tbuckley/cabot-search huggingface dataset:
Outpatient mastectomy clinical pathway.
Authors: J. C. Boughey, J. W. Jakub, A. C. Degnim, J. B. Osborn, J. K. Brodt, L. K. Vanderlei, J. K. Case, J. A. Dilger, C. M. Duncan, J. R. Hebl
Journal: Journal of Clinical Oncology (2011)

144 Background: Many patients require hospitalization after mastectomy, predominantly for pain management and treatment of postoperative nausea and vomiting (PONV). In order to improve a woman's perioperative experience after mastectomy and facilitate mastectomy on an outpatient basis, we initiated a clinical pathway for perioperative management of unilateral mastectomy patients at Mayo Clinic Rochester. Methods: The clinical pathway consists of preoperative oral medications (celecoxib and gabapentin), preoperative ultrasound guided paravertebral block using bupivacaine, intraoperative anesthesia management with total intravenous anesthetic, and minimal use of long-acting opioids and postoperative acetaminophen and oxycodone. All patients are evaluated by the surgical team on the afternoon after surgery and if patients are recovering well are discharged on the day of surgery. The following morning, the surgical team telephones the patient to follow up on management of pain, nausea or vomiting, and drain output. Results: Eighteen patients have been treated on this clinical pathway. Mean age of patients was 66 (range 51-81). Majority of patients (n=16, 89%) underwent unilateral mastectomy with sentinel lymph node biopsy, with 1 patient undergoing bilateral mastectomy and 1 patient undergoing mastectomy and axillary dissection. All patients are evaluated by the surgical team on the afternoon of surgery. Fourteen patients (78%) were without evidence of hematoma or PONV, pain was well-controlled on oral medications and they were discharged on the day of surgery. On morning after telephone calls, pain scale ratings ranged from 1 to 3 and no patients verbalized complaints of nausea. Four patients (22%) treated on this clinical pathway required overnight observation in the hospital, one for urinary retention, two for pain control, and one for high sanguineous drain output. Conclusions: The clinical pathway presented provides preemptive analgesia and regional anesthesia for patients undergoing mastectomy, enabling the majority of patients to be discharged on the day of surgery. The clinical pathway is a safe and effective way to improve the perioperative experience of breast surgery patients and decrease hospital admission.
A retrospective analysis of the efficacy and safety of everolimus in patients with unresectable tumor
Authors: Takayuki Oishi, Masanobu Takahashi, Kota Ohuchi, Hidekazu Takahashi, Gen Imai, Masahiro Takahashi, Takahiro Mori, Shunsuke Katou, Hideki Shimodaira, Chikashi Ishioka
Journal: Annals of Oncology (2015)
The Alternate Activation of Hedgehog Pathway, Either in CD138+ or in CD138-CD19+ Multiple Myeloma Primary Cells, Impacts on Disease Outcome
Authors: Marina Martello, Daniel Remondini, Enrica Borsi, Mauro Procacci, Barbara Santacroce, Annalisa Pezzi, Angela Flores Dico, Elena Zamagni, Paola Tacchetti, Lucia Pantani, Giulia Marzocchi, Giovanni Martinelli, Michele Cavo, Carolina Terragna
Journal: Blood (2015)
Interaction between intratumoral ERCC1 expression and adjuvant treatment with S-1 on the survival of patients enrolled in the ACTS-GC study.
Authors: Koji Kitada, Atsushi Ochiai, Wataru Ichikawa, Masanori Terashima, Issei Kurahashi, Shinichi Sakuramoto, Hitoshi Katai, Takeshi Sano, Hiroshi Imamura, Mitsuru Sasako
Journal: Journal of Clinical Oncology (2012)

53 Background: Excision repair cross-complementing group 1 (ERCC1) is thought to be involved in resistance to platinum-based therapy. Recently, expression of this gene was shown to be associated with the outcome in patients with gastric cancer. Biomarker analysis was conducted to evaluate the influence of this gene expression on the outcomes of patients enrolled in the ACTS-GC study, a randomized phase III trial, which demonstrated the efficacy of adjuvant treatment with S-1 after D2 dissection for stage II and III gastric cancer (Sakuramoto et al., NEJM 2007). Methods: Formalin-fixed paraffin-embedded specimens were available for 829 of a total of 1,059 (78.3%) patients. ERCC1 expression was measured by RT-PCR in the macrodissected tumor specimens and normalized to β-actin expression as the reference gene. The expression of ERCC1 was categorized into low and high values at the median. Results: The ERCC1 expression level was quantifiable in 97% of the 829 specimens and the distribution was balanced across the arms. In the S-1 group, overall survival (OS) tended to be longer in the high ERCC1 expression group than in the low ERCC1 expression group (HR, 0.698; 95% CI, 0.469-1.040; p= 0.076). On the contrary, in the surgery group, the OS was shorter in the high ERCC1 expression group than in the low ERCC1 expression group (HR, 1.216; 95% CI, 0.881-1.679; p= 0.232), although the difference was not statistically significant. The HR for OS of S-1 to surgery alone was smaller in the high-ERCC1 (HR, 0.465; 95% CI, 0.320-0.678) than in the low-ERCC1 group (HR, 0.805; 95% CI, 0.568-1.141). Significant interaction between the S-1 group and ERCC1 expression was observed (p= 0.033). Conclusions: This large biomarker study showed that intratumoral ERCC1 gene expression may be a predictive marker in gastric cancer patients receiving postoperative adjuvant chemotherapy with S-1.
Genetic Evidence That Sequence Variation at the β-Globin Locus Underlies Differences in Cell Hemoglobin Concentration and Cell Hydration in Single (Hbbs) Vs. Diffuse (Hbbd) Inbred Mouse Strains: Implications for Inherited Anemias
Authors: Luanne L. Peters, Amy J. Lambert, Shirngwern Tsaih, Jordan A. Shavit, David Ginsburg, Gary A. Churchill, Carlo Brugnara
Journal: Blood (2008)
Reduced-Intensity Regimens for Allogeneic Stem Cell Transplantation Improve the Outcome in Advanced Multiple Myeloma
Authors: Suzanne M. Cole, Rima Saliba, Matteo Pelosini, Floralyn L Mendoza, Donna Weber, Michael Wang, Sheeba Thomas, Robert Z. Orlowski, Jatin Shah, Amin Alousi, Chitra Hosing, Uday Popat, Partow Kebriaei, Paolo Anderlini, Issa F. Khouri, Richard Champlin, Sergio Giralt, Muzaffar H. Qazilbash
Journal: Blood (2008)
Integrating Structural and Functional Studies Leads to a New Model of β-Globin Activation That Suggests Distinct Initiation and Maintenance States
Authors: M. A. Bender, Davide Bau', Tobias Ragoczy, Rachel Byron, Ye Zhan, Bryan Lajoie, Marc A. Marti-Renom, Job Dekker, Mark T. Groudine
Journal: Blood (2011)
Surveillance for stage I testicular seminoma at a single institution in Japan: Retrospective analysis of prognostic factors for relapse.
Authors: K. Kakimoto, K. Takeda, T. Yoshida, M. Nakayama, Y. Arai, K. Nishimura
Journal: Journal of Clinical Oncology (2011)

234 Background: Treatment options for clinical stage I seminoma include adjuvant radiotherapy (RT) as well as surveillance and adjuvant chemotherapy (CT). Data available from the surveillance, adjuvant RT and adjuvant CT series suggest that all treatment strategies achieve a complete cure in almost 100% of the patients with stage I testicular seminoma. The success of surveillance of patients with stage I nonseminomatous germ cell tumors and the establishment of curative CT for advanced disease have led to re-examination of the standard treatment approach. We report the results of a retrospective analysis of the prognostic factors for stage I testicular seminoma. Methods: We retrospectively reviewed the survey of 87 patients with stage I testicular seminoma who were admitted in an institution between January 1982 and January 2009. We examined if the following tumor characteristics could possibly predict the relapse: age at diagnosis, tumor size, pathological T (pT) stage, elevation of beta-hCG level and/or LDH level, invasion of the rete testis, vascular invasion and lymphatic invasion. The cause-specific survival rate was calculated using the Kaplan-Meier method. Results: During a median follow-up of 8.1 years (range, 1.2-25.7 years), 13 (14.9%) relapses were observed, with an actuarial 5-year relapse-free rate (RFR) of 87.9%. The univariate analysis showed that the following characteristics were not predictive of relapse: age at diagnosis (RFR: 89% [&lt;36 years] vs. 88% [≥36 years]), tumor size (RFR: 90% [&lt;5.6 cm(median)] vs. 85% [≥5.6 cm]), pT stage (RFR: 91% [pT = 1] vs. 84% [pT = 2 and pT = 3]), elevation of beta-hCG level (RFR: 89% [normal] vs. 87% [elevated]), invasion of the rete testis (RFR:90% [absent] vs. 80% [present]), vascular invasion (RFR:86% [absent] vs. 87% [present]), and lymphatic invasion (RFR: 88% [absent] vs. 87% [present]). The overall 5-year survival rate was 97%. Conclusions: Prognostic factors for relapse could not be identified in this retrospective analysis of the patients admitted in a single institution. To identify the prognostic factors for risk-adapted treatment for stage I testicular seminoma, we need to study a large sample population in Japan. No significant financial relationships to disclose.
Hematologic toxicities in renal cell carcinoma and other malignancies treated with bevacizumab: A meta-analysis of clinical trials.
Authors: D. L. Fontes Jardim, Y. Je, F. A. Schutz, T. K. Choueiri
Journal: Journal of Clinical Oncology (2011)

336 Background: Bevacizumab is a humanized monoclonal antibody directed against the VEGF ligand. Clinical trials with this drug mainly included patients with renal cell cancer (in combination with interferon-alpha) and several other solid tumors (in combination with cytotoxic chemotherapy). Although hematologic toxicities are not among the main concerns associated with the addition of bevacizumab, discontinuation of therapy or dose reductions due to these toxicities have been reported. We performed a meta-analysis to determine the incidence and risk of hematologic toxicities associated with bevacizumab use. Methods: The databases of Medline were searched for articles from 1966 to September 2010. Abstracts presented at the American Society of Clinical Oncology meetings were also searched. Eligible studies include randomized trials with bevacizumab, and adequate safety data profile reporting anemia, neutropenia, febrile neutropenia, or thrombocytopenia. Statistical analyses were conducted to calculate the summary incidence, RR, and 95% confidence intervals (CI). Results: A total of 15,239 patients were included in the analysis. The incidence of bevacizumab-associated all-grade anemia, neutropenia and thrombocytopenia were 19.4%, 22.3%, and 14.5%, respectively. The incidences of high-grade events were 3.94%, 18.4% and 3.38%, respectively. Febrile neutropenia was present in 3.75% of patients. Bevacizumab was associated with a decreased risk of high-grade anemia (RR=0.73; 95% CI 0.60-0.89; p=0.002), and increased risks of high-grade neutropenia (RR=1.08; 95% CI 1.02-1.13; p=0.005) and febrile neutropenia (RR=1.31; 95% CI 1.08-1.58; p=0.006), as compared to the non-bevacizumab containing arms. Stratified analysis by the dose of bevacizumab (2.5mg/wk vs. 5mg/wk) demonstrated similar risks. Conclusions: Concurrent use of bevacizumab with chemotherapy or immunotherapy is associated with a lower risk of high-grade anemia and an increased risk of high-grade neutropenia and febrile neutropenia. [Table: see text]
Differences between neurofibromatosis-1-associated malignant peripheral nerve sheath tumors (MPNST) and sporadic MPNST: The Mayo Clinic experience.
Authors: K. N. Johnson, C. H. Stucky, B. A. Pockaj, R. J. Gray, P. S. Rose, N. Wasif
Journal: Journal of Clinical Oncology (2011)

10066 Background: Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder associated with several clinical manifestations, including peripheral neurofibromas. Malignant transformation of these neurofibromas into malignant peripheral nerve sheath tumors (MPNST) is a potential life-threatening sequelae of this syndrome. Methods: A retrospective review of 57 patients with NF1-associated MPNST from 1985-2010 was performed. These patients were compared to 118 patients from the same time period diagnosed with MPNST not associated with NF1 to identify differences in presentations and outcomes. Results: Patients with NF1-associated MPNST were significantly younger at diagnosis than those that were not (39.9 years ±13.7 vs 47.8 years ±17.7, p=<0.01). NF1-associated tumors were also significantly larger (9.89 cm ±6.47 vs. 6.57 cm ±5.55, p=<0.01). No significant difference in tumor grade, depth, location, or recurrence (either local or distant) was found between the two gropus. Furthermore, there were no significant differences between groups with regard to R0/R1 resections, adjuvant radiation or chemotherapy. Survival at 5 years was 45% for patients with NF1 associated tumors, versus 65% for those that were not (p = 0.025). Conclusions: Patients with NF1 associated MPNST are younger and have larger tumors at time of diagnosis compared to sporadic MPNST. A poorer survival is seen with NF1-associated MPNST which may be due to the difficulty in identifying a malignant lesion from the benign neurofibromas seen in these patients.
Significant changes to doctors’ training are needed for future-proof workforce, peers are told
Authors: Adrian O’Dowd
Journal: BMJ (2016)

Changes are needed to the form, length, and approach to doctors’ training to produce a workforce more suited to the NHS’s future needs, peers have been told.

Doctors’ training may need to be shorter, more geared towards producing generalists instead of specialists, and broader ranging so that they are better prepared to deal with multimorbidity, workforce expert witnesses told peers on the House of Lords NHS sustainability committee.

During an evidence session held on 6 December for the committee’s inquiry into the NHS’s long term sustainability, peers asked what needed to change to help the NHS provide for care needs in 2030 and to improve its productivity.

Chris Whitty, chief scientific adviser at the Department of Health, giving evidence, said, …
Role of quantitative gene expression using RT-PCR in the prediction of recurrence risk in resected T1 clear cell renal cell carcinoma (ccRCC).
Authors: S. Campbell, D. Knezevic, T. Maddala, W. F. Novotny, M. Zhou, H. Aydin, P. Elson, L. Parodi, A. D. Goddard, B. I. Rini
Journal: Journal of Clinical Oncology (2011)

338 Background: Current pathology and clinical methods do not accurately estimate risk of recurrence in all patients with pT1 ccRCC. Quantitative RT-PCR (qPCR) analysis was performed on resected ccRCC tumors to identify genes associated with recurrence that significantly augment current prognostic tools. Methods: A retrospective observational cohort consisting of 931 patients (434 T1a, 201 T1b, 296 T2/3) with ccRCC was evaluated. All patients underwent nephrectomy between 1985 and 2003 at Cleveland Clinic and had paraffin-embedded tumor blocks. Patients with inherited ccRCC or inadequate follow-up (&lt; 6 months or no recurrence data) were excluded. qPCR analysis of 732 genes was performed on all patients. Cox Proportional Hazards regression models were used to evaluate the association between gene expression and recurrence-free interval (RFI). Results: 448 genes were significantly (unadj. p &lt; 0.05) associated with RFI, from which 72 genes were carried forward for further study (Rini, ASCO 2010, #4501). Angiogenesis is the strongest among the pathways represented, from which 3 genes (AQP1, NOS3, PPAP2B) were selected for this analysis. Incorporating these 3 genes, a subset of higher risk patients among those classified as low risk by Leibovich criteria was identified. By Leibovich criteria, 85% of the patients in the cohort with pT1 tumors (&lt; 7.0 cm) were identified as low risk - 7% recurrence at 5 years (95% CI: 5%, 9%). Incorporating these 3 genes, 9% of these patients were found to be at increased risk for recurrence - 19% at 5 years (95% CI: 7%, 21%). For the subset of T1a patients (&lt; 4.0 cm), 98.6% were low risk according to the Leibovich criteria - 7% recurrence at 5 years (95% CI: 4%, 10%). Incorporating the 3 genes, 11% of these patients were found to be at increased risk - 20% at 5 years (95% CI: 7%, 31%). Conclusions: Addition of 3 angiogenesis-related genes to the Leibovich criteria in patients with pT1 tumors refines stratification of patient risk in a subset of patients. More precise estimation of recurrence risk will help to tailor surveillance and refine inclusion into clinical trials. These genes will be incorporated into an algorithm that requires validation in an external data set. [Table: see text]
Margin distance as an independent predictor of survival after R0 resection for pancreatic adenocarcinoma.
Authors: George Van Buren, Herbert Zeh, Alyssa M Krasinskas, William E. Gooding, Jennifer Steve, Kenneth K Lee, Deepa Magge, Mustapha Daouadi, David L. Bartlett, Arthur J Moser, Amer H Zureikat
Journal: Journal of Clinical Oncology (2012)

321 Background: Microscopic tumor at the surgical margin is a predictor of recurrence and poor survival for pancreatic ductal adenocarcinoma (PDA). However, the impact of distance between the surgical margin and microscopic tumor on survival remains controversial. We hypothesized that margin distance (MD) would correlate with disease free survival (DFS) and overall survival (OS) in R0 resected PDA. Methods: Retrospective analysis of 191 resections for PDA. Margin distance was measured (0-1, 1-2, 2-4, 4-10, and &gt; 10 mm) and categorized by location. Parameters including age, gender, BMI, TNM, AJCC stage, lymph node (LN) ratio, vascular and perineural invasion, vein resection, and adjuvant therapy were analyzed. Primary endpoints were DFS and disease specific OS. Univariate analysis was used to estimate factors associated with outcomes. The log rank test was applied to selected group comparisons. Results: 149 (78%) R0 outcomes were analyzed. 118 (79%) patients received adjuvant chemotherapy, 31 of whom also received XRT. Univariate analysis demonstrated reduced DFS (HR = 1.65, 95% CI = 1.13 – 2.48, p = .009) and OS (HR = 1.52 95% CI =.98 – 2.35, p = .059) among patients with margins ≤ 2mm compared to margins &gt; 2mm. In addition LN status, LN ratio, tumor size, AJCC stage, vascular invasion, perineural invasion and adjuvant chemotherapy were found to influence OS on univariate analysis. Adjuvant XRT had no measurable effect on DFS or OS. Following adjustment for covariates in a multivariate model, margin distance &gt;2mm did not correlate with DFS (HR = 1.14, 95%CI = .73 – 1.78, p = .57) or OS (HR = 1.13 95% CI = .69 – 1.85, p = .63), whereas adjuvant chemotherapy and presence of vascular invasion significantly affected OS (P=0.0006 and P=0.008 respectively). The retroperitoneal margin was the margin most commonly in close proximity to tumor (43% of Whipple), although there was no correlation between the closest margin and DFS (p=0.94) or OS (p=0.94). Conclusions: Margin distance is not an independent predictor of DFS or OS after R0 resection for PDA. Irrespective of margin distance, adjuvant chemotherapy, but not XRT, was associated with improved OS.
T-Cell Replete Peripheral Blood Haploidentical Donor Transplant Is Frequently Associated with Cytokine Release Syndrome Which Responds to Anti-IL-6 Therapy
Authors: Ramzi Abboud, Jesse Keller, Michael Slade, Michael P. Rettig, Stephanie Meier, John F. DiPersio, Todd A Fehniger, Kathryn Trinkaus, Geoffrey L. Uy, Peter Westervelt, Ravi Vij, Camille N. Abboud, Khoan Vu, Pavan Kumar Bhamidipati, Rizwan Romee
Journal: Blood (2015)
Progress in Understanding the Genetics of Calcium-Containing Nephrolithiasis
Authors: John A. Sayer
Journal: Journal of the American Society of Nephrology (2016)

Renal stone disease is a frequent condition, causing a huge burden on health care systems globally. Calcium-based calculi account for around 75% of renal stone disease and the incidence of these calculi is increasing, suggesting environmental and dietary factors are acting upon a preexisting genetic background. The familial nature and significant heritability of stone disease is known, and recent genetic studies have successfully identified genes that may be involved in renal stone formation. The detection of monogenic causes of renal stone disease has been made more feasible by the use of high-throughput sequencing technologies and has also facilitated the discovery of novel monogenic causes of stone disease. However, the majority of calcium stone formers remain of undetermined genotype. Genome-wide association studies and candidate gene studies implicate a series of genes involved in renal tubular handling of lithogenic substrates, such as calcium, oxalate, and phosphate, and of inhibitors of crystallization, such as citrate and magnesium. Additionally, expression profiling of renal tissues from stone formers provides a novel way to explore disease pathways. New animal models to explore these recently-identified mechanisms and therapeutic interventions are being tested, which hopefully will provide translational insights to stop the growing incidence of nephrolithiasis.
Deferasirox (Exjade®, ICL670) Demonstrates Iron Chelating Efficacy Related to Transfusional Iron Intake in Pediatric Patients.
Authors: C. Kattamis, Y. Kilinc, S. Fattoum, A. Ferster, D. Gallisai, A. Maggio, M. F. Dresse, T. Klingebiel, K. Bourantas, D. Canatan, H. Maseruka, I. Gathmann, J. Ford
Journal: Blood (2005)
A New Case of KLF1 G973A Mutation and Congenital Dyserythropoeitic Anemia (CDA)- Further Definition of Emerging New Syndrome and Possible Association with Gonadal Dysgenesis
Authors: Yaddanapudi Ravindranath, Gerald Goyette, Steven Buck, Manisha Gadgeel, Alan Dombkowski, Laurence A. Boxer, Patrick G. Gallagher, Robert M Johnson
Journal: Blood (2011)
Identification of Risk Pathways and Functional Modules for Coronary Artery Disease Based on Genome-wide SNP Data
Authors: Xiang Zhao, Yi-Zhao Luan, Xiaoyu Zuo, Ye-Da Chen, Jiheng Qin, Lv Jin, Yiqing Tan, Meihua Lin, Naizun Zhang, Yan Liang, Shao-Qi Rao
Journal: Genomics Proteomics & Bioinformatics (2016)

Coronary artery disease (CAD) is a complex human disease, involving multiple genes and their nonlinear interactions, which often act in a modular fashion. Genome-wide single nucleotide polymorphism (SNP) profiling provides an effective technique to unravel these underlying genetic interplays or their functional involvements for CAD. This study aimed to identify the susceptible pathways and modules for CAD based on SNP omics. First, the Wellcome Trust Case Control Consortium (WTCCC) SNP datasets of CAD and control samples were used to assess the joint effect of multiple genetic variants at the pathway level, using logistic kernel machine regression model. Then, an expanded genetic network was constructed by integrating statistical gene-gene interactions involved in these susceptible pathways with their protein-protein interaction (PPI) knowledge. Finally, risk functional modules were identified by decomposition of the network. Of 276 KEGG pathways analyzed, 6 pathways were found to have a significant effect on CAD. Other than glycerolipid metabolism, glycosaminoglycan biosynthesis, and cardiac muscle contraction pathways, three pathways related to other diseases were also revealed, including Alzheimer's disease, non-alcoholic fatty liver disease, and Huntington's disease. A genetic epistatic network of 95 genes was further constructed using the abovementioned integrative approach. Of 10 functional modules derived from the network, 6 have been annotated to phospholipase C activity and cell adhesion molecule binding, which also have known functional involvement in Alzheimer's disease. These findings indicate an overlap of the underlying molecular mechanisms between CAD and Alzheimer's disease, thus providing new insights into the molecular basis for CAD and its molecular relationships with other diseases.