tbuckley/cabot-search huggingface dataset:
Ready. Set. Move! Sports Medicine Australia advocates movement as medicine for all!
Authors: Michelle Bergeron, Liam Richard West, Emmanuel Stamatakis
Journal: British Journal of Sports Medicine (2019)

While we cannot help you with taxes, we are certain that this issue is packed with important new evidence on various less explored aspects of PA that can minimise ageing-related detriments in health. Regular PA improves health outcomes and ‘adds years to life and life to years’. Historically, moderate intensity exercise has been recommended—in at least 10 continuous minute sessions—to see any real improvement in health and fitness. Previous research has struggled to capture bouts of lighter intensity PA, and this has made it difficult to determine its health benefits. Dr Barbara’s Jefferis and colleagues’ ( See page 1013 ) study is among the first to use accelerometers to examine the association of PA of all durations and intensities to investigate all-cause mortality in British men aged 71–92 years. In older age, any intensity or duration of PA was beneficial; this should help motivate these populations to get active. The Jefferis study will be used in forthcoming PA guideline updates, under …
In vivo and in vitro evaluation of a biodegradable magnesium vascular stent designed by shape optimization strategy
Authors: Chenxin Chen, Jiahui Chen, Wei Wu, Yongjuan Shi, Liang Jin, Lorenza Petrini, Li Shen, Guangyin Yuan, Wenjiang Ding, Junbo Ge, Elazer R. Edelman, Francesco Migliavacca
Journal: Biomaterials (2019)
Reliability of imaging biomarkers for response assessment in advanced lung cancer: Influence of expertise and automation.
Authors: Hubert Beaumont, Estanislao Oubel, Antoine Iannessi, Dag Wormanns
Journal: Journal of Clinical Oncology (2012)

e13547 Background: Image-based biomarkers play an important role in the assessment of the response to therapy. The value of imaging biomarkers relies on their reproducibility, which depends on the reviewer and on the measuring system. This study aims at evaluating the impact of readers’ expertise and automation of measurements. Methods: A retrospective study was performed on 10 patients with at least one Non-Small Cell Lung Cancer (NSCLC) lesion, and followed over time (7 time points in average) with Computed Tomography (CT). 2 expert radiologists (ERs) and 5 imaging scientists (ISs) measured the Longest Axial Diameter (LAD) and the volume (VOL) of each lesion at each time point. ERs and ISs segmented the lesions by using a proprietary software providing semi-automatic segmentation processing with manual adjustment. ISs performed an additional session using manual segmentation tools only. From each segmentation, VOL and LAD were automatically computed. The variability of the measurements was calculated by using standard statistics. The response to treatment was assessed according to RECIST thresholds for LAD and with +/-30% thresholds for volume. The inter-reader agreement was measured trough the Kappa coefficient. Finally, the reviewing time with and without automation was analyzed. Results: The use of automated tools by ISs reduced the standard deviation of LAD difference from 10.7% to 8.4%. The inter-reader agreement improved Kappa from 0.57 to 0.68 for LAD, and from 0.52 to 0.69 for VOL. The automation reduced the reviewing time by a factor 4 with respect to the manual assessment. No significant differences in variability were found between ISs and the first ER, but significant differences were observed with respect to the second ER. Conclusions: In a RECIST context, automation improved significantly inter-reader agreement. When using volume as a biomarker, automation not only improved the inter-reader agreement, but also decreased notably the reviewing time. No evidence was found about the influence of the expertise on the volume measurement. The difference in the lesions interpretation by the experts is a relevant factor to account for.
Hodgkin’s lymphoma among veterans: Does race matter?
Authors: R. S. Komrokji, S. F. Mekan, M. M. Safa, Z. A. Nahleh, J. R. Pancoast, A. F. Muhleman, A. R. Jazieh
Journal: Journal of Clinical Oncology (2006)

17538 Background: Racial disparities in Hodgkin’s lymphoma (HL) are not well studied. Earlier studies suggested that black patients received less treatment and had worse outcome. The VA health care system offers a platform to study those racial differences given similar other variables and socioeconomic status among those patients. Methods: This was a retrospective analysis. The VA Central Cancer Registry (VACCR) database was used to identify patients with HL diagnosed between 1995 and 2005. There are approximately 120 VA medical centers diagnosing and/or treating patients with cancer. Data are entered by tumor registrars at the VA medical centers. This site aggregates the data collected by the medical centers’ cancer registries. Data was extrapolated and analyzed using bio-statistical software SPSS. Results: There were 1009 patients with HL at the VA system, 801 white and 183 black patients. Twenty-five patients from other racial groups were excluded from this analysis. The median age of presentation among blacks was 50.8 years compared to 53.8 years among whites (P-value 0.026). More white patients had family history of HL. Black patients had a higher incidence lymphocyte depleted histological subtype 33 (18.0%) vs. 75 (9.4%) and whites had a higher prevalence of nodular sclerosing subtype, 260 (32.5%) vs. 32 (17.5%). Other baseline characteristics such as sex, history of smoking, alcohol, and radiation exposure were similar. Presence of bulky disease and stage of lymphoma at presentation were also similar. Similar proportion of patients received chemotherapy among the two groups, 70 % for blacks and 69% for whites. Among blacks 19.7 % of patients received radiation while 25.5 % white patients did (P-value 0.24). The 5-year overall survival of blacks was 53 % years as opposed to 54% for whites (P-value 0.93) Conclusions: The presenting features, risk factors are similar across black and white races among VA population. Blacks are more likely to present with lymphocyte depleted type of HD. The treatment and outcome of HL among blacks are not different from whites within the VA system. No significant financial relationships to disclose.
Waiting list situation is “utterly unacceptable,” say surgeons, who renew call for five year plan
Authors: Abi Rimmer
Journal: BMJ (2019)

Surgeons have renewed their call for NHS England to put in place a place a five year plan to increase beds and cut backlogs, after new figures showed that waiting times rose in June.

Performance data published by NHS England show that 4.4 million patients were waiting for hospital treatment in June 2019.1 The figures show that 86.3% of patients waiting to start planned, consultant led hospital treatment were seen within 18 weeks, down from 87.8% in June 2018.1 The target is 92%.

The number of patients waiting more than 18 weeks to start treatment rose from 502 000 in June 2018 to 601 000 in June 2019.

The 62 day waiting time target from urgent referral by a GP to first treatment for …
Challenging the Association Between Screen Time and Cognitive Development
Authors: Yaakov Ophir, Refael Tikochinski, Hananel Rosenberg
Journal: JAMA Pediatrics (2019)

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Sepiapterin Reductase Inhibition Leading to Selective Reduction of Inflammatory Joint Pain in Mice and Increased Urinary Sepiapterin Levels in Humans and Mice
Authors: Masahide Fujita, Débora da Luz Scheffer, Bruna Lenfers Turnes, Shane J. F. Cronin, Alban Latrémolière, Michael Costigan, Clifford J. Woolf, Alexandra Latini, Nick A. Andrews
Journal: Arthritis & Rheumatology (2019)

Objective To evaluate the antiinflammatory and analgesic effects of sepiapterin reductase ( SPR ) inhibition in a mouse model of inflammatory joint disease, and to determine whether urinary sepiapterin levels, as measured in mice and healthy human volunteers, could be useful as a noninvasive, translational biomarker of SPR inhibition/target engagement. Methods The collagen antibody–induced arthritis ( CAIA ) model was used to induce joint inflammation in mice. The effects of pharmacologic inhibition of SPR on thresholds of heat‐, cold‐, and mechanical‐evoked pain sensitivity and on signs of inflammation were tested in mice with CAIA . In addition, mice and healthy human volunteers were treated with SPR inhibitors, and changes in urinary sepiapterin levels were analyzed by high‐performance liquid chromatography. Results CAIA in mice was characterized by 2 phases: in the acute inflammation (early) phase, joint inflammation and heat‐, mechanical‐, and cold‐induced pain hypersensitivity were present, while in the postinflammation (late) phase, no joint inflammation was observed but heat‐ and mechanical‐induced hypersensitivity, but not cold hypersensitivity, were present. Inhibition of SPR in mice with CAIA significantly attenuated the heat‐induced hyperalgesia in both phases, and the mechanical allodynia in the late phase. Signs of inflammation were unaffected by SPR inhibition. Urinary tetrahydrobiopterin levels, as a marker of inflammatory pain, were increased during inflammation in mice with CAIA (2‐fold increase over controls; P &lt; 0.05) and significantly reduced by SPR inhibition ( P &lt; 0.05 versus vehicle‐treated mice). Increased urinary sepiapterin levels in the presence of SPR inhibition in both mice and healthy human volunteers were associated with high sensitivity (70–85%) and high specificity (82–88%) for the prediction of SPR inhibition/target engagement. Conclusion SPR inhibition reduces the pain associated with joint inflammation, thus showing its potential utility as an analgesic strategy for inflammatory joint pain. In addition, SPR inhibition increases urinary sepiapterin levels, indicating the potential of this measurement as a noninvasive biomarker of target engagement of SPR inhibitors, such as sulfasalazine, a disease‐modifying antirheumatic drug that is currently used as a first‐line treatment for rheumatoid arthritis.
Allogenic stem cell transplant (ASCT) as initial salvage for patients (pts) with acute myeloid leukemia (AML) refractory to high-dose cytarabine-based induction chemotherapy.
Authors: Naval Guastad Daver, Marcos J.G. De Lima, Hagop Kantarjian, Farhad Ravandi, Mehmet Asim Bilen, Sherry Pierce, Issa F. Khouri, Stephan Joseph Dorkhom, Sergio Giralt, Guillermo Garcia-Manero, Aziz Nazha, Michael Mathisen, Naveen Pemmaraju, Jorge E. Cortes, Stefan Faderl, Elias Jabbour
Journal: Journal of Clinical Oncology (2012)

6544 Background: Outcomes of pts with AML who are refractory to High-dose Cytarabine (HiDAC) based induction are dismal. ASCT as initial salvage may be effective and potentially superior to repeat induction with combination chemotherapies in such pts. Methods: 1597 AML pts were treated with HiDAC-based induction at MD Anderson Cancer Center between 1995 and 2009. 285 primary refractory pts were identified. 28 (10%) of these underwent ASCT as initial salvage and were reviewed. Results: Median age was 56 years (36 to 77) and 50% were males. Median ECOG PS was 1 (0-2). Antecedent hematological disorders were present in 14 pts (50%). Median white cell count, hemoglobin, platelet count and bone marrow (BM) blast percentage at diagnosis were 3.5 x 10 9 /l (0.6 to 73.6), 7.8 g/l (6.5 to 11.4), 44 x 10 9 /l (9 to 615), and 43% (6-82), respectively. 9 pts (32%) had complex cytogenetics. FLT3 mutations were identified in 2 (15%) of 13 evaluated pts. All pts were refractory to HiDAC-based induction. HiDAC was combined with an anthracycline in 16 pts (57%) and non-anthracycline in 12 pts (43%). Median time from induction to ASCT was 76 days (28 to 184). Median BM blast and peripheral blast at ASCT were 28% (3 to 82) and 4% (0 to 41). 21 pts (75%) had matched related donors (18 sibling and 3 haploidentical) and 7 (25%) had matched unrelated donors. Conditioning regimens were melphalan-based, busulfan-based, fludarabine-based or others in 7 (25%), 10 (36%), 8 (29%) and 3 pts (10%); respectively. Complete remission (CR) was achieved in 23 of 28 pts undergoing ASCT (CR = 82%) with median time to CR of 31 days (26 to 134). 12 pts relapsed with median time to relapse of 5 months (2 to 19). 8 pts remain alive with median follow up of 80 months (28 to 118). Median overall survival (OS) for the entire group is 20 months (5 to 118). In historical series of pts with AML refractory to HiDAC-based induction, salvage chemotherapies induced CR rates of 22% with median OS of 4 months. Conclusions: Initial salvage with allogenic SCT is feasible and yields superior outcomes to salvage chemotherapy in primary HiDAC refractory AML pts. Randomized studies are warranted to further explore this treatment option.
External validation of the simple prognostic score in a palliative care clinic at a comprehensive cancer center.
Authors: Brinder Vij, Stacy Marie Stabler, Howard T. Thaler, Paul A. Glare
Journal: Journal of Clinical Oncology (2012)

e19566 Background: Accurate survival predictions are essential for the optimal delivery of palliative care (PC). Clinical predictions of survival are notoriously inaccurate. Tools for making objective survival estimates in ambulatory cancer patients, who have months or years to live, are lacking. The Simple Prognostic Score (SPS) separated Canadian palliative radiotherapy patients into three groups with 12, 6 and 3 months median survivals, respectively. The aim of this study was to test the SPS in an outpatient PC clinic at a U.S. comprehensive cancer center. Methods: Retrospective chart review of 300 consecutive patients referred to one PC clinic at Memorial Sloan-Kettering Cancer Center (MSKCC). Cancer type, metastatic sites and Karnofsky performance status (KPS) score were used to calculate SPS (1 point each for non-breast cancer; non-osseous metastases; KPS score &lt;70%). Outcome was date of death, obtained from the MSKCC institutional data base. Survival analysis was performed. Discrimination (non-overlap between groups) and calibration (percentage difference between estimated and observed survival) were measures of accuracy. Results: 79% (236 of 300) patients had advanced disease. Of them, 90% had cancers other than breast; 76% had metastases in sites other than bone; 27% had a low KPS score. The SPS score was 2 or 3 in 80%. By 10/31/11, 85% had died (median survival 4.9 months). SPS categorized the sample into four prognostic subgroups (see Table), with median survivals of 15, 9, 5 and 2 months respectively (log rank test χ 2 =38.71, d.f .3, p&lt;0.0001). SPS was not very accurate, with poor discrimination (extensive intergroup overlap) but reasonable calibration (6-15% for the different groups). Conclusions: The SPS is user-friendly and helpful at the group level, but inaccurate at the individual level. Additional variables may narrow the prediction intervals, but will make the tool more complex. [Table: see text]
Direct visualization of prostate cancer progression utilizing a bioreactor
Authors: Clayton C. Yates, Donna Beer-Stolz, Linda Griffith, Alan Wells
Journal: Cancer Research (2004)

939  Currently, most methods available to study the behavior of metastatic tumor cells are indirect or capture only brief periods. Problematic with these assays are an inability to follow the complete metastatic program including extravasation, invasion, establishment and growth of the metastatic mass. As such, we are developing an ex vivo model in which tumor cells can be analyzed while in the environment of a major metastatic target, the liver. In this study we assessed whether prostate cancer metastasis, which is among the leading causes of deaths in American males in the United States, could be recreated in a liver bioreactor and observed in real time. In order to accomplish this we utilized a three dimensional liver perfusion culture (bioreactor), which allows for in situ observation and ensures a relatively homogeneous distribution of flow and mass transfer throughout the system to meet the metabolic demands of the livers cells augmented by an appropriate scaffold which facilitates morphogenesis of primary cells into tissue-like structures. This system, formally named a Micro-fabricated Array Bioreactor, affords for the recreation of an in vivo environment for in vitro observation and provides for an optimal device for the study of physiological events. Hepatocytes and nonparenchymal liver cells were obtained and introduced into the bioreactor utilizing established protocols. After allowing 5 days of observed hepatic tissue morphogenesis, DU-145 human prostate carcinoma cells expressing GFP or RFP were introduced into the bioreactor. In situ observation of the co-culture system was observed by fluorescence microscopy over a 30 day period. The rate of growth of prostate cancer cells was assessed with a custom designed spectofluorometer to measure GFP fluorescent intensity throughout the initial growth of the cancer. Tissue architecture of hepatocytes and prostate cancer cells was directly visualized in real time by 2-photon microscopy along with light microscopy. Fluorescent intensity of co-cultures revealed ongoing cell proliferation of the DU-145 cells, which correlated with a visually observed overgrowth of DU-145 cells by 14 days. DU-145 WT cells failed to grow without hepatocytes or even in a 2-D mixed culture. This tumor mass growth resulted in a decline in hepatocyte tissue structure and function. Also metastasis of overflowing DU-145 cells to adjacent hepatocyte filled channels not containing DU-WT cells was observed during this process by 14 days. Histological examination of the tissue revealed DU-145 WT cells invading the hepatocyte parenchyma by 15 days. Finally, biochemical analysis revealed expression of biomarkers associated with prostate cancer and decrease in albumin and urea by the hepatocytes. Although only preliminary, these experiments provide the basis for the development of and ex vivo model system in which to observe and potentially dissect the dynamic process of tumor invasion and metastasis.
Using pegylated arginine deiminase (ADI-PEG20) for the treatment of sarcomas that lack argininosuccinate synthesase 1 expression.
Authors: Brian Andrew Van Tine, Gregory R Bean, Phillip Boone, Munir Tanas, Matthew B Schulze, David Y Chen, John S. Bomalaski, Brian Rubin
Journal: Journal of Clinical Oncology (2013)

10526 Background: To better understand the metabolism of sarcomas, we explored the role of argininosuccinate synthase 1 (ASS1), the rate-limiting enzyme in the conversion of citrulline to arginine in the urea cycle. When ASS1 is not expressed the amino acid arginine becomes an essential amino acid that must be delivered from the diet. The potential for therapeutic manipulation of this pathway with pegylated arginine deiminase (ADI-PEG20) was explored using metabolomic mass spectroscopy. Methods: Immunohistochemistry (IHC) of ASS1 expression on 701 patient specimens representing 45 subtypes of sarcoma was performed. Proliferation and cell death were analyzed in a panel of cell lines. Clonogenic assays were performed using ADI-PEG20 and chloroquine. Autophagy induction and inhibition was assessed. Xenograft models were tested. Metabolomic mass spectroscopy was performed in the presence and absence of ADI-PEG20. Results: lHC analysis demonstrated that ASS1 is not expressed in over 85% of sarcomas (619 of 701 patient samples). Treatment of a panel of LMS, synovial, ASPS, GIST, MPNST, chondrosarcoma, osteosarcoma, and Ewings sarcoma cell lines with ADI-PEG20 resulted in cell cycle arrest but not apoptosis when ASS1 expression was low (13/15 lines). Xenografts of the ASS1 low MNNG/HOS cells and SKLMS1 cells into nude mice followed by treatment with ADI-PEG20 +/- chloroquine demonstrated significantly slower tumor growth as compared to PBS or chloroquine treated controls. Treatment of sarcomas that lack ASS1 with ADI-PEG20 induced autophagy. Global analysis of metabolomic mass spectroscopy demonstrated alterations in PKM2, glutamine dependence, the Warburg effect, the TCA cycle and glutathione biology. Conclusions: This suggests that sarcomas may be sensitive to the arginine depletion therapy using ADI-PEG20. Autophagy induction has global metabolic consequences for sarcoma. Successful control of tumor burden by using arginine deprivation therapy and autophagy inhibition in our preclinical studies will help to orient clinical trials for this innovative treatment in patients with sarcoma that lack ASS1 expression.
Diffuse Pulmonary Metastases From Prostate Cancer on 68Ga PSMA PET/CT
Authors: Nikhil Seniaray, Ritu Verma, Ethel Belho, Dharmender Malik, Harsh Mahajan
Journal: Clinical Nuclear Medicine (2019)

A 63-year-old man, recently diagnosed with carcinoma of the prostate (Gleason's score 4+4), with serum prostate-specific antigen 189.2 ng/mL, underwent Ga PSMA PET/CT scan for pretreatment staging. The study revealed abnormal tracer uptake in the prostatic bed region, the pelvic, abdominal, and mediastinal lymph nodes and diffuse metastases to the bilateral lungs. The lung metastasis was proved to be metastatic adenocarcinoma from analysis of bronchoalveolar lavage.