tbuckley/cabot-search huggingface dataset:
Resectability and agreement between surgeons: Review of CT and MR scan of the CELIM study: (Multicenter randomized trial of cetuximab/FOLFOX versus cetuximab/FOLFIRI in unresectable liver metastases
Authors: W. O. Bechstein, H. Lang, C. Köhne, F. Parisi, H. R. Raab, A. Frilling, R. Konopke, J. Weitz, C. Stroszczynski, G. Folprecht
Journal: Journal of Clinical Oncology (2009)

4091 Background: Liver resection of patients with colorectal cancer liver metastasis (mets) may provide curative therapy. The decision for resection is based on CT- or MRI scans and includes technical aspects (esp. remaining liver tissue) and prognostic factors (i.e. number of metastases). Methods: During two workshops, CT- or MRI scans at baseline (BL) and after 4 months treatment (follow-up, F-U) of CELIM-patients (pts) were presented to surgeons (surg.) who were blinded to each other, the time of investigation (BL or F-U) and clinical data. Scans were allocated to one of the following categories: (1) resection, (2) exploration, (3) borderline resectable (prior chemotherapy preferred) or (4) non-resectable If scans were allocated to category (3) or (4), the reason (technical or poor prognosis) was stated. For evaluation of resectability over time, pts were regarded as resectable according to presented imaging, if ≥ 50% of surg. voted for (1) or (2). Inter-observer variability was evaluated by a reduced model, too: operation (1+2), borderline, primary chemo therapy preferred (3) and non-resectable, chemotherapy (4). Critical disagreements were assumed if ≥1 surg. voted for (4) and ≥ 50% surg. for (1+2) or vice versa. Results: Seven surg. (≥ 5/workshop) participated at the review. A total of 180 scans were reviewed. Both, BL and F-U scans, were available for 75 pts (68% of study pts). During the review, 24 pts changed from ‘non-resectable‘ at BL to ‘resectable‘ at F-U, 5 pts from ‘resectable‘ to ‘non-resectable‘, 29 pts remained ‘non-resectable‘, and 17 pts ‘resectable‘ (19 pts more resectable at F-U; chi-square: p=.021). R0 resection was actually performed in 16/29 pts classified as ‘resectable‘ (55%) and 13/54 pts not classified as ‘resectable‘ (24%) according to presented BL- images. In the full model (6 possibilities), the agreement between surg. was 51.4 %, p&lt;.001. In the clinically more important reduced model, the agreement was 63.5% (p&lt;.001). Critical disagreements were observed in 18 cases (10%). Conclusions: Resectability according to scans increased significantly during the CELIM trial. Regarding the clinical approach, different surgeons had a high degree of agreement. [Table: see text]
The Folate Cycle Enzyme MTHFR Is a Critical Regulator of Cell Response to MYC-Targeting Therapies
Authors: Angela Su, Frank Ling, Camille Vaganay, Gaetano Sodaro, Chaïma Benaksas, Reinaldo Dal Bello, Antoine Forget, Bryann Pardieu, Kevin H. Lin, Justine C. Rutter, Christopher F. Bassil, Gael Fortin, Justine Pasanisi, Iléana Antony-Debré, Gabriela Alexe, Jean-François Benoist, Alain Pruvost, Yana Pikman, Jun Qi, Marie-Hélène Schlageter, Jean-Baptiste Micol, Giovanni Roti, Thomas Cluzeau, Hervé Dombret, Claude Preudhomme, Nina Fenouille, Lina Benajiba, Hava M. Golan, Kimberly Stegmaier, Camille Lobry, Kris C. Wood, Raphael Itzykson, Alexandre Puissant
Journal: Cancer Discovery (2020)

Abstract Deciphering the impact of metabolic intervention on response to anticancer therapy may elucidate a path toward improved clinical responses. Here, we identify amino acid–related pathways connected to the folate cycle whose activation predicts sensitivity to MYC-targeting therapies in acute myeloid leukemia (AML). We establish that folate restriction and deficiency of the rate-limiting folate cycle enzyme MTHFR, which exhibits reduced-function polymorphisms in about 10% of Caucasians, induce resistance to MYC targeting by BET and CDK7 inhibitors in cell lines, primary patient samples, and syngeneic mouse models of AML. Furthermore, this effect is abrogated by supplementation with the MTHFR enzymatic product CH3-THF. Mechanistically, folate cycle disturbance reduces H3K27/K9 histone methylation and activates a SPI1 transcriptional program counteracting the effect of BET inhibition. Our data provide a rationale for screening MTHFR polymorphisms and folate cycle status to nominate patients most likely to benefit from MYC-targeting therapies. Significance: Although MYC-targeting therapies represent a promising strategy for cancer treatment, evidence of predictors of sensitivity to these agents is limited. We pinpoint that folate cycle disturbance and frequent polymorphisms associated with reduced MTHFR activity promote resistance to BET inhibitors. CH3-THF supplementation thus represents a low-risk intervention to enhance their effects. See related commentary by Marando and Huntly, p. 1791. This article is highlighted in the In This Issue feature, p. 1775
Impact of the income-based health service types on survival in patients with metastatic gastric cancer
Authors: S. Oh, H. Oh, S. Yoon, D. Shin, K. Lee, I. Kim
Journal: Journal of Clinical Oncology (2009)

e17574 Background: Subscription to National Health Insurance (NHI) is a national obligation for South Korean people. For low-income citizens (about lower 3% of population), Medicaid is applied. Many recipients of Medicaid are vulnerable people such as old age singles, the homeless or the handicapped. These populations are suspected to have worse prognosis. According to one report, on the other hand, patients with Medicaid were more likely to receive chemotherapy than patients with NHI despite the uniform health insurance coverage within the two types of health cost financing. Owing to these conflicting findings, we investigated the relationship between health insurance type and prognosis. Methods: Patients are stage IV advanced gastric cancer patients who received palliative chemotherapy. Medical records were reviewed from January 2006 to November 2008 in Seoul Medical Center (municipal teaching hospital). Results: Total 37 patients were found. Median age was 61 years (range 31–85) and male constituted 75.7%. Platinum (cisplatin or oxaliplatin) combined with 5-FU was the most frequently used regimen (78.4%). Twelve patients (32.4%) were recipients of Medicaid. Median PFS and OS of NHI group were 6.9 (95% CI, 1.7–12.0) and 7.8 (95% CI, 3.4–12.1). And that of Medicaid were 5.6 (95% CI, 2.6–8.6) and 7.8 (95% CI, 3.4–12.2) months. The difference from two groups were not statistically different (p = 0.739 for PFS and 0.466 for OS). When patients were divided into longer or shorter survivors according to mean OS (14.1 ±2.6 months), NHI recipients had more probability for survival (odds ratio 0.72, 95% CI 0.56–0.92). Conclusions: The question is raised whether recipients of Medicaid have poorer prognosis than patients with NHI in metastatic gastric cancer in South Korea. Although it seems that NHI recipients has better prognosis, still we cannot sure. It should be cleared in large scale cohort study whether this is related to low socio-economic status or other uncontrolled confounder. No significant financial relationships to disclose.
The serial effects of multimodality therapy for stage III non-small cell carcinoma on lung function
Authors: P. J. Mazzone, G. Videtic, S. Murthy, D. Mason, T. Rice, N. Pennell, T. Rich, M. Machuzak, T. Mekhail
Journal: Journal of Clinical Oncology (2009)

7551 Purpose: To describe the effects of multimodality treatment on lung function in patients with stage III non-small cell carcinoma of the lung (NSCLC) Methods: Pulmonary function tests (PFTs) were reviewed for 32 patients with stage III NSCLC who were enrolled in a multimodality protocol that included neoadjuvant (NAd) combined chemoradiotherapy (taxol 50 mg/m2, carboplatin AUC 2 weekly X 3, radiation (XRT) 1.8 Gy BID to 30 Gy + erlotinib 150 mg/d for 28 days, followed by resection (R) and adjuvant (Ad) chemoradiotherapy (same as induction) followed by erlotinib 150mg/d maintenance (M) for 2 years. Changes in PFTs were analyzed at multiple time points (baseline to after NAd, after NAd to after R, after R to after Ad) and for the overall effect of treatment (baseline to the end of treatment). Results: The table below shows changes in percent predicted pulmonary function test values at each step in the treatment course. + signifies an increase and - a decrease. P indicates pneumonectomy and L lobectomy. Numbers in parentheses are the number of patients with complete testing at that time point. Conclusions: Neoadjuvant combined chemoradiotherapy has a small effect on lung function testing. The combined effect of multimodality therapy for stage III lung cancer that includes surgical resection leads to larger declines in lung function than have been reported historically for resection alone. [Table: see text] [Table: see text]
The role of carbon monoxide, heme oxygenase 1, and the Nrf2 transcription factor in the modulation of chronic pain and their interactions with opioids and cannabinoids
Authors: Olga Pol
Journal: Medicinal Research Reviews (2020)

Abstract Chronic pain and its associated comorbidities are difficult to treat, even when the most potent analgesic compounds are used. Thus, research on new strategies to effectively relieve nociceptive and/or emotional disorders accompanying chronic pain is essential. Several studies have demonstrated the anti‐inflammatory and antinociceptive effects of different carbon monoxide‐releasing molecules (CO‐RMs), inducible heme oxygenase 1 (HO‐1), and nuclear factor‐2 erythroid factor‐2 (Nrf2) transcription factor activators in several models of acute and chronic pain caused by inflammation, nerve injury or diabetes. More recently, the antidepressant and/or anxiolytic effects of several Nrf2 transcription factor inducers were demonstrated in a model of chronic neuropathic pain. These effects are mainly produced by inhibition of oxidative stress, inflammation, glial activation, mitogen‐activated protein kinases and/or phosphoinositide 3‐kinase/phospho‐protein kinase B phosphorylation in the peripheral and/or central nervous system. Other studies also demonstrated that the analgesic effects of opioids and cannabinoids are improved when these drugs are coadministered with CO‐RMs, HO‐1 or Nrf2 activators in different preclinical pain models and that these improvements are generally mediated by upregulation or prevention of the downregulation of µ‐opioid receptors, δ‐opioid receptors and/or cannabinoid 2 receptors in the setting of chronic pain. We reviewed all these studies as well as studies on the mechanisms of action underlying the effects of CO‐RMs, HO‐1, and Nrf2 activators in chronic pain. In summary, activation of the Nrf2/HO‐1/carbon monoxide signaling pathway alone and/or in combination with the administration of specific analgesics is a valid strategy for the treatment of chronic pain and some associated emotional disorders.
Is there more to me than soccer? Impact of a career-ending injury
Authors: Frederikke Pultz Madsen
Journal: British Journal of Sports Medicine (2020)

When I was a little girl, I would watch my dad play soccer, and I remember wanting to be just like him. I was thrilled when I joined the local team at age 6. From that moment, and for many years to come, my whole life revolved around soccer. As my passion intensified, I decided to take my game to the next level. I moved to an elite soccer club. I was excited about the new environment and rapidly became an integral part of the team.

Elite athletes experience aches, but as I tried to push through the pain, I eventually knew something was not right. I began to experience a slight pain in my left groin. At first, I figured it was due to overuse, but over time, the pain persisted and worsened. Quickly, it evolved from a mild groin pain to a horrendous hip pain. I went to see my physical therapist, but it was still unclear what the problem was. I was told to take a few weeks off from practice in order to fully recover. Unfortunately, that did not help. My parents brought me to see different kinds of specialists; however, none of them were able to pinpoint the problem. It seemed impossible for me to ever play again. After a couple of months, the pain hindered my ability to complete simple, everyday tasks. Sitting in a chair, going for a walk and regular stuff like that were painful. The whole situation was taking a serious toll on my mood and mental health. After careful consideration, I saw …
Paediatric anterior cruciate ligament injuries: management, treatment rationale and long-term outcomes (PhD Academy Award)
Authors: Guri Ranum Ekås
Journal: British Journal of Sports Medicine (2020)

I am an orthopaedic surgeon focusing on knee injuries especially in the paediatric population. My PhD involved investigating paediatric anterior cruciate ligament (ACL) injury management, treatment rationale and long-term outcomes.

My research questions included:

1.  How should clinicians manage paediatric ACL injuries? Is it possible to reach a consensus?

2.  What are the long-term clinical and radiological outcomes following a primary non-operative treatment approach?

3.  What is the risk of new meniscal tears after ACL injury?

The incidence of paediatric ACL injuries is increasing.1 This trend is alarming due to the high risk of reinjury to the affected knee and the potential for early-onset knee osteoarthritis. Management is controversial—largely guided by local traditions and surgeon preferences (ie, dogma, eminence-based). The prevailing clinical dogma, in many centres, has been to undertake early ACL reconstruction to protect the other knee structures such as menisci and cartilage. Current evidence is sparse.

1.  I contributed to the 2018 International Olympic Committee Consensus Statement on prevention, …
The utility of a specific hepatic CYP-3A4 probe (C<sup>14</sup>-Erythromycin breath test [EBT]) versus the general CYP-P450 probe (antipyrine clearance [ACL] test), for the prediction of docetaxel (D) pharmacokinetics (PK)
Authors: M. Michael, R. J. Booth, A. Milner, A. Hatzamihallis, P. Francis, S. J. Clarke, S. Schlict, C. Cullinane
Journal: Journal of Clinical Oncology (2009)

2523 Background: BSA-based cytotoxic dosing does not account for the individual variability in drug disposition. In the case of D, CYP 3A4 probes such as the EBT have been assessed to individualise dosing, but inconsistently. This report is the first study comparing the EBT directly with the widely available general P450 probe, the ACL test, for the prediction of D PK when given either q 21 days or weekly. Methods: Patients (pts) with pre-treated advanced malignancy suitable for D therapy, Se bilirubin≤1.0xUNL, AST≤1.5xUNL &amp; ALP≤2.5xUNL, were entered. Prior to D therapy, pts underwent EBT and ACL test. Pts were given IV 14 C N-methyl-erythromycin and exhaled breath samples were captured for 14 CO 2 from 5–120 mins post. The EBT parameters determined: 14 CO 2 flux at 10 min (CO 2 f 10 ), &amp; 20 min (CO 2 f 20 ), (iii) terminal rate constant k CO2 (iv) AUC CO2,(0- ∞ ) &amp; AUC CO2,(0–60). For the ACL test, pts was given oral antipyrine 10mg/kg, blood samples were collected from 0, 4 &amp; 24 hrs post, and serum levels measured: ACL was calculated as per Farrell et al.(Br J Clin Pharmacol 18:559). D was given 75mg/m 2 q21 days or 35mg/m 2 weekly. Samples taken for D PK in course 1 day 1, parameters included: half life (t D1/2 ), &amp; clearance (CL D ). Correlations were sought between EBT parameters, ACL values and D PK parameters. Results: 20 pts accrued, M:F= 12:8, Median age= 65. Mean BSA = 1.77m 2 (1.44–2.07). D q21 days:D weekly= 13:7. EBT parameters (N= 19) (Mean, [CV%]): CO 2 f 10 (%/min) 0.051 (106), CO 2 f 20 0.052 (82), k CO2 (min - 1 ) 0.007 (22), AUC CO2,(0- ∞ ) 7.9 (85), AUC CO2,(0–60) 2.64 (81). ACL (N=19) (ml/min); 35.8 (37). No significant differences observed for EBT parameters and ACL between the q21 days vs weekly dosing. D PK parameters (N=19): CL D (l/hr) 57.2 (36), t D1/2 (hrs) 12.7 (33). No correlations were observed between the D PK and EMBT parameters for all pts and regardless of the regimen given. For D weekly pts, a significant linear relationship was observed between CL D and ACL (P =0.007, R 2 = 79.47%). Conclusions: The utility of EBT for the prediction of D PK was not confirmed in this study. The Antipyrine Clearance test may be superior in this regard for D, but regimen dependent and hence warrants further evaluation. No significant financial relationships to disclose.
Follicular Lymphoma Evaluation Index (<scp>FLEX</scp>): A new clinical prognostic model that is superior to existing risk scores for predicting progression‐free survival and early treatment failure after frontline immunochemotherapy
Authors: Farheen Mir, Federico Mattiello, Andrew Grigg, Michael Herold, Wolfgang Hiddemann, Robert Marcus, John F. Seymour, Christopher R. Bolen, Andrea Knapp, Tina Nielsen, Carla Casulo
Journal: American Journal of Hematology (2020)

Abstract Patients with advanced‐stage follicular lymphoma (FL) who progress early after receiving first‐line therapy have poor overall survival (OS). Currently applied clinical prognostic models such as FL International Prognostic Index [FLIPI], FLIPI‐2 and PRIMA‐Prognostic Index [PRIMA‐PI] have suboptimal sensitivity and specificity to predict this poor prognosis subgroup. The primary objective was to develop a novel prognostic model, the FL Evaluation Index (FLEX) score, to identify high‐risk patients and compare its performance with FLIPI, FLIPI‐2 and PRIMA‐PI. Progression‐free survival (PFS) after first‐line immunochemotherapy was the key endpoint, while OS and progression of disease within 24 months (POD24) were also assessed. The model, which includes nine clinical variables, was developed using a cohort of patients with previously untreated advanced‐stage FL from the phase 3 GALLIUM trial (NCT01332968). The performance of the model was validated using data from the SABRINA trial (NCT01200758). In GALLIUM (n = 1004; 127 with and 877 without POD24), FLEX increased the intergroup (low‐risk/high‐risk) difference in 2‐year and 3‐year PFS rates and demonstrated superior intergroup differences in 2‐year and 3‐year OS rates compared with FLIPI, FLIPI‐2 and PRIMA‐PI. Sensitivity for a high‐risk score to predict POD24 was 60% using FLEX compared with 53% for FLIPI and FLIPI‐2, and 69% for PRIMA‐PI, while specificity was 68% for FLEX compared with 58% for FLIPI, 59% for FLIPI‐2 and 48% for PRIMA‐PI. The prognostic value of FLEX in SABRINA was similar to FLIPI. Therefore, FLEX appears to perform better than existing prognostic models in previously untreated FL, in particular for the newer treatment regimens.
Cancer-specific drug-drug nanoparticles of pro-apoptotic and cathepsin B-cleavable peptide-conjugated doxorubicin for drug-resistant cancer therapy
Authors: Man Kyu Shim, Yujeong Moon, Suah Yang, Jinseong Kim, Hanhee Cho, Seungho Lim, Hong Yeol Yoon, Joon-Kyung Seong, Kwangmeyung Kim
Journal: Biomaterials (2020)
Highly sensitive and specific diagnosis of COVID-19 by reverse transcription multiple cross-displacement amplification-labelled nanoparticles biosensor
Authors: Shijun Li, Weijia Jiang, Junfei Huang, Ying Liu, Lijuan Ren, Li Zhuang, Qinni Zheng, Ming Wang, Rui Yang, Yi Zeng, Yi Wang
Journal: European Respiratory Journal (2020)

Background The ongoing outbreak of the novel human coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (also known as 2019-nCoV) has become a global health concern. Rapid and easy-to-use diagnostic techniques are urgently needed to diagnose SARS-CoV-2 infection. Methods We devised a reverse transcription multiple cross-displacement amplification (RT-MCDA) coupled with a nanoparticle-based biosensor assay (RT-MCDA-BS) for rapid, sensitive and specific diagnosis of coronavirus disease 2019 (COVID-19). Two primer sets were designed to target the open reading frame 1a/b and nucleoprotein gene of SARS-CoV-2. A total of 183 clinical samples, including 65 patients with COVID-19 infection and 118 patients with other pathogen infections were used to testify the assay's feasibility. Diagnosis results were reported visually using the biosensor. Findings The assay designed was performed using a simple instrument which could maintain the reaction in a constant temperature at 64°C for only 35 min. The total COVID-19 RT-MCDA-BS test procedure could be finished within 1 h. The COVID-19 RT-MCDA-BS could detect down to five copies of target sequences. Among 65 clinical samples from the COVID-19 patients, 22 (33.8%) positive results were obtained from faeces, nasal, pharyngeal and anal swabs via COVID-19 RT-MCDA-BS assay, while real-time reverse transcription-PCR assay only detected 20 (30.7%) positive results in these samples. No positive results were obtained from clinical samples with non-COVID-19 infections. Interpretation COVID-19 RT-MCDA-BS was a rapid, reliable, low-cost and easy-to-use assay, which could provide an attractive laboratory tool to diagnose COVID-19 in multiple clinical specimens, especially for field, clinic laboratories and primary care facilities in resource-poor settings.
THU0131 Very long-term functional (HAQ) status of ra
Authors: JM Berthelot, Y Laborie, J Glemarec, A Prost, Y Maugars
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Only a few studies have attempted to determine the HAQ level of rheumatoid arthritis twenty years after onset, and how often those patients consider that RA has 'burned-out' by then. <h3>Objectives</h3> To determine how often patients with long-lasting RA (more than 10 years'duration) consider themselves in remission and to assess their HAQ level after mean follow-up of 20 years. <h3>Methods</h3> A questionnaire was sent to 122 patients with typical RA (100% erosive, 79% positive for rheumatoid factor) of more than 10 years'duration who had been randomly selected from the charts of 4 office-based-rheumatologists (N = 61) or a university hospital rheumatology unit (N = 61). The outcome of 33/34 patients who did not return the questionnaire was determined by phone. <h3>Results</h3> Eighty-eight of the 122 patients (63 ± 13 years of age, RA duration 20.1 ± 8.7 years) returned the questionnaire; only 80% of whom had been seen by a rheumatologist within the last year. RA burn-out was not reported, and only 6/88 fulfilled Pinals criteria for remission. However, 26% considered themselves 'in remission' for 8.5 ± 6 months, and pain was estimated at only 4.1 ± 2.3 on a visual analogue scale 0–10. HAQ remained rather low (1.11 ± 0.84) for most patients; 46% had benefited from prosthetic surgery. Among the 34 patients who did not return the questionnaire, 7 had died (at a mean age of 74 years) and the other 27 had not seen a rheumatologist for a mean 3.9 years (even though only 41% considered themselves in remission). <h3>Conclusion</h3> RA 'burn-out' was infrequent, even after 20 years of disease duration. Conversely, more than a fourth of patients considered themselves in remission, and disease activity was frequently low. These two factors probably explain why 40% of these patients had not seen a rheumatologist for at least a year. Although the HAQ level ranged from 0 to 2.6, it was often surprisingly low. Surgery could be largely responsible for the rather good functional outcome following diagnosis of erosive RA, even after more than 20 years' duration.