials of the oral 5-fluorouracil derivative tegafur-uracil (UFT) and tamoxifen (TAM), given alone or in combination, have been simultaneously performed in women with node-negative breast cancer. We performed a pooled analysis, based on the intention to treat, of individual patient data from these 6 trials (involving 2934 patients). Data on overall survival, the primary endpoint, have been reported previously (Noguchi et al., Journal of Clinical Oncology, 2005). We now report data on relapse-free survival (median follow-up, 6.2 years). Methods: Three 3-arm randomized controlled trials (surgery alone vs. surgery plus TAM vs. surgery plus UFT) and three 4-arm randomized controlled trials (surgery alone vs. surgery plus TAM vs. surgery plus UFT vs. surgery plus TAM and UFT) were performed in women with node-negative breast cancer. The results underwent a pooled analysis. Results: The 5-year relapse-free survival rate was 87.9% with surgery alone (n = 860; risk ratio [RR], 1), 90.5% with surgery plus TAM (n = 865; RR, 0.81; confidential interval [CI], 0.60–1.11; P = 0.21), 89.9% with surgery plus UFT (n = 860; RR, 0.83; CI, 0.66–1.21; P = 0.46), and 92.7% with surgery plus UFT and TAM (n = 349; RR, 0.63; CI, 0.39–0.99; P = 0.046). Subset analysis showed that combination therapy with UFT and TAM was not effective for women with estrogen-receptor-negative breast cancer (RR, 0.90; CI, 0.46–1.75; P = 0.75), but was very effective for women with estrogen-receptor-positive breast cancer (RR, 0.39; CI, 0.19–0.79; P = 0.009). Conclusions: Our results suggest that the effectiveness of oral fluoropyrimidine derivatives is enhanced by concurrent treatment with TAM in women with node-negative breast cancer. This contrasts with the results of previous studies showing that the response to anthracycline-based chemotherapy is attenuated in patients concurrently receiving TAM. No significant financial relationships to disclose.
Femoroacetabular impingement is more common in military veterans with end-stage hip osteoarthritis than civilian patients: a retrospective case control study
Authors: Kate N. Jochimsen, Cale A. Jacobs, Stephen T. Duncan
Journal: Military Medical Research (2019)

The purpose of this study was to compare the frequency of femoroacetabular impingement (FAI) between matched groups of military veterans and civilian patients with end-stage hip osteoarthritis (OA). Patients who underwent a primary total hip arthroplasty (THA) between January 1, 2015 and December 31, 2015 at a single Veteran’s Affairs Hospital were identified. Veterans were then matched 1:2 with civilian patients from our prospective outcome registry. The alpha angle and lateral center-edge angle (LCEA) were measured by a single evaluator. Independent t-tests were used to compare joint angles, and Fisher exact tests were used to compare the prevalence of cam (alpha angle ≥60°), pincer (LCEA ≥40°), or mixed-type pathologies. Twenty-one veterans were matched 1:2 with civilian patients. The mean alpha angle did not significantly differ between groups (P = 0.33) nor did the prevalence of cam deformities (P = 0.79). The LCEAs were significantly greater in veterans than in civilians (P = 0.04), and veterans also demonstrated a significantly greater prevalence of pincer and mixed-type deformities than civilians (P = 0.025 and P = 0.004, respectively). These results suggest that FAI is perhaps a more common mechanism in the progression of OA in a veteran population than in a civilian population, as pincer and mixed-type deformities were significantly more common among veterans than civilians. The forces borne by the hip during military training exceed normal physiologic conditions. In addition, the time between symptom onset and surgical correction may be 10–12 months longer for active military personnel than for civilians. The combination of increased physical demands and a protracted time to treatment highlights the need for better recognition of FAI in military members. Future studies are necessary to determine whether earlier intervention may prevent or delay the progression to end-stage OA and the need for total hip arthroplasty.
OC-082 Video case report of early eus-guided cystogastrostomy and endoscopic transgastric necrosectomy
Authors: S Cg, R Ramakrishnan, M Balakrishnan, C Snk
Journal: Gut (2017)

Introduction  Acute necrotising Pancreatitis with parenchymal and peripancreatic necrosis when infected results in significant morbidity and a high risk for mortality.Despite the advent of better accessories and equipment including the LAMS (lumen opposing metal stents), the timing of the intervention is always a question of debate. We are presenting this video capsule on early multimodal intervention in an adult male, with severe, infected extensive pancreatic necrotic collection.  Method  This is a video case report describing the early multimodal therapy using Linear array echo-endoscope guided pseudocyst drainage with lumen opposing metal stent (NagiTM stent) and subsequent necrosectomy with gastroscope and polypectomy snare. Patient also had bilateral percutaneous pigtail drain placed under transabdominal ultrasound guidance.  Results  A 30 year old adult male patient with Acute severe Pancreatitis, aetiology being alcohol. Patient was referred from a district hospital in view of severe necrotising pancreatitis.On week 3rd,a repeat abdominal imaging showed extensive pancreatic necrotic collection extending from the retroperitoneal space upto the pelvis and paracolic gutter with evidence of multiple air pockets within, no clear wall was formed yet around the necrotic collection. EUS guided cystogastrotomy using lumen opposing metal stent (NagiTM stent) was placed transmurally and simultaneously percutaneous transabdominal ultrasound guided pigtail were placed bilaterally to drain the paracolic gutters. Subsequently necrosectomy was performed over three sessions spaced over two weeks in between.Patient did not develop bleeding or any other major complications and was under cover of broad spectrum antibiotics for infected pancreatic necrosis. Healthy granulation tissue noted during the last session and the percutaneous drain was removed subsequently.Patient clinically improved and on followup.  Conclusion  Early minimally invasive multimodal Endotherapy in the setting of infected extensive pancreatic necrosis facilitates to improve clinical outcome with less morbidity.Larger prospective randomised control trials comapring early and delayed interventions are necessary to validate the findings.  Reference  . Freeman ML, Werner J, van Santvoort HC, et al. International Multidisciplinary Panel of Speakers and Moderators. Interventions for necrotizing pancreatitis: summary of a multidisciplinary consensus conference. Pancreas2012;41(8):1176–1194  Disclosure of Interest  None Declared
Epigenetic modulation by VidazaTM induces apoptosis and overcomes in vitro drug resistance in human multiple myeloma cells.
Authors: Tanyel Kiziltepe, Laurence Catley, Teru Hideshima, Noopur Raje, Yasui Hiroshi, Sonia Vallet, Hiroshi Ikeda, Yutaka Okawa, Kenneth Anderson
Journal: Cancer Research (2007)

3193  Methylation of DNA is an epigenetic modification that plays an important role in the regulation of gene expression in mammalian cells. Although DNA methylation is required for normal cell development and function, aberrant methylation and the resulting aberrant expression of genes, such as tumor suppressor genes and oncogenes, contribute to the development of malignancies. Interestingly, aberrant DNA methylation has recently emerged as one of the most frequent molecular alterations in hematologic malignancies, providing a powerful rationale to use inhibitors of DNA methylation as a novel means of targeting hematologic malignancies. VidazaTM  [Pharmion Corporation] (5-azacytidine), an FDA approved drug for the treatment of myelodysplastic syndromes, is an inhibitor of DNA methylation. Multiple myeloma (MM) is currently an incurable hematological malignancy despite all the conventional and novel therapies, and we here examined the biological effects using VidazaTM on human MM cells. We demonstrate here that VidazaTM has significant cytotoxicity in both conventional therapy sensitive (MM1S, RPMI-8226) and resistant (MM1R, RPMI-Dox40, RPMI-LR5) MM cell lines, as well as freshly isolated patient MM tumor cells, with an IC50 of 1.25-4 μM at 72 hours in vitro. Importantly, no cytotoxic effects of VidazaTM were detected in peripheral blood mononuclear cells (PBMNC) obtained from healthy volunteers at ≤ 20 μM, suggesting a therapeutic index. Moreover, VidazaTM overcame the survival and growth advantages conferred by interleukin-6 (IL-6) and insulin-like growth factor-1 (IGF-1), or by adherence of MM cells to bone marrow stromal cells (BMSC). VidazaTM induced apoptosis in MM cells, as determined by flow cytometric analysis using PI and Annexin V staining. VidazaTM-induced apoptosis was associated with PARP, caspase 8 and caspase 9 cleavage. Importantly, pan-caspase inhibitor zVAD-fmk, significantly, but only partially, inhibited apoptosis induced by VidazaTM, suggesting the involvement of both caspase dependent and independent pathways. Taken together, our studies therefore demonstrate that VidazaTM induces apoptosis and overcomes in vitro drug resistance in MM cells. Ongoing studies are delineating the mechanism of action of VidazaTM against MM cells to further provide the preclinical rationale for clinical evaluation of VidazaTM, alone or in combination with other agents, to improve patient outcome in MM.
Stroke Risk in Patients With Atrial Fibrillation Undergoing Electrical Isolation of the Left Atrial Appendage
Authors: Luigi Di Biase, Sanghamitra Mohanty, Chintan Trivedi, Jorge Romero, Veronica Natale, David Briceno, Varuna Gadiyaram, Linda Couts, Carola Gianni, Amin Al-Ahmad, John David Burkhardt, G. Joseph Gallinghouse, Rodney Horton, Patrick M. Hranitzky, Javier E. Sanchez, Andrea Natale
Journal: Journal of the American College of Cardiology (2019)
Effect of well drilling on Buruli ulcer incidence in Benin: a case-control, quantitative survey
Authors: Horace Degnonvi, Sebastien Fleuret, Clement Coudereau, Ronald Gnimavo, Sigrid Giffon, Edouard Yeramian, Roch Christian Johnson, Estelle Marion
Journal: The Lancet Planetary Health (2019)

BackgroundBuruli ulcer is the third most common mycobacterial disease worldwide. The public health burden of this neglected tropical disease is large, particularly in poor areas of west and central Africa. The development of appropriate preventive strategies is hampered by an incomplete understanding of the epidemiology and transmission of the disease. We investigated the effect of the drilling of wells on Buruli ulcer incidence.MethodsIn this case-control, quantitative survey, we obtained field data for Buruli ulcer incidence over a 10-year period from a specialised centre that collected data for the Ouémé and Plateau departments in Benin, and data for well drilling from the Ministry of Energy, Water and Mines in Benin. The coordinates of the wells drilled were obtained during site visits. A case-control study was then done to investigate the role of well water use in protecting against Buruli ulcer.FindingsWe found a strong inverse correlation between the incidence of Buruli ulcer and the number of new wells drilled in the Bonou municipality (r2=0·8818). A case-control study (106 cases and 212 controls) showed that regular use of the water from the wells for washing, bathing, drinking, or cooking was protective against Buruli ulcer (adjusted odds ratio 0·1, 95% CI 0·04–0·44; p=0·0012).InterpretationThis study opens up new possibilities for developing an effective yet affordable policy to fight the disease on a substantial geographical scale. Our study shows that providing access to protected water is an efficient and feasable way to reduce the incidence of Buruli ulcer.FundingFondation Francaise Raoul Follereau, French National Institute of Health and Medical Research, and Région Pays de Loire.
Quasispecies characteristic in “a” determinant region is a potential predictor for the risk of immunoprophylaxis failure of mother-to-child-transmission of sub-genotype C2 hepatitis B virus: a prospective nested case–control study
Authors: Yiwei Xiao, Kuixia Sun, Zhongping Duan, Zhixiu Liu, Yi Li, Ling Yan, Yarong Song, Huaibin Zou, Hui Zhuang, Jie Wang, Jie Li
Journal: Gut (2019)

This study was performed to explore the correlation between the characteristics of hepatitis B virus (HBV) quasispecies in HBV-infected pregnant women and the risk of immunoprophylaxis failure for their infants.In this prospective nested case-control study, the characteristics of HBV quasispecies in mothers whose infants were immunoprophylaxis success (control group) and those whose infants were immunoprophylaxis failure (case group) were analysed by the clone-based sequencing of full-length HBV genome and next-generation sequencing (NGS) of "a" determinant region, and were compared between the two groups.The quasispecies characteristics including mutant frequency, Shannon entropy and mean genetic distance at amino acid level of "a" determinant region were significantly lower in case group than that in control group, using the full-length HBV genome clone-based sequencing assay. These results were confirmed by NGS assay. Notably, we discovered that the differences were also significant at nucleotide level by NGS assay. Furthermore, the risk of immunoprophylaxis failure could be predicted by analysing the three HBV quasispecies characteristics either at nucleotide level or at amino acid level of "a" determinant region, and the corresponding predictive values were tentatively set up.HBV quasispecies with a more complex mutant spectrum in "a" determinant region might be more vulnerable to extinct through mother-to-child-transmission (MTCT). More importantly, analysing HBV quasispecies characteristics in pregnant women with high HBV DNA load might be helpful to predict the high-risk population of immunoprophylaxis failure, and consequently provide accurate intervention against MTCT of HBV.
YM155 sensitivity in pediatric acute lymphoblastic leukemia.
Authors: Bill H. Chang, Abdusebur Jemal, Jeffrey Tyner, Mathew Thayer, Markus Muschen, Brian J. Druker
Journal: Journal of Clinical Oncology (2012)

9555 Background: Despite advances in treatment and outcomes in pediatric acute lymphoblastic leukemia, there continue to be subsets of patients that are refractory to standard intensive chemotherapy. Therefore, novel agents are needed to further advance treatment for this disease. YM155 (Astellas) is a selective suppressant of survivin expression. Survivin has been shown to be over-expressed in malignant cells and in relapsed ALL. Early adult phase I/II studies show promise in both tolerability and possible efficacy in B-cell malignancies. Methods: Fresh diagnostic leukemic patient samples, ALL cell lines, and xenograft samples were obtained and subjected to YM155 at doses ranging from 1nM to 10µM. Samples were then tested for viability using standard methane-thiosulfate, apoptosis using Guava nexin Annexin V binding, protein expression using immunoblot, and P53 activation with phospho-flow cytometry. Results: The median IC 50 for viability and apoptosis for the samples are: NCI standard risk ALL 5.3nM ±3.47, NCI high risk ALL 91.76 nM ±93.42, T-ALL 336.6nM ±147.7, AML 333.6nM ±489, Ph+ALL xenografts 3.8nM ±1.04, and ALL cell lines 18.5nM ±135. Ph+ALL samples, including primary patient, xenograft, and dasatinib (BMS) resistant samples remain significantly sensitive to YM155. For dasatinib sensitive samples, combination therapy suggests an additive effect by isobologram analysis. Immunoblot and RT 2 -PCR Arrays (Qiagen) identify that multiple protein expression are decreased with YM155 treatment. Conclusions: Our data supports the model of the use of YM155 as a treatment for ALL including an added benefit in combination with dasatinib in Ph+ALL. Although initial studies suggested that YM155 is a selective suppressant of survivin, subsequent studies are beginning to identify off target effects. These off target effects may enhance the drugs potential for activating cell death. Finally, we show that screening primary samples with YM155 has the potential to select a target population that is more sensitive to YM155 treatment. Future studies will be designed to develop YM155 as an additional therapeutic agent for pediatric acute lymphoblastic leukemia.
Outcomes to first-line pembrolizumab in patients with non-small cell lung cancer and a PD-L1 tumor proportion score ≥90%.
Authors: Elizabeth Jimenez Aguilar, Biagio Ricciuti, Justin F. Gainor, Mizuki Nishino, Anika E. Adeni, Safiya Subegdjo, Sara Khosrowjerdi, Rachel Peterson, Subba Digumarthy, Corinne Liu, Jennifer L. Sauter, Hira Rizvi, Kathryn Cecilia Arbour, Brett W. Carter, John Heymach, Mehmet Altan, Matthew David Hellmann, Mark M. Awad
Journal: Journal of Clinical Oncology (2019)

9111 Background: In non-small cell lung cancers with a programmed death-ligand 1 (PD-L1) tumor proportion score (TPS) of ≥50%, first-line treatment with the PD-1 inhibitor pembrolizumab improves survival compared to platinum-doublet chemotherapy. Whether higher PD-L1 expression levels within the TPS range of 50-100% predict for even greater benefit to pembrolizumab is currently unknown. Methods: In this multicenter retrospective analysis, we analyzed the impact of PD-L1 expression levels on the overall response rate (ORR), median progression-free survival (mPFS), and median overall survival (mOS) in patients who received commercial pembrolizumab as first-line treatment for advanced NSCLC with a PD-L1 TPS of ≥50%. Results: Among 196 patients with NSCLC treated with first-line pembrolizumab, the ORR was 43.8% (95%CI: 36.8-51.1). At a median follow-up of 12.6 months (95%CI: 11.6-13.7), the mPFS was 6.2 months (95% CI: 4.2-8.2) and the mOS was not reached. The median PD-L1 TPS among patients who experienced a response to pembrolizumab was significantly higher than in patients with stable or progressive disease (TPS 90% vs 70%, P &lt; 0.001), so a TPS cut point of 90% was chosen for further analysis. Baseline clinicopathological characteristics were well-balanced between patients with a PD-L1 TPS of 50-89% vs 90-100%. Compared to patients with a PD-L1 TPS of 50-89% (N = 114, 58.2% of the cohort), patients with a TPS of 90-100% (N = 82, 41.8% of the cohort) had a significantly higher ORR (61.0% versus 31.6%, P &lt; 0.001), a significantly longer mPFS (13.2 versus 3.7 months, HR: 0.48 [95% CI: 0.33-0.71], P &lt; 0.001), and a significantly longer mOS (NR versus 16.0 months, HR: 0.38 [95% CI: 0.21-0.70], P = 0.002). After adjusting for ECOG performance status and smoking history, PD-L1 TPS of 90-100% was significantly associated with improved mPFS (HR: 0.51 [95% CI: 0.34-0.75], P &lt; 0.001) and mOS (HR: 0.38 [95% CI: 0.21-0.70], P = 0.001). Conclusions: Among patients with NSCLC and a PD-L1 TPS ≥50%, clinical outcomes are improved in the subgroup of patients with a PD-L1 TPS of ≥90%. These findings have implications for treatment selection as well as for clinical trial interpretation and design.
The autophagy-activating kinase ULK1 mediates clearance of free α-globin in β-thalassemia
Authors: Christophe Lechauve, Julia Keith, Eugene Khandros, Stephanie Fowler, Kalin Mayberry, Abdullah Freiwan, Christopher S. Thom, Paola Delbini, Emilio Boada Romero, Jingjing Zhang, Irene Motta, Heather Tillman, M. Domenica Cappellini, Mondira Kundu, Mitchell J. Weiss
Journal: Science Translational Medicine (2019)

Rapamycin alleviates β-thalassemia by stimulating ULK1-dependent clearance of toxic free α-globin.
In medical inpatients at nutritional risk, individualized nutritional support reduced adverse clinical outcomes
Authors: Daniel I. Steinberg
Journal: Annals of Internal Medicine (2019)

ACP Journal Club20 August 2019In medical inpatients at nutritional risk, individualized nutritional support reduced adverse clinical outcomesDaniel I. Steinberg, MDDaniel I. Steinberg, MDIcahn School of Medicine at Mount Sinai, New York City, New York, USA (D.I.S.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/ACPJ201908200-018 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationSchuetz P, Fehr R, Baechli V, et al. Individualised nutritional support in medical inpatients at nutritional risk: a randomised clinical trial. Lancet. 2019;393:2312-21. https://pubmed.ncbi.nlm.nih.gov/31030981Clinical Impact RatingsHospitalists: Infectious Disease: Oncology: References1 Bally MR, Blaser Yildirim PZ, Bounoure L, et al. Nutritional support and outcomes in malnourished medical inpatients: a systematic review and meta-analysis. JAMA Intern Med. 2016;176:43-53. [PMID: 26720894] Google Scholar2 Gomes F, Schuetz P, Bounoure L, et al. ESPEN guidelines on nutritional support for polymorbid internal medicine patients. Clin Nutr. 2018;37:336-53. [PMID: 28802519] Google Scholar Author, Article, and Disclosure InformationAffiliations: Icahn School of Medicine at Mount Sinai, New York City, New York, USA (D.I.S.)This article was published at Annals.org on 6 August 2019. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byEffect of Health Education Combined with Dietary Guidance on Nutritional Indicator, Immune Level, and Quality of Life of Patients with Pulmonary Tuberculosis 20 August 2019Volume 171, Issue 4Page: JC18KeywordsChronic kidney diseaseInpatientsIntensive care unitsMortalityNutritionProteinsSaltsStem cell transplantationSurgery ePublished: 20 August 2019 Issue Published: 20 August 2019 Copyright & PermissionsCopyright © 2019 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Small Bowel Healing Detected by Endoscopy in Patients With Crohn’s Disease After Treatment With Antibodies Against Tumor Necrosis Factor
Authors: Kento Takenaka, Toshimitsu Fujii, Kohei Suzuki, Hiromichi Shimizu, Maiko Motobayashi, Shuji Hibiya, Eiko Saito, Masakazu Nagahori, Mamoru Watanabe, Kazuo Ohtsuka
Journal: Clinical Gastroenterology and Hepatology (2019)