tbuckley/cabot-search huggingface dataset:
Trends in Motorcycle Fatalities Associated With Alcohol-Impaired Driving—United States, 1983-2003
Journal: JAMA (2005)

Motorcycles are the most dangerous type of motor vehicle to drive. These vehicles are involved in fatal crashes at a rate of 35.0 per 100 million miles of travel, compared with a rate of 1.7 per 100 million miles of travel for passenger cars. The National Highway Traffic Safety Administration (NHTSA) has reported increasing numbers of motorcycle deaths associated with alcohol-impaired driving in recent years, especially among persons aged > or =40 years. To determine trends by age group in motorcycle fatalities overall and in those involving alcohol impairment, CDC analyzed data from the NHTSA Fatality Analysis Reporting System (FARS) for 1983, 1993, and 2003. This report summarizes the results of that analysis, which indicated that, during 1983-2003, the overall prevalence of elevated blood alcohol concentrations (BACs) among motorcycle drivers who died in crashes declined; however, the peak rate of death among alcohol-impaired motorcycle drivers shifted from those aged 20-24 years to those aged 40-44 years. Strong enforcement of existing BAC laws, together with other public health interventions aimed at motorcyclists, might reduce the crash mortality rate, especially among older drivers.
Impairment of Immunoproteasome Function by Cigarette Smoke and in Chronic Obstructive Pulmonary Disease
Authors: Ilona E. Kammerl, Angela Dann, Alessandra Mossina, Dorothee Brech, Christina Lukas, Oliver Vosyka, Petra Nathan, Thomas M. Conlon, Darcy E. Wagner, Hermen S. Overkleeft, Antje Prasse, Ivan O. Rosas, Tobias Straub, Susanne Krauss-Etschmann, Melanie Königshoff, Gerhard Preissler, Hauke Winter, Michael Lindner, Rudolf Hatz, Jürgen Behr, Katharina Heinzelmann, Ali Ö. Yildirim, Elfriede Noessner, Oliver Eickelberg, Silke Meiners
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Patients with chronic obstructive pulmonary disease (COPD) and in particular smokers are more susceptible to respiratory infections contributing to acute exacerbations of disease. The immunoproteasome is a specialized type of proteasome destined to improve major histocompatibility complex (MHC) class I-mediated antigen presentation for the resolution of intracellular infections.To characterize immunoproteasome function in COPD and its regulation by cigarette smoke.Immunoproteasome expression and activity were determined in bronchoalveolar lavage (BAL) and lungs of human donors and patients with COPD or idiopathic pulmonary fibrosis (IPF), as well as in cigarette smoke-exposed mice. Smoke-mediated alterations of immunoproteasome activity and MHC I surface expression were analyzed in human blood-derived macrophages. Immunoproteasome-specific MHC I antigen presentation was evaluated in spleen and lung immune cells that had been smoke-exposed in vitro or in vivo.Immunoproteasome and MHC I mRNA expression was reduced in BAL cells of patients with COPD and in isolated alveolar macrophages of patients with COPD or IPF. Exposure of immune cells to cigarette smoke extract in vitro reduced immunoproteasome activity and impaired immunoproteasome-specific MHC I antigen presentation. In vivo, acute cigarette smoke exposure dynamically regulated immunoproteasome function and MHC I antigen presentation in mouse BAL cells. End-stage COPD lungs showed markedly impaired immunoproteasome activities.We here show that the activity of the immunoproteasome is impaired by cigarette smoke resulting in reduced MHC I antigen presentation. Regulation of immunoproteasome function by cigarette smoke may thus alter adaptive immune responses and add to prolonged infections and exacerbations in COPD and IPF.
Impact of the number of cautionary/unsuitable risk factors on outcomes following accelerated partial breast irradiation.
Authors: John Ben Wilkinson, Jessica Wobb, Chirag Shah, Ashley Fowler, Christina Mitchell, Michelle Wallace, Inga S. Grills, Jannifer S. Stromberg, Frank Vicini, Peter Y. Chen
Journal: Journal of Clinical Oncology (2012)

146 Background: Current guidelines for APBI stratify appropriateness of treatment outside of a clinical trial. Limited data are available, however, regarding the impact of the number of risk factors (RFs) per patient on clinical outcomes. Methods: 692 patients were treated with APBI at a single institution between 10/1992 and 10/2011. Patients were stratified by the ASTRO guidelines as suitable, cautionary, and unsuitable. Outcomes including ipsilateral/contralateral breast tumor recurrence (IBTR/CBTR), regional recurrence (RR), distant metastases (DM), disease-free survival (DFS), cause specific survival (CSS), and overall survival (OS) were evaluated by risk group and number of RFs. Results: Median follow-up was 5.2 years (range: 0-18.3).Distribution within CP risk-groups was suitable: 240, cautionary: 343, and unsuitable: 109 patients. Increased IBTR (2.0% v. 0.6%, p=0.03), DM (6.5% v. 1.5%, p=0.02), and decreased DFS (92% v. 98%, p=0.01) were noted for patients with 2+ cautionary RFs (n=115) vs. 1 RF (n=228). Those with 2+ unsuitable RFs had higher RR (7.7% v. 1.7%, p=0.05). Pooled analysis revealed increased IBTR/RR for patients with 3+ combined cautionary/unsuitable RFs vs. 2 or fewer combined RFs (Table). Univariate analysis showed increased DM with increasing tumor size/T-stage (p&lt;0.01), ER negativity (p=0.04), LVSI (p=0.01), + LN (p&lt;0.01), and increasing number of RFs (p&lt;0.01). No single RF was associated with an increased risk of local recurrence on UVA. Conclusions: Three or more cautionary or unsuitable APBI RFs is associated with higher local, regional, and distant recurrence. Patients with fewer than 3 total RFs have a 98% locoregional control at 5 years and likely remain good candidates for APBI. Future attempts to risk stratify patients may need to account for the number of RF present in order to appropriately classify patients. [Table: see text]
First efficacy assessment of a phase II study with cyclophosphamide, vincristine, liposomal doxorubicin, and prednisone plus rituximab, administered every two weeks (R-COMP-14) as primary treatment for NHL
Authors: J. Herrero, J. Gómez-Codina, M. Provencio, A. Rueda, M. Llanos, F. Lobo, D. Vicente, P. Sabín, F. García-Arroyo, C. Iglesias
Journal: Journal of Clinical Oncology (2007)

18519 Background: R-CHOP is the standard treatment for CD20+ aggressive B-cell non-Hodgkin lymphoma (DLBCL). Dose dense regimens have shown better outcome and acceptable tolerability compared to standard. Liposomal doxorubicin has demonstrated significant less cardiotoxicity and acute toxicity when compared with standard doxorubicin. The aim of the study is to assess the efficacy and safety of the R- COMP-14 (Myocet™-modified CHOP) in newly diagnosed aggressive DLBCL. Pegfilgrastim was used to provide prophylactic bone marrow support. Methods: Patients (Pts) with stages III, IV or I, II (IPI = 1) were included in this single arm, multicentric, 2-step (Simon design) phase II trial. Treatment: eight biweekly cycles of liposomal doxorubicin 50 mg/m 2 , cyclophosphamide 750mg/m 2 , vincristine 1.4 mg/m 2 (max. 2mg), rituximab 375 mg/m 2 and prednisone 100 mg/d d1–5. Pegfilgrastim was administered on day 2 at standard dose. Interim analysis shows: Twenty-six out of 28 Pts were evaluable for efficacy. Median age: 51 y (28 - 64). Ann Arbor stage: I-II (IPI = 1) 42%, III 29%, IV 29%. Extranodal involvement: 50%. Median basal LVEF was 66% (range 44 - 80). Results: The overall response rate was 84% (CR 64% and PR 20%). Three (12%) Pts had PD and 1 (4%) SD. Median n° cycles was 8 (2-8); the median relative dose intensity per week was 93.5%. Only 4.8% of cycles were delayed and 4.2% of the cycles were administered with dose reduction due to related adverse events. Grade 3–4 neutropenia and thrombocytopenia were observed in 4.0% and 0.6% of cycles respectively. Febrile neutropenia experienced in 3.3% of cycles. Non-hematological G3–4 toxicities per cycles were hepatic (1.7%), emesis (1.2%) and G3 neurotoxicity, asthenia and infection (0.6% each). No other relevant toxicities were observed. Median LVEF after completion of treatment was 63% (range 52 - 76), there was no cardiac clinical event related to the treatment, nor irreversible toxicities. Conclusions: This Interim analysis confirmed the efficacy and safety of the dose-dense regimen in order to continue with the second step of the study. R-COMP-14 treatment with pegfilgrastim bone marrow support warrants further exploration. No significant financial relationships to disclose.
Trends in Memorial Sloan-Kettering Cancer Center risk group distribution according to treatment year for patients with metastatic renal cell carcinoma (mRCC)
Authors: S. Patil, N. M. Ishill, J. Deluca, R. J. Motzer
Journal: Journal of Clinical Oncology (2008)

5092 Background: A MSKCC risk model groups patients by number of poor-prognosis pretreatment features (low hemoglobin, elevated corrected calcium, elevated lactate dehydrogenase, no prior nephrectomy, and low performance status) as favorable (0 factors), intermediate (1,2), poor (≥3) risk groups (JCO Vol. 17, 2530–2540). Risk group frequencies were examined by year of treatment at MSKCC to assess trends. Methods: The distribution of each prognostic factor was examined in 789 patients (pts) with mRCC treated at MSKCC on a first-line therapy clinical trial between the years of 1975 and 2007. The proportion of pts in each of 6 cohorts based on year of diagnosis was calculated for each risk group and type of therapy (Chemotherapy/other, Interferon/interleukin-2, VEGF- targeted). Trends were assessed using the Cochran-Armitage test. The presence of 5 prognostic factors was examined to determine sources of risk group shifts. Results: The median age was 58 yrs (20 to 82) and 70% were male. Most pts had cytokine therapy (55%), 37% had chemotherapy/other and 8% had VEGF-targeted therapies. The proportion of pts in the poor risk group has become smaller while the favorable risk group has increased from 1975 to 2007 (p<.0001, p<.0001). The intermediate risk group has remained at least 50% of the first-line mRCC clinical trial patient population (p=.85). Overall, pts in the later cohorts were lower risk on all five prognostic factors. Conclusions: The risk group distribution for mRCC pts in clinical trials at MSKCC has shifted from 1975 to 2007. The shifts reflect an overall reduction in risk in several prognostic factors. These shifts have direct implications for data analysis, interpretation of mRCC trends, and drug development. Percent of mRCC patients in each cohort for each risk group Cohort 1975–80 1981–85 1986–90 1991–95 1996–01 2001- 07 n=34 n=149 n=128 n=194 n=125 n=159 Favorable 9% 24% 30% 19% 29% 46% Intermediate 59% 49% 56% 60% 58% 50% Poor 32% 27% 14% 21% 13% 5% No significant financial relationships to disclose.
Novel Imaging Diagnosis for Hepatocellular Carcinoma: Consensus from the 5th Asia-Pacific Primary Liver Cancer Expert Meeting (APPLE 2014)
Authors: Bang-Bin Chen, Takamichi Murakami, Tiffany Ting-Fang Shih, Michiie Sakamoto, Osamu Matsui, Byung-Ihn Choi, Myeong-Jin Kim, Jeong Min Lee, Ren-jie Yang, Meng-Su Zeng, Ran-Chou Chen, Ja-Der Liang
Journal: Liver Cancer (2015)

Current novel imaging techniques in the diagnosis of hepatocellular carcinoma (HCC), with the latest evidence in this field, was discussed at the Asia-Pacific Primary Liver Cancer Expert (APPLE) meeting held in Taipei, Taiwan, in July 2014. Based on their expertise in a specific area of research, the novel imaging group comprised 12 participants from Japan, South Korea, Taiwan, and China and it included 10 abdominal radiologists, one hepatologist, and one pathologist. The expert participants discussed topics related to HCC imaging that were divided into four categories: (i) detection method, (ii) diagnostic method, (iii) evaluation method, and (iv) functional method. Consensus was reached on 10 statements; specific comments on each statement were provided to explain the rationale for the voting results and to suggest future research directions.
Subcutaneous fat patterning in athletes: selection of appropriate sites and standardisation of a novel ultrasound measurement technique: ad hoc working group on body composition, health and performance, under the auspices of the IOC Medical Commission
Authors: Wolfram Müller, Timothy G Lohman, Arthur D Stewart, Ronald J Maughan, Nanna L Meyer, Luis B Sardinha, Nuwanee Kirihennedige, Alba Reguant-Closa, Vanessa Risoul-Salas, Jorunn Sundgot-Borgen, Helmut Ahammer, Friedrich Anderhuber, Alfred Fürhapter-Rieger, Philipp Kainz, Wilfried Materna, Ulrike Pilsl, Wolfram Pirstinger, Timothy R Ackland
Journal: British Journal of Sports Medicine (2015)

Background Precise and accurate field methods for body composition analyses in athletes are needed urgently. Aim Standardisation of a novel ultrasound (US) technique for accurate and reliable measurement of subcutaneous adipose tissue (SAT). Methods Three observers captured US images of uncompressed SAT in 12 athletes and applied a semiautomatic evaluation algorithm for multiple SAT measurements. Results Eight new sites are recommended: upper abdomen, lower abdomen, erector spinae, distal triceps, brachioradialis, lateral thigh, front thigh, medial calf. Obtainable accuracy was 0.2 mm (18 MHz probe; speed of sound: 1450 m/s). Reliability of SAT thickness sums (N=36): R 2 =0.998, SEE=0.55 mm, ICC (95% CI) 0.998 (0.994 to 0.999); observer differences from their mean: 95% of the SAT thickness sums were within ±1 mm (sums of SAT thicknesses ranged from 10 to 50 mm). Embedded fibrous tissues were also measured. Conclusions A minimum of eight sites is suggested to accommodate inter-individual differences in SAT patterning. All sites overlie muscle with a clearly visible fascia, which eases the acquisition of clear images and the marking of these sites takes only a few minutes. This US method reaches the fundamental accuracy and precision limits for SAT measurements given by tissue plasticity and furrowed borders, provided the measurers are trained appropriately.
A phase I study of the folate-targeted conjugate EC0489 in patients with refractory or advanced metastatic cancer.
Authors: W. A. Harb, B. A. Conley, P. LoRusso, E. A. Sausville, E. I. Heath, S. R. Chandana, M. Hamm, J. Carter, W. J. Perez, R. A. Messmann
Journal: Journal of Clinical Oncology (2010)

3088 Background: The folate receptor (FR) is expressed on many human tumors (e.g., ovarian, NSCLC, etc.) where it functions as a high-affinity receptor for folic acid. The FR is minimally expressed in normal tissue, making it a logical target for anti-cancer therapy. Indeed, the relevance of FR as a molecular target for anti-tumor agents was discussed in detail at the 2008 ASCO Annual Meeting. Folic acid can be used as a carrier molecule to deliver covalently-linked therapeutic and diagnostic moieties to the FR. EC0489, a conjugate of folic acid and desacetyl vinblastine hydrazide (DAVLBH), is a high-affinity ligand for the FR. This phase I study assessed the safety and pharmacokinetics (PK) of escalating intravenous bolus doses of EC0489. Methods: Eligible patients with adequate performance status and organ function that had previously failed standard therapy were treated with EC0489 on days 1, 3, 5 and 15, 17, 19 of a 28-day cycle. Endpoints included determination of a safe and tolerable EC0489 dose and the development of a PK model. Results: As of DEC 2009, 14 patients had received EC0489 at 1, 2.5 or 5 mg/m2; (n=3, 10 and 1, respectively). EC0489 was well tolerated at dose levels ≤ 2.5 mg/m2 with reversible CTCAE Grade 2 peripheral sensory neuropathy occurring during the second cycle of therapy, after exposure to approximately 27-30 mg/month of EC0489. A single patient in cohort 3 (5.0 mg/m2) manifested 3 (reversible) DLTs: grade 3 fatigue, muscle pain and constipation following week 1 of cycle 1, defining the MTD for this schedule at 2.5 mg/m2. Preliminary PK analysis shows a biphasic elimination of EC0489 from circulation with t1/2 of ≈21 minutes. The Cmax and AUC increased linearly with dose. Conclusions: EC0489 may be administered safely as a 2.5 mg/m2 intravenous bolus dose on days 1, 3, 5 and 15, 17, 19 of a 28-day schedule. We are currently exploring the feasibility of a single weekly dose of EC0489 administered on days 1, 8, 15, and 22 of a 4-week cycle. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Endocyte Endocyte Endocyte
Cutaneous adverse events (AEs) of anti-programmed cell death (PD)-1 therapy in patients with metastatic melanoma: A single-institution cohort
Authors: Shelley Ji Eun Hwang, Giuliana Carlos, Deepal Wakade, Karen Byth, Benjamin Y. Kong, Shaun Chou, Matteo S. Carlino, Richard Kefford, Pablo Fernandez-Penas
Journal: Journal of the American Academy of Dermatology (2016)
Doctors condemn closures at Sudanese teaching hospital
Authors: Adrian O’Dowd
Journal: BMJ (2016)

Doctors have raised concerns over service closures at the Khartoum Teaching Hospital in Sudan, the country’s largest public hospital, claiming that there has been insufficient consultation about the decision and poor planning of how to handle the transfer of patients.

The Sudan Doctors Union in the United Kingdom and Ireland said that it was deeply concerned and dismayed at the recent decision to close the hospital’s emergency services, effective from 31 December. The union claimed that there were reports of air conditioning units and water services already being switched off and patients discharged from wards, as the hospital is closed down in stages over the next few weeks.

A spokesperson for the union said, “This precipitous closure …
Protein A immunoadsorption in the treatment of malignant disease.
Authors: G L Messerschmidt, D H Henry, H W Snyder, J Bertram, A Mittelman, S Ainsworth, J Fiore, M V Viola, J Louie, E Ambinder
Journal: Journal of Clinical Oncology (1988)

Circulating immune complexes (CIC) are known to be present in cancer patients and are responsible for much of the cancer-associated immunosuppression. Removal or modulation of these "blocking factors" can reverse the immunosuppression. Protein A from Staphylococcus aureus has the unusual property of binding to CIC with high avidity. Use of protein A as an immunoadsorbent in extracorporeal immunotherapy affinity columns has resulted in antitumor and antiviral responses in animals. Our group developed a multicenter trial to assess toxicity and antitumor response with this biologic response modifier alone. Overall, 24% (21 of 87 patients) had objective tumor regressions including both partial responses (PR) and less than PR. No complete responses (CR) were observed. Responses were observed in acquired immune deficiency syndrome (AIDS)-related Kaposi's sarcoma (six of 17 PR; two of 17 less than PR; overall, 47%), breast adenocarcinoma (five of 22 PR; three of 22 less than PR; overall response, 36%), colon adenocarcinoma, (one PR, one less than PR; overall response, 11%), and non-oat cell lung carcinoma (two of seven less than PR). The procedure was well tolerated and could be performed on an outpatient basis. No adverse reaction was observed in 735 of 1,113 treatments (66%). The most common adverse effect was an "influenza-like" syndrome consisting of fever and chills. Pain was present in 12% of the patients. There were no study-related deaths. Serum IgG and CIC levels did not statistically change due to therapy in responding or nonresponding patients. Complement levels remained within the normal range. Liver and renal tests remained stable throughout the study. In summary, protein A immunoadsorption of plasma is well tolerated in the outpatient clinic, has demonstrated antitumor activity in resistant solid tumors, and functions as a biologic response modifier.
Quality of life (QOL) and acute toxicities of a pilot study of focal salvage high-dose rate (HDR) prostate brachytherapy in patients with local recurrence after definitive external-beam radiotherapy (XRT).
Authors: Hans T. Chung, Laura D'Alimonte, D. Andrew Loblaw, Ananth Ravi, Matthew Wronski, Melanie Davidson, Masoom A. Haider, Gerard Morton
Journal: Journal of Clinical Oncology (2015)

79 Background: Despite dose-escalated radiotherapy, studies of post-treatment biopsies of the prostate for intermediate-risk prostate cancer suggest that approximately 20% will be positive. Salvage options include surgery, brachytherapy, cryotherapy or high-frequency ultrasound. However, the risk of significant complications (e.g. fistula, incontinence, bladder neck contracture), is not insignificant. The objective of this pilot study is to explore the QOL, toxicities and efficacy of focal salvage HDR prostate brachytherapy. Methods: This study was approved by the institution’s research ethics board. Eligible patients included: biopsy-confirmed local recurrence &gt;30 months after XRT, MRI demonstrating solitary recurrence confined to the prostate, negative metastatic workup, IPSS &lt;15, post-XRT PSA &lt;10ng/mL, prostate volume ≤50cc. Salvage ultrasound-based HDR brachytherapy was performed with a prescription dose of 27Gy divided over two implants separated by 1 week to the target volume (TV) as seen on MRI with dose constraints to the urethra and rectum. Results: Eleven patients (mean age 73 years) have been enrolled in the study. At initial presentation, there were 4, 6 and 1 low-, intermediate- and high-risk disease, and initial XRT received was 70-78Gy. The Gleason score of the local recurrence was 7 and 8-10 in 6 and 5 patients, respectively. The pre-HDR mean PSA was 5.0 (range 1.3 – 9.29). The median size of the recurrence on MRI was 10mm and median volume of the TV was 5.9cc (2.2-16.1), TV V100 96.0%, urethral D10 64.5% and rectal D1cc 42.9%. Ten patients have at least 6 months of follow-up (median 10 months), and no acute GU/GI grade 3-5 toxicities were observed, including urinary retention. The most common acute toxicity was frequency and nocturia. Mean IPSS at baseline, 1-, 3- and 6-months was 6, 8, 7 and 5. At 6-months, 9 of 10 patients had a lower PSA (mean 1.78) than baseline. There was no significant change in EPIC urinary, bowel and sexual domains within the first 6-months. Conclusions: Preliminary data suggests that focal salvage HDR brachytherapy was technically feasible with minimal acute toxicities. Clinical trial information: NCT01583920.