tbuckley/cabot-search huggingface dataset:
Variations of the ER, PR, and HER2 expression status according to operation day in breast cancer patients.
Authors: Zafer Arik, Sercan Aksoy, Mehmet Ali Nahit Sendur, Sebnem Yaman, Kadri Altundag
Journal: Journal of Clinical Oncology (2012)

e11009 Background: Estrogen receptor (ER), progesteron receptor (PR) and HER-2 are prognostic and predictive markers in the management of breast cancer treatment. Delay in fixation of the specimens may reduce the ability to detect breast cancer biomarkers and resulting in false negative immunhistochemical results. Handling of specimens from operation rooms to pathology laboratories may delay sometimes, especially Fridays. We hypothesized that ER, PR and HER-2 expression status may change according to the day of surgical procedure. Methods: Patients who operated between 2005 and 2010 for breast cancer in our Hospital were analyzed retrospectively. Consecutive 462 patients who had breast conserving surgery and modified radical mastectomy were included into the study. Patient’s demographics data and tumor characteristics and surgical procedure day were obtained from medical charts. Results: The mean age of the study population was 50±11 years. There were not differences between the T, N, M stage and age of patients according to operation day. ER, PR, HER-2 expressions were similar in Monday, Tuesday, Wednesday and Thursday. So we grouped the patients operated on Friday and others. Among the patients, 121 (26%) were operated on Friday. ER and PR negativity was higher on Friday procedures than the other weekdays (40% vs 23.2%; p=0.008 and 35.7% vs 27.9%; p=0.08, respectively). HER-2 positivity on Friday was significantly higher than the other weekdays (41.9% versus 23.4%; P=0.005). Conclusions: Cold ischemic time is the interval between removal of the tissue and placement in the tissue fixative. ER and PR are thermolabile proteins whose levels of expression are altered by prolonged cold ischemic time. Studies have shown delays in handling of breast cancer tissues affect biomarkers positivity and some tumors were classified falsely as negative. Specimens obtained on Friday may have more delaying for handling; therefore may have more hormon receptor negative results. In our study we have shown that ER negativity and HER-2 positivity are significantly higher on patients who were operated on Friday. Our study showed that handling of the specimen to the pathology laboratories is crucial and affect the treatment decisions.
Breastfeeding and Future Maternal Health—No Causal Evidence
Authors: Veronica Velle-Forbord, Maria O. Underdal, Eszter Vanky
Journal: JAMA Internal Medicine (2018)

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
Comparative assessment of the efficacy of primary and secondary corneal endothelial dystrophy treatment by isolated descemetorhexis and accelerated collagen crosslinking method
Authors: Sergey Yu. Astakhov, Астахов Сергей Юрьевич, Inna A. Riks, Рикс Инна Александровна, Sanasar S. Papanyan, Папанян Санасар Сурикович, Sergey A. Novikov, Новиков Сергей Александрович, Georgiy Z. Dzhaliashvili, Джалиашвили Георгий Зурабович, Irina B. Bondareva, Бондарева Ирина Борисовна
Journal: Ophthalmology (2018)
Longterm survival benefit of neoadjuvant liposomal doxorubicin, docetaxel, and trastuzumab in HER2-overexpressing breast cancer: A retrospective and multicenter analysis.
Authors: Christine Brunner, Verena Wieser, Thomas Jaeger, Alois Lang, Herbert Stoger, Christoph Suppan, Georg Goebel, Afschin Soleiman, Daniel Egle, Christian Marth, Michael Hubalek
Journal: Journal of Clinical Oncology (2018)

e12653 Background: Concurrent therapy of trastuzumab, anthracycline and taxane for the neoadjuvant treatment of breast cancer (BC) resulted in an improved rate of pathological complete response (pCR). We have previously shown that concomitant chemotherapy with liposomal doxorubicin and Docetaxel in combination with trastuzumab resulted in high pCR rates in HER2-positive breast cancer. At the same time the combination showed acceptable toxicities and low cardiac events. In this follow-up of a retrospective analysis we report data on disease-free und overall survival. Methods: 83 patients were treated in 3 oncologic centers in Austria. All of them received neoadjuvant liposomal doxorubicin (50 - 60 mg/m²), docetaxel (75 mg/m²) and trastuzumab over the course of 6 cycles for HER2 positive stage I-III breast cancer. None of these patients showed cardiovascular disease and had a left ventricular ejection fraction (LVEF) ≥ 55% at baseline. All patients underwent surgery after neoadjuvant chemotherapy. Median follow up was 6.3 years. Results: Median age of the patients was 50 years. After 6 cycles of treatment the overall pCR rate was 47%. No patient progressed during treatment. None of the patients suffered symptomatic heart failure. After a median follow-up of 6.3 years, 11 (13.3%) of all patients experienced a recurrence and 90,4% were still alive. Presence of residual disease in breast and/or node after neoadjuvant chemotherapy was a strong and significant predictor of disease free survival (DFS). 5 year DFS was 87% in 44 patients with residual disease in breast or nodes versus 100% in 39 patients with pCR (p = .001) 5-year OS was 93% (n = 41) in patients with residual disease versus 100% (n = 39) in pCR group (p = 0.24). Conclusions: Patients with HER2 positive breast cancer treated with neoadjuvant liposomal doxorubin, docetaxel and trastuzumab have an excellent long term survival. The pCR after this treatment regimen was associated with an outstanding prognosis for patients. To evaluate the long term survival effect of liposomal doxorubicin, docetaxel and trastuzumab in combination with novel agents like pertuzumab, further studies are necessary.
Targeting FLT3 in acute myeloid leukemia using ligand-based chimeric antigen receptor-engineered T cells
Authors: Ying Wang, Yingxi Xu, Saisai Li, Jia Liu, Yanyan Xing, Haiyan Xing, Zheng Tian, Kejing Tang, Qing Rao, Min Wang, Jianxiang Wang
Journal: Journal of Hematology & Oncology (2018)

Chimeric antigen receptor-engineered T (CAR-T) cells have extraordinary effect in treating lymphoblastic leukemia. However, treatment of acute myeloid leukemia (AML) using CAR-T cells remains limited to date. Leukemogenesis always relates with the abnormalities of cytogenetics, and nearly one third of AML patients have activating mutations in Fms-like tyrosine kinase 3 (FLT3) which reminded poor prognosis. Considering the FLT3 expressed in AML patients' blast cells, it may be a new candidate target for CAR-T therapy to treat FLT3+ AML, especially patients harboring FLT3-ITD mutation. The FLT3L CAR-T using FLT3 ligand as recognizing domain was constructed. The specific cytotoxicity against FLT3+ leukemia cell lines, primary AML cells, and normal hematopoietic progenitor stem cells (HPSCs) in vitro were evaluated. In addition, FLT3+ AML mouse model was used to assess the effect of FLT3L CAR-T therapy in vivo. FLT3L CAR-T cells could specifically kill FLT3+ leukemia cell lines and AML patients' bone marrow mononuclear cells in vitro (with or without FLT3 mutation) and have more potent cytotoxicity to FLT3-ITD cells. In a human FLT3+ AML xenograft mouse model, FLT3L CAR-T cells could significantly prolong the survival of mice. Furthermore, it was found that FLT3L CAR-T cells could activate the FLT3/ERK signaling pathway of FLT3+ leukemia cells with wild-type FLT3; meanwhile, it had no inhibitory effects on the colony formation of CD34+ stem cells derived from normal human umbilical cord blood. The ligand-based FLT3L CAR-T cells could be a promising strategy for FLT3+ AML treatment, especially those carried FLT3 mutation.
Frequency of Germline Mutations in Cancer Susceptibility Genes in Malignant Mesothelioma
Authors: Vasiliki Panou, Meghana Gadiraju, Arthur Wolin, Caroline M. Weipert, Emily Skarda, Aliya N. Husain, Jyoti D. Patel, Buerkley Rose, Shannon R. Zhang, Madison Weatherly, Viswateja Nelakuditi, Amy Knight Johnson, Maria Helgeson, David Fischer, Arpita Desai, Nanna Sulai, Lauren Ritterhouse, Oluf D. Røe, Kiran K. Turaga, Dezheng Huo, Jeremy Segal, Sabah Kadri, Zejuan Li, Hedy L. Kindler, Jane E. Churpek
Journal: Journal of Clinical Oncology (2018)

Purpose The aim of the current study was to determine the prevalence and clinical predictors of germline cancer susceptibility mutations in patients with malignant mesothelioma (MM). Methods We performed targeted capture and next-generation sequencing of 85 cancer susceptibility genes on germline DNA from 198 patients with pleural, peritoneal, and tunica vaginalis MM. Results Twenty-four germline mutations were identified in 13 genes in 23 (12%) of 198 patients. BAP1 mutations were the most common (n = 6; 25%). The remaining were in genes involved in DNA damage sensing and repair (n = 14), oxygen sensing (n = 2), endosome trafficking (n = 1), and cell growth (n = 1). Pleural site (odds ratio [OR], 0.23; 95% CI, 0.10 to 0.58; P &lt; .01), asbestos exposure (OR, 0.28; 95% CI, 0.11 to 0.72; P &lt; .01), and older age (OR, 0.95; 95% CI, 0.92 to 0.99; P = .01) were associated with decreased odds of carrying a germline mutation, whereas having a second cancer diagnosis (OR, 3.33; 95% CI, 1.22 to 9.07; P = .02) significantly increased the odds. The odds of carrying a mutation in BAP1 (OR, 1,658; 95% CI, 199 to 76,224; P &lt; .001), BRCA2 (OR, 5; 95% CI, 1.0 to 14.7; P = .03), CDKN2A (OR, 53; 95% CI, 6 to 249; P &lt; .001), TMEM127 (OR, 88; 95% CI, 1.7 to 1,105; P = .01), VHL (OR, 51; 95% CI, 1.1 to 453; P = .02), and WT1 (OR, 20; 95% CI, 0.5 to 135; P = .049) were significantly higher in MM cases than in a noncancer control population. Tumor sequencing identified mutations in a homologous recombination pathway gene in 52% (n = 29 of 54). Conclusion A significant proportion of patients with MM carry germline mutations in cancer susceptibility genes, especially those with peritoneal MM, minimal asbestos exposure, young age, and a second cancer diagnosis. These data support clinical germline genetic testing for patients with MM and provide a rationale for additional investigation of the homologous recombination pathway in MM.
Home Monitoring Service Improves Mean Arterial Pressure in Patients with Essential Hypertension: A Randomized Controlled Trial
Authors: Mary A. M. Rogers, David Small, Debra A. Buchan, Carl A. Butch, Christine M. Stewart, Barbara E. Krenzer, Harold L. Husovsky
Journal: Circulation (2001)

P99     While the use of telecommunication systems in medicine has  been increasing, there have been few trials to assess the efficacy of  such technology for improving blood pressure (BP) in patients with  essential hypertension. A randomized controlled trial (RCT) was  conducted to assess the efficacy of an home monitoring service which  utilized automatic transmission of BP data over telephone lines,  conversion of the data into report form by computer, and facsimile  transmission of the form weekly to physicians and patients. One hundred  and eleven patients were randomized to either home service or usual  care and followed for a median of 11 weeks. The primary endpoint was  change in mean arterial pressure (MAP) which was assessed using a  24-hour ambulatory blood pressure monitoring (ABPM) device at both  baseline and exit. There was a 3.0 mm Hg decline in MAP from baseline  to exit for patients using the home service and a 1.5 mm Hg increase in  MAP for patients receiving usual care (p=0.0139). There was a 2.1 mm Hg  decline in average diastolic BP (DBP) in the home service group and a  2.3 mm Hg increase in the usual care group (p=0.0120). In addition, the  proportion of 24-hour DBP readings above target levels decreased by  6.8% in patients receiving home service, but increased by 6.2% in  patients receiving usual care (p=0.0057). The reduction in BP was  evident for both genders, for each ethnic group, and for both younger  and older patients. For African-Americans, MAP declined by 9.6 mm Hg  for those receiving the home service and increased by 5.25 mm Hg for  those receiving usual care (p=0.0469). The difference in MAP between  the two study arms remained significant after adjustment for patient  characteristics. The decrease in BP for home service was, in part, due  to more frequent changes in dose and/or type of medication during the  course of the trial. This was the first RCT of a home BP service that  did not rely on patient self-report and which used 24-hour ABPM at  baseline and at exit to assess usual BP. It is recommended that  patients with essential hypertension, who are in the process of  evaluation for a change in antihypertensive therapy, utilize a home  monitoring service.
Chronic traumatic ankle and foot osteomyelitis: a nationwide case-control study
Authors: Maryam Hosseini, Mostafa Allami, Mohammadreza Soroush, Fateme Babaha, Javad Minooeefar, Davood Rahimpoor
Journal: Military Medical Research (2018)

Osteomyelitis (OM) is an atypical consequence of ankle-foot trauma which is associated with long-term mental and physical morbidity and persistent pain. This study aimed to assess the health status of OM patients with war-related ankle-foot injuries. A total of 1129 veterans with ankle-foot injuries participated in a case-control study (2014–2016). Thirty patients with chronic OM of the ankle-foot were compared with 90 non-OM participants as the control group. Quality of life (QOL), life satisfaction and the ability to perform basic and instrumental activities of daily living were measured using the following questionnaires: short-form health survey (SF-36), satisfaction with life scale (SWLS), activity of daily living (ADL) and instrumental activity of daily living (IADL), respectively. OM patients were categorized according to their risk factors as A, B and C hosts using a modified version of the Cierny and Mader classification system. The one sample t-test, 2-independent sample t-test, ANOVA, Pearson correlation coefficient and multiple linear regression analyses were applied to analyze the data. Ankle-foot pain leading to surgery (P < 0.001) and orthosis usage (P = 0.039) were more common in OM patients. There was no significant difference between the two groups in the prevalence of pulmonary and cardiovascular diseases or kidney failure and other related diseases. OM patients showed a significantly lower level of mental health compared to non-OM respondents (P = 0.025). Approximately, 70.0% of ankle-foot injured veterans were dissatisfied with their life, and there was no difference between the two groups (P > 0.05). Mobility was significantly lower in the OM patients than in the control group (P = 0.023). Life satisfaction (P = 0.001) and the ability to perform daily activities were the determinants for poor physical (P = 0.018) and mental (P = 0.012) health-related quality of life. According to the Cierny and Mader classification system, they were all included in the type C host classification, with one major and/or three or more minor risk factors. A low level of quality and satisfaction of life and ability to perform activities of daily living were observed in OM patients with war-related ankle-foot injuries. Surgeries of the ankle and foot due to pain were much more common in OM patients than in non-OM participants. Since all the participants were classified as the C-host, health policy planning seems to be necessary.
An open label, pilot study of veliparib (ABT-888) and lapatinib in patients with metastatic, triple negative (ER, PR, and HER-2 negative) breast cancer.
Authors: Erica Michelle Stringer-Reasor, Eddy Shih-Hsin Yang, Jori E. May, Valerie Caterinicchia, Yufeng Li, Andres Forero-Torres
Journal: Journal of Clinical Oncology (2018)

1095 Background: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer (BC), often resistant to standard of care therapies. We previously showed an induced synthetic lethal interaction with combined EGFR (epidermal growth factor receptor) and PARP (Poly (ADP-ribose)-polymerase) inhibition in TNBC cells. Therefore, we tested a pilot clinical trial using lapatinib and veliparib in patients with locally advanced unresectable or metastatic TNBC. Here we report safety results and clinical activity of the combination of veliparib and lapatinib. Methods: Key eligibility criteria include histologically confirmed TNBC (ER negative, PR negative, HER-2-Neu negative), measurable disease, failed anthracyclines and taxanes in the neoadjuvant, adjuvant, or metastatic setting, left ventricular ejection fracture ≥ 50, and ECOG PS of 0-2. Patients with known germline BRCA 1 or 2 mutations were excluded. Eligible patients received continuous doses of lapatinib 1250 mg PO daily and veliparib 200 mg PO twice daily. Dose limiting toxicity (DLT) evaluation period was 28 days (cycle 1). Adverse events (AEs) were assessed by CTCAE v4.03 and best objective response per RECIST v1.1. Results: Twenty patients were enrolled and 17 were evaluable for response. The median number of prior therapies for advanced BC was 1 (range 0-2). Fifty percent of the patients enrolled were Caucasian, 45% African-American, and 5% Hispanic. Of the evaluable patients, 4 had a partial response and 2 had stable disease. There were no dose-limiting toxicities. The majority of toxicities occurred during cycles 2 and 3. Toxicities were manageable. Most adverse events (AEs) were limited to grade 1 or 2 (no grade 5). Common treatment-related AEs were fatigue (6.4%), diarrhea (5.1%), constipation (5.5%), insomnia (4.5%), vomiting (2.9%), anemia (2.6%), headache (2.6%), dizziness (2.3%), dyspnea (2.3%), and rash (2.3%). Conclusions: Lapatinib plus veliparib in the treatment of advanced TNBC resistant to SoC has a manageable safety profile and promising antitumor activity. Further investigation of EGFR inhibition in combination with a PARP inhibitor is needed. Clinical trial information: NCT02158507.
Were the “Pioneer” Clinical Ethics Consultants “Outsiders”? For Them, Was “Critical Distance” That Critical?
Authors: Bruce D. White, Wayne N. Shelton, Cassandra J. Rivais
Journal: The American Journal of Bioethics (2018)

"Clinical ethics consultants" have been practicing in the United States for about 50 years. Most of the earliest consultants-the "pioneers"-were "outsiders" when they first appeared at patients' bedsides and in the clinic. However, if they were outsiders initially, they acclimated to the clinical setting and became "insiders" very quickly. Moreover, there was some tension between traditional academics and those doing applied ethics about whether there was sufficient "critical distance" for appropriate reflection about the complex medical ethics dilemmas of the day if one were involved in the decision making. Again, the pioneers deflected concerns by identifying and instituting safeguards to assure professional objectivity in clinical ethics consultation services. One might suggest that in moving inside and establishing normative practices, the pioneer clinical ethics consultants anticipated adoption of their routines and professionalization of the field.
Acellular vascular matrix grafts from human placenta chorion: Impact of ECM preservation on graft characteristics, protein composition and in vivo performance
Authors: Karl H. Schneider, Marjan Enayati, Christian Grasl, Ingrid Walter, Lubos Budinsky, Gabriel Zebic, Christoph Kaun, Anja Wagner, Klaus Kratochwill, Heinz Redl, Andreas H. Teuschl, Bruno K. Podesser, Helga Bergmeister
Journal: Biomaterials (2018)
Multimodal analgesia to reduce NSAID induced myocardial Infarction
Authors: Leigh White, Gun Hee An, Ruan Vlok
Journal: Annals of the Rheumatic Diseases (2018)

Multimodal analgesia to reduce NSAID induced myocardial InfarctionWe read with great interest the extended report by Dubreuil et al on 'Risk of myocardial infarction with use of selected non-steroidal anti-inflammatory drugs in patients with spondyloarthritis and osteoarthritis'. 1 This study raises interesting point that the use of certain non-steroidal anti-inflammatory drugs (NSAIDs) such as diclofenac increases the risk of myocardial infarction (MI) in patients with spondyloarthritis by twofold to threefold.][6] The analgesic benefit of NSAIDs appears to be dose dependent, interestingly, so too is the risk of MI. 7 8 Furthermore, Bhala and colleagues demonstrated that use of certain NSAIDs increase the risk of MI in people without a history of cardiovascular disease. 7 9Currently, EULAR recommends physicians to consider additional analgesics for residual pain after previous suboptimal treatments.Given the likely dose-dependent risk of MI, it may also be necessary to recommend the use a multimodal analgesic approach in an effort to reduce the required NSAID dosing.Previously, a Cochrane review found that there was no added benefit when comparing monotherapy versus combination therapy in adults aged 18 years or older with diagnosis of inflammatory arthritis: rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis and other spondyloarthritis.However, previous studies do not report on the ability of additional analgesic agents to reduce the required dose of NSAIDs.Within the Cochrane review, three studies showed some benefit with the addition of paracetamol. 10t is worth noting that none of these studies assess the value of combination therapy for patients with inflammatory arthritis who have persistent pain despite optimal disease suppression.In this situation, it may be found that anti-inflammatory analgesic may be of no greater benefit than other simple analgesics such as paracetamol.Additional agents that may prove beneficial in reducing the required doses of NSAIDs, if not improving pain control in acute flares include pregabalin, 11 duloxetine, 11 tramadol, 12 tapentadol 13 and buprenorphine. 14