tbuckley/cabot-search huggingface dataset:
The presence and extent of extracapsular extension (ECE) and the need for axillary lymph node dissection (ALND) in patients who meet ACOSOG Z11 eligibility criteria.
Authors: Lynn Dengel, Hiram S. Cody, Tari A. King, Kimberly J. Van Zee, Sujata Patil, Adriana Corben, Mahmoud El-Tamer, Michelle Stempel, Lisa M. Sclafani, Alexandra S. Heerdt, Mary Gemignani, Deborah Capko, Virgilio Sacchini, George Plitas, Monica Morrow
Journal: Journal of Clinical Oncology (2013)

1019 Background: Whether ECE mandates ALND in patients with ≤2 positive sentinel nodes (SN) is controversial. ACOSOG Z11 excluded patients with matted nodes, but did not comment on microscopic ECE. In a prospective, consecutive series of patients, we sought to determine if ECE correlates with the number of positive axillary lymph nodes (LN) and if ECE ≤2mm clinically differs from ECE &gt;2mm. Methods: In 8/2010 an institutional treatment algorithm based on the Z11 results was prospectively applied to consecutive patients having BCS. ALND was performed for ≥3 +SNs. The approach to ECE was not specified. Characteristics of patients with and without ECE were compared with Fisher’s exact test and the Wilcoxon rank sum test. Results: From 8/10-11/12, 2157 invasive breast cancer patients had BCS; 381 had LN metastasis, 287 met Z11 selection criteria, and ALND was avoided in 242 (84%). ECE was present in 111 (39%), of whom 23% had ≥3 +SNs (vs 2% without ECE; p&lt;0.0001) and 35% had ALND (vs 3% without ECE; p&lt;0.0001). The presence of ECE was associated with tumor size (1.9cm vs 1.6; p=.01) but not with age, grade, or receptor status. The degree of ECE was associated with age, grade, number of +SNs, and performance of ALND (Table). In 45 cases, ALND was advised for ≥3 +SNs (n=29) or &lt;3 +SNs with ECE (n=16). 39 patients had ALND and 34 of these had ECE. Additional +LNs were seen in 5/9 patients with ≤2mm ECE and 20/25 with &gt;2mm ECE; median of 1 additional +LN in each group. Seven or more additional +LNs were seen in 6 patients with &gt;2mm ECE; 1 patient with ≤2mm ECE had 6 additional +LNs, the remainder had ≤3. Conclusions: The presence of ECE was associated with ≥3 +SNs and the need for ALND. Only a minority of patients with ≤2mm of ECE had ≥3 +SNs, and nodal disease at ALND in this group was limited, suggesting that ≤2mm ECE may not be an indication for ALND. [Table: see text]
Surgical treatment of recurrent varicose veins in the lower limbs associated with endovascular treatment of iliac vein stenosis
Authors: Jie Kong, Peng Liu, Jinyong Li, Xueqiang Fan, Jianyan Wen, Jianbin Zhang, Rongwei Xu, Yiyao Cui, Xia Zhen, Zhidong Ye
Journal: International Journal of Surgery (2018)
Cost per median overall month of survival in multiple myeloma patients with ≥3 lines of therapy or were double refractory.
Authors: Eric M. Maiese, Maria Dimova, Gianluca Baio, Charles Makin
Journal: Journal of Clinical Oncology (2016)

8057 Background: Daratumumab (DARA) was recently FDA approved for the treatment of patients with multiple myeloma (MM) with ≥ 3 prior lines of therapy (LOTs) including a proteasome inhibitor (PI) and an immunomodulatory agent (IMiD), or who are double refractory (DR) to a PI and an IMiD. The aim of this analysis was to evaluate the cost per median month of survival (mOS) for DARA and other novel MM treatments in this population. Methods: A model was developed to estimate the average cost per mOS in MM patients who either received ≥ 3 prior LOTs or were DR to a PI and an IMiD; received ≥ 3 prior LOTs regardless of DR status; or were DR to a PI and an IMiD regardless of number of prior LOTs. DARA, carfilzomib (CAR), and pomalidomide+dexamethasone (POM+D) were included in the analysis since these treatments had published data in these populations. Drug, pre- and post-medication, administration, monitoring, auxiliary, and adverse events (AE) costs were included. Drug costs were based on Wholesale Acquisition Costs published in RedBook. Monitoring, auxiliary, and AE costs were based on Medicare fee schedules and publications. Treatment duration was assumed to be median progression-free survival (mPFS), as treatment duration is not consistently reported and treatment is typically until progression. mPFS and mOS were from the Sirius (DARA), FOCUS (CAR), PX-171-003-A1 (CAR DR subgroup), and MM-003 (POM+D DR subgroup) trials. Dosing and proportion of patients with AEs were based on FDA labels. Results: The average cost per mOS was $4,261 for DARA, $4,883 for CAR (FOCUS), $4,213 for CAR (PX-171-003-A1 DR subgroup) and $5,160 for POM+D (MM-003 DR subgroup) (TABLE). Conclusions: In this analysis cost per mOS was lowest for DARA and CAR and highest for POM+D. The analysis may be helpful to support comprehensive healthcare decision-making considering the efficacy and safety benefits of MM treatments. DARA (Sirius) CAR (FOCUS) CAR (PX-171-003-A1 DR subgroup) POM+D (MM-003 DR subgroup) mOS (months) 17.5 10.2 11.9 11.1 Average Cost per mOS ($) Drug 4,011 4,381 3,755 4,406 Pre- and post-medication 10 2 2 0 Administration 158 186 186 0 Monitoring and auxiliary 15 49 42 30 AE 67 265 228 724 Total Average Cost per mOS 4,261 4,883 4,213 5,160
Risk Factors for Depression: An Autobiographical Review
Authors: Constance Hammen
Journal: Annual Review of Clinical Psychology (2018)

I have been given a priceless opportunity to reflect on my career in the remarkably productive field of risk factors for depression. Psychological research on depression exploded in the early years of my work. I try to give an account of the choices and challenges, and reflect on the influences, some calculated and some serendipitous, that determined the paths I have followed. I focus mostly on the robust depression risk factors that have influenced my research, including dysfunctional cognitions, stressful life events and circumstances, parental depression, interpersonal dysfunction, and being female, and I cover some of what I did but also the influential work of others. This is a selective review of depression research in the past 40 or so years, noting some of the big developments that set the stage for the remarkable activity that continues today. In the conclusion, there is a brief statement of aspirations for future developments in our field.
Endocrinologist charged with murder of wife who threatened to reveal his opioid dealing
Authors: Owen Dyer
Journal: BMJ (2018)

An endocrinologist from New Jersey has been charged with hiring a man to kill his wife after she threatened to reveal his illegal oxycodone distribution scheme, which he ran with a local biker gang.

James Kauffman, 68, gave a gun to Francis Mullholland of the Pagan Outlaw gang and left his front door open when he left for work on 10 May 2012, prosecutors allege. According to the indictment, Mullholland entered the house and shot dead April Kauffman, a well known local radio host.

The unsolved murder remained a subject of media interest for …
Abstract 15694: Roles of Nitrite and Metformin in Severe Pulmonary Arterial Hypertension (PAH) and Pulmonary Hypertension in Heart Failure With Preserved Ejection Fraction (PH-HFpEF)
Authors: Yen-Chun Lai, Diana Tabima, Rebecca Vanderpool, Jian Hu, Dmitry Goncharov, Elena Goncharova, Stevan Tofovic, Ana Mora, Mark Gladwin
Journal: Circulation (2015)

Background: PAH (Group I) is a disease of the small pulmonary arteries, characterized by vasoconstriction, vascular proliferation and remodeling. PH-HFpEF (Group II) is known to occur secondary to the LV diastolic dysfunction and is recognized as a clinical complication of metabolic syndrome, with no currently approved therapies. Since the use of conventional therapies for PAH in PH-HFpEF patients is often ineffective, targeting both pulmonary vascular disease and metabolic disorders appears to be a key strategy for the treatment of PH-HFpEF. We, as well as others, have reported that nitrite exhibits therapeutic efficacy in moderate PAH models and improves glucose metabolism. In addition, metformin, the canonical AMPK activator and the first-line anti-diabetic drug, has been found to prevent the development of moderate PAH. In this work, we examined the effects of nitrite and metformin in PH-HFpEF, and compared their effects in severe PAH. Methods and Results: Nitrite (100mg/L) and metformin (300mg/kg) were given in drinking water to rats with Su5416/hypoxia-induced severe PAH or to rats with Su5416/metabolic syndrome-induced PH-HFpEF for 6 and 14 weeks, respectively. In the PH-HFpEF rats, our data showed that both nitrite and metformin treatments reduced pulmonary pressures and pathological vascular remodeling and limited hyperglycemia, which correlated with increased SIRT3-AMPK activation in skeletal muscles and AMPK activation in pulmonary vessels. Similar protective effect of nitrite was also observed in Su5416/hypoxia rats, together with increased activation of SIRT3 and AMPK in skeletal muscles. However, metformin failed to reduce pulmonary pressures and vascular remodeling in Su5416/hypoxia rats, with unchanged activation levels of SIRT3 and AMPK, suggesting metformin may favorably affect PH only in the presence of metabolic disorders. In addition, the AMPK agonist AICAR was found incapable of limiting PAH in Su5416/hypoxia rats. Conclusions: Our findings indicate that oral nitrite treatment limits PH-HFpEF, as well as PAH, while metformin treatment more preferentially improves PH-HFpEF. Our findings also indicate that activation of SIRT3-AMPK may represent a potential therapeutic route in the treatment of both PAH and PH-HFpEF.
The deubiquitinase USP9X regulates FBW7 stability and suppresses colorectal cancer
Authors: Omar M. Khan, Joana Carvalho, Bradley Spencer-Dene, Richard Mitter, David Frith, Ambrosius P. Snijders, Stephen A. Wood, Axel Behrens
Journal: Journal of Clinical Investigation (2018)

The tumor suppressor FBW7 targets oncoproteins such as c-MYC for ubiquitylation and is mutated in several human cancers. We noted that in a substantial percentage of colon cancers, FBW7 protein is undetectable despite the presence of FBW7 mRNA. To understand the molecular mechanism of FBW7 regulation in these cancers, we employed proteomics and identified the deubiquitinase (DUB) USP9X as an FBW7 interactor. USP9X antagonized FBW7 ubiquitylation, and Usp9x deletion caused Fbw7 destabilization. Mice lacking Usp9x in the gut showed reduced secretory cell differentiation and increased progenitor proliferation, phenocopying Fbw7 loss. In addition, Usp9x inactivation impaired intestinal regeneration and increased tumor burden in colitis-associated intestinal cancer. c-Myc heterozygosity abrogated increased progenitor proliferation and tumor burden in Usp9x-deficient mice, suggesting that Usp9x suppresses tumor formation by regulating Fbw7 protein stability and thereby reducing c-Myc. Thus, we identify a tumor suppressor mechanism in the mammalian intestine that arises from the posttranslational regulation of FBW7 by USP9X independent of somatic FBW7 mutations.
Epigenome-wide Association Study of the Effect of Maternal Age on Offspring DNA Methylation
Authors: John W. Holloway, Cory H. White, Ahmad Alzahrani, Hongmei Zhang, Susan Ewart, Linda S. Mansfield, Hasan Arshad, Wilfried Karmaus, Faisal I. Rezwan
Journal: Journal of Allergy and Clinical Immunology (2018)
Impact of <i>CYP2C19</i> Genotype on Escitalopram Exposure and Therapeutic Failure: A Retrospective Study Based on 2,087 Patients
Authors: Marin M. Jukić, Tore Haslemo, Espen Molden, Magnus Ingelman-Sundberg
Journal: American Journal of Psychiatry (2018)

The antidepressant escitalopram is predominantly metabolized by the polymorphic CYP2C19 enzyme. The authors investigated the effect of CYP2C19 genotype on exposure and therapeutic failure of escitalopram in a large patient population.A total of 4,228 escitalopram serum concentration measurements from 2,087 CYP2C19-genotyped patients 10-30 hours after drug intake were collected retrospectively from the drug monitoring database at Diakonhjemmet Hospital in Oslo. The patients were divided into subgroups based on CYP2C19 genotype: those carrying inactive (CYP2C19Null) and gain-of-function (CYP2C19*17) variant alleles. The between-subgroup differences in escitalopram exposure (endpoint: dose-harmonized serum concentration) and therapeutic failure (endpoint: switching to another antidepressant within 1 year after the last escitalopram measurement) were evaluated by multivariate mixed model and chi-square analysis, respectively.Compared with the CYP2C19*1/*1 group, escitalopram serum concentrations were significantly increased 3.3-fold in the CYP2C19Null/Null group, 1.6-fold in the CYP2C19*Null/*1 group, and 1.4-fold in the CYP2C19Null/*17 group, whereas escitalopram serum concentrations were significantly decreased by 10% in the CYP2C19*1/*17 group and 20% in the CYP1C19*17/*17 group. In comparison to the CYP2C19*1/*1 group, switches from escitalopram to another antidepressant within 1 year were 3.3, 1.6, and 3.0 times more frequent among the CYP2C19Null/Null, CYP2C19*1/*17, and CYP1C19*17/*17 groups, respectively.The CYP2C19 genotype had a substantial impact on exposure and therapeutic failure of escitalopram, as measured by switching of antidepressant therapy. The results support the potential clinical utility of CYP2C19 genotyping for individualization of escitalopram therapy.
Making Sense of the Surreal: Guiding Families and Patients When Last-Ditch Medical Efforts Fail
Authors: Matthew J. Drago
Journal: The American Journal of Bioethics (2018)

"Making Sense of the Surreal: Guiding Families and Patients When Last-Ditch Medical Efforts Fail." The American Journal of Bioethics, 18(1), pp. 30–31
Abstract 12740: Clinical Impact of the Residual Syntax Score in Acute Coronary Syndrome Patients
Authors: Seiichi Hiramori, Makoto Hyodo, Yoshimitsu Soga, Shinichi Shirai, Kenji Ando
Journal: Circulation (2016)

Introduction: Some studies have shown prognostic value of the residual Syntax score (rSS) in patients with multivessel coronary artery disease. However, it remains unclear that how much impact the rSS has on clinical outcomes in ACS patients. Hypothesis: A reduction of rSS may relate to the improvement of clinical outcomes in ACS patients. Methods: This study was an observational study examining consecutive ACS patients from January 2009 to December 2014 at our institution. Study population included 2025 ACS cases. The rSS was derived from post primary and primarily scheduled PCI angiography. Patients were dichotomized into low (&lt;8) and high rSS (≥8) groups and outcomes were compared between groups. The primary outcome of net adverse cardiovascular events (NACE) consisted of a composite of all-cause mortality, non-fatal MI, and any revascularization at 1 year. Results: The mean rSS was 5.1 (±6.6). The incidence of NACE at 1 year was significantly higher in high rSS group than low rSS group (48.7% versus 26.5%, p&lt;.0001). The incidence of all-cause death (17.4% versus 6.5%, p&lt;.0001) and any revascularization (36.4% versus 21.1%, p&lt;.0001) were also higher in high rSS group. On the other hands, there was no significantly difference between two groups in non-fatal MI (1.9% versus 1.8%, p=.88). After adjustment for confounders, a high rSS was also an independent predictor of the primary outcome with a hazard ratio of 1.94 (95% confidential interval [CI], 1.58-2.39; p&lt;.0001). Conclusions: Our study suggests that high residual Syntax score (≧8) is significantly associated with poor clinical outcomes.
Pathogenesis of bone disease in multiple myeloma: from bench to bedside
Authors: Evangelos Terpos, Ioannis Ntanasis-Stathopoulos, Maria Gavriatopoulou, Meletios A. Dimopoulos
Journal: Blood Cancer Journal (2018)

Abstract Osteolytic bone disease is the hallmark of multiple myeloma, which deteriorates the quality of life of myeloma patients, and it affects dramatically their morbidity and mortality. The basis of the pathogenesis of myeloma-related bone disease is the uncoupling of the bone-remodeling process. The interaction between myeloma cells and the bone microenvironment ultimately leads to the activation of osteoclasts and suppression of osteoblasts, resulting in bone loss. Several intracellular and intercellular signaling cascades, including RANK/RANKL/OPG, Notch, Wnt, and numerous chemokines and interleukins are implicated in this complex process. During the last years, osteocytes have emerged as key regulators of bone loss in myeloma through direct interactions with the myeloma cells. The myeloma-induced crosstalk among the molecular pathways establishes a positive feedback that sustains myeloma cell survival and continuous bone destruction, even when a plateau phase of the disease has been achieved. Targeted therapies, based on the better knowledge of the biology, constitute a promising approach in the management of myeloma-related bone disease and several novel agents are currently under investigation. Herein, we provide an insight into the underlying pathogenesis of bone disease and discuss possible directions for future studies.
B Cell Chronic Lymphoid Leukemia Is More Frequent Than Chronic Myeloid Leukemia in West Central Mexico: Interinstitutional Epidemiology
Authors: Virgina Campos-Cabrera, Jose-Luis Campos-Villagomez, Salvador Campos-Cabrera, Alicia Rivera-Trujillo, Sonia Hernandez-Rodriguez, Miguel-Angel Gomez-Guijosa, Maria Mora-Torres, Luis Pita-Ramirez, Noe-Benjamin Vega-Tapia, Maria-Luisa Pedraza-Colin, Sandra-Guadalupe Pulido-Sanchez, Sergio Cuin-Macedo, Gregorio Campos-Cabrera
Journal: Blood (2017)
Biomarkers of immunotherapy in urothelial and renal cell carcinoma: PD-L1, tumor mutational burden, and beyond
Authors: Jason Zhu, Andrew J. Armstrong, Terence W. Friedlander, Won Kim, Sumanta K. Pal, Daniel J. George, Tian Zhang
Journal: Journal for ImmunoTherapy of Cancer (2018)

Immune checkpoint inhibitors targeting the PD-1 pathway have greatly changed clinical management of metastatic urothelial carcinoma and metastatic renal cell carcinoma. However, response rates are low, and biomarkers are needed to predict for treatment response. Immunohistochemical quantification of PD-L1 was developed as a promising biomarker in early clinical trials, but many shortcomings of the four different assays (different antibodies, disparate cellular populations, and different thresholds of positivity) have limited its clinical utility. Further limitations include the use of archival specimens to measure this dynamic biomarker. Indeed, until PD-L1 testing is standardized and can consistently predict treatment outcome, the currently available PD-L1 assays are not clinically useful in urothelial and renal cell carcinoma. Other more promising biomarkers include tumor mutational burden, profiles of tumor infiltrating lymphocytes, molecular subtypes, and PD-L2. Potentially, a composite biomarker may be best but will need prospective testing to validate such a biomarker.
Management of psoriasis in patients with inflammatory bowel disease: From the Medical Board of the National Psoriasis Foundation
Authors: Scott M. Whitlock, Clinton W. Enos, April W. Armstrong, Alice Gottlieb, Richard G. Langley, Mark Lebwohl, Joseph F. Merola, Caitriona Ryan, Michael P. Siegel, Jeffrey M. Weinberg, Jashin J. Wu, Abby S. Van Voorhees
Journal: Journal of the American Academy of Dermatology (2018)
Guidelines of care for the management of basal cell carcinoma
Authors: John Y.S. Kim, Jeffrey H. Kozlow, Bharat Mittal, Jeffrey Moyer, Thomas Olencki, Phillip Rodgers, Christopher Bichakjian, April Armstrong, Christian Baum, Jeremy S. Bordeaux, Marc Brown, Klaus J. Busam, Daniel B. Eisen, Vivek Iyengar, Clifford Lober, David J. Margolis, Jane Messina, Alexander Miller, Stanley Miller, Eliot Mostow, Christen Mowad, Kishwer Nehal, Kristi Schmitt-Burr, Aleksandar Sekulic, Paul Storrs, Joyce Teng, Siegrid Yu, Conway Huang, Kevin Boyer, Wendy Smith Begolka, Murad Alam
Journal: Journal of the American Academy of Dermatology (2018)
Chemoimmunotherapy with 5-fluouracil, leucovorin and interferon alpha-2b as adjuvant therapy after surgery in Gastric Carcinoma patients
Authors: H. A. Gonzalez, H. Londoño, J. Quiroz, A. Parra, A. Ramirez, M. González, A. Rodríguez, C. Varón, N. Romero
Journal: Journal of Clinical Oncology (2007)

4581 Background: The main treatment of Gastric Carcinoma(GC) is Surgery, but 5 years recurrence risk is 70% and mortality 50%. So that, effective adyuvant therapy, like chemotherapy, is needed to impact on survival ; results, however have been inconsistent at best. Inmunotherapy with interferon alpha, in gastric carcinoma, has only been employed in metastatic disease. The objective of this study was evaluate chemoimmmunotherapy role of interferon alpha - 2b,5-FU and LCV as adjuvant therapy in GC Methods: This is a randomized prospective study. Beginning 2/Oct /97 and finalizing 31/march/2005. Patiens with gastric adenocarcinoma, clinical stages II, III and non metastatic IV, after gastrectomy, without cancer antecedent were included. Treatment groups were assigned at random: Group A: 5-FU: 400 mg/m 2 , days (1–3), leucovorin: 50 mg. days (1–3), interferon alpha - 2b: 5x10^6 units sq, every other day, days (1–15). Group B: 5-FU, LCV without interferon alpha, at the same doses. Nine (9) monthly cycles were aplied. Clinical and paraclinical follow up was made appropriately. Statistic analysis was performed by Kaplan Meier method. Results: 52 patients were studied, 25 in group A and 27 in group B. Both of them had similar characteristics in median age, sex, histology, differentiation grade, gastric location, clinical stage: A: II: 28%, III: 72% (IIIB: 56%). B: II: 29,6%, III: 70% (IIIB: 55%).General survival (SG) analysis: Mean SG (%): A: 64%. B: 18,5%. Mean SG (months): A: 68,5 m. (CI 95%: 59–78,15). B: 27,98 ( CI 95%: 18,92–37,04). Survival curves comparison, minimum until 5 years: Log Rank, Breslow, Tarone Ware: P&lt;0,00001, all of them in favor to group A. Mortality: Total:31/52: 59,6%. A: 36%. B: 81,48% (P&lt;0,05). Disease free survival (DFS) analysis: Mean DFS (%): A: 52%. B: 18, 52%. Mean DFS(months): A: 58,85m (CI 95%: 47,4–70.3). B: 24,98m (CI 95 %: 15,3–34.6). DFS curves comparison: Log Rank: 0,0008. Breslow: 0,0003. Tarone Ware: 0,0004. All of them in favor to group A. Recurrence (%): Total: 34/52:65%. A: 48%. B: 81,48% ( P &lt;0,05). Conclusions: This is the first study of adjuvant chemoimmunotherapy (CI) that includes interferon alpha - 2b in GC. This study shows CI with 5-FU, LCV and interferon alpha -2b is effective as adjuvant treatment in GC. No significant financial relationships to disclose.