tbuckley/cabot-search huggingface dataset:
Does anatomic location of deep venous thrombosis affect the clinical findings and course in the patient of pulmonary embolism
Authors: Eylem Sercan Ozgur, Kerem Karaca, Cengiz Ozge, Sibel Atis Nayci
Journal: European Respiratory Journal (2011)

Aim:  Deep venous thrombosis (DVT) in proximal veins carries a significantly higher risk of pulmonary embolism (PE) than in distal veins. However, the effect of DVT anatomic location on clinical findings and course of PE is not known. We, therefore, investigated whether anatomic location of DVT could affect the clinical findings and course of PE.   Methods:  Data of 81 patients diagnosed as PE between 2007-2011 were evaluated retrospectively. The patients were divided into two subgroups as proximal (safen, femoral, iliac veins) and distal disease (popliteal, crucial veins) according to DVT anatomic location. The patients with and without DVT, and also the subgroups of DVT were compared in respect of clinical severity PE, duration of hospitalisation, mortality rate, echocardiographic and laboratory findings.   Results:  Doppler USG of 72 patients showed that 26 (36.1%) had no DVT, 29 (40.3%) proximal, and 17 (23.6%) distal disease. Dyspnea were more common (p=0.036) and mean PaO 2  were significantly lower (p=0.022) in the patients with DVT than without DVT, while there were no significant differences between two groups in respect of PE clinical severity, hospitalisation duration, mortality rate, echocardiographic findings, PaCO 2 , D-Dimer and troponin levels. Additionally, there were no significant differences between proximal and distal disease subgroups in respect of any symptom, clinical or laboratory findings evaluated.   Conclusion:  This study showed that the patients with PE had more common rate of dyspnea symptom and hypoxemia in DVT existing than without DVT, however, anatomic location of the thrombosis did not affect the clinical findings and course of PE.
Locally advanced gastric cancer treated with neoadjuvant chemotherapy: Epirubicin, oxaliplatin, and capecitabine (EOX).
Authors: U. Pluschnig, J. Zacherl, S. Schoppmann, M. Raderer, G. Prager, R. Bartsch, A. Ba-Ssalamah, W. Lamm, C. Zielinski, M. Hejna
Journal: Journal of Clinical Oncology (2011)

136 Background: Gastric cancer is a worldwide common malignant disease with a high mortality rate. Adjuvant chemotherapy did not result in a survival advantage in Caucasian populations. Therapeutic chemotherapy options consist of either monotherapy or of polychemotherapy and have been applied as neoadjuvant chemotherapy with combinations of epirubicin, cyclophosphamide and 5-fluorouracil or capecitabine as well as cisplatin or oxaliplatin. The aim of this retrospective analysis was to investigate the use of the EOX regimen in the neoadjuvant setting which had shown activity in advanced gastric cancer. Methods: 23 patients (pts) (median age: 70, range 36-85, years; 16 pts &gt;65 years) with locally advanced adenocarcinoma of the upper GI-tract received 3 courses of preoperative chemotherapy with epirubicin 50 mg/m 2 , day1, oxaliplatin 130 mg/m 2 , day 1, and capecitabine 2,000 mg/m 2 , days 1-14, of a 3-week cycle. Toxicity was assessed by CTC (Common Toxicity Criteria) after every cycle. Progression free survival (PFS) was defined as time from surgery to disease progression assessed by PET-CT which was performed at diagnosis and after 3 cycles chemotherapy. Results: 20 pts completed all three planned cycles of preoperative chemotherapy, 2 pts received only 1 cycle because of rapid tumor progression and 1 pt. is currently still on treatment. 16 pts. underwent surgery with curative resection with 2 pCRs on pathological review. 6 pts. remained inoperable despite chemotherapy and 1 pt is currently scheduled for surgery. After surgery, 2 pts. died after a median of 9 months (8-10). 4 pts. died without surgery due to disease progression. After a median follow-up of eight months (range 5-26), median PFS and overall survival was not reached yet. In 2 pts., grade 3-4 toxicities including nausea, diarrhea and hand-foot syndrome and one non-life-threatening pulmonary embolism occurred. Conclusions: In summary, EOX is a well tolerated, safe, and efficacious neoadjuvant treatment in also elderly patients with locally advanced adenocarcinoma of the upper GI-tract. However, more studies with a larger population are needed to corroborate the current results of this promising treatment schedule. [Table: see text]
Diabetes and the risk of death in men with favorable or high-risk prostate cancer following radiation therapy
Authors: A. V. D'Amico, M. H. Braccioforte, B. J. Moran, M. Chen
Journal: Journal of Clinical Oncology (2009)

5157 Background: An increased risk of all cause mortality (ACM) has been observed in patients with cancer who have diabetes mellitus (DM) (JAMA 2008:300:2754–2764). Yet, how a diagnosis of DM affects survival across the risk-strata of men with prostate cancer (PC) remains unknown. Methods: The study cohort comprised 7041 men of median age 69.6 years treated with brachytherapy with or without external beam radiation therapy (RT) between 10/97 and 7/07. Short course neoadjuvant hormonal therapy (HT) was used in men with pubic arch interference in order to make them eligible for brachytherapy. Cox regression multivariable analyses were performed in men with Gleason score 8 to 10 disease and also in men with favorable-risk (low or intermediate) disease to assess whether men with DM were at increased risk for ACM compared to men without DM. The hazard ratios (HR) and 95% Confidence intervals (CI) reported were adjusted for age, extent of RT, history of myocardial infarction (MI), use of HT and known PC prognostic factors. Estimates of PC-specific mortality (PCSM) were estimated using a cumulative incidence method. Results: After a median follow-up of 4.1 years, 544 (8%) men had died. In the 466 men with Gleason score 8 to 10 cancers 31% (22/70) of deaths were from PC and a diagnosis of DM was not associated with an increased risk of ACM (Adjusted HR (AHR): 1.1 [95% CI: 0.6 to 2.2]; p = 0.78). However, as shown in the Table , for the 6575 men with favorable-risk disease where only 10% (49/474) of deaths were from PC, there was an increased risk of ACM (AHR: 1.5 [95% CI: 1.2 to 2.0]; p &lt; 0.001) in men with diabetes as compared to those without diabetes. PCSM estimates were significantly higher (p &lt; 0.001) in men with Gleason 8 to 10 as compared to low or intermediate-risk PC reaching 10% and 1% respectively by 7 years. Conclusions: These data highlight the importance of aggressive management of DM in men with favorable-risk PC where death from PC is unlikely. [Table: see text] No significant financial relationships to disclose.
Walking the tightrope: communicating overdiagnosis in modern healthcare
Authors: Kirsten J McCaffery, Jesse Jansen, Laura D Scherer, Hazel Thornton, Jolyn Hersch, Stacy M Carter, Alexandra Barratt, Stacey Sheridan, Ray Moynihan, Jo Waller, John Brodersen, Kristen Pickles, Adrian Edwards
Journal: BMJ (2016)

Communication that empowers the public, patients, clinicians, and policy makers to think differently about overdiagnosis will help support a more sustainable healthcare future for all, argue <b>Kirsten McCaffery and colleagues</b>
Anxiety, depression and coping in patients awaiting lung transplantation
Authors: Torunn Stavnes Soyseth, Aasta Heldal, Gro Killi Haugstad, Vidar Soyseth, Oystein Bjortuft, May Brit Lund
Journal: European Respiratory Journal (2011)

Knowledge is scarce about the mental aspects of living with terminal lung disease. We aimed to assess anxiety, depression and coping in patients waiting for lung transplantation.   Material and methods:  A national cohort of 121 consecutive patients were evaluated by psychometric instruments, Hospital Anxiety and Depression Scale (HAD) and General Health Questionnaire (GHQ).89 (45 females) had COPD, 18 (9 females) fibrosis, and 14 (8 females) various other lung diseases. Mean (SD) age was respectively 56 (5), 52 (6) and 46 (8) years. Patients with cystic fibrosis were excluded.   Results:  See table.  For all groups, mean values were within the normal range. However, the ranges were wide. Males tended to be more depressive than females (mean (SD) HAD score 4,1 (3,0)  vs  3,1 (2,5), p=0,07), and have higher restrained coping scores than females (mean (SD) GHQ score 1,05 (0,05)  vs  0,93 (0,05), p=0,08). The association between anxiety and restrained coping was highly significant, p=0,0001 as well as the association between depression and restrained coping, p=0,0001.   Conclusions:  The strong association between anxiety and depression and restrained coping may be of clinical relevance after transplantation. Males may be more vulnerable than females in this respect.
Sequencing the genome of hope.
Authors: Anna K. Ferguson, Evan J. Lipson
Journal: Journal of Clinical Oncology (2014)

234 Background: Hope is widely regarded as essential to the emotional health of cancer pts, yet remains under-studied. We sought to explore the concept of hope and develop a teaching module to educate providers about the importance of hope in optimizing oncology care. Methods: We audio recorded interviews with oncology patients. Questions focused on what hope means, the role it plays in their ability to manage their illness, and ways in which they felt oncology providers could engender hope and positively impact their experience. We also interviewed oncology providers, including physicians, nurses, and social workers. Questions focused on the role they feel hope plays for their pts, whether or not they have received training in how to discuss hope, and tools they use to discuss hope with their pts. Common themes were extracted to form the backbone of a webcast-style teaching module. Results: A total of 24 volunteers were enrolled in an IRB approved protocol. One half of the subjects were pts and the other half were oncology providers (n = 6 physicians, 3 nurses, 3 social workers). Hope emerged as an important element to good quality of life in 12/12 (100%) pts.. The overwhelming majority (11/12, 92%) further expressed that feeling “well cared for” as well as receiving clear, honest information about their disease greatly increased their hopefulness. Hope also was recognized as essential to pts’ wellness and ability to manage their illness by all 12 (100%) of the providers. Although all providers recognized hope as essential to their pts, only the social workers reported that they had received some level of training in how to discuss hope, while the physicians and nurses felt that they had received little to no training. All providers expressed desire to contribute positively to their pts’ sense of hope. Conclusions: Both pts and providers view hope as a vital element in how oncology pts manage their illness. This point of connection between providers and their pts offers a mechanism to enhance the care of patients and impact their overall experience with cancer, yet most providers have little to no training in how to discuss hope. Development of an education module is underway to help increase awareness of the importance of hope and teach providers strategies to better engage with their pts on the subject of hope.
Role of bone morphogenetic protein signalling in bone destruction and niche maintenance in a mouse model of multiple myeloma
Authors: Sarah Gooding, Siobhan Webb, Seint Lwin, Sam Olechnowitz, Ann Snaith, Kinda Al-Hourani, Andrew Armitage, Sant-Rayn Pasricha, Karthik Ramasamy, Claire Edwards, Hal Drakesmith
Journal: The Lancet (2016)
Authors’ reply to Beales
Authors: Laila Staerk, Gregory Y H Lip
Journal: BMJ (2016)

We thank Beales for his comments about our paper.1 2

It is correct that current guidelines for atrial fibrillation do not include antiplatelet agents for stroke prophylaxis. However, we thought it important to examine all possible antithrombotic treatments after a gastrointestinal bleed to compare the effectiveness and safety of oral anticoagulation versus non-resumption or antiplatelet agents. The results suggested that independent of the antithrombotic treatment regimen used before the bleed, patients with atrial fibrillation benefited …
A Novel Bruton′s Tyrosine Kinase Inhibitor CC-292 In Combination With The Proteasome Inhibitor Carfilzomib Iimpacts Multiple Myeloma Bone Microenviroment With Resultant Anti-Myeloma Activity
Authors: Homare Eda, Loredana Santo, Diana D Cirstea, Andrew J Yee, Tyler A Scullen, Neeharika Nemani, Yuko Mishima, Shirin Arastu-Kapur, Erica Evans, Juswinder Singh, Christopher J Kirk, William F Westlin, Noopur S Raje
Journal: Blood (2013)
SELDI may facilitate the management of germ cell tumor
Authors: C. Pan, M. Brames, L. Dobrolecki, L. Cheng, R. Hickey, L. Einhorn
Journal: Journal of Clinical Oncology (2005)

4580 Background: Germ cell tumors (GCT) are highly curable. Nevertheless, some patients relapse and develop chemotherapy-resistant GCT. Surface-enhanced laser desorption/ ionization time-of-flight mass spectrometry (SELDI) can determine protein mass profiles based on the biological and electrophysical properties of proteins. SELDI has been successfully applied to diagnose cancer, identify tumor markers, and determine sensitivity and response to chemotherapy. In this study, we performed a SELDI analysis to differentiate curable versus persistent GCT after chemotherapy, and to identify those patterns that are associated with chemoresistance. Our long-term goal is to identify markers that are associated with GCT and chemoresistance. Methods: SELDI analysis with serum samples was performed to determine proteomic patterns. Serum samples were collected from patients who remained disease-free over 2 years (NED). The samples were also collected from patients with newly diagnosed (most likely to be chemosensitive) and recurrent (resistant to first-line chemotherapy) GCT, both before and after chemotherapy. The proteomic patterns are correlated with clinical outcomes (i.e. NED vs. active disease, chemosensitive vs. resistant). In the long term, a prediction system will be generated based on the correlation between proteomic patterns and clinical outcomes. An independent test cohort will be used to validate the prediction system. Results: SELDI analysis has been performed in 24 NED serum samples, 20 samples with newly diagnosed GCT and 11 samples with recurrent GCT following initial chemotherapy. The SELDI mass spectral patterns were essentially homogenous within each group, but significantly different between these three groups. Seven and 10 protein peaks, having a p-value of less than 0.05, were identified to distinguish between the active GCT and NED groups; and the newly diagnosed from recurrent GCT groups, respectively. The proteomic patterns will be correlated with clinical outcomes (cure vs. relapse, chemosensitivity vs. resistance). Conclusions: SELDI may be able to distinguish between patients with active GCT and those who are free of the disease. The technique can readily identify chemosensitive versus chemoresistant GCT. No significant financial relationships to disclose.
Genomic structure, chromosomal localization, start of transcription, and tissue expression of the human p40-phox, a new component of the nicotinamide adenine dinucleotide phosphate-oxidase complex
Authors: S Zhan, N Vazquez, S Zhan, FB Wientjes, ML Budarf, E Schrock, T Ried, ED Green, SJ Chanock
Journal: Blood (1996)
Deficient interleukin-17 production in response to<i>Mycobacterium abscessus</i>in cystic fibrosis
Authors: Katharina L. Becker, Jakko van Ingen, Jaap ten Oever, Peter J. Merkus, Gerben Ferwerda, Mihai G. Netea, Cecile Magis-Escurra, Monique H. Reijers, Frank L. van de Veerdonk
Journal: European Respiratory Journal (2016)

The respiratory tract of patients with cystic fibrosis (CF) is colonised with a high diversity of micro-organisms. Nontuberculous mycobacteria (NTM) show a high and increasing prevalence. 40% of these positive NTM cultures are caused by Mycobacterium abscessus [1], one of the rapidly growing NTMs present in the environment. Patients with M. abscessus infection are difficult to treat, due to natural and acquired antibiotic resistance [2, 3], and an infection with M. abscessus is controversially discussed as a contraindication for lung transplantation [4]. Mycobacterium abscessus -specific IL-17 deficiency is present in cystic fibrosis patients with M. abscessus <http://ow.ly/U2DNL> The authors thank Liesbeth Jacobs and Trees Jansen (Dept of Internal Medicine, Radboud University Medical Centre, Nijmegen, the Netherlands) for their help with the cytokine stimulation assay.
Phase I study of ABT-751 in combination with CAPIRI (capecitabine and irinotecan) and bevacizumab in patients with advanced colorectal cancer
Authors: W. A. Messersmith, M. A. Rudek, D. Laheru, M. Zhao, P. He, R. Walker, A. Jimeno, W. T. Purcell, R. C. Donehower, M. Hidalgo
Journal: Journal of Clinical Oncology (2006)

13553 Background: ABT-751 (A) is an orally (PO) bioavailable sulfonamide with antimitotic properties. We are performing a non-randomized phase I/II dose-escalation study of A in combination with capecitabine (C), irinotecan (I) and bevacizumab (B) to define the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and pharmacokinetics (PK) in patients with advanced colorectal cancer (1st or 2nd line). Methods: Patients are treated with A QD for 7d (lead-in) and then begin 21-d cycles of treatment with A (QD) and C (BID) d1–14 PO, I d1 IV, and B d1 IV. Dose escalation started at dose level (DL) 1 at A 150 mg, I 200 mg/m 2 , and C 1600 mg/m 2 (total daily dose) and escalated to full dose CAPIRI (I 250 mg/m 2 , and C 2000 mg/m2) for DL2. B was then added as standard of care at 7.5 mg/kg for DL2b (and later, DL1b). Blood samples were collected for pharmacogenomics (PG), pharmacodynamics (PD), steady-state PK of A and A metabolites when administered alone or in combination with C, I, and B, and PK of I and I metabolites. Serial dynamic contrast MRI’s, before and after the ABT-751 monotherapy lead-in period, are being performed in a subset of subjects. Results: Eight patients have been treated at dose levels 1 (3), 2 (2), and 2b (3). One patient on DL2 experienced g3 transaminitis and another on DL2b had F&amp;N which were dose-limiting. Dose level 1 is being expanded to 6 patients, now with B (DL1b). Other g3/4 toxicities have included g4 neutropenia (1 subject DL2, 1 DL2b). The formation of A glucuronide appears decreased during combination therapy (see table). I PK, PD, and PG samples were collected and analysis is pending. Of 8 subjects, there have been 4 PD and 4 SD after 2 cycles. Conclusions: The combination therapy of A 150 mg and 20% dose-reduced CAPIRI appears well-tolerated. Patient accrual continues at DL1b. [Table: see text] No significant financial relationships to disclose.
Analysis of the dynamics in the immune system of patients with metastatic melanoma in response to systemic therapy with metastatic melanoma in response to systemic therapy.
Authors: A. A. Leontovich, R. S. Dronca, W. K. Nevala, V. Suman, L. A. Kottschade, M. L. Ashdown, J. S. Kaur, G. Croghan, S. Markovic
Journal: Journal of Clinical Oncology (2010)

e19003 Background: Biorhythmic fluctuations of cellular function are well established in human hematopoietic and immune systems. Evidence exists that efficacy and toxicity of anticancer drug therapy may be influenced by immune biorhythms in animal models. Longer periods (circaseptan – 7 days and ifradian – 19-22 days) are poorly studied. A recent publication demonstrated 12-14 days periodicity of the serum level of C- reactive protein (CRP) in HIV patients. The role and mechanism of the circaseptan and ifradian rhythms of immunity in human cancer are unknown. Measurements of peripheral blood oscillations of C-reactive protein (CRP) and other immune biomarkers could be used as a surrogate for the periodicity of the antitumor immune response and be potentially utilized for timed delivery of chemotherapy. Methods: Eleven patients with metastatic melanoma underwent measurements of 27 cytokines and 25 immune cell counts every 2-3 days for 2 weeks. Chemotherapy was initiated at the time of the predicted peak of CRP concentration for the given patient. Results: We constructed time-depended profiles of cytokine concentrations and cell counts and analyzed the dynamic of these variables. We developed an index which characterizes the immuno-activity of each variable at any point in its biorhythm profile. This index correlated with clinical outcome. The PFS for the two patients with the highest index rank was > 2 years, compared to < 5 months for all other patients. The fluctuations of most variables fitted to cosine functions with discrete periods (multiples of 3 days). Administration of therapy relative to the dynamic trend of a cytokine/cell count correlated with PFS. Computer simulation was performed to estimate sensitivity and specificity of data fitting to cosine curve. The analysis confirmed periodical pattern of the described fluctuations. Conclusions: Components of immune homeostasis change in a regular fashion, many of them follow a periodical pattern. This temporal variation correlates with clinical outcome (PFS) and may be utilized for timing of chemotherapy relative to the immune cycle. No significant financial relationships to disclose.
Examining ethnic differences for bevacizumab-induced hypertension and proteinuria
Authors: Y. M. Choi, S. Shord, S. Cuellar, J. Villano
Journal: Journal of Clinical Oncology (2007)

21168 Background: Bevacizumab is an increasingly used anti-cancer treatment with common side effects including hypertension (htn) and proteinuria which occur in approximately 10% and 20% of the patients, respectively. Little is known regarding ethnic variations of bevacizumab induced htn and proteinuria, particularly in African-Americans (AA) who have a high prevalence of htn and susceptibility to kidney disease. Methods: We conducted a retrospective chart review of patients who completed bevacizumab alone or as a chemotherapy regimen at the University of Illinois at Chicago for an 18-month study period. We collected blood pressure (BP) measurements and urinanalyses before starting bevacizumab, during bevacizumab and after stopping bevacizumab, in addition to concurrent medications, past medical history and demographics. Htn and proteinuria were graded by CTC v3.0. Patients with less than two successive doses of bevacizumab or unreliable ethnicity were excluded. Results: 27 subjects were eligible. Eighteen AA (67%) and 9 (33%) non-AA were included. Twenty-two (81%) had colorectal cancer. AA received a median of 10 cycles and non-AA received a median of 6 cycles. Six subjects (22%) developed any grade htn toxicity; maximum grade: grade 2=4 (15%), grade 3=2 (7%). Htn toxicity occurred in 28% AA and 11% non-AA (p=NS). Previous history of hypertension was found in 15 subjects (55%): AA=14 vs. non-AA=1 (p=0.002) and was not correlated with hypertensive toxicity. Twelve subjects (44%) developed any grade proteinuria; maximum grade: grade 1=9 (33%), grade 2=3 (11%). Proteinuria toxicity occurred in 50% AA and 33% non-AA (p=NS). Presence of hypertensive toxicity was associated with increased risk of proteinuria. Clinical benefit (PR, SD) was seen in 15 subjects (55%). Rate of clinical benefit was 67% in AA and 33% in non-AA (p=NS). Clinical benefit did not correlate with hypertensive or proteinuria toxicities. Conclusions: AA were more prone than non-AA to bevacizumab induced hypertension and proteinuria toxicity in this retrospective study. Higher clinical benefit was seen in AA. No significant financial relationships to disclose.
Rps14 haploinsufficiency causes a block in erythroid differentiation mediated by S100A8 and S100A9
Authors: Rebekka K Schneider, Monica Schenone, Monica Ventura Ferreira, Rafael Kramann, Cailin E Joyce, Christina Hartigan, Fabian Beier, Tim H Brümmendorf, Ulrich Germing, Uwe Platzbecker, Guntram Büsche, Ruth Knüchel, Michelle C Chen, Christopher S Waters, Edwin Chen, Lisa P Chu, Carl D Novina, R Coleman Lindsley, Steven A Carr, Benjamin L Ebert
Journal: Nature Medicine (2016)