tbuckley/cabot-search huggingface dataset:
Phase I/II study of neoadjuvant bevacizumab with radiation therapy and 5-fluorouracil in patients with rectal cancer: initial results
Authors: C. Willett, D. Duda, Y. Boucher, E. di Tomaso, J. Clark, L. Blaszkowsky, B. Czito, J. Bendell, R. Jain
Journal: Journal of Clinical Oncology (2007)

4041 Background: A phase I/II study of neoadjuvant bevacizumab with 5-fluorouracil and radiation therapy in patients with locally advanced rectal cancer was undertaken to determine whether inhibition of VEGF is safe and has clinical benefits by enhancing chemo- radiation therapy. Methods: 22 patients with endoscopic ultrasound or surface coil MRI staged T3/T4 non-metastatic rectal cancer were enrolled from 2001–2006. All patients completed 4 cycles of neoadjuvant therapy including: 1) bevacizumab infusion (5 or 10 mg/kg) on day 1 of each cycle; 2) peripheral venous infusion 5-FU (225 mg/m 2 /24 hours) administration each treatment week of cycles 2 - 4; 3) external beam irradiation delivery (50.4 Gy in 28 fractions over 5.5 weeks); and 4) surgery 7 to 9 weeks after completion of all neoadjuvant therapy. Correlative studies were undertaken before and during the trial. We collected serial tumor biopsies, PET-FDG scans, and analyzed blood and urine for potential biomarkers. Results: Mean pre-therapy tumor size was 4.7 cm (2–9 cm). Post-treatment surgical specimens usually had well-demarcated shallow ulcerations with a mean diameter of 2.4 cm (0.7–6 cm). In response to the neoadjuvant regimen, all patients had significantly (p&lt;0.01) decreased FDG-uptake by PET. Histologic examination showed no residual primary cancer in 5 patients (ypT0). Of 17 patients with residual disease, microscopic disease usually occurred as malignant glands embedded in fibrosis (ypT1 in 3 patients, ypT2 in 4 patients, ypT3 in 10 patients). Downstaging was seen in 12/22 tumors. 8 patients had microscopic nodal metastases. Bevacizumab alone and combined treatment were both associated with increased plasma VEGF and PlGF levels in 18/18 patients (P&lt;0.01 at all 4 timepoints compared to baseline). Viable CECs were decreased by VEGF blockade at day 3 (P&lt;0.01 compared to baseline), and peak CEC levels during treatment was correlated with histologic tumor response (2.77 [1.18–3.18] for T3 patients, n=9 versus 1.14 [0.82–1.53] for T0-T2 patients, n=12; p=0.05). Conclusions: Addition of bevacizumab at a dose of 5 mg/kg to standard chemo-radiation is safe in patients with locally advanced rectal cancer. Bevacizumab is active and the combined regimen yields promising results. [Table: see text]
Book: Time out of Mind
Authors: Sabina Dosani
Journal: BMJ (2003)

I confess a certain dread before settling down to read this book. Another celebrity falls foul of an illness and charts her decline or recovery. Almost always doctors come out of these accounts less favourably than we like to see ourselves.​ourselves.




Figure 1



Jane Lapotaire

Virago, £16.99, pp 320 ISBN 1 86049 977 5

Rating: ★★★★




But Time out of Mind is in a league of its own. Jane Lapotaire, an eminent film and television actor and a member of the Royal Shakespeare Company, uses skills and techniques acquired in her job to dramatise her life since just after the start of the new millennium, when she collapsed in Paris with a subarachnoid haemorrhage. The bulk of the book, starting with a chapter entitled “Nearly Dying is the Easy Bit,” plots her convoluted journey back to a partial recovery.

Lapotaire writes without sparing anyone's feelings. While it is true that she is probably harder on herself than anyone else, hardly any of her friends, family, or doctors come out of this account without criticism. Dr Vinikoff, a French neurosurgeon “who saved my life,” is chastised for sitting on her bed: “Doctors aren't supposed to do that, are they?” Nurses tie her to the bed in intensive care: “I was never told it was bad for me to move.” A British neurosurgeon, referred to by Lapotaire as “Mr H for Hell,” has “all the Rolls Royce attributes of the brain surgeon: softly spoken, luxurious office, Mont Blanc pen.” He is also patronising, condescending, and rude. He implies she is wrong about her second aneurysm: “statistically unlikely.” When she is upset and angry he accuses her of “over-reacting.” When Mr H sees her second aneurysm on a magnetic resonance image, he tells her triumphantly that breast cancer will probably kill her first.

The chapter “At the Doctor's” left me squirming. Lapotaire's general practitioner, who had been a friend, dismisses clinical depression with “Well, you are an actress.” When she asks her doctor why her attitude has changed, she is told: “I realised I was treating you differently from my other patients. I was losing my grip.”

During the course of the book Lapotaire makes a paradigm switch. Before her collapse she is a bit of a martyr, responsible for everything. By page 300 she has changed role to a fully fledged victim. She learns to censor outspoken rudeness and intolerance of others, but the feelings are still there. She has learnt not to blame herself, but her expectation that carers, friends, and even total strangers should show understanding, empathy, and selflessness is breathtaking.

This remarkable book—disturbing and hateful but also humbling—is one I am grateful to have read. I started by admiring the author's powers of description and style and finished with a new insight, seeing the shortcomings of our profession through patients' eyes.
Activity of dianhydrogalactitol alone or with platinum drugs against non-small cell lung cancer cell lines.
Authors: Anne Steino, Guangan He, Jeffrey A. Bacha, Sarath Kanekal, Dennis Brown, Zahid Hussain Siddik
Journal: Journal of Clinical Oncology (2015)

e19145 Background: Non-small cell lung cancer (NSCLC) is usually treated with surgery followed by treatment with either tyrosine kinase inhibitors or platinum-based regimens, but long-term prognosis is poor. Dianhydrogalactitol (VAL-083) is a bi-functional alkylating agent with proven activity against NSCLC in preclinical and clinical trials. Here we aimed to investigate in vitro i) the role of p53 status in VAL-083 activity, ii) VAL-083 activity in comparison to cisplatin and oxaliplatin and iii) the combination of VAL-083 with cisplatin or oxaliplatin. Methods: Dependence on p53 status was investigated in isogenic HCT-116p53-/- and HCT-116p53+/+models. VAL-083 cytotoxicity was tested in a panel of 9 human NSCLC cell lines: 4 wild-type (wt), 4 mutant and 1 null for p53. The combination potential was investigated by determining superadditivity and synergy using the criteria of combination index (CI) < 1. Cytotoxicity was monitored on day 5 with the MTT assay. Results: Studies in HCT-116 models demonstrated that loss of p53 increased resistance to cisplatin and oxaliplatin by 3- and 6-fold, respectively, while resistance to VAL-083 was < 2-fold. As single agents, VAL-083, cisplatin and oxaliplatin showed good cytotoxicity in all NSCLC cell lines to varying degrees, with H460 as the most sensitive (IC50< 0.5 uM). The IC50 in the other cell lines ranged from 0.9-6.1 μM, 0.5-2.2 μM and 0.6-2.6 μM for VAL-083, cisplatin and oxaliplatin, respectively, and there was no overt difference in drug sensitivity between the wt and mutant/null p53 group. This suggests that either wt p53 is not activated and/or other genetic alterations reduce cytotoxic activities. The combination of VAL-083 with cisplatin or oxaliplatin in the A549 NSCLC model, demonstrated significant superadditivity (p < 0.05) and synergism (CI < 1) for both combinations. This strongly favors non-overlapping mode of action between the platinum drugs and VAL-083. Conclusions: VAL-083 is less dependent on p53 for activity than cisplatin and oxaliplatin. VAL-083 further demonstrates superadditivity/synergy against NSCLC cell lines when combined with cisplatin or oxaliplatin, suggesting a potential for VAL-083 as part of a combination treatment in NSCLC.
Recommendations for the Standardization and Interpretation of the Electrocardiogram
Authors: Jay W. Mason, E. William Hancock, Leonard S. Gettes
Journal: Circulation (2007)

This statement provides a concise list of diagnostic terms for ECG interpretation that can be shared by students, teachers, and readers of electrocardiography. This effort was motivated by the existence of multiple automated diagnostic code sets containing imprecise and overlapping terms. An intended outcome of this statement list is greater uniformity of ECG diagnosis and a resultant improvement in patient care. The lexicon includes primary diagnostic statements, secondary diagnostic statements, modifiers, and statements for the comparison of ECGs. This diagnostic lexicon should be reviewed and updated periodically.
Genetic variants in the MRPS30 region and postmenopausal breast cancer risk
Authors: Ying Huang, Dennis G Ballinger, James Y Dai, Ulrike Peters, David A Hinds, David R Cox, Erica Beilharz, Rowan T Chlebowski, Jacques E Rossouw, Anne McTiernan, Thomas Rohan, Ross L Prentice
Journal: Genome Medicine (2012)
Jejunojejunal intussusception after polypectomy by spiral enteroscopy in Peutz–Jeghers syndrome
Authors: Gabriel Rahmi, Bertrand Brieau, Elia Samaha, Olivier Clément, Christophe Cellier
Journal: Endoscopy (2015)

Enteroscopy makes it possible to resect small-bowel polyps and avoid intestinal obstruction in patients with Peutz–Jeghers syndrome [1]. We report the case of a 54-year-old man with Peutz–Jeghers syndrome, referred to our center because of recurrent episodes of intestinal occlusion.
Fluid-Management Strategies in Acute Lung Injury
Authors: Alex Morizio, Yizhak Kupfer, Sidney Tessler
Journal: New England Journal of Medicine (2006)

To the Editor: The results of the Fluid and Catheter Treatment Trial (FACTT) conducted by the National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network (June 15 issue)1 support a conservative strategy of fluid management in patients with acute lung injury. This strategy should be recognized as only a step in the right direction. The furosemide dosing algorithm in the conservative-strategy group (range, 128 to 167 mg per 24 hours) simply resulted in an even — not negative — net fluid balance, which may have mitigated the potential magnitude of the benefit. Protocol-guided diuretic management, with individualized titration of the dose to achieve a net diuresis, can be readily and safely implemented in the intensive care unit (ICU) and is typically associated with higher doses of furosemide (range, 400 to 440 mg per 24 hours) than those used in FACTT, with the potential for even faster resolution of pulmonary edema.2 The FACTT algorithm should not yet be viewed as “optimal” therapy, but only as an improvement on what heretofore has been considered “conventional” therapy.
Non-alcoholic fatty liver disease with and without metabolic syndrome: Different long-term outcomes
Authors: Aki Juhani Käräjämäki, Risto Bloigu, Heikki Kauma, Y. Antero Kesäniemi, Olli-Pekka Koivurova, Juha Perkiömäki, Heikki Huikuri, Olavi Ukkola
Journal: Metabolism (2016)
Incidence and relative-risk (RR) of cardiovascular toxicity in patients treated with new hormonal agents for metastatic castration-resistant prostate cancer (mCRPC)
Authors: M. Cossu Rocca, D. Cullurà, R. Iacovelli, G. Aurilio, E. Verri, C. Crescio, S. Detti, O. De Cobelli, F. Nolè
Journal: Annals of Oncology (2015)
Reconstitution of normal megakaryocytopoiesis and immunologic functions in Wiskott-Aldrich syndrome by marrow transplantation following myeloablation and immunosuppression with busulfan and cyclophosphamide
Authors: N Kapoor, D Kirkpatrick, RM Blaese, J Oleske, MH Hilgartner, RS Chaganti, RA Good, RJ O'Reilly
Journal: Blood (1981)
Précoupe précoce pour l’accès biliaire difficile afin de diminuer l’incidence de la pancréatite post-CPRE: un essai randomisé.
Authors: M. Palazzo
Journal: Endoscopy (2016)

La précoupe de l’infundibulum papillaire est une technique utilisée en cas d’échec de cathétérisme biliaire par l’orifice papillaire. Dans la littérature, ce geste est associé à une augmentation du risque de pancréatite aiguë (PA) post-CPRE. Néanmoins, comme la précoupe est généralement faite après des échecs répétés de cannulation biliaire (un facteur de risque connu de PA post-CPRE), il est possible qu’il s’agisse de facteurs confondants.
ARID1A Is Recurrently and Significantly Mutated in Follicular Lymphoma (FL) and Impairs DNA Repair Efficiency
Authors: Deepak Bararia, Michael Heide, Tatiana Romashova, Pastore Alessandro, Boris G. Wilson, Charles W.M. Roberts, Wolfgang Hiddemann, David M. Weinstock, Oliver Weigert
Journal: Blood (2014)
195P Carboplatin for operable oesophageal and gastric adenocarcinoma (OGA): Royal Marsden (RMH) experience 2001-2010
Authors: E. Fontana, E.C. Smyth, D. Cunningham, W. Allum, J. Thompson, T. Waddell, C. Peckitt, S. Rao, N. Starling, I. Chau, D. Watkins
Journal: Annals of Oncology (2015)
CheckMate-032: Phase I/II, open-label study of safety and activity of nivolumab (nivo) alone or with ipilimumab (ipi) in advanced and metastatic (A/M) gastric cancer (GC).
Authors: Yelena Yuriy Janjigian, Johanna C. Bendell, Emiliano Calvo, Joseph W. Kim, Paolo Antonio Ascierto, Padmanee Sharma, Patrick Alexander Ott, Petri Bono, Dirk Jaeger, T.R. Jeffry Evans, Filippo G. De Braud, Ian Chau, Marina Tschaika, Christopher T. Harbison, Chen-Sheng Lin, Dung T. Le
Journal: Journal of Clinical Oncology (2016)

4010 Background: Chemotherapy-refractory GC is a uniformly fatal illness and an unmet therapeutic need. Nivo is a fully human anti-PD-1 monoclonal antibody with a manageable safety profile and efficacy in solid tumors. We report results of a completed A/M GC cohort of CheckMate-032 study evaluating nivo monotherapy and nivo with ipi in pts with solid tumors. Methods: Pts with A/M, histologically confirmed GC, esophageal (EC), or gastroesophageal junction cancer (GEC), irrespective of PD-L1 status, who had progressed on chemotherapy, were treated with nivo 3 mg/kg Q2W (N3), nivo 1 mg/kg + ipi 3 mg/kg (N1+I3), or nivo 3 mg/kg + ipi 1 mg/kg (N3+I1) Q3W x 4 cycles, followed by nivo 3 mg/kg Q2W until confirmed disease progression or intolerable toxicity. Primary endpoint was ORR; other endpoints included safety, OS, and biomarker status. Results: 160 pts with A/M GC were treated with N3 (n = 59), N1+I3 (n = 49), or N3+I1 (n = 52). Baseline characteristics were comparable across cohorts; the majority of pts had ≥ 2 prior regimens. Treatment-related AEs (TRAE) of any grade occurred in 70% (N3), 84% (N1+I3), and 75% (N3+I1) of pts; Grade 3-4 TRAEs occurred in 17%, 45%, and 27% of pts. 12% of pts stopped therapy due to treatment toxicity: 5% (N3), 22% (N1+I3), and 12% (N3+I1). Treatment-related serious AEs (TRSAEs) of any grade and Grade 3-4 TRSAE occurred in 10% and 5% (N3), 43% and 35% (N1+I3), and 23% and 15% (N3+I1) of pts. There was one Grade 5 TRSAE of tumor lysis syndrome (N3+I1). 154 (96%) pts were evaluable for efficacy with the confirmed ORR 16%: 14% (N3), 26% (N1+I3), and 10% (N3+I1), including 2 pts with CR (1 in N3; 1 in N1+I3) and a disease control rate (ORR+SD) of 38%. OS data are in the Table below with 15 pts (9%) remaining on therapy. Updated biomarker data will be presented. Conclusions: TRAEs for nivo and nivo + ipi were consistent with those previously reported. Clinical activity and OS in pts with chemotherapy refractory disease are encouraging. These data support ongoing evaluation of nivo and nivo + ipi in A/M GC/EC/GEC. Clinical trial information: NCT01928394. N3 N1+I3 N3+I1 OS Rate, % (95% CI) 6 mo 49 (35–62) 54 (39–67) 43 (29–57) 12 mo 36 (21–51) 34 (19–50) NA Median OS, mo (95% CI) 5.0 (3.4–12.4) 6.9 (3.6–NA) 4.8 (3.0–9.1)
Current concepts in chronic inflammatory diseases: Interactions between microbes, cellular metabolism, and inflammation
Authors: Holger Garn, Sabine Bahn, Bernhard T. Baune, Elisabeth B. Binder, Hans Bisgaard, Talal A. Chatila, Triantafyllos Chavakis, Carsten Culmsee, Udo Dannlowski, Steffen Gay, James Gern, Tari Haahtela, Tilo Kircher, Ulf Müller-Ladner, Markus F. Neurath, Klaus T. Preissner, Christoph Reinhardt, Graham Rook, Shannon Russell, Bernd Schmeck, Thaddeus Stappenbeck, Ulrich Steinhoff, Jim van Os, Scott Weiss, Michael Zemlin, Harald Renz
Journal: Journal of Allergy and Clinical Immunology (2016)
Current Perspective of Chemotherapy in Metastatic Breast Cancer: New Evidence From Select Bc Trial
Authors: Junji Tsurutani, Tsutomu Takashima, Fumikata Hara, Yoshiaki Sagara, Takanori Watanabe, Yasuo Hozumi, Shigeru Imoto, Reiki Nishimura, Yasuo Ohashi, Hirofumi Mukai
Journal: Annals of Oncology (2014)
Manipulating Angiogenesis by Targeting Endothelial Metabolism: Hitting the Engine Rather than the Drivers—A New Perspective?
Authors: Lucas Treps, Lena-Christin Conradi, Ulrike Harjes, Peter Carmeliet
Journal: Pharmacological Reviews (2016)

Excessive angiogenesis (i.e., the formation of new blood vessels) contributes to different pathologies, among them cancer and ocular disorders. Conversely, dysfunction of endothelial cells (ECs) contributes to cardiovascular complications, as is the case in diabetes. Inhibition of pathologic angiogenesis in blinding eye disease and cancer by targeting growth factors such as vascular endothelial growth factor has become an accepted therapeutic strategy. However, recent studies also unveiled the emerging importance of EC metabolism in controlling angiogenesis. In this overview, we will discuss recent insights in the metabolic regulation of angiogenesis, focusing on the best-characterized metabolic pathways, and highlight deregulation of EC metabolism in cancer and diabetes. We will give an outlook on how targeting EC metabolism can be used for blocking pathologic angiogenesis and for normalizing EC dysfunction.
Low-Density Lipoprotein Cholesterol Levels and Statin Treatment—A Moving Target?
Authors: Simon B. Ascher, Blake R. Charlton, Rita F. Redberg
Journal: JAMA Internal Medicine (2016)

Morton Leibowitz, MD; Tomas Karpati, MD; Chandra J. Cohen-Stavi, MPA; Becca S. Feldman, ScD; Moshe Hoshen, PhD; Haim Bitterman, MD; Samy Suissa, PhD; Ran D. Balicer, MD, PhD
TAC (docetaxel, doxorubicin, and cyclophosphamide) adjuvant chemotherapy supported by G-CSF without dose-reduction in node-positive breast cancer
Authors: Y. Suh, S. Oh, B. Song, S. Jung
Journal: Journal of Clinical Oncology (2009)

e11606 Background: For node-positive breast cancer, TAC (Docetaxel-Doxorubicin-Cyclophosphamide) chemotherapy is preferred as an adjuvant treatment. However, due to its high toxicity profiles such as severe neutropenia, TAC is a lot beyond enthusiasm. G-CSF support or even prophylaxis has been recommended to help patients recover from nadir, along with some dose-reduction schedule. We tried to evaluate whether TAC with G-CSF support from day 5 can be sustained without dose reduction in women under 69-years old. Methods: After getting IRB approval, between Mar. 2005 and Oct. 2008, 61 node-positive breast cancer patients (33 - 69 years old) had underwent TAC chemotherapy as an adjuvant treatment after curative resection after getting informed consent. Total of 366 cycles (6 cycles per patient, 75–50–500 mg/m2)were completed, G-CSF support was initiated from day 5 to full neutrophil recovery. In case of neutropenia, prophylactic antibiotics (cefoperazone 2 g and tobramycin 200 mg iv) were given. Results: Among 366 cycles, not a single cycle should be delayed to recover from any hematologic shortcomings such as neutropenia, anemia or thrombocytopenia. Interval of three weeks between each cycle could be maintained. No other problem happened for any patient to stop or postpone scheduled chemotherapy. None of antibiotics except prophylaxis with cefoperazone and tobramycin was needed. Conclusions: Maximum tolerable dose of chemotherapeutic agents should be given to patients to get the best oncologic outcome to fight against cancer. It is evident that huge scale prospective clinical trials can answer this question, but we presume that node-positive breast cancer patients between in her fourth and seventh decade can stand TAC chemotherapy with G-CSF support without dose reduction as routine. No significant financial relationships to disclose.
Localization of Radiolabeled Somatostatin Analogs in the Spleen
Authors: Marleen Melis, Daniel Kaemmerer, Jan de Swart, Harshad R. Kulkarni, Amelie Lupp, Jörg Sänger, Harald C. Groen, Mark W. Konijnenberg, Marion de Jong, Richard P. Baum
Journal: Clinical Nuclear Medicine (2015)

Radiolabeled somatostatin (SST) analogs, used to visualize and treat SST receptor (SSTR)-expressing neuroendocrine tumors, also accumulate in the spleen. There is a high interpatient variation and no significant radiation-induced splenic toxicity; however, an absorbed dose-related reduction in spleen size was detected. However, the exact localization of radioactivity and the role of SST receptors in splenic retention are unknown. Therefore, we performed ex vivo micro-SPECT of the isolated spleen from a patient with a pancreatic neoplasm after 1 GBq (27 mCi) Lu-DOTATATE administration, followed by autoradiography and immunohistochemistry. Ex vivo autoradiography demonstrated convincingly that most radioactivity accumulated in red pulp.
A Point‐of‐Care Raman Spectroscopy–Based Device for the Diagnosis of Gout and Pseudogout: Comparison With the Clinical Standard Microscopy
Authors: Bolan Li, Nora G. Singer, Yener N. Yeni, Donard G. Haggins, Emma Barnboym, Daniel Oravec, Steven Lewis, Ozan Akkus
Journal: Arthritis & Rheumatology (2016)

Objective To demonstrate the usefulness of a novel medical device based on Raman spectroscopy for the rapid point‐of‐care diagnosis of gout and pseudogout. Methods A shoebox‐sized point‐of‐care Raman spectroscopy (POCRS) device was developed for use in the diagnosis of gout and pseudogout. The device included a disposable syringe microfiltration kit to collect arthropathic crystals from synovial fluid and a customized automated Raman spectroscopy system to chemically identify crystal species. Diagnosis according to the findings of POCRS was compared with the clinical standard diagnosis based on compensated polarized light microscopy (CPLM) of synovial fluid aspirates collected from symptomatic patients (n = 174). Kappa coefficients were used to measure the agreement between POCRS and CPLM findings. Results Overall, POCRS and CPLM results were consistent in 89.7% of samples (156 of 174). For the diagnosis of gout, the kappa coefficient for POCRS and CPLM was 0.84 (95% confidence interval [95% CI] 0.75–0.94). For the diagnosis of pseudogout, the kappa coefficient for POCRS and CPLM was 0.61 (95% CI 0.42–0.81). Conclusion Kappa coefficients indicated that there was excellent agreement between POCRS and CPLM for the diagnosis of gout, with good agreement for the diagnosis of pseudogout. The POCRS device holds the potential to standardize and expedite the time to clinical diagnosis of gout and pseudogout, especially in settings where certified operators trained for CPLM analysis are not available.
Case 24-1970
Authors: Richard C. Cabot, Benjamin Castleman, Betty U. McNeely, Warren Point, Benjamin Castleman
Journal: New England Journal of Medicine (1970)

Presentation of CaseA 69-year-old woman was admitted to the hospital because of nausea and vomiting.Two years previously she consulted her physician because of exertional dyspnea and fatigue; the diagnosis of mitral stenosis was confirmed by cardiac catheterization. Digitalis therapy was begun. Six weeks before entry an open mitral valvuloplasty with a cardiopulmonary bypass was performed under nitrous oxide and halothane anesthesia for a 45-minute period. Immediately after the operation dense right-sided hemiplegia and aphasia were observed, and two days later jaundice developed. The urea nitrogen was 14 mg, the bilirubin 16 mg (direct-reacting, 12 mg), and the protein . . .