tbuckley/cabot-search huggingface dataset:
Phase II trial of second-line chemotherapy in metastatic pancreas cancer with the combination of oxaliplatin (Ox) and capecitabine (Cp)
Authors: J. Gasent Blesa, V. Alberola Candel, V. Giner Marco, O. Juan, M. Provencio Pulla, C. Llorca, C. Gravalos
Journal: Journal of Clinical Oncology (2009)

e15561 Background: Gemcitabine (G) based chemotherapy is the standard treatment for patients (Pt) with pancreatic cancer. In spite of an active first line chemotherapy, second-line chemotherapy treatment is yet an unmet medical need. Ox and Cp have shown activity in different settings of the disease. We performed this prospective phase II trial to evaluate the efficacy and safety of the combination of Ox and Cp in second-line pancreatic cancer chemotherapy. Methods: From May 2007 to October 2008 15 Pt PS0–2 were included. All Pt had received G 1000 mg/sqm D1, D8 and D15 every 28 days as adjuvant (2 Pt) or first- line therapy (13 Pt). Gender: male/female 8/7, mean age was 64.1 years (47–82), in Pt with elevated CA-19.9 at diagnosis mean CA-19.9 was 337.6 (47–689). Mean time from diagnosis to initiation of second line chemotherapy was 219.3 days (121–457). Metastases (Mt): 11 liver Mt and 8 Pt liver and other Mt sites. Mean number of G cycles received was 6.8 (3–14). All Pt ended G treatment because of disease progression. After progression, all patients received second-line chemotherapy consisting of Ox 100 mg/sqm D1 and Cp 1000 mg/sqm bid D1-D14, every 21 days (XELOX). Results: Median number of cycles of XELOX administered was 4.5 (1–16). Mean CA-19.9 at start of second-line chemotherapy was 714.6 UI/ml (154–1536). Best radiological response was: complete response 1 Pt, stable disease 5 Pt, progressive disease 9 Pt. Median PFS was 124 days (21–480, censored data). Median OS was 301 days (censored data; 150–760). Median survival since the beginning of second line chemotherapy, was 163 days (censored data). In the responding-stable disease patients CA 19.9 level at the beginning of the chemotherapy changed from a median of 241 UI/ml (67–457) to 44.26 (9–86) at the last evaluation with a median decrease of 81.5 %(72–88%). Reported toxicity was the following: Diarrhea G1 in 1 Pt and G2 in 1 Pt, paresthesia G1 in 2 Pt, and hematological toxicity G1 in 1 Pt. Conclusions: As a second-line therapy after standard G treatment, XELOX offers clinical activity that warrants further investigation in this unmet medical need. No significant financial relationships to disclose.
Population pharmacokinetics of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone in cancer patients
Authors: J. Kolesar, R. Brundage, M. Pomplun, Z. Jiang, W. Schelman, D. Alberti, K. Holen, A. Traynor, P. Ivy, G. Wilding
Journal: Journal of Clinical Oncology (2009)

2508 Background: 3-Aminopyridine-2-carboxaldehyde thiosemicarbazone (3AP) is an inhibitor of ribonucletoide reductatse with activity in hematological malignancies as well as melanoma and prostate cancer. This study describes the population PK of 3AP and the relationship between 3AP disposition and patient covariates. Methods: 40 pts with advanced cancer from two phase 1 studies were included in the PK model building. Pts received 3AP 25–105 mg/m2 IV on day 1. 3AP plasma and erythrocyte levels were sampled at 10 timepoints over a 24-hour period and measured by a validated HPLC method. Data were analyzed by a nonlinear mixed- effects modeling approach with NONMEM system Version V. Xpose10 and S-PLUS were used for goodness-of-fit assessment and model evaluation to obtain clearance (CL), volume of distribution (V) for compartment (C) 1, plasma (V1); V for C2, erythrocytes (V2); and V for C3 (V3). 15 covariates were evaluated, including: weight, BSA, gender, PS, age, ABCB1[C1236T, G2667T, C3436T] genotypes, toxicity, concurrent chemotherapy [irinotecan, doxorubicin], response and number of cycles administered. Normal renal and hepatic function were required for study entry and were not included as covariates. Response was assessed after 2 cycles of therapy. Results: 3AP PK were described as a 3-compartment model with first-order elimination. Estimated paramaters were: V1 =5.68 L/m2 (95%CI 4.3–7.1); V2=18.9 L/m2 (95%CI 14.6–23.2); V3= 40.0 L/m2 (95%CI 23.8–55.4); CL 25.4 L/hr/m2 (95%CI 22.4–28.4). Gender was associated with V; women had a lower V2 (p&lt;0.05). This may be related to a lower hemoglobin in women. The number of cycles administered was associated with decreased CL; those with decreased CL received less than 2 cycles before going off study. Conclusions: Women had a lower V2 than men and pts with decreased CL received less than 2 cycles of therapy, suggesting PK may be helpful in individualizing dosing. ABCB1 genotypes and concurrent irinotecan or doxorubicin do not influence 3AP disposition. Supported by: U01CA062491 “Early Clinical Trials of Anti-Cancer Agents with Phase I Emphasis” NCI; CTEP TRI Funding 24XS090, and 1ULRR025011 Clinical and Translational Science Award of the National Center for Research Resources, NIH. No significant financial relationships to disclose.
Assessment of palpitations
Authors: Chris P Gale, A John Camm
Journal: BMJ (2016)

#### What you need to know

Palpitations are a symptom characterised by awareness of the heartbeat, often described as a strong, skipping, fluttering, racing, pounding, thudding, or jumping sensation in the chest. Some patients describe a sensation of having to cough or their breath being taken away. However, patients occasionally mean something other than palpitations, such as chest discomfort, which may need a different line of investigation.

Most palpitations are benign (being atrial, nodal, or ventricular extrasystoles1), and probably less than half of cases are due to heart rhythm abnormalities or arrhythmias. Anxiety is a common cause of palpitations; up to a third have psychological causes.2 Infrequently, however, they may be incapacitating and can lead to syncope or sudden cardiac death. Equally, a large proportion of patients with palpitations (67% in one study3) are diagnosed as having panic, stress, or anxiety when, instead, they have an …
Impact Of Umbilical Cord Unit Banking Conditions On Clinical Outcomes In Double Cord Transplant Recipients
Authors: Sarah Nikiforow, Shuli Li, Erin Coughlin, Emma Breault, Deborah Liney, Grace Kao, Karen Snow, Richard L. Haspel, Joanne Kurtzberg, Andromachi Scaradavou, Elizabeth J Shpall, Brett Glotzbecker, Philippe Armand, John Koreth, Vincent T. Ho, Edwin P. Alyea, Jerome Ritz, Robert J. Soiffer, Joseph H. Antin, Bimalangshu R. Dey, Steven McAfee, Yi-Bin Chen, Thomas R. Spitzer, David Avigan, Corey S. Cutler, Karen K. Ballen
Journal: Blood (2013)
Cabazitaxel Versus Topotecan in Patients with Small-Cell Lung Cancer with Progressive Disease During or After First-Line Platinum-Based Chemotherapy
Authors: Tracey L. Evans, Byoung Chul Cho, Katalin Udud, Juergen R. Fischer, Frances A. Shepherd, Pablo Martinez, Rodryg Ramlau, Konstantinos N. Syrigos, Liji Shen, Mustapha Chadjaa, Martin Wolf
Journal: Journal of Thoracic Oncology (2015)
Daratumumab monotherapy in patients with treatment-refractory multiple myeloma (SIRIUS): an open-label, randomised, phase 2 trial
Authors: Sagar Lonial, Brendan M Weiss, Saad Z Usmani, Seema Singhal, Ajai Chari, Nizar J Bahlis, Andrew Belch, Amrita Krishnan, Robert A Vescio, Maria Victoria Mateos, Amitabha Mazumder, Robert Z Orlowski, Heather J Sutherland, Joan Bladé, Emma C Scott, Albert Oriol, Jesus Berdeja, Mecide Gharibo, Don A Stevens, Richard LeBlanc, Michael Sebag, Natalie Callander, Andrzej Jakubowiak, Darrell White, Javier de la Rubia, Paul G Richardson, Steen Lisby, Huaibao Feng, Clarissa M Uhlar, Imran Khan, Tahamtan Ahmadi, Peter M Voorhees
Journal: The Lancet (2016)
Abstract 18670: Histological Analysis of Neointimal Characteristics in Drug-eluting and Bare Metal Stents Implanted in Human Coronary Arteries: Autopsy Study
Authors: Masataka Nakano, Fumiyuki Otsuka, Aloke V Finn, Elena R Ladich, Frank D Kolodgie, Renu Virmani
Journal: Circulation (2012)

Background: The histological characteristics of neointima in DES and BMS has not been fully investigated. Methods and Results: From our autopsy registry, 15 coronary segments with DES showing restenosis (&gt;75% cross-sectional narrowing within the stent) and 15 restenotic BMS lesions with matched implant duration were selected. The coronary segments were processed at 3-4 mm intervals and assessed histologically at the section with the severest narrowing. The implant duration were similar in DES (361 days) and BMS (330 days). Atherosclerotic change within stent (neoatherosclerosis) was seen in 5 of DES lesions (33%) and 1 of BMS lesions (7%). Cells in neointima around lumen mainly consisted of SMC where DES showed lower cellularity than BMS (904 vs. 1409 cells/mm 2 , p=0.014). However, α-SMA positive area were equivalent in both stent groups (DES 9.5 %, BMS 10.5 %, p=0.66), suggesting the phenotype difference of SMC with varying levels of actin expression. Percent area occupied by collagen was lower in DES (22.8%) than in BMS (33.2%) (p=0.14) with the latter showing more mature feature (Collagen score: DES 1.0 vs. BMS 1.4, p=0.022). On the contrary, % area of proteoglycan-rich ECM was predominate in DES (69.3%) as compared to BMS (48.0%) (p=0.032). Macrophage and T-lymphocyte infiltration was observed in both stent groups and frequently accompanied by microcapillaries. The number of macrophages identified in BMS (224 /mm 2 ) was slightly higher than in DES (316 /mm 2 ) (p=0.15). T-lymphocyte counts were significantly higher in BMS (312 /mm 2 ) than in BMS (545 /mm 2 ) (p=0.047). The temporal changes of parameters above are summarized in the figure. Conclusion: The histopathological difference of neointimal characteristics in DES and BMS might be associated with the incidence of late events attributed to neoatherosclerosis or thrombosis. Targeting for modification of SMC phenotype or ECM after stenting will be of use for newer DES to improve long-term clinical outcome.
Wider group of health professionals should be located in emergency departments, college says
Authors: Gareth Iacobucci
Journal: BMJ (2016)

The Royal College of Emergency Medicine has urged the government to co-locate general practitioners, psychiatrists, mental health teams, and community pharmacists in all hospital emergency departments in England to help ease current pressures.

Clifford Mann, chairman of the college, is to hold talks with the Department of Health this week to discuss plans to pilot the “hub” model across the country, after record attendances were reported at emergency departments in 2015.

Some emergency departments in England already have co-located GPs to triage patients and to ensure the …
Abstract 16611: Hemodynamic Goal Directed Therapy in Comatose Survivors of Cardiac Arrest
Authors: Sajid Kadir, Shiva Shashidharan, Nishit Vaghasia, Patrick Coppler, Jonathan Janiczek, Monesh Sheth, Vishal Patel, Michael Pinsky, Cameron Dezfulian
Journal: Circulation (2014)

Introduction:  Evidence based hemodynamic goal directed therapy guidelines do not currently exist for comatose cardiac arrest survivors. No studies have examined dedicated resuscitation protocols with cardiac output and systemic vascular tone being employed to meet hemodynamic goals   Hypothesis:  Targeting first cardiac index (CI)>2, then MAP>80 mmHg and evaluating volume responsiveness before inotropes or vasopressors use will yield improved resuscitation   Methods:  We matched 22/31 comatose post-arrest protocol patients to historical controls with similar degrees of shock based on need for vasopressors, initial lactate within 2.5 mmol/L and initial MAP within 10 mm Hg. Patients were age matched as ≤60 or >60 years old. In protocol patients, fluid was administered before inotropes or vasopressors using stroke volume variation >13% or response to passive leg raise/ fluid challenge to predict fluid responsiveness. In the historical controls MAP>65 mm Hg was generally targeted without any guideline as to how this goal was achieved. Differences in resuscitation strategy were assessed by examining the fluid intake and output, MAP and cumulative vasopressor index (CVI) for the first 6h after ICU admission. Lactate clearance and change in Creatinine over 24 hours was examined. Statistical analysis was done using Student’s t-test and repeated measures ANOVA.   Results:  The protocol patients achieved higher hourly MAP (p=0.04) over the first 6 hours. The hourly administration of fluid in the ICU was greater earlier on in the control patients compared to the protocol patients (p=0.03) with 6 hour average intake being similar. Hourly urine output in the first 6 hours was higher in the protocol group (p 0.045). Hourly CVI over the first six hours was higher in the control group (p=0.03). Our protocol patients showed improved change in creatinine over 24 hours (p= 0.03). Both groups had similar lactate clearance   Conclusions:  Protocolized post-arrest resuscitation resulted higher MAP, lower CVI, higher hourly urine output and differing fluid intake pattern over six hours post ICU admission, with improved creatinine clearance and similar lactate clearance. Whether this translates into improvement in clinical outcomes requires further investigation.
IL-6 promotes an increase in human mast cell numbers and reactivity through suppression of suppressor of cytokine signaling 3
Authors: Avanti Desai, Mi-Yeon Jung, Ana Olivera, Alasdair M. Gilfillan, Calman Prussin, Arnold S. Kirshenbaum, Michael A. Beaven, Dean D. Metcalfe
Journal: Journal of Allergy and Clinical Immunology (2016)
Safe allogeneic hematopoietic stem cell transplantation for renal cell carcinoma: Novel approach using selective depletion of alloreactive donor T cells
Authors: L. Hanak, J. Michalek, E. Matejkova, V. Foltankova, L. Lauerova, E. Vitetta
Journal: Journal of Clinical Oncology (2008)

19509 Background: A major challenge in the field of hematopoietic stem cell transplantation (HSCT) is to prevent the alloreactivity of donor T-cells which leads to acute graft-versus-host (GVH) disease while preserving a graft-versus-tumor (GVT) effect. Methods: renal carcinoma cells cells and peripheral blood mononuclear cells (PBMC) of ten patients were used with healthy donor PBMC in a primary mixed leukocyte reaction (MLR) where non-cancer irradiated PBMC from renal cell carcinoma patients served as stimulators and GVH target. GVH-reactive donor T cells were selectively depleted with anti-CD25 IT. Allodepleted donor T cells were then repeatedly stimulated using irradiated shortly cultured renal cell carcinoma tumor cells from the same cancer patient (to simulate GVT effect) or using irradiated PBMC from the same patient (to simulate GVH effect). HLA class I was monitored on the surface of renal cell carcinoma as well. Results: Long-term culture of renal cell carcinoma was succesful in 8 out of ten tumor cell cultures and reached 80–280 million tumor cells in 6–17 weeks. Selective depletion of alloreactive donor T-cells with anti-CD25 IT led to more than 2log depletion (99,2 - 100%, median 99,8%). GVT effect of donor T-cells was preserved (1,8% of donor T cells were GVT-reactive) while GVH reactivation of donor cells was negligible even after 3 rounds of repeated stimulation with patient’s non-tumor PBMC. Immunohistochemical staining for surface HLA class I revealed partial or complete loss of HLA antigens (50 - 100 %) in 4 cultures during 2–6 months of cultivation, 3 cultures remained stable and one culture was negative from the beginning. Conclusions: It is possible to selectively deplete donor alloreactive T-cells with anti-CD25 IT minimizing or eliminating the risk of GVH disease. This strategy eliminates alloreactivity and preserves GVT reactivity in patients with renal cell carcinoma. Thus the allogeneic hematopoietic stem cell transplantation using selectively allodepleted donor T cells seems to be a valuable alternative to recent treatment strategies in patients with renal cell carcinoma.Supported by the Ministry of Education of the Czech Republic, NPVII-2B06058. No significant financial relationships to disclose.
Lonidamine significantly increases the activity of epirubicin in patients with advanced breast cancer: results from a multicenter prospective randomized trial.
Authors: L Dogliotti, A Berruti, T Buniva, P Zola, M G Baù, A Farris, M G Sarobba, A Bottini, P Alquati, F Deltetto, P Gosso, C Monzeglio, G Moro, M Sussio, D Perroni
Journal: Journal of Clinical Oncology (1996)

PURPOSE Some evidence in vitro and in vivo shows that lonidamine (LND) can positively modulate the activity of doxorubicin and epirubicin (EPI). On this basis, a multicenter prospective randomized trial was performed in patients with advanced breast cancer (BC) to determine if the addition of LND to EPI could increase the response rate of EPI alone. PATIENTS AND METHODS From May 1991 to May 1993, 207 patients were enrolled onto this study and randomized to receive intravenous (IV) EPI (60 mg/m2 on days 1 and 2) alone or with LND (600 mg orally daily). EPI administration was repeated every 21 days until tumor progression or for a maximum of eight cycles. LND was administered continuously until chemotherapy withdrawal. RESULTS Response rate was significantly superior for the EPI plus LND scheme compared with the single-agent EPI either considering assessable patients (60.0% v 39.8%; P &lt; .01) or including all registered patients according to an intention-to-treat analysis (55.3% v 37.5%; P &lt; .02). The distribution of the response rate according to the site of disease did not show any significant difference between the treatment arms, except for the patient subgroup with liver metastases in which the combination EPI plus LND resulted in a significant improvement of responses than EPI alone. Toxicity was moderate, and except for myalgia, no adjunctive side effects were observed in the EPI plus LND arm. Overall survival and time to progression were similar in both groups. CONCLUSION This study confirms in vivo that the administration of EPI is enhanced by the concomitant LND administration.
Driving Thoughts
Authors: Robert E Johnstone
Journal: JAMA (2009)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Opioid Prescribing After Nonfatal Overdose and Association With Repeated Overdose
Authors: Marc R. Larochelle, Jane M. Liebschutz, Fang Zhang, Dennis Ross-Degnan, J. Frank Wharam
Journal: Annals of Internal Medicine (2015)

Background: Nonfatal opioid overdose is an opportunity to identify and treat substance use disorders, but treatment patterns after the overdose are unknown. Objective: To determine prescribed opioid dosage after an opioid overdose and its association with repeated overdose. Design: Retrospective cohort study. Setting: A large U.S. health insurer. Participants: 2848 commercially insured patients aged 18 to 64 years who had a nonfatal opioid overdose during long-term opioid therapy for noncancer pain between May 2000 and December 2012. Measurements: Nonfatal opioid overdose was identified using International Classification of Diseases, Ninth Revision, Clinical Modification, codes from emergency department or inpatient claims. The primary outcome was daily morphine-equivalent dosage (MED) of opioids dispensed from 60 days before to up to 730 days after the index overdose. We categorized dosages as large (≥100 mg MED), moderate (50 to <100 mg MED), low (<50 mg MED), or none (0 mg MED). Secondary outcomes included time to repeated overdose stratified by daily dosage as a time-varying covariate. Results: Over a median follow-up of 299 days, opioids were dispensed to 91% of patients after an overdose. Seven percent of patients (n = 212) had a repeated opioid overdose. At 2 years, the cumulative incidence of repeated overdose was 17% (95% CI, 14% to 20%) for patients receiving high dosages of opioids after the index overdose, 15% (CI, 10% to 21%) for those receiving moderate dosages, 9% (CI, 6% to 14%) for those receiving low dosages, and 8% (CI, 6% to 11%) for those receiving no opioids. Limitation: The cohort was limited to commercially insured adults. Conclusion: Almost all patients continue to receive prescription opioids after an overdose. Opioid discontinuation after overdose is associated with lower risk for repeated overdose. Primary Funding Source: Health Resources and Services Administration.
Efficacy of zoledronic acid versus placebo on biochemical markers of bone metabolism in patients with breast cancer metastatic to bone
Authors: N. Kohno, K. Aogi, H. Minami, S. Takashima
Journal: Journal of Clinical Oncology (2006)

10559 Background: Zoledronic acid reduces the levels of bone markers and the risk of skeletal complications in patients with bone metastases. Recently, a correlation between the levels of biochemical markers of bone metabolism and the risk of clinical complications (ie, skeletal complications, disease progression, and death) in patients with bone metastases has been reported. The effect of zoledronic acid on bone marker levels was assessed in patients with bone metastases from breast cancer in a multicenter randomized trial conducted in Japan. Methods: Women with bone metastases secondary to breast cancer (N = 228) were randomized to 4 mg zoledronic acid (n = 114) or placebo (n = 114) every 4 weeks for 1 year. Levels of urinary N-telopeptide (NTX), a sensitive marker of bone resorption, were measured at baseline and regularly throughout the study. Results: The table shows that zoledronic acid reduced NTX levels in patients compared with placebo. Patients treated with zoledronic acid had a mean decrease of 61% from baseline NTX levels at week 2. This decrease was maintained throughout the study in this treatment group and was 54% at week 52. In contrast, patients in the placebo group had a mean increase of 27% from baseline NTX levels at week 2, and levels of NTX continued to increase during the study, reaching 146% above baseline at week 52. Conclusions: This analysis shows that treatment with zoledronic acid reduced NTX levels in patients with bone metastases from breast cancer compared with placebo. These results are consistent with published reports in patients with prostate or lung cancer and are consistent with the significant reduction in skeletal morbidity observed in this trial in breast cancer patients. Zoledronic acid demonstrated a 39% reduction in skeletal morbidity in this patient population. [Table: see text] No significant financial relationships to disclose.
A Phase Ib study of neoadjuvant immune biomarker modulation with cetuximab and motolimod in head and neck cancer (HNC)
Authors: Robert L Ferris, Benjamin A Kansy, Sandra Gibson, Raghvendra M Srivastava, James Bryan, Robert M Hershberg
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts HNC is immunosuppressive, with low absolute lymphocyte counts, impaired activity of effectors such as natural killer cells (NK), and poor antigen-presenting function. The anti-EGFR monoclonal antibody cetuximab (CTX) prolongs survival in HNC, but only in a subset of patients. The