tbuckley/cabot-search huggingface dataset:
Combining Genome Change Index (GCI) and liquid biopsy to predict and monitor therapeutic responses.
Authors: Ekkehard Schütz, Julia Beck, Donald Peter Braun, Howard B. Urnovitz, Balazs Dome, Anita Rozsas, Vivek Khemka, Ashish Sangal, Madappa N. Kundranda, Glen J. Weiss
Journal: Journal of Clinical Oncology (2015)

e22020 Background: Genomic instability of tumor cells has been associated with a poor prognosis. However, impaired DNA repair pathways leading to genomic instability are also described to increase tumor sensitivity to DNA damaging agents. A comprehensive Genomic Change Index (GCI) as an indicator of defective DNA repair is proposed as a potential predictor of cytotoxic chemotherapy (chemo) response. Cell-free tumor DNA (cftDNA) has the potential to provide minimally invasive patient specific biomarkers to monitor tumor burden (liquid biopsy). Methods: 18 patients (pts) with advanced esophageal cancer (EC; n = 1), pancreatic ductal adenocarcinomas (PDAC; n = 4), small cell (SCLC; n = 6) and non-small cell lung cancer (NSCLC; n = 7) were included. The chemo regimen for PDAC was gemcitabine & nab-paclitaxel. All other pts received carboplatin/cisplatin, with etoposide (SCLC), etoposide, pemetrexed, or paclitaxel (NSCLC; EC). Chemo-resistant cancers (R) were defined as having progressive disease (PD), chemo-sensitive cancers (S) as stable disease (SD) or partial response (PR) on initial therapy. DNA was extracted either from tumor tissue or pre-treatment plasma samples. Copy-numbers were called from shallow shotgun sequencing (~2.5x107reads, Illumina) in genomic windows of 500kbp and converted into a score based on Gaussian transformations. Somatic mutations were called from targeted sequencing and quantified in follow-up plasma DNA by digital PCR. Results: Significantly lower GCI were detected in R vs. S (p = 0.03). Liquid biopsies were obtained for 6 patients with PD, SD, or PR. Decreasing cftDNA levels were detected as early as 2h after starting the first cycle in a pt who received 6 cycles of chemo showing SD. In the one EC pt (PR) < 6 cftDNA copies/mL plasma were detected at end of treatment. Rising cftDNA concentration were detected in 3 PD pts. One NSCLC pt (PD) showed a slight cftDNA decrease from baseline to cycle 2 with still very high concentrations ( > 1000 cp/mL plasma). Conclusions: As shown for other cancers, GCI may serve as predictor of therapy response to DNA-damaging chemo for the investigated cancer types. Liquid biopsy with cftDNA is a highly specific, sensitive and rapid surveillance biomarker.
Genetic Determinants of Busulfan Clearance and Outcomes in Pediatric Patients Undergoing Hematopoietic Stem Cell Transplantation- Result of a Multicentric Prospective Study on Behalf of the Pediatric Disease Working Party of the European Blood and Marrow Transplantation Group
Authors: Marc Ansari, M A Rezgui, Chakradhara Rao S Uppugunduri, Yves Théoret, Yves Chalandon, LL Dupuis, Tal Schechter, IH Bartelink, Jaap Jan Boelens, Jean-Hugues Dalle, Saba Azarnoush, Petr Sedlacek, Victor A. Lewis, S Mezziani, M-F Vachon, Michel Duval, Martin A. Champagne, Christina Peters, Henrique Bittencourt, Maja Krajinovic
Journal: Blood (2014)
PR Interval Prolongation in a Patient With Infective Endocarditis
Authors: Bhaskar Bhardwaj, Devika Kapuria, Shariq Shamim
Journal: JAMA Internal Medicine (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Addition of dipeptidyl peptidase-4 inhibitors to sulphonylureas and risk of hypoglycaemia: systematic review and meta-analysis
Authors: Francesco Salvo, Nicholas Moore, Mickael Arnaud, Philip Robinson, Emanuel Raschi, Fabrizio De Ponti, Bernard Bégaud, Antoine Pariente
Journal: BMJ (2016)

To quantify the risk of hypoglycaemia associated with the concomitant use of dipeptidyl peptidase-4 (DPP-4) inhibitors and sulphonylureas compared with placebo and sulphonylureas.Systematic review and meta-analysis.Medline, ISI Web of Science, SCOPUS, Cochrane Central Register of Controlled Trials, and clinicaltrial.gov were searched without any language restriction.Placebo controlled randomised trials comprising at least 50 participants with type 2 diabetes treated with DPP-4 inhibitors and sulphonylureas.Risk of bias in each trial was assessed using the Cochrane Collaboration tool. The risk ratio of hypoglycaemia with 95% confidence intervals was computed for each study and then pooled using fixed effect models (Mantel Haenszel method) or random effect models, when appropriate. Subgroup analyses were also performed (eg, dose of DPP-4 inhibitors). The number needed to harm (NNH) was estimated according to treatment duration.10 studies were included, representing a total of 6546 participants (4020 received DPP-4 inhibitors plus sulphonylureas, 2526 placebo plus sulphonylureas). The risk ratio of hypoglycaemia was 1.52 (95% confidence interval 1.29 to 1.80). The NNH was 17 (95% confidence interval 11 to 30) for a treatment duration of six months or less, 15 (9 to 26) for 6.1 to 12 months, and 8 (5 to 15) for more than one year. In subgroup analysis, no difference was found between full and low doses of DPP-4 inhibitors: the risk ratio related to full dose DPP-4 inhibitors was 1.66 (1.34 to 2.06), whereas the increased risk ratio related to low dose DPP-4 inhibitors did not reach statistical significance (1.33, 0.92 to 1.94).Addition of DPP-4 inhibitors to sulphonylurea to treat people with type 2 diabetes is associated with a 50% increased risk of hypoglycaemia and to one excess case of hypoglycaemia for every 17 patients in the first six months of treatment. This highlights the need to respect recommendations for a decrease in sulphonylureas dose when initiating DPP-4 inhibitors and to assess the effectiveness of this risk minimisation strategy.
Size-Dependent Deposition, Translocation, and Microglial Activation of Inhaled Silver Nanoparticles in the Rodent Nose and Brain
Authors: Esther Shin Patchin, Donald S. Anderson, Rona M. Silva, Dale L. Uyeminami, Grace M. Scott, Ting Guo, Laura S. Van Winkle, Kent E. Pinkerton
Journal: Environmental Health Perspectives (2016)

Silver nanoparticles (AgNP) are present in personal, commercial, and industrial products, which are often aerosolized. Current understanding of the deposition, translocation, and health-related impacts of AgNP inhalation is limited.
Clinical phenomenology and neurobiology of cocaine abstinence: a prospective inpatient study
Authors: S L Satel, L H Price, J M Palumbo, C J McDougle, J H Krystal, F Gawin, D S Charney, G R Heninger, H D Kleber
Journal: American Journal of Psychiatry (1991)

This study was undertaken to document symptoms and changes in dopaminergic function emerging after abrupt cessation of cocaine use.After admission, 22 patients with DSM-III-R cocaine dependence were observed drug free for 3 weeks. The patient-rated Ribicoff Abstinence Rating Scale, Symptom Rating Scale, Physical Symptom Scale, Patient Rated Anxiety Scale, Beck Depression Inventory, and visual analogue scales for 16 subjective states were completed daily, and nurses rated 13 patients with the global anxiety and depression items of the Short Clinical Rating Scale. Serial blood samples were obtained three times weekly, and the patients' levels of prolactin, growth hormone (GH), and homovanillic acid (HVA) were measured. Their prolactin and GH values were compared with those of matched normal subjects.A total of 62 subjective symptom variables were evaluated. At baseline, the symptom ratings were mildly elevated. At 3 weeks there were significant decreases from baseline in 28 variables and nearly significant decreases in six additional variables. Nurse-rated anxiety and depression also changed, but in a more variable pattern. There was a small but significant increase from baseline over time in plasma prolactin, but there were no significant changes in GH or HVA. The patients' prolactin and GH values did not differ from those of the normal subjects.These findings suggest that symptoms after inpatient cessation of uncomplicated cocaine addiction are relatively mild and decrease linearly over the first month. Evidence of dysregulated central dopamine function was limited. The findings do not support routine use of pharmacological agents in the inpatient management of such patients.
Decreased blood platelet MAO activity in unmedicated chronic schizophrenic patients
Authors: E F Domino, S S Khanna
Journal: American Journal of Psychiatry (1976)

The authors found lower platelet monoamine oxidase (MAO) activity in 13 unmedicated chronic schizophrenic male patients in comparison to 13 mentally normal control male subjects--a finding that agrees with previous studies showing MAO activity to be low in the platelets of chronic schizophrenic patients. The authors urge that studies exploring endocrine factors and the role of hospitalization be undertaken to attempt to explain this finding.
PWE-327 Epigenetic changes influence extramural vascular invasion in rectal cancer
Authors: HG Jones, N Williams, P Griffiths, G Jenkins, D Harris, J Beynon
Journal: Gut (2015)

<h3>Introduction</h3> Patients with colorectal cancers that have pathological extramural vascular invasion (EMVI+) are known to have a poorer prognosis than those with EMVI – tumours. EMVI status influences the need for neoadjuvant radiotherapy and adjuvant chemotherapy. There is a growing body of evidence to suggest that DNA hypermethylation in specific gene promoter regions (CpG islands) is an important pathway in colorectal cancer tumourigenesis. Previous work by our group has suggested a link between these two processes. The purpose of this work is therefore to explore the relationship between CpG island methylator phenotype (CIMP) grade and EMVI in rectal cancer. <h3>Method</h3> In this study tissue blocks were obtained from 30 consecutive patients with known EMVI+ve tumours and 43 patients with EMVI-ve tumours who did not receive neoadjuvant chemoradiotherapy. Following targeted DNA extraction, CIMP status was determined by methylation specific PCR (MSP) using a two panel approach. MSP is accomplished by performing bisulfite conversion of genomic DNA (Imprint DNA Modification Kit, Sigma Aldrich, USA). This is followed by a PCR reaction with primers for the methylated and unmethylated promoter regions of 8 DNA mismatch repair genes (hMLH, SOCS1, MINT1, ADAMSTS, HAND1, THBD, NEUROG and IGFBP3). The sample is then identified as CIMP-High, Intermediate or Low. <h3>Results</h3> DNA samples from 73 patients were analysed (30 EMVI+ve and 43 EMVI-ve) comprising 55 males and 18 females with median age 70 (range 45–84 years). As expected, the postoperative histopathological tumour (T) and nodal (N) status was more advanced in the EMVI+ tumours (p = 0.007 and &lt;0.001 respectively). A greater proportion of EMVI+ tumours had the CIMP-high and CIMP-intermediate epigenotype compared to EMVI- tumours, which demonstrated mostly the CIMP-low epigenotype (p = 0.002). Of the 8 genes in the CIMP panel, two (IGFBP3 and ADAMSTS) had significantly greater methylation in the EMVI+ve group (p &lt; 0.001 and 0.004 respectively). <h3>Conclusion</h3> These early results have demonstrated that there is a clear relationship between extramural vascular invasion and CIMP status in rectal cancer. The finding warrants further exploration given the drive to utilise methylation biomarker panels to inform treatment decisions in rectal cancer. Further research is underway to explore the molecular mechanisms responsible for this pathway. <h3>Disclosure of interest</h3> None Declared.
Gene conversions in the horse alpha-globin gene complex.
Authors: J B Clegg
Journal: Molecular Biology and Evolution (1987)

The sequences of the linked alpha 2- and alpha 1-globin genes of the equine BI and BII haplotypes are greater than 99% identical within a 1.2-kb region extending from approximately 75 bp upstream of the putative cap site to a point approximately 150 bp 3' to the poly A addition signal. Differences between the alpha 2 and alpha 1 genes that are common to both haplotypes indicate that a major gene conversion occurred approximately 12 Myr ago and that this has been followed by shorter, more localized, conversions. Interhaplotype (allelic) comparisons at the alpha loci suggest that the BI and BII haplotypes have probably existed independently greater than or equal to 0.5 Myr and that the alpha 1 genes may have undergone a recent interchromosomal gene conversion.
Accuracy of First- and Second-Generation Colon Capsules in Endoscopic Detection of Colorectal Polyps: A Systematic Review and Meta-analysis
Authors: Cristiano Spada, Shabana F. Pasha, Seth A. Gross, Jonathan A. Leighton, Felice Schnoll-Sussman, Loredana Correale, Begoña González Suárez, Guido Costamagna, Cesare Hassan
Journal: Clinical Gastroenterology and Hepatology (2016)

Colon capsule endoscopy (CCE) is a noninvasive technique used to explore the colon without sedation or air insufflation. A second-generation capsule was recently developed to improve accuracy of detection, and clinical use has expanded globally. We performed a systematic review and meta-analysis to assess the accuracy of CCE in detecting colorectal polyps.We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and other databases from 1966 through 2015 for studies that compared accuracy of colonoscopy with histologic evaluation with CCE. The risk of bias within each study was ascertained according to Quality Assessment of Diagnostic Accuracy in Systematic Reviews recommendations. Per-patient accuracy values were calculated for polyps, overall and for first-generation (CCE-1) and second-generation (CCE-2) capsules. We analyzed data by using forest plots, the I2 statistic to calculate heterogeneity, and meta-regression analyses.Fourteen studies provided data from 2420 patients (1128 for CCE-1 and 1292 for CCE-2). CCE-2 and CCE-1 detected polyps >6 mm with 86% sensitivity (95% confidence interval [CI], 82%-89%) and 58% sensitivity (95% CI, 44%-70%), respectively, and 88.1% specificity (95% CI, 74.2%-95.0%) and 85.7% specificity (95% CI, 80.2%-90.0%), respectively. CCE-2 and CCE-1 detected polyps >10 mm with 87% sensitivity (95% CI, 81%-91%) and 54% sensitivity (95% CI, 29%-77%), respectively, and 95.3% specificity (95% CI, 91.5%-97.5%) and 97.4% specificity (95% CI, 96.0%-98.3%), respectively. CCE-2 identified all 11 invasive cancers detected by colonoscopy.The sensitivity in detection of polyps >6 mm and >10 mm increased substantially between development of first-generation and second-generation colon capsules. High specificity values for detection of polyps by CCE-2 seem to be achievable with a 10-mm cutoff and in a screening setting.
Case 2-1983
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, Betty U. McNeely, Barry L. Fanburg, Eugene J. Mark
Journal: New England Journal of Medicine (1983)

Presentation of CaseA 33-year-old woman was admitted to the hospital because of dyspnea.She was well until 2 1/2 months earlier, when she began to have a persistent dry cough. A month and a half before admission exertional dyspnea appeared and worsened until she became short of breath on speaking. She became anorectic and experienced myalgia on prolonged exposure to cold air. She went to another hospital, where an x-ray film of the chest showed possible early pneumonia. Tetracycline was prescribed, without improvement. Three weeks before entry she saw another physician, who heard crackling rales over both lungs. An . . .
Adipose-derived Stem Cells Counteract Urethral Stricture Formation in Rats
Authors: Fabio Castiglione, Karel Dewulf, Lukman Hakim, Emmanuel Weyne, Francesco Montorsi, Andrea Russo, Luca Boeri, Trinity J. Bivalacqua, Dirk De Ridder, Steven Joniau, Maarten Albersen, Petter Hedlund
Journal: European Urology (2016)
Assessment of the MSF triage system, separating patients into different wards pending Ebola virus laboratory confirmation, Kailahun, Sierra Leone, July to September 2014
Authors: Florian Vogt, Gabriel Fitzpatrick, Gabriela Patten, Rafael van den Bergh, Kathryn Stinson, Luigi Pandolfi, James Squire, Tom Decroo, Hilde Declerck, Michel Van Herp
Journal: Eurosurveillance (2015)

Prevention of nosocomial Ebola virus (EBOV) infection among patients admitted to an Ebola management centre (EMC) is paramount. Current Médecins Sans Frontières (MSF) guidelines recommend classifying admitted patients at triage into suspect and highly-suspect categories pending laboratory confirmation. We investigated the performance of the MSF triage system to separate patients with subsequent EBOV-positive laboratory test (true-positive admissions) from patients who were initially admitted on clinical grounds but subsequently tested EBOV-negative (false-positive admissions). We calculated standard diagnostic test statistics for triage allocation into suspect or highly-suspect wards (index test) and subsequent positive or negative laboratory results (reference test) among 433 patients admitted into the MSF EMC Kailahun, Sierra Leone, between 1 July and 30 September 2014. 254 (59%) of admissions were classified as highly-suspect, the remaining 179 (41%) as suspect. 276 (64%) were true-positive admissions, leaving 157 (36.3%) false-positive admissions exposed to the risk of nosocomial EBOV infection. The positive predictive value for receiving a positive laboratory result after being allocated to the highly-suspect ward was 76%. The corresponding negative predictive value was 54%. Sensitivity and specificity were 70% and 61%, respectively. Results for accurate patient classification were unconvincing. The current triage system should be changed. Whenever possible, patients should be accommodated in single compartments pending laboratory confirmation. Furthermore, the initial triage step on whether or not to admit a patient in the first place must be improved. What is ultimately needed is a point-of-care EBOV diagnostic test that is reliable, accurate, robust, mobile, affordable, easy to use outside strict biosafety protocols, providing results with quick turnaround time.
Haploidentical transplant for myelodysplastic syndrome: registry-based comparison with identical sibling transplant
Authors: Y Wang, H-X Wang, Y-R Lai, Z-M Sun, D-P Wu, M Jiang, D-H Liu, K-L Xu, Q-F Liu, L Liu, J-B Wang, F Gao, J Ou-Yang, S-J Gao, L-P Xu, X-J Huang
Journal: Leukemia (2016)
Outcome after second stem cell transplantation for relapsed multiple myeloma
Authors: L. Simpson, R. Verma, S. Kumar, M. Lacy, A. Dispenzieri, S. Hayman, S. V. Rajkumar, M. R. Litzow, M. Gertz
Journal: Journal of Clinical Oncology (2007)

8118 Background: Autologous stem cell transplantation (ASCT) improves survival and remains the standard of care for patients with newly diagnosed myeloma considered eligible for transplant. However, ASCT is not curative and patients relapse after a median interval of 24–30 months. While new therapeutic options have become available for relapsed MM, repeat ASCT remains an option especially when previously collected stem cells are available. The outcome of pts going to a second SCT in the relapsed setting has not been studied extensively. Methods: We identified pts with myeloma who received a second SCT from a prospectively maintained database. Planned tandem ASCTs were excluded. 56 pts received a second SCT for relapsed MM, including 11 allogeneic SCTs. Among the 45 second ASCTs, 5 were followed by reduced intensity allogeneic SCT and were analyzed with the allogeneic group. Results: The median age at second ASCT was 60.2 yrs (range, 41.3–74.4) and 27 (68%) were males. The median time to second ASCT from diagnosis, first ASCT and relapse were 47.4 mos (22.8–158.6), 36.3 mos (13.5–129.8) and 7.2 mos (1–32) respectively. Among patients receiving second APBSC, 14 (35%) patients were alive with a median follow up of 10.5 mos (1–45 mos). All patients received melphalan conditioning. The median time to neutrophil engraftment was 15 days and platelet engraftment was 16 days. The median hospitalization was 4 days (range 0–33) and there was one transplant related death in the group. The best response included 13 pts with CR (33%), 4 with VGPR (10%), and 19 with PR (48%). MM has relapsed in 22 (55%) pts with a median PFS of 12.5 mos from second ASCT. The median estimated OS from diagnosis, first ASCT and second ASCT were 100.5 mos, 65.9 mos, and 30.6 mos respectively. Among the 16 pts receiving allogeneic SCT, 8 pts (50%) were alive at analysis with a median PFS and OS from transplant of 17.9 mos and 33.5 mos respectively. Conclusions: Second ASCT as salvage therapy for relapsed MM is a viable approach and has a favorable outcome in this selected group of patients. The toxicity, engraftment kinetics, hospitalization and the response rates are comparable to patients undergoing initial ASCT. Allogeneic SCT with or with out a preceding ASCT results in comparable survival in selected patients with high risk disease. No significant financial relationships to disclose.
Noninvasive Ventilation and Outcomes Among Immunocompromised Patients—Reply
Authors: Virginie Lemiale, Djamel Mokart, Elie Azoulay
Journal: JAMA (2016)

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P-279 Cetuximab as third line treatment of metastatic colorectal carcinoma (mCRC) – 5-year experience from the Institute of Oncology and Radiology of Serbia
Authors: J. Spasic, N. Stanic, M. Ristic, F. Djordjevic, N. Nikolic, V. Nikolic, S. Pupovac, D. Radasavljevic
Journal: Annals of Oncology (2015)