tbuckley/cabot-search huggingface dataset:
Enhancing evaluation of cancer cachexia (CC) and sarcopenia through skeletal muscle mass (SMM) determination in patients (pts) with non-small cell lung cancer (NSCLC), assessing at the L1 level on routine chest CT: A prospective study of accuracy for cancer patients.
Authors: Jose Nahun Galeas, Alejandro Recio Boiles, Bayruch Goldwasser, Karla Sanchez, Jesus Anampa, David Gordon, Patricia J Hollen, Richard J. Gralla
Journal: Journal of Clinical Oncology (2015)

e20725 Background: Sarcopenia and CC reportedly occur in up to 60% of pts with NSCLC and have been linked to several negative outcomes. SMM assessment by CT (SD < 1.2kg) is more accurate than Dual X ray absorptiometry (DXA, SD 3kg) or by bioelectrical impedance (SD 9.3kg). A single slice on CT at the third lumbar vertebra, L3, correlates highly (r = 0.924) with total body SMM in healthy individuals. The L3 level is often used in CC studies; however, routine chest CT scans rarely extend to L3. While, prior studies demonstrated high correlation (r = 0.903) at L1, this has not been assessed in pts with cancer. Methods: This study enlisted pts with NSCLC and performed SMM measurements at L1 using Slice-O-Matic software for muscle mass in the Hounsfield unit range of -29 to +150. Pts were assessed for accuracy of using the L1 level for imaging quality and the ability to use the software properly. Results: 23 pts with NSCLC (47 CT assessments) were enlisted. Characteristics: 58% female; medians: age 57, KPS 80%; BMI 24.1, weight 72.2 kg, SM index 57.9. Sarcopenia was detected in 32% of pts (63% of males < 55.5 cm2/M2; 10% of females < 38.5cm2/M2) with all having normal or overweight BMI. Of the 47 CT images, 98% included L1. 3 additional images (7%) were difficult to evaluate for SMM due to ascites or effusions; also, 1 pt was too obese for proper imaging. As previously reported with assessment at L3 (r = 0.35), the correlation of BMI with SMM in this study at L1 was also low (r = 0.34). Conclusions: This study indicates that SMM assessment at L1 is achievable on routine chest CT, with 98% of pts having images at this level, and 91% have acceptable quality for SMM evaluation. Evaluability would not have been improved at L3. The low correlation and poor sensitivity of BMI to identify sarcopenia was equally demonstrated in this trial as it had been previously at L3. Use of L1 enhances patient evaluation for SMM without needing additional testing or radiation exposure, and allows many more pts with NSCLC to have assessment of SMM in clinical trials or in patient management. Funding in part: NIH / NCI 1 R01 CA157409-01A1 Clinical trial information: NCT01924416.
Robert C Gray
Authors: Arthur Williamson
Journal: BMJ (2017)

For nearly 30 years Robert C Gray (“Bob”) was the head of the respiratory intensive care unit at the Royal Victoria Hospital, Belfast. He has been described as a “medical statesman,” and a “brilliant clinician and teacher.” Outstanding for his intelligence, compassion, wit, geniality, and integrity, he was also an inveterate storyteller and entertainer with a prodigious memory. He was a master of the mot juste , immortalised by colleagues who collected his pithy sayings.

In the late 1950s lockjaw/tetanus was almost always fatal. Inspired by research findings from Sweden, Bob Gray successfully introduced mechanical ventilation, only possible with …
Fungal dysbiosis in cirrhosis
Authors: Jasmohan S Bajaj, Eric J Liu, Raffi Kheradman, Andrew Fagan, Douglas M Heuman, Melanie White, Edith A Gavis, Phillip Hylemon, Masoumeh Sikaroodi, Patrick M Gillevet
Journal: Gut (2017)

Objective Cirrhotics have a high rate of infections, which are increasingly fungal or culture-negative in nature. While infected cirrhotics have bacterial dysbiosis, the role of fungi is unclear. We aimed to evaluate gut bacterial and fungal dysbiosis in cross-sectional and longitudinal analyses of outpatient and inpatient cirrhotics and prediction of hospitalisations. Methods Cross-sectional: Age-matched controls, outpatients (with/without antibiotics) and hospitalised uninfected, culture-negative and culture-positive cirrhotics were included and followed for 90 days. Longitudinal: Three studies were conducted: (1) cirrhotics followed over 6 months, (2) outpatient cirrhotics administered antibiotics per standard of care for 5 days and (3) cirrhotics and controls administered omeprazole over 14 days. In all studies, stool bacterial/fungal profiles were analysed. Results Cross-sectional: In 143 cirrhotics and 26 controls, bacterial and fungal diversities were significantly linked. Outpatients on antibiotics and patients with culture-positive infections had the lowest diversities. Bacterial and fungal correlations were complex in uninfected, outpatient and control groups but were markedly skewed in infected patients. 21% were admitted on 90-day follow-up. A lower Bacteroidetes/Ascomycota ratio was associated with lower hospitalisations. Longitudinal: Fungal and bacterial profiles were stable on follow-up (5 days and 6 months). After antibiotics, a significantly reduced bacterial and fungal diversity, higher Candida and lower autochthonous bacterial relative abundance were seen. After omeprazole, changes in bacterial diversity and composition were seen but fungal metrics remained stable. Conclusion There is a significant fungal dysbiosis in cirrhosis, which changes differentially with antibiotics and proton pump inhibitor use, but is otherwise stable over time. A combined bacterial–fungal dysbiosis metric, Bacteroidetes/Ascomycota ratio, can independently predict 90-day hospitalisations in patients with cirrhosis. Clinical trial number NCT01458990.
Preclinical Development of a Cord Blood (CB)-Derived Hematopoietic Stem Cell (HSC) Product for Allogeneic Transplantation in Patients with Hematological Malignancies
Authors: Camelia Iancu-Rubin, Helen Fong, Goar Mosoyan, Ami Patel, Rachel Sabado, Meseck Marcia, Erin Moshier, Umut Ozbek, Alla Keyzner, Nina Bhardwaj, Ian K. McNiece, Jay Tong, Ronald Hoffman
Journal: Blood (2016)
Organ dysfunction, injury and failure in acute heart failure: from pathophysiology to diagnosis and management. A review on behalf of the Acute Heart Failure Committee of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC)
Authors: Veli‐Pekka Harjola, Wilfried Mullens, Marek Banaszewski, Johann Bauersachs, Hans‐Peter Brunner‐La Rocca, Ovidiu Chioncel, Sean P. Collins, Wolfram Doehner, Gerasimos S. Filippatos, Andreas J. Flammer, Valentin Fuhrmann, Mitja Lainscak, Johan Lassus, Matthieu Legrand, Josep Masip, Christian Mueller, Zoltán Papp, John Parissis, Elke Platz, Alain Rudiger, Frank Ruschitzka, Andreas Schäfer, Petar M. Seferovic, Hadi Skouri, Mehmet Birhan Yilmaz, Alexandre Mebazaa
Journal: European Journal of Heart Failure (2017)
Reporting quality of case reports in international dermatology journals
Authors: D. Miguel, N. Gonzalez, T. Illing, P. Elsner
Journal: British Journal of Dermatology (2017)

Medical case reports provide new and often important information about diseases, pathogeneses, adverse effects, or treatments. [1] However, they have been shown to favor positive results and can lead to publication bias. [2, 3] Some leading journals have been reducing space for case reports or even declining them because of concerns about impact factor. [4]

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Abstract 125: The E2F1 Transcription Factor Suppresses Cardiac Fibrosis via Downregulating Syndecan-4 Expression and Smad2/3 Phosphorylation
Authors: Dauren Biyashev, Chan Boriboun, Asish K Ghosh, Shuling Han, Raj Kishore, Douglas W Losordo, Gangjian Qin
Journal: Circulation Research (2015)

Rationale: The E2F1 transcription factor is best known as a cell-cycle regulator; recent reports suggest its important role in cardiovascular system. Objective: To determine whether E2F1 regulates cardiac fibrosis. Methods and Results: Following Angiotensin II (Ang II) administration, E2F1-null (E2F1-KO) mice displayed a more severe cardiac fibrosis and higher levels of cardiac phospho-Smad2 (pSmad2) and pSmad3 than WT mice. Consistently, levels of pSmad2 and pSmad3 were elevated in E2F1-KO fibroblasts, which was associated with a significantly increased expression of collagen I (Col I) and α-smooth muscle actin (α-SMA) and interestingly, cell surface proteoglycan syndecan-4 (Sdc4). Knockdown of Sdc4 significantly attenuated the elevation in Smad2/3 phosphorylation and Col I and α-SMA expression in E2F1-KO fibroblasts. Remarkably, either chemical inhibition of Smad2/3 signaling or morpholino-mediated knockdown of Sdc4 expression abrogated the difference in the degree of Ang II-induced cardiac fibrosis between WT and E2F1-KO animals. Conclusions: E2F1 suppresses Ang II-induced cardiac fibrosis by downregulating Sdc4 expression and Sdc4-mediated Smad 2/3 activation.
Utility of Follow-up Dopamine Transporter SPECT With 123I-FP-CIT in the Diagnostic Workup of Patients With Clinically Uncertain Parkinsonian Syndrome
Authors: Ivayla Apostolova, Daulat S. Taleb, Axel Lipp, Imke Galazky, Dennis Kupitz, Catharina Lange, Marcus R. Makowski, Winfried Brenner, Holger Amthauer, Michail Plotkin, Ralph Buchert
Journal: Clinical Nuclear Medicine (2017)

Purpose Dopamine transporter SPECT with 123I-FP-CIT is registered for detection (or exclusion) of nigrostriatal degeneration to support the etiologic classification of parkinsonian syndromes. In case of uncertainty in the interpretation of SPECT findings or unexpected clinical course, follow-up SPECT might be useful. However, the utility of follow-up FP-CIT SPECT has not yet been clarified. Methods One hundred forty-one patients (65.1 ± 10.4 years) from 3 sites with follow-up FP-CIT SPECT 22.4 ± 13.7 months after baseline SPECT were included. Retrospective visual interpretation of FP-CIT SPECT scans was performed by 2 experienced readers according to the following 7-point score: "normal," some minor degree of uncertainty due to "mild asymmetry" or mild to moderate "uniform reduction," "Parkinson disease (PD) reduction type 1/2/3," and "atypical reduction." Results Normal FP-CIT SPECT or PD characteristic reduction was confirmed by follow-up SPECT in all cases (n = 58). Among patients with some minor degree of uncertainty at baseline (n = 65), the majority (72%) did now show abnormalities in follow-up SPECT, but 20% showed clear progression suggesting nigrostriatal degeneration. The latter was very rare at age younger than 60 years. The final categorization as normal or neurodegenerative was not affected by the time delay between baseline and follow-up SPECT. Conclusions Follow-up FP-CIT SPECT cannot be generally recommended in case of completely normal baseline SPECT or PD characteristic reduction. It also cannot be recommended in patients younger than 60 years, even in case of some minor degree of uncertainty in the baseline SPECT. There is no evidence to delay follow-up FP-CIT SPECT longer than 12 months.
The Lumleian Lectures on Bright's Disease
Authors: R. Southey
Journal: BMJ (1881)

An antiserum against the crustacean neuropeptide pigment-dispersing hormone stains a small set of neurons in the optic lobes of several hemimetabolous and holometabolous insects. These cells, the primary branches of which in the optic lobe lie in the accessory medulla, fulfill several criteria predicted for neurons of the circadian clock. For example, in fruit flies they express <i>timeless</i> and<i>period</i>, which are two molecular components of the circadian pacemaker. To test whether pigment-dispersing hormone fulfills a circadian function in the cockroach <i>Leucophaea maderae</i>, 150 fmol of synthetic peptide was injected into the vicinity of the accessory medulla. This resulted in a stable phase-dependent resetting of the phase of the circadian locomotor activity rhythm, which depended on the amount of pigment-dispersing hormone injected. The resulting phase–response curve differs from that obtained with light pulses, suggesting that pigment-dispersing hormone-immunoreactive neurons are not part of the visual input pathway to the pacemaker but an integral part of it and/or part of a nonphotic input into the clock. A possible role of these neurons in coupling the bilaterally paired circadian pacemakers is discussed.
ALK, ROS1, and NTRK Rearrangements in Metastatic Colorectal Cancer
Authors: Filippo Pietrantonio, Federica Di Nicolantonio, Alexa B Schrock, Jeeyun Lee, Sabine Tejpar, Andrea Sartore-Bianchi, Jaclyn F Hechtman, Jason Christiansen, Luca Novara, Niall Tebbutt, Giovanni Fucà, Carlotta Antoniotti, Seung Tae Kim, Danielle Murphy, Rosa Berenato, Federica Morano, James Sun, Bosun Min, Philip J Stephens, Marissa Chen, Luca Lazzari, Vincent A Miller, Robert Shoemaker, Alessio Amatu, Massimo Milione, Jeffrey S Ross, Salvatore Siena, Alberto Bardelli, Siraj M Ali, Alfredo Falcone, Filippo de Braud, Chiara Cremolini
Journal: JNCI Journal of the National Cancer Institute (2017)

ALK, ROS1, and NTRK fusions occur in 0.2% to 2.4% of colorectal cancers. Pioneer cases of metastatic colorectal cancer (mCRC) patients bearing rearrangements who benefited from anti-ALK, ROS, and TrkA-B-C therapies have been reported previously. Here we aimed at characterizing the clinical and molecular landscape of ALK, ROS1, and NTRK rearranged mCRC.Clinical features and molecular characteristics of 27 mCRC patients bearing ALK, ROS1, and NTRK rearranged tumors were compared with those of a cohort of 319 patients not bearing rearrangements by means of Fisher's exact, χ2 test, or Mann-Whitney test as appropriate. Overall survival curves were estimated with the Kaplan-Meier method and compared using the log-rank test. A Cox proportional hazard model was adopted in the multivariable analysis. Deep molecular and immunophenotypic characterizations of rearranged cases, including those described in The Cancer Genome Atlas database, were performed. All statistical tests were two-sided.Closely recalling the "BRAF history," ALK, ROS1, and NTRK rearrangements more frequently occurred in elderly patients (P = .02) with right-sided tumors (P < .001) and node-spreading (P = .03), RAS wild-type (P < .001), and MSI-high (P < .001) cancers. All patients bearing ALK, ROS1, and NTRK fusions had shorter overall survival (15.6 months, 95% confidence interval [CI] = 0.0 to 20.4 months) than negative patients (33.7 months, 95% CI = 28.3 to 42.1 months), both in the univariate (hazard ratio [HR] = 2.17, 95% CI = 1.03 to 4.57, P < .001) and multivariable models (HR = 2.33, 95% CI = 1.10 to 4.95, P = .02). All four evaluable patients with rearrangements showed primary resistance to anti-epidermal growth factor receptor agents. Frequent association with potentially targetable RNF43 mutations was observed in MSI-high rearranged tumors.ALK, ROS1, and NTRK rearrangements define a new rare subtype of mCRC with extremely poor prognosis. Primary tumor site, MSI-high, and RAS and BRAF wild-type status may help to identify patients bearing these alterations. While sensitivity to available treatments is limited, targeted strategies inhibiting ALK, ROS, and TrkA-B-C provided encouraging results.
SL-401, a Targeted Therapy Directed to the Interleukin-3 Receptor (CD123), and SL-801, a Reversible Inhibitor of Exportin-1 (XPO1), Display Synergistic Anti-Tumor Activity Against Hematologic Malignancies in Vitro
Authors: John Gionco, Janice Chen, Ross Lindsay, Vince Macri, Christopher L. Brooks
Journal: Blood (2016)
European Association for Neuro-Oncology (EANO) guidelines for palliative care in adults with glioma
Authors: Andrea Pace, Linda Dirven, Johan A F Koekkoek, Heidrun Golla, Jane Fleming, Roberta Rudà, Christine Marosi, Emilie Le Rhun, Robin Grant, Kathy Oliver, Ingela Oberg, Helen J Bulbeck, Alasdair G Rooney, Roger Henriksson, H Roeline W Pasman, Stefan Oberndorfer, Michael Weller, Martin J B Taphoorn
Journal: The Lancet Oncology (2017)
Prevalence and outcome of mutations (mut) in the Fanconi anemia (FA) DNA repair pathway among head and neck cancer (H&amp;N Ca) patients (pts).
Authors: Nooshin Hashemi Sadraei, Kakajan Komurov, Ann Marie Egloff, Lindsey Romick-Rosendale, Jung Ying, Susanne Wells, Jennifer Grandis
Journal: Journal of Clinical Oncology (2014)

6036 Background: Almost all survivors of FA, an inherited DNA repair deficiency syndrome, will develop H&N Ca. Preclinical data in H&N Ca cells harboring FA mut show increased sensitivity to chemo (CT) and radiation (RT) therapy. Little is known about prevalence and outcome of FA mut in general population of H&N Ca . Methods: Whole exome sequencing data from tumor samples of pts with H&N Ca were analyzed for 15 FA genes. Disease related characteristics and outcome data was collected. Results: A total of 124 pts were identified between 3/2003 - 5/2011 based on fresh frozen tissue availability. Overall, 21 (16.9%) pts had at least one mut in an FA pathway gene. For the entire cohort the median age was 59 (range 19-90), 77% were male, and 10% were HPV+ . Oral cavity was most frequent site (54%), followed by larynx (27%), oropharynx (10%), hypopharynx (8%) and sinonasal (1 %). Overall, T3-T4 and N1-3 was seen in 72% and 65%. PNI and ECS in 55% and 54%. RT was delivered in 68% and 71% received CT. Loco-regional recurrence occurred in 29 (23%). Median survival (OS) was 23 months (m) (2-89m) There were no significant differences in tumor characteristics (T, N, PNI, ECS) between FA mut and wild type pts (p> 0.48). However, recurrence occurred in only 2/19 ( 11%) HPV(-), FA mut pts compared to 34/92 ( 37%) HPV(-) wild type FA , p=0.02. No such difference was seen in the HPV(+) pts. Median OS was 22 m in the HPV + wild type vs 14 m in the HPV+FA mut pts ( p=0.1) (HR=3.4, p=0.1) Conclusions: Mut in FA pathway genes are detectable in a variety of H&N Ca. Recurrence and survival may be differentin FA mut and wild type H&N Ca depending on HPV status: In absence of HPV, these mut may result in a lower disease recurrence rate, which may reflect increased sensitivity to treatment. In the presence of HPV, the presence of an FA mut may negatively impact prognosis. These findings may suggest distinct biological consequences of FA mut in HPV (–) versus HPV (+) pts.
18F-FDG PET/CT Imaging of Popliteal Vasculitis Associated With Polyarteritis Nodosa
Authors: Romain Schollhammer, Paul Schwartz, Marie-Laure Jullie, Anne Pham-Ledard, Patrick Mercie, Philippe Fernandez, Jean-Baptiste Pinaquy
Journal: Clinical Nuclear Medicine (2017)

We report an F-FDG linear uptake of the right popliteal artery in a 25-year-old man who underwent a PET/CT scan for unexplained chronic asthenia associated with fever symptoms, arthralgia, and subcutaneous nodes, in favor of vasculitis. The patient had a history of saphenous vein thrombosis. Thrombophilia screening finds a blood lupus anticoagulant. A biopsy of subcutaneous nodes finds an anatomopathologic lesion of polyarteritis nodosa. F-FDG PET can be useful in initial staging of polyarteritis nodosa for an early diagnosis of vasculitis, and thus, early treatment can prevent arterial complications such as occlusion or aneurysm.
Targeting <i>BRAF</i>-Mutant Colorectal Cancer: Progress in Combination Strategies
Authors: Raghav Sundar, David S. Hong, Scott Kopetz, Timothy A. Yap
Journal: Cancer Discovery (2017)

Abstract Summary: BRAF mutations in colorectal cancer portend a poor prognosis, with first-line treatment often involving triplet or quadruplet chemotherapy, and single-agent targeted therapy with BRAF inhibitors failing to demonstrate clinical activity. Blockade of multiple critical nodes along the MAPK and other pathways may be necessary to improve response rates and survival. Cancer Discov; 7(6); 558–60. ©2017 AACR. See related article by van Geel et al., p. 610.
Characterization of circulating progenitors in patients with myelofibrosis: clonal origin of progenitor cells and prevalence of colony forming unit-megacaryocyte
Authors: Giovanna Piaggio, Marina Podesta, Mario Sessarego, Anna Pitto, Enrica Painelli, Edoardo Rossi, Vittorio Rosti, Gaetano Bergamaschi, Giovanni Barosi, Francesco Frassoni, Andrea Bacigalupo
Journal: Blood (2000)
A comparison of programmable and nonprogrammable compression devices for treatment of lymphoedema using an administrative health outcomes dataset
Authors: P. Karaca-Mandic, A.T. Hirsch, S.G. Rockson, S.H. Ridner
Journal: British Journal of Dermatology (2017)

Patients with lymphoedema experience lifelong swelling and recurrent cellulitis despite use of complete decongestive therapy. Pneumatic compression devices (PCDs), including nonprogrammable and programmable devices that meet individual patient needs, support long-term self-care in the home.Patients with either a nonprogrammable device (NP-PCD) or a dynamic pressure programmable device [P-PCD; Flexitouch® (Tactile Medical, Minneapolis, MN, U.S.A.)] were evaluated to compare associated clinical and health utilization outcomes pre-/postdevice acquisition.Retrospective analysis of deidentified administrative claims from 2007 through 2013 of a large U.S. insurer. Outcome variables included rates of lymphoedema-related cellulitis, manual therapy use, outpatient services and inpatient hospitalizations. Multivariate regression analysis was performed to (i) compare outcomes for the 12 months pre- and postdevice acquisition and (ii) compare these two device types for their treatment-associated benefits.The sample consisted of 1013 NP-PCD and 718 P-PCD recipients. Compared with the NP-PCD group, P-PCD patients' baseline cellulitis rate was higher, whereas their postdevice cellulitis rate was lower. In the cancer cohort, the NP-PCD group had a 53% reduction in episodes of cellulitis (from 17·9% to 8·5%), compared with a greater 79% reduction in the P-PCD group (from 23·7% to 5·0%) (P < 0·001). In the noncancer cohort, the P-PCD group also experienced a larger 76% decline (from 31·0% to 7·4%) vs. 54% decline (from 22·9% to 10·6%) in cellulitis rates (P = 0·003). Outpatient service use reduced in both device groups, with greater reductions observed in the P-PCD group. Both device groups experienced reductions in manual therapy use. Inpatient hospitalizations were largely stable with reductions observed only in the noncancer cohort of the P-PCD group.P-PCD receipt was associated with superior lymphoedema-related health outcomes and reductions in cellulitis.
Clinical Management and Tumor Surveillance Recommendations of Inherited Mismatch Repair Deficiency in Childhood
Authors: Uri Tabori, Jordan R. Hansford, Maria Isabel Achatz, Christian P. Kratz, Sharon E. Plon, Thierry Frebourg, Laurence Brugières
Journal: Clinical Cancer Research (2017)

Abstract Replication proofreading is crucial to avoid mutation accumulation in dividing cells. In humans, proofreading and replication repair is maintained by the exonuclease domains of DNA polymerases and the mismatch repair system. Individuals harboring germline mutations in genes involved in this process are at increased risk of early cancers from multiple organs. Biallelic mutations in any of the four mismatch repair genes MSH2, MSH6, MLH1, and PMS2 result in one of the most aggressive childhood cancer predisposition syndromes, termed constitutional mismatch repair deficiency or constitutional mismatch repair deficiency syndrome (CMMRD). Data gathered in the last decade allow us to better define the clinical manifestations, tumor spectrum, and diagnostic algorithms for CMMRD. In this article, we summarize this information and present a comprehensive consensus surveillance protocol for these individuals. Ongoing research will allow for further definition of replication repair–deficient cancer syndromes, assessing the cost-effectiveness of such surveillance protocols and potential therapeutic interventions for these children and families. Clin Cancer Res; 23(11); e32–e37. ©2017 AACR. See all articles in the online-only CCR Pediatric Oncology Series.
Evaluation of direct oral anticoagulants in superficial-vein thrombosis – Authors' reply
Authors: Jan Beyer-Westendorf, Sebastian M Schellong, Horst Gerlach, Eberhard Rabe, Jeffrey I Weitz, Katja Jersemann, Kurtulus Sahin, Rupert Bauersachs
Journal: The Lancet Haematology (2017)