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4.
Oncotarget ; 8(61): 102888-102897, 2017 Nov 28.
Article in English | MEDLINE | ID: mdl-29262531

ABSTRACT

Primary breast lymphoma is a rare form of extra-nodal lymphoid neoplasm. The most common histological type is the diffuse large B-cell lymphoma, which represents 60-80% of all the cases. Our study analyzes the mutational profile of the primary lymphoma of the breast through targeted massive sequencing with a panel of 38 genes in a group of 17 patients with primary breast diffuse large B-cell lymphoma. Seventy-point-five percent of the patients presented with stage IE and 29.5% with stage IIE. 44% of the cases correspond to lymphomas with germinal center phenotype and 33.3% to activated B-cell. The genes with a higher mutational frequency include PIM1 (in 50% of the analyzed samples), MYD88 (39%), CD79B, PRDM1 and CARD11 (17%), KMT2D, TNFIAP3 and CREBBP (11%). The profile of mutant genes involves mostly the NFκB signaling pathway. The high frequency of mutations in PIM1 compared with other lymphomas may have implications in the clinical presentation and evolution of this type of lymphoma.

5.
Trauma Surg Acute Care Open ; 2(1): e000068, 2017.
Article in English | MEDLINE | ID: mdl-29766082

ABSTRACT

BACKGROUND: Benchmark data from the Trauma Quality Improvement Program (TQIP) identified an opportunity for improvement in our trauma programme. Our unexpected return to the intensive care unit (ICU) was found to be higher than the national averages and we also noticed that our readmission rate had increased. We chose to address these complications as continuous quality improvement projects. It was hypothesized that restructuring the workflow of the trauma advanced practice providers (APPs) to focus on the delivery of comprehensive clinical care would decrease return to ICU and readmission rates of trauma patients. METHODS: The development of the APP programme occurred from 2012 to 2014. First, APP daily shifts were extended to mirror the resident physicians' coverage. Second, the APPs' original job description was expanded from 'task-oriented' workflow to providing comprehensive clinical care. Third, the APPs were involved in the evaluation and decision-making process for transferring trauma patients from the ICU. Finally, the APPs implemented a new discharge process that included all information in a standardized format and a follow-up phone call 24-48 hours after discharge. The trauma registry at our verified, academic level I trauma center was use to assess our ICU and hospital readmission rates during the time we instituted the new APP workflow programme. RESULTS: In 2012, our ICU readmission rate was 5.7% (TQIP=1.9%) but then decreased to 4.4% in 2013 (TQIP=2.5%) and 2.1% in 2014 (TQIP=2.8%). Our hospital readmission rate was 2.0% in 2012 but then decreased to 1.38% and 0.96% over the next 2 years. CONCLUSIONS: After extending the APP service coverage, implementing a comprehensive clinical care model and standardizing the discharge process, our unplanned return to ICU rates have decreased to below the TQIP national average and hospital readmission rates have also decreased by half. LEVEL OF EVIDENCE: III.

6.
Clin Lymphoma Myeloma Leuk ; 17(3): 186-191, 2017 03.
Article in English | MEDLINE | ID: mdl-27847267

ABSTRACT

INTRODUCTION: Primary breast lymphoma is a rare form of localized extranodal lymphoma, which affects the mammary glands unilaterally or bilaterally, and can also affect the regional lymph nodes. MATERIALS AND METHODS: We reviewed 55 patients, with disease stages IE and IIE, diagnosed in 16 Spanish institutions between 1989 and 2016. A serial of clinical variables and treatment were collected, and overall survival (OS) and progression-free survival (PFS) were calculated. RESULTS: Of the 55 patients, 96.4% were women with an average age of 69 years. A total of 53 patients corresponded to non-Hodgkin lymphoma (NHL), of whom 36.3% had lymph node involvement upon diagnosis. Of the patients, 58.2% were stage IE, and 41.8% were stage IIE. Treatments received included radiotherapy (36.3%), chemotherapy (85.5%), and rituximab (in 38 of the 45 patients with NHL treated with chemotherapy). In all, 82.2% of complete responses were achieved. OS and progression-free survival at 5 years in NHL patients was 76% and 73%, respectively. CONCLUSION: Current treatments (chemotherapy, immunotherapy, and radiotherapy) achieve good control of the disease, with an OS of 5 years in 80% of the patients, although there is no consensus in treatment, given the scarce incidence of these lymphomas.


Subject(s)
Antineoplastic Agents/therapeutic use , Breast Neoplasms, Male/drug therapy , Breast Neoplasms/drug therapy , Lymphoma/drug therapy , Adult , Aged , Aged, 80 and over , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Breast Neoplasms, Male/mortality , Breast Neoplasms, Male/pathology , Disease-Free Survival , Female , Humans , Lymph Nodes/pathology , Lymphoma/mortality , Lymphoma/pathology , Lymphoma, Non-Hodgkin/drug therapy , Lymphoma, Non-Hodgkin/mortality , Male , Middle Aged , Prognosis , Treatment Outcome
7.
J Biomed Opt ; 20(8): 88003, 2015 Aug.
Article in English | MEDLINE | ID: mdl-26315280

ABSTRACT

A quantification method to measure endocytosis was designed to assess cellular uptake and specificity of a targeting nanoparticle platform. A simple N -hydroxysuccinimide ester conjugation technique to functionalize 100-nm hollow silica nanoshell particles with fluorescent reporter fluorescein isothiocyanate and folate or polyethylene glycol (PEG) was developed. Functionalized nanoshells were characterized using scanning electron microscopy and transmission electron microscopy and the maximum amount of folate functionalized on nanoshell surfaces was quantified with UV-Vis spectroscopy. The extent of endocytosis by HeLa cervical cancer cells and human foreskin fibroblast (HFF-1) cells was investigated in vitro using fluorescence and confocal microscopy. A simple fluorescence ratio analysis was developed to quantify endocytosis versus surface adhesion. Nanoshells functionalized with folate showed enhanced endocytosis by cancer cells when compared to PEG functionalized nanoshells. Fluorescence ratio analyses showed that 95% of folate functionalized silica nanoshells which adhered to cancer cells were endocytosed, while only 27% of PEG functionalized nanoshells adhered to the cell surface and underwent endocytosis when functionalized with 200 and 900 µg , respectively. Additionally, the endocytosis of folate functionalized nanoshells proved to be cancer cell selective while sparing normal cells. The developed fluorescence ratio analysis is a simple and rapid verification/validation method to quantify cellular uptake between datasets by using an internal control for normalization.


Subject(s)
Endocytosis/physiology , Folic Acid/pharmacokinetics , Microscopy, Fluorescence/methods , Nanocapsules/chemistry , Nanocapsules/ultrastructure , Silicon Dioxide/chemistry , Folic Acid/chemistry , HeLa Cells , Humans , Nanopores/ultrastructure , Particle Size
8.
PM R ; 7(12): 1243-1253, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26003872

ABSTRACT

BACKGROUND: Handball is one of the most challenging sports for the knee joint. Persistent biomechanical and jumping capacity alterations can be observed in athletes with an anterior cruciate ligament (ACL) injury. Commonly identified jumping biomechanical alterations have been described by the use of laboratory technologies. However, portable and easy-to-handle technologies that enable an evaluation of jumping biomechanics at the training field are lacking. OBJECTIVE: To analyze unilateral/bilateral acceleration and orientation jumping performance differences among elite male handball athletes with or without previous ACL reconstruction via a single inertial sensor unit device. DESIGN: Case control descriptive study. SETTING: At the athletes' usual training court. PARTICIPANTS: Twenty-two elite male (6 ACL-reconstructed and 16 uninjured control players) handball players were evaluated. METHODS: The participants performed a vertical jump test battery that included a 50-cm vertical bilateral drop jump, a 20-cm vertical unilateral drop jump, and vertical unilateral countermovement jump maneuvers. MAIN OUTCOME MEASUREMENTS: Peak 3-dimensional (X, Y, Z) acceleration (m·s(-2)), jump phase duration and 3-dimensional orientation values (°) were obtained from the inertial sensor unit device. Two-tailed t-tests and a one-way analysis of variance were performed to compare means. The P value cut-off for significance was set at P < .05. RESULTS: The ACL-reconstructed male athletes did not show any significant (P < .05) residual jumping biomechanical deficits regarding the measured variables compared with players who had not suffered this knee injury. A dominance effect was observed among non-ACL reconstructed controls but not among their ACL-reconstructed counterparts (P < .05). CONCLUSIONS: Elite male handball athletes with previous ACL reconstruction demonstrated a jumping biomechanical profile similar to control players, including similar jumping performance values in both bilateral and unilateral jumping maneuvers, several years after ACL reconstruction. These findings are in agreement with previous research showing full functional restoration of abilities in top-level male athletes after ACL reconstruction, rehabilitation and subsequent return to sports at the previous level.


Subject(s)
Anterior Cruciate Ligament Injuries , Anterior Cruciate Ligament Reconstruction , Athletic Injuries/rehabilitation , Exercise Therapy/methods , Knee Injuries/rehabilitation , Knee Joint/physiopathology , Orientation/physiology , Acceleration , Adult , Athletic Injuries/physiopathology , Athletic Injuries/surgery , Biomechanical Phenomena , Follow-Up Studies , Humans , Knee Injuries/physiopathology , Knee Injuries/surgery , Male , Range of Motion, Articular/physiology , Young Adult
9.
Chem Mater ; 24(21): 4222-4230, 2012 Nov 13.
Article in English | MEDLINE | ID: mdl-23185106

ABSTRACT

A simple scalable method to fabricate luminescent monodisperse 200 nm europium doped hollow TiO(2) nanoshell particles is reported. Fluorophore reporter, Eu(3+) ions, are incorporated directly in the NS matrix, leaving the surface free for functionalization and the core free for payload encapsulation. Amine functionalized polystyrene beads were used as templates, and the porous walls of europium doped titania nanoshells were synthesized using titanium(IV) t-butoxide and europium(III) nitrate as reactants. X-ray diffraction analysis identified anatase as the predominant titania phase of the rigid nanoshell wall structure, and photoluminescence spectra showed that the Eu(III) doped TiO(2) nanoshells exhibited a red emission at 617 nm due to an atomic f-f transition. Nanoshell interactions with HeLa cervical cancer cells in vitro were visualized using two-photon microscopy of the Eu(III) emission, and studied using a luminescence ratio analysis to assess nanoshell adhesion and endocytosis.

10.
J Biomed Opt ; 16(6): 066012, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21721813

ABSTRACT

A simple method to fabricate Eu(3+) doped silica nanoshells particles with 100 and 200 nm diameters is reported. Amino polystyrene beads were used as templates, and an 8 to 10 nm thick silica gel coating was formed by the sol-gel reaction. After removing the template by calcination, porous dehydrated silica gel nanoshells of uniform size were obtained. The Eu(3+) doped silica nanoshells exhibited a red emission at 615 nm on UV excitation. The porous structure of the silica shell wall was characterized by transmission electron microscopy measurements, while particle size and zeta potentials of the particles suspended in aqueous solution were characterized by dynamic light scattering. Two-photon microscopy was used to image the nanoshells after assimilation by HeLa cancer cells.


Subject(s)
Cell Adhesion/physiology , Endocytosis/physiology , Europium/chemistry , Nanoshells/chemistry , Silicon Dioxide/chemistry , Cytoplasm/metabolism , HeLa Cells , Hot Temperature , Humans , Luminescent Agents , Microscopy, Electron, Scanning , Microscopy, Electron, Transmission , Nanoshells/ultrastructure , Nanotechnology , Particle Size , Polystyrenes , Porosity
12.
Laryngoscope ; 113(1): 167-72, 2003 Jan.
Article in English | MEDLINE | ID: mdl-12514403

ABSTRACT

OBJECTIVES/HYPOTHESIS: Proteins p53 and cyclin D1 play a crucial role in cell cycle control. Protein p53 mutations are one of the most common genetic alterations in human cancer, and cyclin D1 gene amplification has been found to be associated with poor prognosis in different types of tumors. Functional alterations of these proteins may play an important role both in the carcinogenesis of squamous carcinomas of the head and neck and in the clinical evolution of these tumors. The objective of the present study was to evaluate whether the presence of p53 and/or cyclin D1 proteins (detected by immunohistochemical analysis) could serve as relevant variables for the assessment of the prognosis of laryngeal squamous cell carcinoma. STUDY DESIGN: Retrospective multicentric study. METHODS: Paraffin-embedded biopsy specimens from 62 human epidermoid laryngeal carcinomas were randomly selected. The expression of p53 and cyclin D1 was examined by means of immunohistochemical analysis with a view to evaluating whether there is a correlation between the aberrant expression of these proteins and disease prognosis. RESULTS: In the sample, the presence of immunohistochemically detectable p53 is associated with shorter survival and disease-free intervals, as shown in Kaplan-Meier survival curve analysis. Indeed, multivariate statistical analysis revealed that the accumulation of p53 is an independent prognostic factor, which is associated with shorter survival. This association was not evident in the case of cyclin D1. CONCLUSION: A more precise prognosis of patients with laryngeal epidermoid carcinomas could be achieved by taking into account the presence of p53 (as assayed by immunohistochemical analysis) in biopsy tissue


Subject(s)
Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/pathology , Cyclin D1/genetics , Genes, p53/genetics , Genetic Predisposition to Disease , Laryngeal Neoplasms/genetics , Laryngeal Neoplasms/pathology , Mutation , Adult , Aged , Biomarkers, Tumor/analysis , Biopsy, Needle , Carcinoma, Squamous Cell/mortality , Female , Humans , Immunohistochemistry , Laryngeal Neoplasms/mortality , Male , Middle Aged , Multivariate Analysis , Neoplasm Staging , Prognosis , Proportional Hazards Models , Reference Values , Retrospective Studies , Sensitivity and Specificity , Survival Analysis
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