tbuckley/cabot-search huggingface dataset:
Sorafenib-induced loss of polarity of zymogen granules in pancreatic acinar cells.
Authors: Tatsuo Ito, Ryuichiro Doi, Shinji Uemoto
Journal: Journal of Clinical Oncology (2012)

236 Background: Sorafenib is an oral multi-kinase inhibitor which is regarded as a key drug for HCC and RCC. It has been unexpectedly found that the compound causes an increase of serum pancreatic enzyme levels without clinically recognized pancreatitis. The reason for this event is not well understood yet. The aim of this study was to clarify the mechanisms involved in this phenomenon. Methods: Eight-week old BALB/cA male mice were used in in vivo studies. Sorafenib tosylate was administered per os once daily at a dose of 150 mg/kg body weight. Control mice were given vehicle alone. Mice were sacrificed 24 hr after 1-, 2-, 3- and 7-day administration of the compound, and blood samples and pancreatic tissue samples were obtained (n=5 for each group). The tissue samples were used for hematoxylin and eosin (HE) staining, immunohistochemistry, electron microscopy (EM), western blot and RT-quantitative PCR studies. Results: Serum amylase levels were elevated after sorafenib administration. The amylase level hit the peak after 2-day administration, and then gradually decreased. By HE staining, the control group without sorafenib showed a basophilic stained area in the baso-lateral site of the acinar cells. In contrast, the acinar cytoplasm after 2-day administration of sorafenib was totally eosinophilic. The typical findings of acute pancreatitis were not seen in the both group. By EM examination, zymogen granules (ZGs) of the sorafenib group spread into basal site of the acinar cells. ZGs mounted up on both of apical and baso-lateral plasma membrane and showed exocytosis. The levels of amylase mRNA were not elevated by sorafenib. In addition the expression of N-ethylmaleimidesensitive factor attachment protein receptor (SNARE) proteins was not changed. Conclusions: The results suggest that the amount of acinar amylase production was not changed but the distribution of ZGs was altered by sorafenib. Sorafenib seemed to cause temporary loss of polarity of ZGs secretion in acinar cells by blocking apical exocytosis. Acute pancreatitis was not evident; thus the current model was not similar to the pancreatitis model caused by the supra-maximal secretagogue stimulation which blocks the apical exocytosis.
Empathy, sympathy and compassion in healthcare: Is there a problem? Is there a difference? Does it matter?
Authors: David Jeffrey
Journal: Journal of the Royal Society of Medicine (2016)

Empathy, sympathy and compassion are defined and conceptualised in many different ways in the literature and the terms are used interchangeably in research reports and in everyday speech.1 This conceptual and semantic confusion has practical implications for clinical practice, research and medical education. Empathy, sympathy and compassion also share elements with other forms of pro-social behaviour such as generosity, kindness and patient-centredness.2 There is a need for conceptual clarity if doctors are to respond to the calls to provide more ‘compassionate care’.3 This paper argues that there is currently a problem in the balance between scientific–technical and psychosocial elements of patient care. A broad model of empathy is suggested which could replace the vaguer concepts of sympathy and compassion and so enable improvements in patient care, psycho-social research and medical education.
Atypical lipomatous tumors/well-differentiated liposarcoma of the extremity: Analysis of a series of 65 patients treated in a single institution.
Authors: M. M. Cimino, C. E. Mussi, P. Bagnoli, A. Brocchi, P. Colombo, A. Santoro, V. Quagliuolo
Journal: Journal of Clinical Oncology (2011)

e20502 Background: Atypical lipomatous tumours (ALT) of the extremity are a subgroup of mesenchymal neoplasm that are commonly encountered by primary care clinicians, clinical oncologist, surgeon and pathologist. Although their histological and molecular features are well defined their clinical behaviour and outcome are still not clear. Even if ALT have a favourable control after resection and almost negligible effects on patients survival some cases of dedifferentiation (6-17% in the literature) and distant metastases are described. Methods: A total of 65 ALT of the extremity and superficial trunk were identified from a soft tissue tumour database between January 1998 and July 2010. All patients with primitive lesions (PL) underwent radical but function preserving surgery. All patients treated in other centres that came at our attention after recurrence (R) or marginal surgery (MS) were treated with surgery. All patients entered in a standard follow up that consist in a MR or ultrasonography every 6 months. The end points for this study are local recurrence free survival (LRFS), distant metastases free survival (DMFS) and the incidence of tumour dedifferentiation. Results: Most patients (n=36) presented with PL; 18 patients with R and 11 patients with MS. Lesions median size was 12 cm (range 2-21 cm). Five patients had multiple recurrence before treatment at our institution. The median follow-up time for the 65 patients was 41 months (range 6-158). The overall LRFS was 90% at 5 and 10 years. Only 3 patients developed local recurrence after treatment at our institution and their characteristics are listed in the table. No cases of dedifferentiation and distant metastases were reported. Conclusions: ALT are well-differentiated liposarcoma with a favorable course. Radical surgery with adequate margins ensures a good local control and prevents dedifferentiation. Demographic data of patients who experienced recurrence after surgery at our center. Cases Age Sex Site Size (cm) Presentation Time to recurrence (mo) Status 1 66 F Lower limb 17 P 44 AWD 2 49 M Back 3, 5 MS 29 NED 3 28 F Abdominal wall 5 P 53 NED Abbreviations: AWD, alive with disease; NED, no evidence of disease.
Myocardial Fibrosis Progression in Duchenne and Becker Muscular Dystrophy
Authors: Marly Conceição Silva, Tiago Augusto Magalhães, Zilda Maria Alves Meira, Carlos Henrique Reis Esselin Rassi, Amanda Cristina de Souza Andrade, Paulo Sampaio Gutierrez, Clerio Francisco Azevedo, Juliana Gurgel-Giannetti, Mariz Vainzof, Mayana Zatz, Roberto Kalil-Filho, Carlos Eduardo Rochitte
Journal: JAMA Cardiology (2016)

In Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD), interventions reducing the progression of myocardial disease could affect survival.To assess the effect of early angiotensin-converting enzyme (ACE) inhibitor therapy in patients with normal left ventricular function on the progression of myocardial fibrosis (MF) identified on cardiovascular magnetic resonance (CMR).A randomized clinical trial conducted in 2 centers included 76 male patients with DMD or BMD undergoing 2 CMR studies with a 2-year interval for ventricular function and MF assessment. In a non-intent-to-treat trial, 42 patients with MF and normal left ventricular ejection fraction (LVEF) were randomized (1:1) to receive or not receive ACE inhibitor therapy. The study was conducted from June 26, 2009, to June 30, 2012. Data analysis was performed from June 30, 2013, to October 3, 2016.Randomization (1:1) to receive or not receive ACE inhibitor therapy.Primary outcome was MF progression from baseline to the 2-year CMR study.Of the 76 male patients included in the study, 70 had DMD (92%) and 6 had BMD (8%); mean (SD) age at baseline was 13.1 (4.4) years. Myocardial fibrosis was present in 55 patients (72%) and LV systolic dysfunction was identified in 13 patients (24%). Myocardial fibrosis at baseline was an independent indicator of lower LVEF at follow-up (coefficient [SE], -0.16 [0.07]; P = .03). Among patients with MF and preserved LVEF (42 [55%]), those randomized (21 patients in each arm) to receive ACE inhibitors demonstrated slower MF progression compared with the untreated group (mean [SD] increase of 3.1% [7.4%] vs 10.0% [6.2%] as a percentage of LV mass; P = .001). In multivariate analysis, ACE inhibitor therapy was an independent indicator of decreased MF progression (coefficient [SE], -4.51 [2.11]; P = .04). Patients with MF noted on CMR had a higher probability of cardiovascular events (event rate, 10 of 55 [18.2%] vs 0 of 21 [0%]; log-rank P = .04).In this 2-year, follow-up, randomized clinical trial of patients with Duchenne or Becker muscular dystrophy whose LVEF was preserved and MF was present as determined on CMR, ACE inhibitor therapy was associated with significantly slower progression of MF. The presence of MF was associated with worse patient prognosis.clinicaltrials.org Identifier: NCT02432885.
Tumor burden reduction between primary and metastatic sites in advanced pancreatic cancer patients (pts) undergoing chemotherapy with nab-paclitaxel (Nab-P) and gemcitabine (Gem)
Authors: J. Ventriglia, M.M. Laterza, B. Savastano, A. Petrillo, G. Tirino, A. Diana, T. Troiani, F. Ciardiello, F. De Vita
Journal: Annals of Oncology (2015)
Depletion of Gut Microbiota Protects against Renal Ischemia-Reperfusion Injury
Authors: Diba Emal, Elena Rampanelli, Ingrid Stroo, Loes M. Butter, Gwendoline J. Teske, Nike Claessen, Geurt Stokman, Sandrine Florquin, Jaklien C. Leemans, Mark C. Dessing
Journal: Journal of the American Society of Nephrology (2016)

An accumulating body of evidence shows that gut microbiota fulfill an important role in health and disease by modulating local and systemic immunity. The importance of the microbiome in the development of kidney disease, however, is largely unknown. To study this concept, we depleted gut microbiota with broad-spectrum antibiotics and performed renal ischemia-reperfusion (I/R) injury in mice. Depletion of the microbiota significantly attenuated renal damage, dysfunction, and remote organ injury and maintained tubular integrity after renal I/R injury. Gut flora–depleted mice expressed lower levels of F4/80 and chemokine receptors CX3CR1 and CCR2 in the F4/80 + renal resident macrophage population and bone marrow (BM) monocytes than did control mice. Additionally, compared with control BM monocytes, BM monocytes from gut flora–depleted mice had decreased migratory capacity toward CX3CL1 and CCL2 ligands. To study whether these effects were driven by depletion of the microbiota, we performed fecal transplants in antibiotic-treated mice and found that transplant of fecal material from an untreated mouse abolished the protective effect of microbiota depletion upon renal I/R injury. In conclusion, we show that depletion of gut microbiota profoundly protects against renal I/R injury by reducing maturation status of F4/80 + renal resident macrophages and BM monocytes. Therefore, dampening the inflammatory response by targeting microbiota-derived mediators might be a promising therapy against I/R injury.
Bloodstream Infections in Hematological Cancer Patients Colonized By Multiresistant Bacteria: Results of a Multicentric Prospective Observational Seifem Study
Authors: Chiara Cattaneo, Roberta Di Blasi, Crisitina Skert, Anna Candoni, Marco Picardi, Maria Rosaria De Paolis, Valentina Mancini, Mario Delia, Francesco Mazziotta, Luca Facchini, Francesco Marchesi, Domenico Russo, Vincenza Orlando, Bruno Martino, Stelvio Ballanti, Mario Tumbarello, Giuseppe Rossi, Livio Pagano
Journal: Blood (2015)
Cytokines Behaviour in Multiple Myeloma during Zoledronic Acid Treatment.
Authors: Giuseppe Avvisati, Maria T. Petrucci, Ombretta Annibali, Francesco Bartolozzi, Barbara Giannetti, Anna Levi, Fabrizio Battistoni, Michele Gavasci, Giordano Dicuonzo, Bruno Vincenzi, Daniele Santini, Robin Foa, Franco Mandelli
Journal: Blood (2004)
Real-Life Rates of Disease Monitoring in Clinical Practice in Europe: The “Unmet Needs in CML and Ph+ALL” (UNIC) Study.
Authors: Enrica Morra, Mauricette Michallet, Juan Steegmann, David Marin Costa, Gert Ossenkoppele, Gregor Verhoef, Thomas Kühr, Mats Björeman, Cosimo Paga, Carine Cohen, Isidro Villanueva, Véronique Halkin, Michele Intorcia, Karin Cerri
Journal: Blood (2007)
Association between exposure to ambient particulate matter and chronic obstructive pulmonary disease: results from a cross-sectional study in China
Authors: Sha Liu, Yumin Zhou, Suixin Liu, Xinyu Chen, Weifeng Zou, Dongxing Zhao, Xiaochen Li, Jinding Pu, Lingmei Huang, Jinlong Chen, Bing Li, Shiliang Liu, Pixin Ran
Journal: Thorax (2016)

<h3>Objective</h3> The association between exposure to ambient particles with a median aerodynamic diameter less than 10/2.5 µm (particulate matter, PM<sub>10</sub>/<sub>2.5</sub>) and COPD remains unclear. Our study objective was to examine the association between ambient PM<sub>10</sub>/<sub>2.5</sub> concentrations and lung functions in adults. <h3>Methods</h3> A cross-sectional study was conducted in southern China. Seven clusters were randomly selected from four cities across Guangdong province. Residents aged ≥20 years in the participating clusters were randomly recruited; all eligible participants were examined with a standardised questionnaire and spirometry. COPD was defined as a post-bronchodilator FEV<sub>1</sub>/FVC less than 70%. Atmosphere PM sampling was conducted across the clusters along with our survey. <h3>Results</h3> Of the subjects initially recruited, 84.4% (n=5993) were included for analysis. COPD prevalence and atmosphere PM concentration varied significantly among the seven clusters. COPD prevalence was significantly associated with elevated PM concentration levels: adjusted OR 2.416 (95% CI 1.417 to 4.118) for &gt;35 and ≤75 µg/m<sup>3</sup> and 2.530 (1.280 to 5.001) for &gt;75 µg/m<sup>3</sup> compared with the level of ≤35 µg/m<sup>3</sup> for PM<sub>2.5</sub>; adjusted OR 2.442 (95% CI 1.449 to 4.117) for &gt;50 and ≤150 µg/m<sup>3</sup> compared with the level of ≤50 µg/m<sup>3</sup> for PM<sub>1</sub>. A 10 µg/m<sup>3</sup> increase in PM<sub>2.5</sub> concentrations was associated with a 26 mL (95% CI −43 to −9) decrease in FEV<sub>1</sub>, a 28 mL (−49 to −8) decrease in FVC and a 0.09% decrease (−0.170 to −0.010) in FEV<sub>1</sub>/FVC ratio. The associations of COPD with PM<sub>10</sub> were consistent with PM<sub>2.5</sub> but slightly weaker. <h3>Conclusions</h3> Exposure to higher PM concentrations was strongly associated with increased COPD prevalence and declined respiratory function. <h3>Trial registration number</h3> ChiCTR-OO-14004264; Post-results.
Breast cancer leptomeningeal metastasis.
Authors: Y. Tadokoro, N. Nishikawa, A. Ogiya, K. Tanaka, K. Takahashi, K. Mitsuya, J. Watanabe, S. Yamasaki, T. Uematsu, M. Kasami
Journal: Journal of Clinical Oncology (2011)

e11524 Background: Breast cancer leptomeningeal metastasis(BLM) occurs in approximately 5% of patients with metastatic breast cancer and, due to the lack of an established treatment, these patients have an extremely poor prognosis. Methods: The clinical characteristics of BML and outcomes were investigated in 14 patients at our Center between 2004 and 2010. The present study investigates the clinical characteristics of the disease and the treatment outcomes obtained at our Center. Results: The clinical characteristics of breast cancer leptomeningeal metastasis was as follows. The mean age of subjects was 50.8 years.T stage, 4 patients were T1, 4 patients were T2, 5 patients were T4, and 1 patient was unknown. N stage, 0 patients were N0, 5 patients were N1, 3 patients were N2, and 6 patients were N3. By histopathological type, invasive ductal carcinoma occurred in 13 patients and invasive lobular carcinoma in 1 patient. By histological grade, 0 patients were assessed as low, 2 patient as intermediate, 9 patients as high, and 3 patients as unknown. Triple-negative phenotype accounted for 50% of patients.13 patients underwent treatment with intrathecal methotrexate (MTX) via an Ommaya reservoir and whole-brain radiation.The changes from baseline in symptoms were as follows. At the onset of BLM, headache was reported in 9 patients, vomiting in 4 patients, dizziness in 3 patients, light-headed feeling in 3 patients, anorexia and nausea in 2 patient, disorientation in 2 patient, strange sensation in left ear in 1 patient, and double vision in 1 patient. In 8 of 13 patients, the symptoms had resolved at discharge following treatment, 5 patients had mild symptoms. In all cases, however, the symptoms relieved and they were once discharged.The median survival period at our Center for the 11 treated subjects was 9.5 months. Conclusions: A treatment regimen of intrathecal MTX via on Ommaya reservoir and whole-brain radiation makes it possible to alleviate symptoms and for patients to be discharged from hospital, with an improved QOL and a longer survival period reported in some patients.
A noninvasive multimodal sono-contrast NIR spectroscopy system for breast cancer diagnosis: Clinical trial.
Authors: K. Yan, Y. Yu, L. Liao
Journal: Journal of Clinical Oncology (2011)

68 Background: A noninvasive multimodal sono-constrast spectroscopy system was developed to detect breast cancer from benign mass. An IRB approved clinical study has been carried out to evaluate its diagnostic power. Fourteen patients with histologically-proven cancer and 26 with benign mass were enrolled with informed consent. Methods: This system combines three modules: diffuse reflectance spectroscopy, ultrasonography and low intensity focused ultrasound (LIFU). It reports the optical functional difference in cancer and benign mass after transient LIFU interaction with vascular flow. The optical intensity and LIFU signals were collected during each study. The ratio of optical intensities at wavelengths 685 nm and 830 nm was decomposed into low frequency and high frequency components using wavelet analysis. Results: Comparison of the high frequency component showed that LIFU stimulated transitory fluctuation in benign mass, but not in malignant tissue, as quantified by mean absolute deviation (MAD). The ratios of MAD during LIFU vs. baseline in cancer and benign mass are [mean (max/min/std)] 2.04 (3.27/1.41/0.43) and 3.00 (4.29/1.86/0.62). This suggests that high frequency fluctuation was amplified in benign mass during LIFU stimulation. There are a few outliers due to poor patient setup or patient movement during procedure. The MAD ratios are significantly different in cancer vs. benign mass (p&lt;&lt;0.01). An ROC curve was generated by varying threshold MAD values. The area under ROC curve (AUC) was calculated to be 0.91. With threshold 2.3, sensitivity of 92.8% and specificity of 80.8% can be achieved. Backward stepwise regression study reveals that system performance is not affected by patient age (hormone status), tumor depth and tumor size. Conclusions: Current results demonstrate the effectiveness of the multimodal system in characterizing breast cancer vs. benign mass. LIFU appears to exert more pronounced influence on blood flow in benign mass than in tumor. This lack of response to LIFU in breast cancer is possibly due to its abnormal blood vasculature. The analysis is ongoing to incorporate ultrasound imaging parameters with spectroscopy to further improve the diagnostic power.
Elective nodal irradiation for prostate cancer patients: Comparison of available dynamic techniques.
Authors: H. Urbanczyk, L. Hawrylewicz, R. Kulik, K. Szczepanik, J. Ciechowicz, R. Tarnawski
Journal: Journal of Clinical Oncology (2011)

96 Background: The few recent studies showed that regional lymph node metastases of prostate cancer (PCa) could be successfully treated. It means that role of pelvic nodes (PN) irradiation could increase in next period. A problem is rectal and bladder toxicities of this treatment. Intensity modulated dynamic irradiation techniques (DT) may potentially help to reduce treatment related side effects. The aim of study is to compare three different radiotherapy techniques: conformal (CRT), static field intensity modulated (SF IMRT) and rapid arc (RA) for elective pelvic lymph nodes irradiation. Methods: We analyzed CRT, IMRT and RA plans of irradiation PN for ten patients. PTVs included PN iliac, iliac external upper then acetabulum, iliac internal and obturatory. Prescribed doses were 44 Gy/22 fractions. We compared the doses delivered to PTV rectum and bladder using dose volume histograms. The U Mann-Whitney, W Shapiro-Wilk and ANOVA rang Kruskal-Wallis tests were used for statistical analysis. Results: The median PTV doses were not statistically different in analyzed plans. The minimum doses for PTV were significantly lower in IMRT and RA plans but the differences were not clinically significant. Maximum doses were significantly higher for CRT plans. The doses calculated for rectum and bladder were statistically significantly lower for dynamic techniques in whole range of volumes and doses. SF IMRT is the most efficient technique in reducing the dose to bladder. The doses observed in half of the rectum and bladder volumes bladder were also statistically significant different (p=0.002 for rectum and 0.001 for bladder). The median doses for rectum were 43.6 Gy for CRT plans, 33.5 Gy for IMRT and 37.9 Gy for RA, median doses calculated for bladder were 44 Gy for CRT, 35.6 Gy for IMRT and 39.6 Gy for RA. Conclusions: CRT does not allow to reduce the dose to organs at risk. Both DT reduce the doses to bladder and rectum while maintaining the high homogenous dose to PTV. SF IMRT is more efficient in reducing the dose to bladder than RA. SF IMRT technique seems to be better than Rapid Arc for PN irradiation. It is probably because the nodal PTVs are large and their structures are complicated. No significant financial relationships to disclose.
A Retrospective Analysis of Mantle Cell Lymphoma Patients Series Treated Upfront by Sequential High Dose Immunochemotherapy Supported by In Vivo Purged Stem Celle Double Autologous Transplantation: A Monocentric Experience
Authors: Andrea Ferrario, Giorgia Saporiti, Nicola Orofino, Francesco Onida, Daniele Vincenti, Claudia Basilico, Francesca Gaia Rossi, Barbara Olivero, Maria Cecilia Goldaniga, Elena Tagliaferri, Claudio Annaloro, Luca Baldini
Journal: Blood (2011)