79 research outputs found
Mediastinal staging in lung cancer: a rational approach
imaging techniques such as CT (Computed Tomography) and PET (Positron Emission Tomography), mini-invasive techniques, as TBNA (Transbronchial Needle Aspiration), EBUS-TBNA (Ultrasound-Guided Transbronchial Needle Aspiration), EUS-FNA (Endoscopic Ultra Sound Fine-Needle Aspiration), and/or surgical techniques as mediastinoscopy, thoracoscopy, mediastinothomy. Each of these techniques provides different sensitivity, specificity and predictive value: all these characteristics need to be well considered and adequately used to achieve the best possible outcome, best exploitation of available resources and least discomfort for the patient. Particularly, indicators which may suggest the need for further examination of mediastinum, following a negative CT and PET, will be discussed in this review; need for surgical confirmation after negative TBNA will be considered, also
Lobar collapse therapy using endobronchial valves as a new complementary approach to treat cavities in multidrug-resistant tuberculosis and difficult-to-treat tuberculosis: A case series
Die Bedeutung von Rhamnolipiden in der Pathogenese epithelialer Pseudomonas aeruginosa Infektionen
Pseudomonas aeruginosa (P. aeruginosa) ist ein ubiquitĂ€r vorkommendes, gramnegatives, monotrich begeiĂeltes, aerob lebendes StĂ€bchenbakterium. Das opportunistisches Pathogen befĂ€llt Menschen, Tiere, Insekten, Nematoden und Pflanzen und ist unter anderem aufgrund seiner Toleranz gegenĂŒber einer Vielzahl von Desinfektionsmitteln und Antibiotika einer der wichtigsten Verursacher von nosokomialen Infektionen.
Die Ergebnisse dieser Arbeit geben einen Hinweis darauf, dass P. aeruginosa das angeborene Immunsystem mit Hilfe von Rhamnolipid, einem vom Bakterium selbst produzierten Surfactant, umgeht.
In der vorliegenden Arbeit konnte nachgewiesen werden, dass die Flagellin-induzierte hBD2-Expression in humanen Keratinozyten durch bakterielle ĂberstĂ€nde von P. aeruginosa, die in der stationĂ€ren Phase generiert wurden, supprimiert wird. Der supprimierende Faktor konnte in Versuchen als hitzestabil und durch SĂ€ure ausfĂ€llbar identifiziert werden. AuĂerdem blieb er bei Behandlung mit Proteinase K unbeeinflusst, es handelt sich deshalb nicht um ein Protein. Weitere Untersuchungen konnten den Faktor als Rhamnolipid identifizieren.
Eine Kostimulation von Keratinozyten mit aufgereinigtem Rhamnolipid in Mengen unterhalb der zytotoxischen Konzentration zusammen mit Flagellin zeigte ebenfalls eine Supprimierung der induzierten hBD2-Expression. Ăhnliche Effekte konnten bei Kostimulation der Keratinozyten mit Flagellin und BAPTA-AM, einem intrazellulĂ€ren Calciumchelator, erreicht werden. Neben Flagellin als Induktor lieĂ sich auch die PMA-induzierte hBD2-Expression supprimieren. Dies lĂ€sst vermuten, dass Rhamnolipide mit Calcium-abhĂ€ngigen Signalkaskaden, wie der PKC-Signalkaskade, interferieren.
Die Versuche dieser Arbeit zeigen damit einen Weg, ĂŒber den es P. aeruginosa möglich ist, sich auf der Haut zu etablieren, ohne seinen HauptpathogenitĂ€tsfaktor, das Flagellin, verstecken zu mĂŒssen
Integrating transposable elements in the 3D genome
Chromosome organisation is increasingly recognised as an essential component of genome regulation, cell fate and cell health. Within the realm of transposable elements (TEs) however, the spatial information of how genomes are folded is still only rarely integrated in experimental studies or accounted for in modelling. Whilst polymer physics is recognised as an important tool to understand the mechanisms of genome folding, in this commentary we discuss its potential applicability to aspects of TE biology. Based on recent works on the relationship between genome organisation and TE integration, we argue that existing polymer models may be extended to create a predictive framework for the study of TE integration patterns. We suggest that these models may offer orthogonal and generic insights into the integration profiles (or "topography") of TEs across organisms. In addition, we provide simple polymer physics arguments and preliminary molecular dynamics simulations of TEs inserting into heterogeneously flexible polymers. By considering this simple model, we show how polymer folding and local flexibility may generically affect TE integration patterns. The preliminary discussion reported in this commentary is aimed to lay the foundations for a large-scale analysis of TE integration dynamics and topography as a function of the three-dimensional host genome
Incorporating weekly carboplatin in anthracycline and paclitaxel-containing neoadjuvant chemotherapy for triple-negative breast cancer: propensity-score matching analysis and TIL evaluation
Background The generation of data capturing the risk-benefit ratio of incorporating carboplatin (Cb) to neoadjuvant chemotherapy (NACT) for triple-negative breast cancer (TNBC) in a clinical practice setting is urgently needed. Tumour-infiltrating lymphocytes (TILs) have an established role in TNBC receiving NACT, however, the role of TIL dynamics under NACT exposure in patients receiving the current standard of care is largely uncharted. Methods Consecutive TNBC patients receiving anthracycline-taxane [A-T] +/- Cb NACT at three Institutions were enrolled. Stromal-TILs were evaluated on pre-NACT and residual disease (RD) specimens. In the clinical cohort, propensity-score-matching was used to control selection bias. Results In total, 247 patients were included (A-T = 40.5%, A-TCb = 59.5%). After propensity-score-matching, pCR was significantly higher for A-TCb vs A-T (51.9% vs 34.2%, multivariate: OR = 2.40, P = 0.01). No differences in grade >= 3 haematological toxicities were observed. TILs increased from baseline to RD in the overall population and across A-T/A-TCb subgroups. TIL increase from baseline to RD was positively and independently associated with distant disease-free survival (multivariate: HR = 0.43, P = 0.05). Conclusions We confirmed in a clinical practice setting of TNBC patients receiving A-T NACT that the incorporation of weekly Cb significantly improved pCR. In addition, A-T +/- Cb enhanced immune infiltration from baseline to RD. Finally, we reported a positive independent prognostic role of TIL increase after NACT exposure
Nonequilibrium Chromosome Looping via Molecular Slip Links
We propose a model for the formation of chromatin loops based on the
diffusive sliding of a DNA-bound factor which can dimerise to form a molecular
slip-link. Our slip-links mimic the behaviour of cohesin-like molecules, which,
along with the CTCF protein, stabilize loops which organize the genome. By
combining 3D Brownian dynamics simulations and 1D exactly solvable
non-equilibrium models, we show that diffusive sliding is sufficient to account
for the strong bias in favour of convergent CTCF-mediated chromosome loops
observed experimentally. Importantly, our model does not require any
underlying, and energetically costly, motor activity of cohesin. We also find
that the diffusive motion of multiple slip-links along chromatin may be
rectified by an intriguing ratchet effect that arises if slip-links bind to the
chromatin at a preferred "loading site". This emergent collective behaviour is
driven by a 1D osmotic pressure which is set up near the loading point, and
favours the extrusion of loops which are much larger than the ones formed by
single slip-links.Comment: 37 pages, 12 figures, Supplementary Movies can be downloaded at
http://www2.ph.ed.ac.uk/~dmarendu/Cohesin/SMX.mp4; with X=1, 2 or
The largest multicentre data collection on prepectoral breast reconstruction: The iBAG study
Background and Objectives: In the last years, prepectoral breast reconstruction has increased its popularity, becoming a standard reconstructive technique by preserving pectoralis major anatomy and functionality. Nevertheless, the lack of solid and extensive data negatively impacts on surgeons\u2019 correct information about postoperative complication rates and proper patient selection. This study aims to collect the largest evidence on this procedure. Methods: A multicentre retrospective audit, promoted by the Barcelona Hospital, collected the experience of 30 centers on prepectoral breast reconstruction with Braxon ADM. The study had the scientific support of INPECS and IIB societies which provided the online database Clinapsis. Results: A total of 1450 procedures were retrospectively collected in a 6-year period. Mean age 52.4 years, BMI 23.9, follow-up 22.7 months. Reconstruction was carried out after a tumor in 77.1% of the cases, 20.1% had prophylactic surgery, 2.8% had revisions. Diabetes, smoke, and immunosuppression had an influence on complications occurrence, as well as implant weight. Capsular contracture was associated with postoperative radiotherapy, but the overall rate was low (2.1%). Complications led to implant loss in 6.5% of the cases. Conclusions: The international Braxon Audit Group multicentre data collection represents a milestone in the field of breast reconstruction, extensively improving the knowledge of this procedure
Preservation of Axillary Lymph Nodes Compared with Complete Dissection in T1â2 Breast Cancer Patients Presenting One or Two Metastatic Sentinel Lymph Nodes: The SINODAR-ONE Multicenter Randomized Clinical Trial
Background: The SINODAR-ONE trial is a prospective noninferiority multicenter randomized study aimed at assessing the role of axillary lymph node dissection (ALND) in patients undergoing either breast-conserving surgery or mastectomy for T1â2 breast cancer (BC) and presenting one or two macrometastatic sentinel lymph nodes (SLNs). The endpoints were to evaluate whether SLN biopsy (SLNB) only was associated with worsening of the prognosis compared with ALND in terms of overall survival (OS) and relapse. Methods: Patients were randomly assigned (1:1 ratio) to either removal of â„ 10 axillary level I/II non-SLNs followed by adjuvant therapy (standard arm) or no further axillary treatment (experimental arm). Results: The trial started in April 2015 and ceased in April 2020, involving 889 patients. Median follow-up was 34.0 months. There were eight deaths (ALND, 4; SNLB only, 4), with 5-year cumulative mortality of 5.8% and 2.1% in the standard and experimental arm, respectively (p = 0.984). There were 26 recurrences (ALND 11; SNLB only, 15), with 5-year cumulative incidence of recurrence of 6.9% and 3.3% in the standard and experimental arm, respectively (p = 0.444). Only one axillary lymph node recurrence was observed in each arm. The 5-year OS rates were 98.9% and 98.8%, in the ALND and SNLB-only arm, respectively (p = 0.936). Conclusions: The 3-year survival and relapse rates of T1â2 BC patients with one or two macrometastatic SLNs treated with SLNB only, and adjuvant therapy, were not inferior to those of patients treated with ALND. These results do not support the use of routine ALND
The impact of immediate breast reconstruction on the time to delivery of adjuvant therapy: the iBRA-2 study
Background:
Immediate breast reconstruction (IBR) is routinely offered to improve quality-of-life for women requiring mastectomy, but there are concerns that more complex surgery may delay adjuvant oncological treatments and compromise long-term outcomes. High-quality evidence is lacking. The iBRA-2 study aimed to investigate the impact of IBR on time to adjuvant therapy.
Methods:
Consecutive women undergoing mastectomyâ±âIBR for breast cancer JulyâDecember, 2016 were included. Patient demographics, operative, oncological and complication data were collected. Time from last definitive cancer surgery to first adjuvant treatment for patients undergoing mastectomyâ±âIBR were compared and risk factors associated with delays explored.
Results:
A total of 2540 patients were recruited from 76 centres; 1008 (39.7%) underwent IBR (implant-only [nâ=â675, 26.6%]; pedicled flaps [nâ=â105,4.1%] and free-flaps [nâ=â228, 8.9%]). Complications requiring re-admission or re-operation were significantly more common in patients undergoing IBR than those receiving mastectomy. Adjuvant chemotherapy or radiotherapy was required by 1235 (48.6%) patients. No clinically significant differences were seen in time to adjuvant therapy between patient groups but major complications irrespective of surgery received were significantly associated with treatment delays.
Conclusions:
IBR does not result in clinically significant delays to adjuvant therapy, but post-operative complications are associated with treatment delays. Strategies to minimise complications, including careful patient selection, are required to improve outcomes for patients
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