Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

Transnasal Endoscopic Resection of a Cavernous Sinus Hemangioma: Technical Note and Review of the Literature

Objective/Importance: Hemangiomas of the cavernous sinus are rare lesions. Complete removal through a transcranial route often causes ocular motor palsies. Because the cranial nerves in the cavernous sinus are lateral to the carotid, a medial approach to the cavernous sinus may be less traumatic to the cranial nerves. Clinical Presentation: A 50-year-old man with headaches, dizziness, diplopia, and magnetic resonance imaging that demonstrated a right cavernous sinus mass expanding into the sella and sphenoid sinus. Intervention: A gross total removal of a cavernous sinus hemangioma was performed through an extended endoscopic transsphenoidal approach. Conclusion: This is the first report of a complete removal of a cavernous sinus hemangioma using an endoscopic transnasal approach. The endoscopic transnasal approach to the medial cavernous sinus may be less traumatic than the transcranial route based on the lateral location of the cranial nerves

Robotic partial nephrectomy for renal tumours in obese patients: Perioperative outcomes in a multi-institutional analysis

INTRODUCTION: We sought to evaluate the association of obesity with surgical outcomes of robotic partial nephrectomy (RPN) using a large, multicentre database. METHODS: We identified 1836 patients who underwent RPN from five academic centres from 2006-2014. A total of 806 patients were obese (body mass index [BMI] ≥30 kg/m(2)). Patient characteristics and outcomes were compared between obese and non-obese patients. Multivariable analysis was used to assess the association of obesity on RPN outcomes. RESULTS: A total of 806 (44%) patients were obese with median BMI of 33.8kg/m(2). Compared to non-obese patients, obese patients had greater median tumour size (2.9 vs. 2.5cm, p\u3c0.001), mean RENAL nephrometry score (7.3 vs. 7.1, p=0.04), median operating time (176 vs. 165 min, p=0.002), and median estimated blood loss (EBL, 150 vs. 100 ml, p=0.002), but no difference in complications. Obesity was not an independent predictor of operative time or EBL on regression analysis. Among obese patients, males had a greater EBL (150 vs. 100 ml, p\u3c0.001), operative time (180 vs. 166 min, p\u3c0.001) and warm ischemia time (WIT, 20 vs. 18, p=0.001), and male sex was an independent predictor of these outcomes on regression analysis. CONCLUSIONS: In this large, multicentre study on RPN, obesity was not associated with increased complications and was not an independent predictor of operating time or blood loss. However, in obese patients, male gender was an independent predictor of greater EBL, operative time, and WIT. Our results indicate that obesity alone should not preclude consideration for RPN

Use of the Satinsky clamp for hilar clamping during robotic partial nephrectomy: indications, technique, and multi-center outcomes.

A Satinsky clamp may be a backup option for hilar clamping during robotic partial nephrectomy (RPN) if there are challenges with application of bulldog clamps, but there are potential safety concerns. We evaluate outcomes of RPN using Satinsky vs. bulldog clamps, and provide tips for safe use of the Satinsky as a backup option. Using a multi-center database, we identified 1073 patients who underwent RPN between 2006 and 2013, and had information available about method of hilar clamping (bulldog clamp vs. Satinsky clamp). Patient baseline characteristics, tumor features, and perioperative outcomes were compared between the Satinsky and bulldog clamp groups. A Satinsky clamp was used for hilar clamping in 94 (8.8 %) RPN cases, and bulldog clamps were used in 979 (91.2 %) cases. The use of a Satinsky clamp was associated with greater operative time (198 vs. 175 min, p \u3c 0.001), estimated blood loss (EBL, 200 vs. 100 ml, p \u3c 0.001), warm ischemia time (WIT, 20 vs. 19 min, p = 0.036), transfusion rate (12.8 vs. 4.8 %, p = 0.001), and hospital stay (3 vs. 2 days, p \u3c 0.001). Tumor characteristics and number of renal vessels were similar between groups. There were six intraoperative complications in the Satinsky clamp group, but none were directly related to the Satinsky clamp. On multivariable analysis, the use of the Satinsky clamp was not associated with increase in intraoperative or Clavien ≥3 postoperative complications, positive surgical margin rate or percentage change in estimated glomerular filtration rate. A Satinsky clamp can be a backup option for hilar clamping during challenging RPN cases, but requires careful technique, and was rarely necessary

Urinary fistula after robot-assisted partial nephrectomy: a multicentre analysis of 1 791 patients.

OBJECTIVE: To evaluate the incidence of and risk factors for a urine leak in a large multicentre, prospective database of robot-assisted partial nephrectomy (RPN). PATIENTS AND METHODS: A database of 1 791 RPN from five USA centres was reviewed for urine leak as a complication of RPN. Patient and tumour characteristics were compared between patients with and those without postoperative urine leaks. Fisher\u27s exact test was used for qualitative variables and Wilcoxon sum-rank tests were used for quantitative variables. A review of the literature on PN and urine leak was conducted. RESULTS: Urine leak was noted in 14/1 791 (0.78%) patients who underwent RPN. The mean (sd) nephrometry score of the entire cohort was 7.2 (1.9), and 8.0 (1.9) in patients who developed urine leak. The median (range) postoperative day of presentation was 13 (3-32) days. Patients with urine leak presented in delayed fashion with fever (two of the 14 patients, 14%), gastrointestinal complaints (four patients, 29%), and pain (five patients, 36%). Eight of the 14 patients (57%) required admission, while eight (57%) and nine (64%) had a drain or stent placed, respectively. Drains and stents were removed after a median (range) of 8 (4-13) days and 21 (8-83) days, respectively. Variables associated with urine leak included tumour size (P = 0.021), hilar location (P = 0.025), operative time (P = 0.006), warm ischaemia time (P = 0.005), and pelvicalyceal repair (P = 0.018). Upon literature review, the historical incidence of urine leak ranged from 1.0% to 17.4% for open PN and 1.6-16.5% for laparoscopic PN. CONCLUSION: The incidence of urine leak after RPN is very low and may be predicted by some preoperative factors, affording better patient counselling of risks. The low urinary leak rate may be attributed to the enhanced visualisation and suturing technique that accompanies the robotic approach

Anti-tumour immunity induces aberrant peptide presentation in melanoma

Extensive tumour inflammation, which is reflected by high levels of infiltrating T cells and interferon-γ (IFNγ) signalling, improves the response of patients with melanoma to checkpoint immunotherapy1,2. Many tumours, however, escape by activating cellular pathways that lead to immunosuppression. One such mechanism is the production of tryptophan metabolites along the kynurenine pathway by the enzyme indoleamine 2,3-dioxygenase 1 (IDO1), which is induced by IFNγ3-5. However, clinical trials using inhibition of IDO1 in combination with blockade of the PD1 pathway in patients with melanoma did not improve the efficacy of treatment compared to PD1 pathway blockade alone6,7, pointing to an incomplete understanding of the role of IDO1 and the consequent degradation of tryptophan in mRNA translation and cancer progression. Here we used ribosome profiling in melanoma cells to investigate the effects of prolonged IFNγ treatment on mRNA translation. Notably, we observed accumulations of ribosomes downstream of tryptophan codons, along with their expected stalling at the tryptophan codon. This suggested that ribosomes bypass tryptophan codons in the absence of tryptophan. A detailed examination of these tryptophan-associated accumulations of ribosomes-which we term 'W-bumps'-showed that they were characterized by ribosomal frameshifting events. Consistently, reporter assays combined with proteomic and immunopeptidomic analyses demonstrated the induction of ribosomal frameshifting, and the generation and presentation of aberrant trans-frame peptides at the cell surface after treatment with IFNγ. Priming of naive T cells from healthy donors with aberrant peptides induced peptide-specific T cells. Together, our results suggest that IDO1-mediated depletion of tryptophan, which is induced by IFNγ, has a role in the immune recognition of melanoma cells by contributing to diversification of the peptidome landscape

Anti-tumour immunity induces aberrant peptide presentation in melanoma

Extensive tumour inflammation, which is reflected by high levels of infiltrating T cells and interferon-γ (IFNγ) signalling, improves the response of patients with melanoma to checkpoint immunotherapy1,2. Many tumours, however, escape by activating cellular pathways that lead to immunosuppression. One such mechanism is the production of tryptophan metabolites along the kynurenine pathway by the enzyme indoleamine 2,3-dioxygenase 1 (IDO1), which is induced by IFNγ3-5. However, clinical trials using inhibition of IDO1 in combination with blockade of the PD1 pathway in patients with melanoma did not improve the efficacy of treatment compared to PD1 pathway blockade alone6,7, pointing to an incomplete understanding of the role of IDO1 and the consequent degradation of tryptophan in mRNA translation and cancer progression. Here we used ribosome profiling in melanoma cells to investigate the effects of prolonged IFNγ treatment on mRNA translation. Notably, we observed accumulations of ribosomes downstream of tryptophan codons, along with their expected stalling at the tryptophan codon. This suggested that ribosomes bypass tryptophan codons in the absence of tryptophan. A detailed examination of these tryptophan-associated accumulations of ribosomes-which we term 'W-bumps'-showed that they were characterized by ribosomal frameshifting events. Consistently, reporter assays combined with proteomic and immunopeptidomic analyses demonstrated the induction of ribosomal frameshifting, and the generation and presentation of aberrant trans-frame peptides at the cell surface after treatment with IFNγ. Priming of naive T cells from healthy donors with aberrant peptides induced peptide-specific T cells. Together, our results suggest that IDO1-mediated depletion of tryptophan, which is induced by IFNγ, has a role in the immune recognition of melanoma cells by contributing to diversification of the peptidome landscape