tbuckley/cabot-search huggingface dataset:
CARCINOMA OF THE COLON UNDER THE AGE OF 40
Authors: J A EZZO, J F SULLIVAN, R E MACK
Journal: Annals of Internal Medicine (1958)

Excerpt Carcinoma of the colon is a common disease. What is not appreciated is that it is one of the most common malignant growths found in young adults. Although there is ample literature dealing with colonic carcinoma, no report has been published concerning this disease in the younger age groups. On the basis of a recent experience our suspicion was raised that this disease might be a more malignant process in young adults. We have therefore conducted a review of the cases of colonic carcinoma seen at the St. Louis University Hospitals in order to investigate this point. MATERIAL FOR REVIEW
Targeting of Cell Surface Proteolysis of Collagen XVII Impedes Squamous Cell Carcinoma Progression
Authors: Célimène Galiger, Stefanie Löffek, Marc P. Stemmler, Jasmin K. Kroeger, Venugopal R. Mittapalli, Lisa Fauth, Philipp R. Esser, Johannes S. Kern, Frank Meiss, Silke Laßmann, Leena Bruckner-Tuderman, Claus-Werner Franzke
Journal: Molecular Therapy (2017)
Efficacy of 12 weeks neoadjuvant nab-paclitaxel combined with carboplatinum vs. gemcitabine in triple-negative breast cancer: WSG-ADAPT TN randomized phase II trial.
Authors: Oleg Gluz, Ulrike Nitz, Matthias Christgen, Eva-Maria Grischke, Helmut Forstbauer, Michael Wilhelm Braun, Mathias Warm, Christoph Uleer, Bahriye Aktas, Claudia Schumacher, John Hackmann, Nikola Bangemann, Peter Staib, Christoph Lindner, Sherko Kummel, Cornelia Liedtke, Ronald E. Kates, Rachel Wuerstlein, Hans Heinrich Kreipe, Nadia Harbeck
Journal: Journal of Clinical Oncology (2015)

1032 Background: Pathological complete response (pCR) is associated with improved prognosis in TNBC, but optimal chemotherapy remains unclear. Neoadjuvant weekly nab-paclitaxel (Nab-Pac) has higher efficacy than conventional paclitaxel, with maximum benefit in TNBC. Both gemcitabine (Gem) and carboplatinum (Carbo) are interesting partners for taxane combinations, as metastastic BC data reveal. Methods: ADAPT TN compares 12-week neoadjuvant regimens: Carbo vs. Gem combined with Nab-Pac and aims to identify early-response markers for pCR (yPN0 and ypT0/is). TNBC patients (ER/PR < 1%, centrally HER2 neg.), cT1c-cT4c, cN0/+ were randomized to arm A (Nab-Pac 125/Gem 1000 d1,8 q3w) vs. B (Nab-Pac 125/Carbo AUC2 d1,8 q3w). The trial is powered for pCR comparison by therapy arm and by presence vs. absence of early response. Pre-planned interim analysis aimed to identify a dynamic biomarker, e.g. drop of 3-week Ki-67, and to validate trial assumptions. Results: The first 130 randomized patients were assessed for interim analysis: 69 in arm A, 61 in arm B; 84% vs. 93% completed study therapy (p = 0.1), respectively. Median age was 50y. At baseline, 93% had G3 tumors, median Ki-67 was 65%; 64% had cT2-4c tumors, 23% cN+. SAE analysis: 20 SAEs in 10 patients (A) vs. 5 SAEs in 5 patients (B) were reported (p = 0.3). pCR occurred in 36% of patients overall; A: 25%, B: 49.2% (p = .006). In contrast to a strong association of baseline Ki-67 with pCR, no significant association between pCR and dynamic Ki-67 change was detected among patients with at least 500 tumor cells in the 3-week biopsy; however, 49% of patients had less than 500 tumor cells, and this condition appeared to be positively associated with pCR. Conclusions: Early results suggest rather intriguing high efficacy and favorable toxicity of short-term therapy with Nab-Pac + Carbo vs. Gem in unselected TNBC. Identification of early-proliferation responders by pre-specified protocol for Ki-67 drop failed, possibly due to substantial tumor necrosis already after first therapy cycle. 336 pts were enrolled at 45 sites by 01/2015. The study will be completed in April, 2015. Clinical trial information: NCT01815242.
Serial monitoring of BCR-ABL in newly diagnosed Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) treated with imatinib.
Authors: Sung-nam Lim, Young-Don Joo, Il-Hwan Kim, Won-Sik Lee, Sang Min Lee
Journal: Journal of Clinical Oncology (2016)

e18523 Background: The positive impact of imatinib on treatment outcome in Ph+ ALL is well known. The aim of this study was to evaluate the relationship between imatinib dose intensity and molecular response of BCR-ABL. Methods: Molecular response monitoring was performed at the central lab with quantitative RT-PCR assays for BCR-ABL RNA in serial; at the time of diagnosis, at hematologic complete remission (HCR), and every 3 months thereafter. The molecular response was defined as complete (MCR) if the BCR-ABL/G6PDH ratio was less than 1x10-5. Results: Between October 2005 and February 2009, total 87 patients, aged 16-71 years, were enrolled with median follow-up of 5 years among survivors (range: 2.6-8.9 years). Eighty-two patients (94%) achieved HCR at a median 25 days (range, 14-69 days) and 45 patients (57.7%) of 78 evaluable patients achieved MCR at the same time. Within three months after induction treatment, 59 patients (67.8%) achieved MCR. Total MCR rate was 88.5% during the entire study period and the median time from treatment to MCR was 54 days (range, 13-384 days). Among these 77 MCR patients, 32 experienced molecular recurrence. After allogeneic HCT, 49 of 50 evaluated patients (98%) achieved MCR. Median time of MCR duration was 13 months (range, 0.9-60.3 months) and median molecular relapse-free survival (RFS) was 28 months. Thirty two patients who lost of MCR had significantly inferior RFS (P<0.0001) and OS (P=0.001) then 41 who maintained MCR. MCR achievement within 3 months after remission induction was significant predictor of RFS (P=0.004) and OS (P=0.003). Multivariate analyses after adjusting the Cox model was described in Table 1. Conclusions: Prospective assessment of molecular response and imatinib dose intensity is useful in identifying subgroups of Ph+ALL patients at a high risk of relapse. Clinical trial information: NCT00618501.Risk Factor Molecular relapse-free survival P HR 95% CI Initial imatinib dose intensity within 7 weeks ≥90% 0.017 0.405 0.192-0.853 <90% 1 Early complete molecular response within 3 months Yes 0.001 0.251 0.111-0.570 No 1 Underwent allogeneic stem cell transplantation Yes 0.002 0.284 0.130-0.621 No 1
Clinically resolved psoriatic lesions contain psoriasis-specific IL-17–producing αβ T cell clones
Authors: Tiago R. Matos, John T. O’Malley, Elizabeth L. Lowry, David Hamm, Ilan R. Kirsch, Harlan S. Robins, Thomas S. Kupper, James G. Krueger, Rachael A. Clark
Journal: Journal of Clinical Investigation (2017)

In psoriasis, an IL-17-mediated inflammatory skin disease, skin lesions resolve with therapy, but often recur in the same locations when therapy is discontinued. We propose that residual T cell populations in resolved psoriatic lesions represent the pathogenic T cells of origin in this disease. Utilizing high-throughput screening (HTS) of the T cell receptor (TCR) and immunostaining, we found that clinically resolved psoriatic lesions contained oligoclonal populations of T cells that produced IL-17A in both resolved and active psoriatic lesions. Putative pathogenic clones preferentially utilized particular Vβ and Vα subfamilies. We identified 15 TCRβ and 4 TCRα antigen receptor sequences shared between psoriasis patients and not observed in healthy controls or other inflammatory skin conditions. To address the relative roles of αβ versus γδ T cells in psoriasis, we carried out TCR/δ HTS. These studies demonstrated that the majority of T cells in psoriasis and healthy skin are αβ T cells. γδ T cells made up 1% of T cells in active psoriasis, less than 1% in resolved psoriatic lesions, and less than 2% in healthy skin. All of the 70 most frequent putative pathogenic T cell clones were αβ T cells. In summary, IL-17-producing αβ T cell clones with psoriasis-specific antigen receptors exist in clinically resolved psoriatic skin lesions. These cells likely represent the disease-initiating pathogenic T cells in psoriasis, suggesting that lasting control of this disease will require suppression of these resident T cell populations.
ACCF/AHA 2009 Performance Measures for Primary Prevention of Cardiovascular Disease in Adults
Authors: Rita F. Redberg, Emelia J. Benjamin, Vera Bittner, Lynne T. Braun, David C. Goff, Stephen Havas, Darwin R. Labarthe, Marian C. Limacher, Donald M. Lloyd-Jones, Samia Mora, Thomas A. Pearson, Martha J. Radford, Gerald W. Smetana, John A. Spertus, Erica W. Swegler
Journal: Journal of the American College of Cardiology (2009)
Treatment decision and outcome in mRCC patients with different ECOG performance status.
Authors: Ulrika Harmenberg, Kajsa Stenmo, Caroline De Flon, Peter Wersäll, Per Sandström
Journal: Journal of Clinical Oncology (2013)

e15553 Background: Phase III studies with targeted agents have shown improved survival for mRCC. There is limited outcome data for the whole mRCC patient group. We collect data in a clinical registry at Karolinska for all patients with mRCC in the Greater Stockholm Region since 2007. Here we present the relationship between ECOG performance status and treatment outcome in this population. Methods: Between 2007 and 2012, 273 patients with mRCC were included in the registry. Patients were divided in two groups: Those that were treated with targeted agents and non- treated patients (symptomatically treated). Results: ECOG PS, available for 63%, was lower for patients treated (n=127) compared to patients not treated with systemic therapy (n=46) (median 1 vs. 2. Median OS from diagnosis to death in respective group was 731 day (n=106) and 269 days (n=55). The median OS from date of first metastasis to death was 500 days and 176 days respectively. In the treated group median OS from start of systemic therapy to death was 321 days. There was a difference in median OS from start of systemic therapy to death between patients who received 1 (n=52)(A), 2 (n=32)(B), 3 (n=16)(C) or &gt; 3 lines (n=6)(D) with a median OS of 160.5 days, 395 days, 641 days and 728.5 days respectively. Mean PS at first line treatment was 1.36 for patients who received only one line and ≤ 1 for patients who received several lines. 13/18 patients with ECOG PS 0 at 1 st line received &gt;1 line, corresponding numbers for PS 1, 2 and 3 at 1 st line were 21/40, 3/14 and 0/4. The average/ medians ECOG PS at time for the last treatment line were 1.36/1 (A), 1.47/1 (B), 1.64/2 (C) and 1.67/2 (D). Median OS from start of systemic treatment to death was dependent on PS at the start of treatment, ECOG 0 (n=18) 622 days, 1 (n=40) 724 days, ECOG2 (n=14) 226 days, ECOG3 (n=4) 44 days. Irrespective of treatment line, patients with PS 0-1 at initiation of any line of therapy had a 55% chance (47/86) of receiving a subsequent line of treatment, while patients with PS 2-3 only had a 19% chance (7/37). Conclusions: Patients with a good performance status, ECOG 0-1 at treatment start, had longer OS and received more lines of treatment. Patients with ECOG PS 3 could in our hands not be treated at all with targeted agents.
Cardiovascular Features of Heart Failure With Preserved Ejection Fraction Versus Nonfailing Hypertensive Left Ventricular Hypertrophy in the Urban Baltimore Community
Authors: Vojtech Melenovsky, Barry A. Borlaug, Boaz Rosen, Ilan Hay, Luigi Ferruci, Christopher H. Morell, Edward G. Lakatta, Samer S. Najjar, David A. Kass
Journal: Journal of the American College of Cardiology (2006)
What treatment options exist for patients with femoroacetabular impingement syndrome but without surgical indication?
Authors: Nicola C Casartelli, Mario Bizzini, Joanne Kemp, Florian D Naal, Michael Leunig, Nicola A Maffiuletti
Journal: British Journal of Sports Medicine (2017)

The most appropriate management for patients with femoroacetabular impingement (FAI) syndrome is a subject of much debate in sports medicine and orthopaedics. The recent Warwick Consensus Meeting proposed three main treatment approaches for patients with FAI syndrome: conservative care, physiotherapy-led rehabilitation or hip surgery.1 Most of the ongoing research focuses on investigating the effectiveness of hip surgery for FAI syndrome. Such studies—even if highly relevant—provide little information on non-surgical protocols for managing patients with a diagnosis of FAI syndrome who are still not candidates for hip surgery.2 

Recently, the Warwick Consensus Meeting agreed on the criteria that should lead to a diagnosis of FAI syndrome.1 These criteria include the presence of symptoms, clinical signs and imaging findings. In contrast, indications for hip surgery in patients with a diagnosis of FAI syndrome are vague.3 Besides the level of hip joint damage, which might favour the surgical option for patients with early stages of chondral lesion and severe morphologies, the failure of non-surgical management is frequently considered the most important …
A phase III study of rovalpituzumab tesirine maintenance therapy following first-line platinum-based chemotherapy in patients with extensive disease small cell lung cancer (ED SCLC).
Authors: Philip B. Komarnitsky, Ho-Jin Lee, Manan Shah, Shekman Wong, Sanja Gauthier, Juliann Dziubinski, Stacy Osbaugh, Fan Zhang
Journal: Journal of Clinical Oncology (2017)

TPS8583 Background: SCLC embodies 15-20% of lung cancers. Patients (pts) are staged with either limited or extensive disease; the standard front-line treatment for the latter is chemotherapy with carbo- or cisplatin combined with etoposide or irinotecan. Response rates are high with limited duration. Recurrence may be attributable to chemo-resistant tumor initiating cells (TICs). Delta-like protein 3 (DLL3) is an inhibitory Notch receptor ligand identified as a novel target in SCLC TICs. DLL3 is highly expressed in SCLC but not normal tissue. Rovalpituzumab tesirine (Rova-T) is an antibody-drug conjugate composed of a DLL3-targeting IgG1 monoclonal antibody tethered to a DNA cross-linking toxin. Rova-T has shown activity in recurrent/relapsed ED SCLC patients (Rudin et al., Lancet Oncol, 2016). Given DLL3 expression in TICs, exploration of Rova-T front-line maintenance strategies in ED SCLC is warranted. The postulated mechanism of action of Rova-T and its clinical activity indicate potential to improve progression-free and overall survival in this setting. Methods: This is a Phase 3, randomized, double-blind, placebo-controlled, international study (NCT03033511, no pts enrolled yet as of 7 February 2017). Approximately 740 ED SCLC pts will be enrolled to include ~480 pts with high DLL3 expression. Eligibility: pts ≥ 18 years; histologically or cytologically confirmed ED SCLC with ongoing clinical benefit (complete/partial response or stable disease) after 4 cycles of 1 st line platinum-based therapy; definitively treated CNS metastases allowed; &gt; 3 but ≤ 9 wks between the administration of the last cycle of platinum-based chemotherapy and randomization; available tumor tissue for DLL3 expression testing; ECOG performance score 0-1. Pts will be randomly assigned 1:1 to receive 0.3 mg/kg Rova-T or placebo on Day 1 of each 6-wk cycle, omitting every 3 rd cycle. Primary objectives: determine if Rova-T improves progression-free and overall survival. Secondary objectives: assess Rova-T antitumor activity by determining objective response rate, clinical benefit rate, duration of response, and changes in pt reported outcomes. Clinical trial information: NCT03033511.
A Randomized Phase <scp>II</scp>b Study of Mavrilimumab and Golimumab in Rheumatoid Arthritis
Authors: Michael E. Weinblatt, Iain B. McInnes, Joel M. Kremer, Pedro Miranda, Jiri Vencovsky, Xiang Guo, Wendy I. White, Patricia C. Ryan, Alex Godwood, Marius Albulescu, David Close, Gerd R. Burmester
Journal: Arthritis & Rheumatology (2017)

This 24-week, phase IIb, double-blind study was undertaken to evaluate the efficacy and safety of mavrilimumab (a monoclonal antibody to granulocyte-macrophage colony-stimulating factor receptor α) and golimumab (a monoclonal antibody to tumor necrosis factor [anti-TNF]) in patients with rheumatoid arthritis (RA) who have had an inadequate response to disease-modifying antirheumatic drugs (DMARDs) (referred to as DMARD-IR) and/or inadequate response to other anti-TNF agents (referred to as anti-TNF-IR).Patients with active RA and a history of DMARD-IR (≥1 failed regimen) or DMARD-IR (≥1 failed regimen) and anti-TNF-IR (1-2 failed regimens) were randomized 1:1 to receive either mavrilimumab 100 mg subcutaneously every other week or golimumab 50 mg subcutaneously every 4 weeks alternating with placebo every 4 weeks, administered concomitantly with methotrexate. The primary end points were the American College of Rheumatology 20% improvement (ACR20), 50% improvement, and 70% improvement response rates at week 24, percentage of patients achieving a Disease Activity Score in 28 joints using C-reactive protein level (DAS28-CRP) of <2.6 at week 24, percentage of patients with a score improvement of >0.22 on the Health Assessment Questionnaire (HAQ) disability index (DI) at week 24, and safety/tolerability measures. This study was not powered to formally compare the 2 treatments.At week 24, differences in the ACR20, ACR50, and ACR70 response rates between the mavrilimumab treatment group (n = 70) and golimumab treatment group (n = 68) were as follows: in all patients, -3.5% (90% confidence interval [90% CI] -16.8, 9.8), -8.6% (90% CI -22.0, 4.8), and -9.8% (90% CI -21.1, 1.4), respectively; in the anti-TNF-IR group, 11.1% (90% CI -7.8, 29.9), -8.7% (90% CI -28.1, 10.7), and -0.7% (90% CI -18.0, 16.7), respectively. Differences in the percentage of patients achieving a DAS28-CRP of <2.6 at week 24 between the mavrilimumab and golimumab groups were -11.6% (90% CI -23.2, 0.0) in all patients, and -4.0% (90% CI -20.9, 12.9) in the anti-TNF-IR group. The percentage of patients achieving a >0.22 improvement in the HAQ DI score at week 24 was similar between the treatment groups. Treatment-emergent adverse events were reported in 51.4% of mavrilimumab-treated patients and 42.6% of golimumab-treated patients. No deaths were reported, and no specific safety signals were identified.The findings of this study demonstrate the clinical efficacy of both treatments, mavrilimumab at a dosage of 100 mg every other week and golimumab at a dosage of 50 mg every 4 weeks, in patients with RA. Both regimens were well-tolerated in patients who had shown an inadequate response to DMARDs and/or other anti-TNF agents.
Six of the best: how excellent qualitative research can contribute to practice
Authors: P.A. Nelson, P. Magin, A. R. Thompson
Journal: British Journal of Dermatology (2017)

Linked Articles:Bath-Hextall et al. Br J Dermatol 2017; 177:666–687 Simpson et al. Br J Dermatol 2017; 177:742–750 Santer et al. Br J Dermatol 2017; 177: 751–757 Corr et al. Br J Dermatol 2017; 177:771–778 Smit et al. Br J Dermatol 2017; 177:779–790 Nelson et al. Br J Dermatol 2017; 177: 758–770
Phase I/II study of durvalumab and tremelimumab in patients with unresectable hepatocellular carcinoma (HCC): Phase I safety and efficacy analyses.
Authors: Robin Kate Kelley, Ghassan K. Abou-Alfa, Johanna C. Bendell, Tae-You Kim, Mitesh J. Borad, Wei-Peng Yong, Michael Morse, Yoon-Koo Kang, Marlon Rebelatto, Mallory Makowsky, Feng Xiao, Shannon R. Morris, Bruno Sangro
Journal: Journal of Clinical Oncology (2017)

4073 Background: Durvalumab and tremelimumab, investigational monoclonal antibodies against PD-L1 and CTLA-4 immune checkpoints, respectively, have shown efficacy in monotherapy and offer promise in combination for patients (pts) with HCC. This is a phase I/II, open-label, randomized study of durvalumab combined with tremelimumab in unresectable HCC. Methods: Phase I part of this study is a safety run-in cohort treated at the recommended phase II doses of the durvalumab/tremelimumab combination (20 and 1 mg/kg IV Q4W respectively for 4 doses followed by 20 mg/kg Q4W durvalumab alone) in pts with unresectable HCC with or without concomitant HBV or HCV infection who progress on, are intolerant to, or have refused sorafenib therapy. Secondary objectives include evaluation of antitumor activity. Here we present results of a preplanned analysis from the completed phase I part of the study. Results: As of 10 January 2017, 40 pts have been enrolled (11 HBV+, 9 HCV+, 20 uninfected). 30% had no prior systemic therapy; 93% were Child Pugh Class A. 24 (60%) had ≥1 treatment-related AE; 20% had ≥1 grade ≥3 related AE. Most common (≥15%) treatment-related AEs: fatigue (20%), increased ALT (18%), pruritus (18%), and increased AST (15%). Most common grade ≥3 related AE was asymptomatic increased AST (10%). 24 pts have discontinued treatment: 3 due to treatment-related AEs (grade 3 pneumonitis, grade 3 colitis/diarrhea, asymptomatic grade 4 elevated AST and ALT), 16 due to progressive disease, 4 due to death unrelated to treatment (cardiac arrest, variceal bleed, progressive disease, probable HCC rupture), and 1 other (pt entered hospice care). 40 pts were evaluable for response at ≥16 weeks follow-up. Conclusions: No unexpected safety signals with durvalumab and tremelimumab were seen in this unresectable HCC population. Clinical activity observed predominantly in uninfected pts though interpretation limited by small subsets. Enrollment to the phase II portion of the study is ongoing. Clinical trial information: NCT02519348. [Table: see text]
Role of serum urate in neurocognitive function and dementia: new evidence contradicts old thinking
Authors: Jasvinder A Singh
Journal: Annals of the Rheumatic Diseases (2017)

In ARD, Latourte et al used the data from a community-based prospective French cohort study of healthy 4931 elderly people 65 years or older, examined at six clinical visits (including cognitive examinations) over 12 years, and analysed 1598 participants with a baseline serum urate level (serum uric acid (sUA)), no diagnosis of dementia, a Mini-Mental State Examination (MMSE) score of >24 and at least one follow-up visit.1 Dementia was diagnosed in a 3-step process, screening using the MMSE and the Isaacs Set Test by trained psychologists, additional neuropsychological testing by a physician, and adjudication based on criteria by an independent committee of neurologists. Dementia developed in 110 subjects during the 13 357 person years of follow-up. Multivariable-adjusted HR with the highest (≥5.8 mg/dL in men, ≥4.9 mg/dL in women) versus the lowest sUA quartile (≤4.37 and ≤3.51 mg/dL, respectively) was 1.79 for incident dementia (95% CI 1.17 to 2.73; p=0.007). A strong association was seen with vascular or mixed dementia (HR=3.66 (95% CI 1.29 to 10.41), p=0.015), and no significant association was noted with Alzheimer’s disease (HR=1.55 (95% CI 0.91 to 2.61), p=0.10). Several important aspects of this study need to be carefully considered while interpreting findings: (1) patients on urate-lowering therapies (ULTs) were excluded; (2) there was no significant association between sUA levels and MRI markers of cerebrovascular disease or hippocampal volume; and (3) the association between sUA and vascular or mixed dementia was no longer significant, when adjusted for interim strokes. The authors carefully noted that these findings were not generalisable to hyperuricaemia or gout cohorts or to those younger than 65 years.

When one examines other studies in this area, the evidence is contradictory. Some studies showed that hyperuricaemia was associated with a lower risk of dementia,2–4 while other studies showed an opposite effect.5–10 A major limitation is that most of these studies providing the evidence …