Multidisciplinary approach to treatment with immune checkpoint inhibitors in patients with HIV, tuberculosis, or underlying autoimmune diseases

Autoimmune diseases; Checkpoint inhibition therapy; Human immunodeficiency virusEnfermedades autoinmunes; Terapia de inhibición de puntos de control; Virus de inmunodeficiencia humanaMalalties autoimmunes; Teràpia d'inhibició del punt de control; Virus de la immunodeficiència humanaWe reviewed the available information on the use of immune checkpoint inhibitors (ICIs) in populations with special conditions, namely, patients with HIV, tuberculosis, or underlying autoimmune disease. Available data show that treatment with ICIs is safe in patients with HIV; it is advisable, however, that these patients receive adequate antiretroviral therapy and have an undetectable viral load before ICIs are initiated. Tuberculosis reactivation has been reported with the use of ICIs, possibly due to immune dysregulation. Tuberculosis has also been associated with the use of immunosuppressors to treat immune-related adverse events (irAEs). Active tuberculosis must be ruled out in patients with symptoms or signs, and selected patients may benefit from screening for latent tuberculosis infection, although more data are required. Limited data exist regarding the safety of ICIs in patients with cancer and autoimmune disease. Data from observational studies suggest that up to 29% of patients with a preexisting autoimmune disease treated with an ICI present with an autoimmune disease flare, and 30% present with a de novo irAE of any type. The frequency of flares appears to differ according to the type of ICI received, with higher rates associated with PD-1/PD-L1 inhibitors. The most common autoimmune diseases for which patients reported flares with ICI therapy are rheumatoid arthritis, other inflammatory arthritis, and psoriasis. Most studies have reported flares or de novo irAEs associated with ICIs that were mild to moderate, with low rates of discontinuation and no deaths due to flares. Therefore, the use of ICIs in these patients is possible, but careful monitoring is required.ML-O's work is supported by the National Cancer Institute (#CA237619)

A Systematic Review of Clinical Practice Guidelines for Cancer Screening in Patients with Autoimmune Diseases

https://openworks.mdanderson.org/sumexp23/1110/thumbnail.jp

Comparative evaluation of three semi-quantitative radiographic grading techniques for knee osteoarthritis in terms of validity and reproducibility in 1759 X-rays: report of the OARSI–OMERACT task force

OBJECTIVE: The objective of this work was to compare the measurement properties of three categorical X-ray scoring methods of knee osteoarthritis (OA), both on semiflexed and extended views. METHODS: In data obtained from trials and cohorts, X-rays were graded using Kellgren and Lawrence (KL), the OA Research Society International (OARSI) joint space narrowing score, and measurement of joint space width (JSW). JSW was analyzed as a categorical variable. Construct validity was assessed through logistic regression between X-ray stages and Western Ontario and McMaster Universities OA Index. Inter-observer reliability was assessed in 50 subjects for extended views by weighted kappa. Intra-observer reliability and sensitivity to change were assessed separately for extended and semiflexed views in 50 patients who had both views performed, over a 30-month interval, by weighted kappa and standardized response mean (SRM). RESULTS: Extended views were available from three trials and two cohorts (1759 X-rays), including one trial in which both extended and semiflexed views (antero-posterior) were obtained. Correlation with clinical parameters was low for the three scoring methods, except for the single community-based cohort. Inter-rater reliability was higher for categorical JSW in extended views (kappa, 0.86 vs 0.56 and 0.48 for KL and OARSI, respectively). Intra-rater reliability was higher for categorical JSW, both in extended views (0.83 vs 0.61 and 0.71) and in semiflexed views (0.89 vs 0.50 and 0.67). Sensitivity to change was also higher for categorical JSW, particularly in semiflexed views (SRM, 0.49 vs 0.22 and 0.34). CONCLUSION: These results indicate categorical JSW, in particular on semiflexed views, may be the preferred method to evaluate structural severity in knee OA clinical trials

Patient Decision Aids for Colorectal Cancer Screening

Decision aids (DAs) prepare patients to make decisions about healthcare options consistent with their preferences. Helping patients choose among available options for colorectal cancer (CRC) screening is important because rates are lower than screening for other cancers. This systematic review describes studies evaluating patient DAs for CRC screening in average-risk adults and their impact on knowledge, screening intentions, and uptake

Physician Views On the Provision of information On Immune Checkpoint inhibitor therapy to Patients With Cancer and Pre-Existing autoimmune Disease: a Qualitative Study

Immune checkpoint inhibitors (ICIs) have improved cancer outcomes but can cause severe immune-related adverse events (irAEs) and flares of autoimmune conditions in cancer patients with pre-existing autoimmune disease. The objective of this study was to identify the information physicians perceived as most useful for these patients when discussing treatment initiation with ICIs. Twenty physicians at a cancer institution with experience in the treatment of irAEs were interviewed. Qualitative thematic analysis was performed to organize and interpret data. The physicians were 11 medical oncologists and 9 non-oncology specialists. The following themes were identified: (1) current methods used by physicians to provide information to patients and delivery options; (2) factors to make decisions about whether or not to start ICIs in patients who have cancer and pre-existing autoimmune conditions; (3) learning points for patients to understand; (4) preferences for the delivery of ICI information; and (5) barriers to the implementation of ICI information in clinics. Regarding points to discuss with patients, physicians agreed that the benefits of ICIs, the probability of irAEs, and risks of underlying autoimmune condition flares with the use of ICIs were most important. Non-oncologists were additionally concerned about how ICIs affect the autoimmune disease (e.g., impact on disease activity, need for changes in medications for the autoimmune disease, and monitoring of autoimmune conditions)

Role of dense shelf water in the development of Antarctic submarine canyon morphology

Increased ocean heat supply to the Antarctic continental shelves is projected to cause accelerated ice sheet loss and contribute significantly to global sea-level rise over coming decades. Changes in temperature or salinity of dense shelf waters around Antarctica, resulting from increased glacial meltwater input, have the potential to significantly impact the location and structure of the global Meridional Overturning Circulation, with seabed irregularities such as submarine canyons, driving these flows toward the abyss. Submarine canyons also influence the location of intruding warm water currents by acting as preferential routes for rising Circumpolar Deep Water. These global changes have implications for large-scale effects to atmospheric and oceanic circulation. The ability for numerical modellers to predict these future behaviours is dependent upon our ability to understand both modern and past oceanic, sedimentological and glaciological processes. This knowledge allows ocean models to better predict the flux and pathways of Circumpolar Deep Water delivery to the shelf, and consequently to ice shelf cavities where melt is concentrated. Here we seek to understand how dense shelf water and other continental slope processes influence submarine canyon morphology by analysing newly collected geophysical and oceanographic data from a region of significant and prolonged dense shelf water export, the Hillary Canyon in the Ross Sea. We find that cascading flows of dense shelf water do not contribute to significant gully incision at the shelf edge during interglacial periods, however, are strong enough to prevent gully infilling and contribute to canyon-levee aggradation down-slope. We find buried paleo-gullies beneath gullies incising the modern seafloor. Paleo-gullies occur as single gullies and in complexes indicating that gully activity was continuous over multiple glacial cycles and formed an important role in the development of the shelf edge and upper slope. Glacial cycles likely drive large-scale shifts in canyon head processes with periods of intense seafloor erosion and significant gully incision likely occurring when ice grounded near to the shelf edge, during glacial and deglacial periods, when sediment-laden subglacial meltwater was released at the shelf edge. We put slope morphology observed at the Hillary Canyon head into global perspective to show that cascading flows of dense shelf water do not exert consistent patterns of erosion on high-latitude continental margins

Measurements of Higgs boson production and couplings in diboson final states with the ATLAS detector at the LHC

Measurements are presented of production properties and couplings of the recently discovered Higgs boson using the decays into boson pairs, H →γ γ, H → Z Z∗ →4l and H →W W∗ →lνlν. The results are based on the complete pp collision data sample recorded by the ATLAS experiment at the CERN Large Hadron Collider at centre-of-mass energies of √s = 7 TeV and √s = 8 TeV, corresponding to an integrated luminosity of about 25 fb−1. Evidence for Higgs boson production through vector-boson fusion is reported. Results of combined fits probing Higgs boson couplings to fermions and bosons, as well as anomalous contributions to loop-induced production and decay modes, are presented. All measurements are consistent with expectations for the Standard Model Higgs boson

Standalone vertex finding in the ATLAS muon spectrometer

A dedicated reconstruction algorithm to find decay vertices in the ATLAS muon spectrometer is presented. The algorithm searches the region just upstream of or inside the muon spectrometer volume for multi-particle vertices that originate from the decay of particles with long decay paths. The performance of the algorithm is evaluated using both a sample of simulated Higgs boson events, in which the Higgs boson decays to long-lived neutral particles that in turn decay to bbar b final states, and pp collision data at √s = 7 TeV collected with the ATLAS detector at the LHC during 2011

Measurement of the top quark-pair production cross section with ATLAS in pp collisions at \sqrt{s}=7\TeV

A measurement of the production cross-section for top quark pairs(\ttbar) in $pp$ collisions at \sqrt{s}=7 \TeV is presented using data recorded with the ATLAS detector at the Large Hadron Collider. Events are selected in two different topologies: single lepton (electron $e$ or muon $\mu$) with large missing transverse energy and at least four jets, and dilepton ($ee$, $\mu\mu$ or $e\mu$) with large missing transverse energy and at least two jets. In a data sample of 2.9 pb-1, 37 candidate events are observed in the single-lepton topology and 9 events in the dilepton topology. The corresponding expected backgrounds from non-\ttbar Standard Model processes are estimated using data-driven methods and determined to be $12.2 \pm 3.9$ events and $2.5 \pm 0.6$ events, respectively. The kinematic properties of the selected events are consistent with SM \ttbar production. The inclusive top quark pair production cross-section is measured to be \sigmattbar=145 \pm 31 ^{+42}_{-27} pb where the first uncertainty is statistical and the second systematic. The measurement agrees with perturbative QCD calculations.Comment: 30 pages plus author list (50 pages total), 9 figures, 11 tables, CERN-PH number and final journal adde

Measurement of the top quark pair cross section with ATLAS in pp collisions at √s=7 TeV using final states with an electron or a muon and a hadronically decaying τ lepton

A measurement of the cross section of top quark pair production in proton-proton collisions recorded with the ATLAS detector at the Large Hadron Collider at a centre-of-mass energy of 7 TeV is reported. The data sample used corresponds to an integrated luminosity of 2.05 fb -1. Events with an isolated electron or muon and a τ lepton decaying hadronically are used. In addition, a large missing transverse momentum and two or more energetic jets are required. At least one of the jets must be identified as originating from a b quark. The measured cross section, σtt-=186±13(stat.)±20(syst.)±7(lumi.) pb, is in good agreement with the Standard Model prediction