tbuckley/cabot-search huggingface dataset:
Randomized trial of chemoendocrine therapy started before or after surgery for treatment of primary breast cancer.
Authors: T J Powles, T F Hickish, A Makris, S E Ashley, M E O'Brien, V A Tidy, S Casey, A G Nash, N Sacks, D Cosgrove
Journal: Journal of Clinical Oncology (1995)

PURPOSE To evaluate in a randomized clinical trial systemic chemoendocrine therapy used as primary (neo-adjuvant) treatment before surgery in women with primary operable breast cancer. PATIENTS AND METHODS Patients aged less than 70 years with clinically palpable, primary operable breast cancer diagnostically confirmed by fine-needle aspiration cytology (FNAC) and suitable for treatment with surgery, radiotherapy, cytotoxic chemotherapy, and tamoxifen were considered eligible. Patients randomized to neoadjuvant treatment received four cycles of chemo-therapy for 3 months before surgery followed by another four cycles after surgery, and were compared with patients randomized to adjuvant therapy who received eight cycles of chemotherapy over 6 months after surgery. RESULTS Of 212 patients who were randomized to receive either adjuvant (n = 107) or neoadjuvant (n = 105) chemoendocrine therapy, 200 are now assessable for response. The two groups are comparable for age, menopausal status, disease stage, and surgical requirements. The overall clinical response rate was 85%, with a complete histologic response rate of 10%. There was a significant reduction in the requirement for mastectomy in patients who received neoadjuvant treatment (13%) as compared with those who received adjuvant therapy (28%) (P &lt; .005). Symptomatic and hematologic acute toxicity was low and similar for adjuvant and neoadjuvant therapy. The median follow-up period for patients in this trial is 28 months, during which time four patients have relapsed locally and 20, including one of the local relapses, have developed metastatic disease, 19 of whom have died. The follow-up period is too brief to evaluate relapse rate or survival duration. CONCLUSION This trial confirms previous reports of a high rate of response to neoadjuvant therapy, but is the first to include small primary cancers and to show, in the context of a randomized trial, a reduction in the requirement for mastectomy. Until disease-free and overall survival data are available from the larger National Surgical Adjuvant Breast and Bowel Project (NSABP)-18 trial, such neoadjuvant treatment cannot be recommended outside of a clinical trial.
Clinical features of adults with seven-valent- conjugated-vaccine- serotype pneumococcal pneumonia
Authors: Chamira Rodrigo, Thomas Bewick, Carmen Sheppard, Sonia Greenwood, Mary Slack, Caroline Trotter, Robert George, Wei Shen Lim
Journal: European Respiratory Journal (2013)

Background: A reduction in adult invasive pneumococcal infection has followed the introduction of a seven-valent childhood pneumococcal conjugate vaccine (PCV7) in 2006 and a thirteen-valent vaccine in 2010 in the UK. The characteristics of adults who continue to have PCV7-serotype pneumococcal pneumonia have not been described.  Methods: Adults hospitalised with community acquired pneumonia from September 2008 to August 2011 were prospectively studied. Pneumococcal serotyping was performed using a validated multiplex assay. Patients with PCV7-serotype disease were compared with non-PCV7-serotype disease.  Results: Of 1166 patients with CAP, 415 (35.6%) had pneumococcal disease. PCV7 serotypes were identified in 77 (27.1%) of 284 patients with a pneumococcal serotype determined. These patients were significantly older (median years 73.3 inter-quartile range (IQR)(60.8-84.4) versus 65.0 IQR (46.1-78.0); p=0.001) and had more co-morbidities (cognitive impairment (odds ratio (OR) 4.76, 95% confidence interval (95%CI) 1.77-12.78), chronic kidney disease (OR 2.87, 95%CI 1.04-7.94), stroke disease (OR 3.44, 95%CI 1.69-6.99)) compared to other patients. The proportion of patients with a World Health Organisation (WHO) performance status ≥1 was significantly greater in the PCV7-serotype group (OR 2.05, 95%CI 1.21-3.50). Adjusted 30-day mortality (OR 3.96, 95%CI 1.53-10.29; p=0.005) and 30-day re-admission rates (OR 3.22, 95%CI 1.28-8.10, p=0.013) were significantly associated with PCV7-disease.  Conclusions: CAP due to PCV7 serotypes was associated with older patients with greater co-morbidity. Thirty-day mortality and re-admission rates were independently associated with PCV7 serotypes.
Continuing Evolution in Breast Cancer Surgical Management
Authors: Eleftherios P. Mamounas
Journal: Journal of Clinical Oncology (2005)

The surgical management of primary breast cancer underwent significant evolution in the last quarter of the 20th century as a result of changes in the biologic understanding and clinical presentation of the disease. The proposal of an alternative hypothesis for the mechanism of tumor dissemination challenged the previously accepted Halstedian principles that had governed surgical management for the better part of that century. Randomized clinical trials were supportive of this alternative hypothesis and eventually established breast-conserving surgery plus radiotherapy as the preferred option for treating appropriate candidates with primary breast cancer. The alternative hypothesis was also supported by results from clinical trials indicating that the administration of adjuvant systemic therapy significantly improved disease-free and overall survival of patients with early-stage breast cancer. Adjuvant systemic therapy played an important role in the successful adoption of breast-conserving surgery plus radiotherapy by decreasing the rates of locoregional failure and by expanding the pool of candidates (by its use as preoperative or neoadjuvant therapy).
Evaluation of the effectiveness of neuromuscular training to reduce anterior cruciate ligament injury in female athletes: a critical review of relative risk reduction and numbers-needed-to-treat analyses
Authors: Dai Sugimoto, Gregory D Myer, Jennifer M McKeon, Timothy E Hewett
Journal: British Journal of Sports Medicine (2012)

Since previous numbers-needed-to-treat (NNT) and relative risk reduction (RRR) report, a few studies were published to evaluate prophylactic effectiveness of neuromuscular training for anterior cruciate ligament (ACL) injury in female athletes. The purpose of the current analyses was to determine the effectiveness of neuromuscular training interventions in reducing both non-contact and overall ACL injury risk in female athletes through RRR and NNT. The keywords ‘knee’, ‘anterior cruciate ligament’, ‘ACL’, ‘prospective’, ‘neuromuscular’, ‘training’, ‘female’ and ‘prevention’ were searched to find studies published from 1995 to 2011 in PubMed and EBSCO (CINAHL, Health source, MEDLINE and SPORT Discus). Inclusion criteria required that relevant studies: recruited physically active young girls as subjects, documented the number of ACL injuries, employed a neuromuscular training intervention, and used a prospective controlled study design. The numbers of non-contact and overall ACL injuries, subjects and observation time period were used to calculate RRR and NNT for each study. A total of 12 studies met the inclusion criteria. There was a 73.4% (95% CI 62.5% to 81.1%) and 43.8% (95% CI 28.9% to 55.5%) of RRR for non-contact and overall ACL injuries. From the NNT analysis, it was determined that, respectively, 108 (95% CI 86 to 150) and 120 (95% CI 74 to 316) individuals would need to be trained to prevent one non-contact or one overall ACL injury over the course of one competitive season. Although the RRR analysis indicated prophylactic benefits of neuromuscular training, the relatively large NNT indicated that many athletes are needed to prevent one ACL injury. A future direction to reduce NNT and improve the efficiency of ACL injury-prevention strategies is to develop a screening system for identifying at-risk athletes.
Elastase 2 is expressed in human and mouse epidermis and impairs skin barrier function in Netherton syndrome through filaggrin and lipid misprocessing
Authors: Chrystelle Bonnart, Céline Deraison, Matthieu Lacroix, Yoshikazu Uchida, Céline Besson, Aurélie Robin, Anaïs Briot, Marie Gonthier, Laurence Lamant, Pierre Dubus, Bernard Monsarrat, Alain Hovnanian
Journal: Journal of Clinical Investigation (2010)

The human epidermis serves 2 crucial barrier functions: it protects against water loss and prevents penetration of infectious agents and allergens. The physiology of the epidermis is maintained by a balance of protease and antiprotease activities, as illustrated by the rare genetic skin disease Netherton syndrome (NS), in which impaired inhibition of serine proteases causes severe skin erythema and scaling. Here, utilizing mass spectrometry, we have identified elastase 2 (ELA2), which we believe to be a new epidermal protease that is specifically expressed in the most differentiated layer of living human and mouse epidermis. ELA2 localized to keratohyalin granules, where it was found to directly participate in (pro-)filaggrin processing. Consistent with the observation that ELA2 was hyperactive in skin from NS patients, transgenic mice overexpressing ELA2 in the granular layer of the epidermis displayed abnormal (pro-)filaggrin processing and impaired lipid lamellae structure, which are both observed in NS patients. These anomalies led to dehydration, implicating ELA2 in the skin barrier defect seen in NS patients. Thus, our work identifies ELA2 as a major new epidermal protease involved in essential pathways for skin barrier function. These results highlight the importance of the control of epidermal protease activity in skin homeostasis and designate ELA2 as a major protease driving the pathogenesis of NS.
Body mass index in male patients with COPD: correlation with low attenuation areas on CT
Authors: E Ogawa, Y Nakano, T Ohara, S Muro, T Hirai, S Sato, H Sakai, M Tsukino, D Kinose, M Nishioka, A Niimi, K Chin, P D Pare, M Mishima
Journal: Thorax (2008)

<h3>Background and objectives</h3> Nonsteroidal anti-inflammatory drugs (NSAIDs) have been associated with AKI. Their association with nephrotic syndrome has not been systematically studied. This study aimed to assess the risk of nephrotic syndrome associated with NSAID use. <h3>Design, setting, participants, &amp; measurements</h3> A matched case-control study was performed in the UK primary care database. Cases were patients with a first diagnosis of nephrotic syndrome and controls were those without nephrotic syndrome. NSAID exposure (grouped either based on cyclooxygenase enzyme selectivity and chemical groups) was classified as either current (use at the nephrotic syndrome diagnosis date and corresponding date in the control group), recent, or past use. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using unconditional logistic regression analysis. <h3>Results</h3> We included 2620 cases and 10,454 controls. Compared with non-use, current use of 15–28 days and &gt;28 days of conventional NSAIDs was associated with a higher relative risk of nephrotic syndrome: adjusted OR, 1.34; 95% CI, 1.06 to 1.70, and OR, 1.42; 95% CI, 0.79 to 2.55, respectively. Also, recent use (discontinuation 1–2 months before nephrotic syndrome diagnosis date; OR, 1.55; 95% CI, 1.11 to 2.15) and past use (discontinuation 2 months-2 years; OR, 1.24; 95% CI, 1.07 to 1.43), but not current use of &lt;15 days (OR, 0.78; 95% CI, 0.46 to 1.31) nor past use (discontinuation &gt;2 years; OR, 0.96; 95% CI, 0.85 to 1.09) were associated with a higher relative risk of nephrotic syndrome as well as past use of selective COX-2 inhibitors (discontinuation 2–24 months; OR, 1.24; 95% CI, 0.98 to 1.58). Categorization based on chemical groups showed that acetic acid and propionic acid derivatives were associated with a higher risk of nephrotic syndrome. <h3>Conclusions</h3> The use of conventional NSAIDs was associated with a higher risk of nephrotic syndrome starting from at least 2 weeks of exposure, as well as for recent and past exposure up to 2 years before the diagnosis of nephrotic syndrome. This higher risk appeared mainly attributable to acetic acid and propionic acid derivatives.
Impact of Target Organ Damage Assessment in the Evaluation of Global Risk in Patients with Essential Hypertension
Authors: Francesca Viazzi, Giovanna Leoncini, Denise Parodi, Elena Ratto, Simone Vettoretti, Valentina Vaccaro, Angelica Parodi, Valeria Falqui, Cinzia Tomolillo, Giacomo Deferrari, Roberto Pontremoli
Journal: Journal of the American Society of Nephrology (2005)

Accurate assessment of cardiovascular risk is a key step toward optimizing the treatment of hypertensive patients. We analyzed the impact and cost-effectiveness of routine, thorough assessment of target organ damage (TOD) in evaluating risk profile in hypertension. A total of 380 never-treated patients with essential hypertension underwent routine work-up plus evaluation of albuminuria and ultrasonography of cardiac and vascular structures. The impact of these tests on risk stratification, as indicated by European Society of Hypertension-European Society of Cardiology guidelines, was assessed in light of their cost and sensitivity. The combined use of all of these tests greatly improved the detection of TOD, therefore leading to the identification of a higher percentage of patients who were at high/very high risk, as compared with those who were detected by routine clinical work-up (73% instead of 42%; P < 0.0001). Different signs of TOD only partly cluster within the same subgroup of patients; thus, all three tests should be performed to maximize the sensitivity of the evaluation process. The diagnostic algorithm yielding the lowest cost per detected case of TOD is the search for microalbuminuria, followed by echocardiography and then carotid ultrasonography. Adopting lower cut-off values to define microalbuminuria allows us to optimize further the cost-effectiveness of diagnostic algorithms. In conclusion, because of its low cost and widespread availability, measuring albuminuria is an attractive and cost-effective screening test that is especially suitable as the first step in the large-scale diagnostic work-up of hypertensive patients.
Sex Chromosomal Transposable Element Accumulation and Male-Driven Substitutional Evolution in Humans
Authors: Rikard Erlandsson, James F. Wilson, Svante Pääbo
Journal: Molecular Biology and Evolution (2000)

We sequenced the genomic region containing the human Y-linked zinc finger gene (ZFY). Comparison of ZFY to the related region on the X chromosome (ZFX) and to autosomal sequences reveals a significant accumulation of transposable elements on the sex chromosomes. In addition, five times as many retroviruslike elements (RLEs) are present in the ZFY region as in the ZFX region. Thus, transposable elements accumulate more rapidly on the sex chromosomes, and the insertion of RLEs may occur more frequently in the male than in the female germ line. When the accumulation of substitutions in Alu elements was analyzed, it was found that the Alu elements at the Y-chromosomal locus diverged significantly faster than those at the X-chromosomal locus, whereas the divergence of autosomal Alu elements was intermediate. The male-to-female mutation rate ratio was estimated to be 2.5.
Functional Disconnection Between the Prefrontal and Parietal Cortices During Working Memory Processing in Schizophrenia: A [<sup>15</sup>O]H<sub>2</sub>O PET Study
Authors: Jae-Jin Kim, Jun Soo Kwon, Hae Jeong Park, Tak Youn, Do Hyung Kang, Myung Sun Kim, Dong Soo Lee, Myung Chul Lee
Journal: American Journal of Psychiatry (2003)

OBJECTIVE: The prefrontal-parietal circuits have been reported to play an important role in working memory. The purpose of this study was to use direct neuroimaging to address whether interregional correlation in the prefrontal-parietal circuits is impaired in schizophrenia. METHOD: [15O]H2O positron emission tomography was used to compare regional blood flow changes in 12 schizophrenic and 12 healthy comparison subjects during the n-back sequential-picture working memory task. Interregional correlation was assessed by correlating the regional activation of the lateral prefrontal area with that of other activated areas in each subject group. RESULTS: Dorsolateral prefrontal activation was observed around the right superior frontal sulcus in the healthy subjects, and ventrolateral prefrontal activation below the right inferior frontal sulcus was observed in the schizophrenic patients. Activation in the right lateral prefrontal cortex was significantly correlated with activation in the bilateral inferior parietal region in the healthy subjects but was not correlated with any regional activation in the patients. CONCLUSIONS: The findings suggest prefrontal-parietal functional disconnection, particularly prefrontal dissociation and abnormal prefrontal-parietal interaction, during working memory processing in schizophrenia.
Comprehensive 4-Dimensional Magnetic Resonance Flow Analysis After Successful Heart Transplantation Resolves Controversial Intraoperative Findings and Reveals Complex Hemodynamic Alterations
Authors: Michael Markl, Julia Geiger, Raoul Arnold, Anna Stroh, Domagoj Damjanovic, Daniela Föll, Friedhelm Beyersdorf
Journal: Circulation (2011)
Positionally cloned genes and age-specific effects in asthma and atopy: an international population-based cohort study (ECRHS)
Authors: F. Castro-Giner, R. de Cid, J. R. Gonzalez, D. Jarvis, J. Heinrich, C. Janson, E. R. Omenaas, M. C. Matheson, I. Pin, J. M. Anto, M. Wjst, X. Estivill, M. Kogevinas
Journal: Thorax (2009)

<h3>Background</h3> Several genes identified by positional cloning have been associated with asthma and atopy, but few findings have been replicated. Age at onset of asthma has been associated with different phenotypic characteristics, and with variants at chromosome 17q21 identified through genome-wide association. This study examined the associations and age-specific effects on asthma, atopy and bronchial hyper-responsiveness (BHR) of five candidate genes previously identified by positional cloning (<i>ADAM33, PHF11, NPSR1, DPP10, SPINK5</i>). <h3>Methods</h3> 51 polymorphisms from 2474 participants from 13 countries who took part in the European Community Respiratory Health Survey (1990–2000) were studied. Asthma and age at onset of asthma were assessed by questionnaire data, BHR by methacholine challenge and atopy by specific immunoglobulin E to four common allergens. <h3>Results</h3> Significant associations with asthma, atopy and particularly for asthma with atopy were observed for a large region of 47 kb in the <i>NPSR1</i> gene, even after Bonferroni correction for multiple comparisons (p&lt;0.001). The associations with <i>NPSR1</i> were stronger in those reporting a first attack of asthma before the age of 15, with statistically significant interactions with age of onset found for three SNPs. The evidence for <i>ADAM33</i> and BHR and for an age-specific effect of two SNPs in <i>DPP10</i> and asthma was weaker. <h3>Conclusion</h3> This study provides further evidence for an effect of <i>NPSR1</i> on asthma, atopy and atopic asthma. In addition, this analysis suggests a role for <i>NPSR1</i> in early-onset asthma driven by the strong effect of this gene on atopic asthma.
Hematopoietic Cell Transplantation for Systemic Mature T-Cell Non-Hodgkin Lymphoma
Authors: Sonali M. Smith, Linda J. Burns, Koen van Besien, Jennifer LeRademacher, Wensheng He, Timothy S. Fenske, Ritsuro Suzuki, Jack W. Hsu, Harry C. Schouten, Gregory A. Hale, Leona A. Holmberg, Anna Sureda, Cesar O. Freytes, Richard Thomas Maziarz, David J. Inwards, Robert Peter Gale, Thomas G. Gross, Mitchell S. Cairo, Luciano J. Costa, Hillard M. Lazarus, Peter H. Wiernik, Dipnarine Maharaj, Ginna G. Laport, Silvia Montoto, Parameswaran N. Hari
Journal: Journal of Clinical Oncology (2013)

To analyze outcomes of hematopoietic cell transplantation (HCT) in T-cell non-Hodgkin lymphoma.Outcomes of 241 patients (112 anaplastic large-cell lymphoma, 102 peripheral T-cell lymphoma not otherwise specified, 27 angioimmunoblastic T-cell lymphoma) undergoing autologous HCT (autoHCT; n = 115; median age, 43 years) or allogeneic HCT (alloHCT; n = 126; median age, 38 years) were analyzed. Primary outcomes were nonrelapse mortality (NRM), relapse/progression, progression-free survival (PFS), and overall survival (OS). Patient, disease, and HCT-related variables were analyzed in multivariate Cox proportional hazard models to determine association with outcomes.AutoHCT recipients were more likely in first complete remission (CR1; 35% v 14%; P = .001) and with chemotherapy-sensitive disease (86% v 60%; P < .001), anaplastic large-cell histology (53% v 40%; P = .04), and two or fewer lines of prior therapy (65% v 44%; P < .001) compared with alloHCT recipients. Three-year PFS and OS of autoHCT recipients beyond CR1 were 42% and 53%, respectively. Among alloHCT recipients who received transplantations beyond CR1, 31% remained progression-free at 3 years, despite being more heavily pretreated and with more refractory disease. NRM was 3.5-fold higher (95% CI, 1.80 to 6.99; P < .001) for alloHCT. In multivariate analysis, chemotherapy sensitivity (hazard ratio [HR], 1.8; 95% CI, 1.16 to 2.87) and two or fewer lines of pretransplantation therapy (HR, 5.02; 95% CI, 2.15 to 11.72) were prognostic of survival.These data describe the roles of autoHCT and alloHCT in T-cell non-Hodgkin lymphoma and suggest greater effectiveness earlier in the disease course, and limited utility in multiply relapsed disease. Notably, autoHCT at relapse may be a potential option for select patients, particularly those with anaplastic large-cell lymphoma histology.
Five-Year Course and Outcome of Dysthymic Disorder: A Prospective, Naturalistic Follow-Up Study
Authors: Daniel N. Klein, Joseph E. Schwartz, Suzanne Rose, Julie B. Leader
Journal: American Journal of Psychiatry (2000)

OBJECTIVE: There have been few naturalistic follow-up studies of dysthymic disorder. This study describes the 5-year course and outcome of dysthymic disorder.METHOD: The authors conducted a prospective, longitudinal follow-up study of 86 outpatients with early-onset dysthymic disorder and 39 outpatients with episodic major depressive disorder. Follow-ups, conducted 30 and 60 months after entry into the study, rated patients on the Longitudinal Interval Follow-Up Evaluation and the Modified Hamilton Rating Scale for Depression.RESULTS: The estimated 5-year recovery rate from dysthymic disorder was 52.9%. Among patients who recovered, the estimated risk of relapse was 45.2% during a mean of 23 months of observation. Patients with dysthymic disorder spent approximately 70% of the follow-up period meeting the full criteria for a mood disorder. During the course of the follow-up the patients with dysthymic disorder exhibited significantly greater levels of symptoms and lower functioning and were significantly more likely to attempt suicide and to be hospitalized than were patients with episodic major depressive disorder. Finally, among patients with dysthymic disorder who had never experienced a major depressive episode before entry into the study, the estimated risk of having a first lifetime major depressive episode was 76.9%.CONCLUSIONS: Dysthymic disorder is a chronic condition with a protracted course and a high risk of relapse. In addition, almost all patients with dysthymic disorder eventually develop superimposed major depressive episodes. Although patients with dysthymic disorder tend to show mild to moderate symptoms, from a longitudinal perspective, the condition is severe.