tbuckley/cabot-search huggingface dataset:
Magnitude of Trastuzumab Benefit in Patients With HER2-Positive, Invasive Lobular Breast Carcinoma: Results From the HERA Trial
Authors: Otto Metzger-Filho, Marion Procter, Evandro de Azambuja, Brian Leyland-Jones, Richard D. Gelber, Mitchell Dowsett, Sherene Loi, Kamal S. Saini, David Cameron, Michael Untch, Ian Smith, Luca Gianni, Jose Baselga, Christian Jackisch, Richard Bell, Christos Sotiriou, Giuseppe Viale, Martine Piccart-Gebhart
Journal: Journal of Clinical Oncology (2013)

To evaluate the benefit of adjuvant trastuzumab in patients diagnosed with human epidermal growth factor receptor 2 (HER2) -positive invasive lobular carcinoma (ILC) enrolled onto the Herceptin Adjuvant (HERA) trial.Patients randomly assigned to receive one year of trastuzumab and one year of observation in the HERA trial were included (n = 3,401). Centrally reviewed estrogen receptor (ER), progesterone receptor (PgR), and HER2 copy numbers were used. First site-specific relapse pattern was evaluated for ILC and invasive ductal carcinoma (IDC). The magnitude of trastuzumab benefit was assessed using the Cox proportional hazards model for disease-free survival (DFS) and overall survival (OS).Median follow-up time was 4 years. A total of 187 ILC and 3,213 IDC patients were included. High Allred scores (6 to 8) were more common in patients with ILC than IDC for both ER (36.9% v 22.7%) and PgR (44.1% v 28.5%). A trend toward decreased HER2 copy number was observed in the ILC group. The ILC and IDC subgroups had similar patterns of first site of disease relapse. DFS hazard ratios (HRs) comparing 1 year of trastuzumab versus observation were 0.63 for ILC (95% CI, 0.34 to 1.15) and 0.77 for IDC (95% CI, 0.67 to 0.89; P for interaction = .49). The OS HRs comparing 1 year of trastuzumab versus observation were 0.60 for ILC (95% CI, 0.27 to 1.31) and 0.86 for IDC (95% CI, 0.71 to 1.06; P for interaction = .29).In this retrospective analysis, there was no suggestion that patients in the ILC cohort experienced a different magnitude of benefit from adjuvant trastuzumab than those in the IDC cohort.
Development of Focal Segmental Glomerulosclerosis after Anabolic Steroid Abuse
Authors: Leal C. Herlitz, Glen S. Markowitz, Alton B. Farris, Joshua A. Schwimmer, Michael B. Stokes, Cheryl Kunis, Robert B. Colvin, Vivette D. D'Agati
Journal: Journal of the American Society of Nephrology (2009)

Anabolic steroid abuse adversely affects the endocrine system, blood lipids, and the liver, but renal injury has not been described. We identified an association of focal segmental glomerulosclerosis (FSGS) and proteinuria in a cohort of 10 bodybuilders (six white and four Hispanic; mean body mass index 34.7) after long-term abuse of anabolic steroids. The clinical presentation included proteinuria (mean 10.1 g/d; range 1.3 to 26.3 g/d) and renal insufficiency (mean serum creatinine 3.0 mg/dl; range 1.3 to 7.8 mg/dl); three (30%) patients presented with nephrotic syndrome. Renal biopsy revealed FSGS in nine patients, four of whom also had glomerulomegaly, and glomerulomegaly alone in one patient. Three biopsies revealed collapsing lesions of FSGS, four had perihilar lesions, and seven showed ≥40% tubular atrophy and interstitial fibrosis. Among eight patients with mean follow-up of 2.2 yr, one progressed to ESRD, the other seven received renin-angiotensin system blockade, and one also received corticosteroids. All seven patients discontinued anabolic steroids, leading to weight loss, stabilization or improvement in serum creatinine, and a reduction in proteinuria. One patient resumed anabolic steroid abuse and suffered relapse of proteinuria and renal insufficiency. We hypothesize that secondary FSGS results from a combination of postadaptive glomerular changes driven by increased lean body mass and potential direct nephrotoxic effects of anabolic steroids. Because of the expected rise in serum creatinine as a result of increased muscle mass in bodybuilders, this complication is likely underrecognized.
Cardiovascular function at rest and on exercise in patients with cryptogenic fibrosing alveolitis.
Authors: A Bush, C M Busst
Journal: Thorax (1988)

<h3>Objectives</h3> We previously identified long-lived plasma cells (PCs) are an essential component of the pathogenic immunologic memory, which is resistant to immunosuppressive and B cell depleting therapies and contributes to the chronicity of SLE. We recently demonstrated that their targeting with the proteasome inhibitor bortezomib resulted in therapeutically relevant plasma cell depletion in refractory cases of SLE. Here we investigated in detail the cellular and serologic responses of bortezomib treatment. <h3>Methods</h3> Eight patients received a median of two 21-day cycles of intravenous bortezomib 1.3mg/m<sup>2</sup> as induction therapy for active SLE. Disease activity was assessed using the SLEDAI-2K score. Serum concentrations of anti-double-stranded DNA (anti-dsDNA), vaccine-induced antibodies and BAFF levels were monitored. Flow cytometry was performed to analyse peripheral blood B cells, T cells and PCs and Siglec-1 expression on monocytes as surrogate marker for type-I interferon (IFN). <h3>Results</h3> Upon proteasome inhibition, serum levels for anti-double-stranded (ds)DNA (~60%) and vaccine-induced antibodies for Measels, Mumps, TT (~30%) significantly declined, complement levels and serum BAFF levels significantly increased and SLEDAI significantly decreased (p=0.014). The level of bone marrow PCs decreased by 50%, affecting both CD19<sup>+</sup> and CD19<sup>-</sup> CD138/CD38 expressing PCs. While number and phenotype of peripheral blood T- and B cells remained unaffected, proteasome inhibition was associated with a significant depletion of HLA-DR<sup>+</sup> (p=0.024), HLA-DR<sup>-</sup> (p=0.038) and IgA<sup>+</sup> (p=0.032) PCs, but their regeneration was fast. Within ten days from the last bortezomib injection, their numbers significantly increased (beta=2.1; 95% CI: 0.5, 3.7; p=0.012), an effect that was more pronounced in HLA-DR<sup>+</sup> short-lived than in HLA-DR<sup>-</sup> long-lived PCs. Overall, the magnitude of increase over time did not significantly decrease. Siglec-1 expression on monocytes significantly declined. <h3>Conclusions</h3> These findings identify proteasome inhibitors as a promising novel treatment option for patients with refractory SLE by targeting short- and long-lived PCs and type I IFN activity. Bortezomib efficiently induces short-term remissions but would require additional B cell directed treatment approaches to inhibit PC regeneration from their precursors for sustained efficacy.
Genetic Testing for<i>BRCA</i>Mutations Today and Tomorrow—About the ABOUT Study
Authors: Steven Narod
Journal: JAMA Oncology (2015)

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 Oncology 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 Oncology journal
An Ixodes scapularis protein required for survival of Anaplasma phagocytophilum in tick salivary glands
Authors: Bindu Sukumaran, Sukanya Narasimhan, John F. Anderson, Kathleen DePonte, Nancy Marcantonio, Manoj N. Krishnan, Durland Fish, Sam R. Telford, Fred S. Kantor, Erol Fikrig
Journal: The Journal of Experimental Medicine (2006)

Anaplasma phagocytophilum is the agent of human anaplasmosis, the second most common tick-borne illness in the United States. This pathogen, which is closely related to obligate intracellular organisms in the genera Rickettsia, Ehrlichia, and Anaplasma, persists in ticks and mammalian hosts; however, the mechanisms for survival in the arthropod are not known. We now show that A. phagocytophilum induces expression of the Ixodes scapularis salp16 gene in the arthropod salivary glands during vector engorgement. RNA interference–mediated silencing of salp16 gene expression interfered with the survival of A. phagocytophilum that entered ticks fed on A. phagocytophilum–infected mice. A. phagocytophilum migrated normally from A. phagocytophilum–infected mice to the gut of engorging salp16-deficient ticks, but up to 90% of the bacteria that entered the ticks were not able to successfully infect I. scapularis salivary glands. These data demonstrate the specific requirement of a pathogen for a tick salivary protein to persist within the arthropod and provide a paradigm for understanding how Rickettsia-like pathogens are maintained within vectors.
Novel Models of Myxoid Liposarcoma Xenografts Mimicking the Biological and Pharmacologic Features of Human Tumors
Authors: Roberta Frapolli, Elena Tamborini, Emanuela Virdis, Ezia Bello, Eva Tarantino, Sergio Marchini, Federica Grosso, Roberta Sanfilippo, Alessandro Gronchi, Juan Carlos Tercero, Gabriella Peloso, Paolo Casali, Silvana Pilotti, Maurizio D'Incalci
Journal: Clinical Cancer Research (2010)

Abstract Purpose: Myxoid liposarcoma is a common subtype of liposarcoma. It is associated in more than 90% of cases with the chromosomal translocation t(12;16)(q13;p11) leading to the fusion FUS-CHOP gene that is responsible for the oncogenic transformation of preadipocytes. Recently the marine natural product trabectedin has shown highly selective activity for myxoid liposarcoma, even in the most aggressive round-cell subtype. Experimental Design: Fragments of 17 sarcomas were transplanted s.c. in female athymic NCr-nu/nu mice. Xenografts were established and characterized by morphology, fluorescence in situ hybridization analysis for the translocation and reverse transcriptase-PCR analysis for fusion transcripts. Trabectedin was injected i.v. Results: Seven of 17 tumors grew as continuous xenografts, five of them being myxoid liposarcoma of the round-cell subtype. The chromosomal rearrangement and fusion transcripts in different passages were the same as in the human tumors from which they were derived. The responsiveness to trabectedin in type II myxoid liposarcoma xenografts was as high as in patients. The pathologic response was associated with the presence of the FUS-CHOP fusion gene, indicating that the drug does not totally eradicate the disease. Type III myxoid liposarcoma xenografts seemed much less sensitive to trabectedin, confirming previous clinical observations. Conclusions: This study reports for the first time the characterization of human myxoid liposarcoma xenografts that adequately mimic the biological and pharmacologic features of the human tumor. These models offer a useful tool for investigating the mechanism of selectivity of trabectedin, testing new combinations with this drug and evaluating novel therapies for myxoid liposarcoma. Clin Cancer Res; 16(20); 4958–67. ©2010 AACR.
Noninvasive Coronary Angiography With Multislice Computed Tomography
Authors: Martin H. K. Hoffmann
Journal: JAMA (2005)

Multislice computed tomography (MSCT) has recently evolved as a modality for noninvasive coronary imaging.To assess the accuracy and robustness of MSCT vs the criterion standard of invasive coronary angiography for detection of obstructive coronary artery disease.Prospective, single-center study conducted in a referral center setting in Germany and enrolling 103 consecutive patients (mean age, 61.5 [SD, 9.7] years) from November 2003-August 2004 who were undergoing both invasive coronary angiography and MSCT using a scanner with 16 detector rows.Blinded results for both modalities compared using the patient as the primary unit of analysis, with supplementary segment- and vessel-based analyses.One thousand three hundred eighty-four segments (> or =1.5 mm diameter) were identified by invasive coronary angiography; nondiagnostic image quality of MSCT was identified for only 88 (6.4%) of these segments, mainly due to faster heart rates. Compared with invasive coronary angiography for detection of significant lesions (>50% stenosis), segment-based sensitivity, specificity, and positive and negative predictive values of MSCT were 95%, 98%, 87%, and 99%, respectively. Quantitative comparison of MSCT and invasive coronary angiography showed good correlation (r = 0.87, P<.001), with MSCT systematically measuring greater-percentage stenoses (bias, +12%). In the patient-based analysis, the area under the receiver operating characteristic curve was 0.97 (95% confidence interval, 0.90-1.00), indicating high discriminative power to identify patients who might be candidates for revascularization (>50% left main artery stenosis and/or >70% stenosis in any other epicardial vessel). Threshold optimization allowed either detection of these patients with 100% sensitivity at a reasonable false-positive rate (specificity, 76.5%; MSCT stenosis, >66%) or optimization of both the sensitivity and specificity (>90%; MSCT stenosis, >76%).Multislice computed tomography provides high accuracy for noninvasive detection of suspected obstructive coronary artery disease. This promising technology has potential to complement diagnostic invasive coronary angiography in routine clinical care.
The relation between cigarette smoking and risk of acute myeloid leukemia: An updated meta‐analysis of epidemiological studies
Authors: Sophia Fircanis, Priscilla Merriam, Naushaba Khan, Jorge J. Castillo
Journal: American Journal of Hematology (2014)

Smoking has been postulated as an environmental risk factor for acute myeloid leukemia (AML). The primary objective of this meta‐analysis of observational studies was to evaluate the epidemiologic relationship between smoking and the risk of development of AML. Twenty‐three studies published between January 1993 and December 2013 were included in our analysis, and accounted for 7,746 cases of AML. The outcome of interest was the relative risk (RR) with 95% confidence interval (CI) of developing AML in adult cigarette smokers in comparison with non‐smokers, and was estimated using the random‐effects model. Our results showed that current and ever smokers have 40% (RR 1.40, 95% CI 1.22–1.60; P &lt; 0.001) and 25% (RR 1.25, 95% CI 1.15–1.36; P &lt; 0.001) increased risk of developing AML when compared with non‐smokers. The increased RR of AML was increased regardless of sex, study design, geographical region, and quality of the studies. Intensity of smoking of &lt;10, 10–20, 20–30, and &gt;30 cigarettes per day was associated with RRs of AML of 1.27, 1.36, 1.55, and 1.77, respectively ( P &lt; 0.001 for trend). Duration of smoking of &lt;20 and &gt;20 years was associated with RRs of 1.07 and 1.44, respectively ( P &lt; 0.001 for trend). Cumulative smoking of &lt;10, 10–20, 20–30, and &gt;30 pack‐years was associated with RRs of 1.13, 1.23, 1.39, and 1.71, respectively ( P &lt; 0.001 for trend). Overall, cigarette smoking proves to be a significant risk factor for the development of AML in adults. Am. J. Hematol. 89:E125–E132, 2014. © 2014 Wiley Periodicals, Inc.
The Impact of Comorbid Posttraumatic Stress Disorder on Short-Term Clinical Outcome in Hospitalized Patients With Depression
Authors: Paul E. Holtzheimer, Joan Russo, Douglas Zatzick, Christopher Bundy, Peter P. Roy-Byrne
Journal: American Journal of Psychiatry (2005)

Posttraumatic stress disorder (PTSD) is often comorbid with other psychiatric disorders but often goes unrecognized. The effects of PTSD comorbidity are unclear, especially in patients with severe mental illness. The authors assessed short-term clinical outcome in severely depressed psychiatric inpatients with and without comorbid PTSD.From patients hospitalized between 1995 and 2000, all patients with depression and comorbid PTSD (N=587) were selected and matched with depressed patients without PTSD (N=587). Clinical outcome was assessed with a semistructured, physician-administered battery. Differences between the two groups were examined, with overall burden of psychiatric illness entered as a covariate in the analyses.Relative to depressed patients without PTSD, depressed patients with PTSD had, at discharge, greater psychiatric symptom severity and higher levels of depression and hostility. Depressed patients with comorbid PTSD also had a significantly higher rate of being discharged against medical advice (odds ratio=6.10, 95% CI 2.96-12.57).PTSD comorbidity correlates with poorer short-term clinical outcome and greater likelihood of discharge against medical advice in severely depressed psychiatric inpatients. Better recognition of PTSD comorbidity may improve overall care of these patients.
Intensive cognitive behaviour therapy for chronic schizophrenia
Authors: D. Curtis, N. Tarrier
Journal: BMJ (1999)

Editor—Tarrier et al’s randomised controlled trial of intensive cognitive behaviour therapy for patients with chronic schizophrenia seems to show that cognitive behaviour therapy offers advantages over routine care alone. It is not clear, however, that the patients receiving cognitive behaviour therapy did better than a third group, which received non-specific supportive counselling. The outcomes in this group were intermediate between those for the cognitive behaviour therapy and routine care groups and apparently did not differ significantly from either, although the paper is not as clear as it could be on this point.

This study provides some evidence that the course of schizophrenia can be improved by psychological support, but we cannot conclude that cognitive behaviour therapy exerts any specific effect. This is important for two reasons. Firstly, understanding what interventions affect the course of the illness may help us to understand the pathological mechanisms involved. Secondly, cognitive behaviour therapy is likely to be substantially more expensive than supportive counselling. Many schizophrenic patients already receive supportive counselling as part of their routine care, perhaps as part of sessions with a key worker at a day centre or in their supported accommodation. Finally, the authors did not mention the fact that of the patients available for follow up, 8 of 32 receiving cognitive behaviour therapy dropped out or refused follow up while only 3 of 24 receiving supportive counselling did so. This difference is not significant, but it is as noteworthy as several of the results that the authors do draw attention to.
Increasing Use of Radical Prostatectomy for Nonlethal Prostate Cancer in Sweden
Authors: Ruth Etzioni, Lorelei Mucci, Shu Chen, Jan-Erik Johansson, Katja Fall, Hans-Olov Adami
Journal: Clinical Cancer Research (2012)

The number of patients in Sweden treated with radical prostatectomy for localized prostate cancer has increased exponentially. The extent to which this increase reflects treatment of nonlethal disease detected through prostate-specific antigen (PSA) screening is unknown.We undertook a nationwide study of all 18,837 patients with prostate cancer treated with radical prostatectomy in Sweden from 1988 to 2008 with complete follow-up through 2009. We compared cumulative incidence curves, fit Cox regression and cure models, and conducted a simulation study to determine changes in treatment of nonlethal cancer, in cancer-specific survival over time, and effect of lead-time due to PSA screening.The annual number of radical prostatectomies increased 25-fold during the study period. The 5-year cancer-specific mortality rate decreased from 3.9% [95% confidence interval (CI), 2.5-5.3] among patients diagnosed between 1988 and 1992 to 0.7% (95% CI, 0.4-1.1) among those diagnosed between 1998 and 2002 (P(trend) < 0.001). According to the cure model, the risk of not being cured declined by 13% (95% CI, 12%-14%) with each calendar year. The simulation study indicated that only about half of the improvement in disease-specific survival could be accounted for by lead-time.Patients overdiagnosed with nonlethal prostate cancer appear to account for a substantial and growing part of the dramatic increase in radical prostatectomies in Sweden, but increasing survival rates are likely also due to true reductions in the risk of disease-specific death over time. Because the magnitude of harm and costs due to overtreatment can be considerable, identification of men who likely benefit from radical prostatectomy is urgently needed.
SCAR HETEROGENEITY ON CARDIAC MAGNETIC RESONANCE IMAGING IS A PREDICTOR OF APPROPRIATE IMPLANTABLE CARDIOVERTER DEFIBRILLATOR THERAPY: 10 YEARS OF EXPERIENCE
Authors: Hussein Rayatzadeh, Alex Tan, Thomas Hauser, Jaime Shaw, Shalin Patel, Susie Hong, Raymond Chan, Peter Zimetbaum, Alfred Buxton, Mark Josephson, Warren Manning, reza nezafat
Journal: Journal of the American College of Cardiology (2012)
Surgical treatment of partial tears of the proximal origin of the hamstring muscles
Authors: L Lempainen, J Sarimo, J Heikkilä, K Mattila, S Orava
Journal: British Journal of Sports Medicine (2006)

Background: Hamstring injuries are common especially in athletes. Partial and complete tears of the proximal origin may cause pain and functional loss. Objective: To evaluate the results of surgical treatment for partial proximal hamstring tears. Methods: Between 1994 and 2005, 47 athletes (48 cases, 1 bilateral) with partial proximal hamstring tears were operated on. The cases were retrospectively analysed. Before surgery, 42 of the patients had undergone conservative treatment with unsatisfactory results, whereas in five patients the operation was performed within four weeks of the injury. Results: The mean length of the follow up was 36 months (range 6–72). The result of the operation was rated excellent in 33 cases, good in nine, fair in four, and poor in two. Forty one patients were able to return to their former level of sport after an average of five months (range 1–12). Conclusion: In most cases, excellent or good results can be expected after surgical repair of partial proximal hamstring tears even after conservative treatment has failed.