Patients with cancer may be at high risk of adverse outcomes from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We analyzed a cohort of patients with cancer and coronavirus ...2019 (COVID-19) reported to the COVID-19 and Cancer Consortium (CCC19) to identify prognostic clinical factors, including laboratory measurements and anticancer therapies.
Patients with active or historical cancer and a laboratory-confirmed SARS-CoV-2 diagnosis recorded between 17 March and 18 November 2020 were included. The primary outcome was COVID-19 severity measured on an ordinal scale (uncomplicated, hospitalized, admitted to intensive care unit, mechanically ventilated, died within 30 days). Multivariable regression models included demographics, cancer status, anticancer therapy and timing, COVID-19-directed therapies, and laboratory measurements (among hospitalized patients).
A total of 4966 patients were included (median age 66 years, 51% female, 50% non-Hispanic white); 2872 (58%) were hospitalized and 695 (14%) died; 61% had cancer that was present, diagnosed, or treated within the year prior to COVID-19 diagnosis. Older age, male sex, obesity, cardiovascular and pulmonary comorbidities, renal disease, diabetes mellitus, non-Hispanic black race, Hispanic ethnicity, worse Eastern Cooperative Oncology Group performance status, recent cytotoxic chemotherapy, and hematologic malignancy were associated with higher COVID-19 severity. Among hospitalized patients, low or high absolute lymphocyte count; high absolute neutrophil count; low platelet count; abnormal creatinine; troponin; lactate dehydrogenase; and C-reactive protein were associated with higher COVID-19 severity. Patients diagnosed early in the COVID-19 pandemic (January-April 2020) had worse outcomes than those diagnosed later. Specific anticancer therapies (e.g. R-CHOP, platinum combined with etoposide, and DNA methyltransferase inhibitors) were associated with high 30-day all-cause mortality.
Clinical factors (e.g. older age, hematological malignancy, recent chemotherapy) and laboratory measurements were associated with poor outcomes among patients with cancer and COVID-19. Although further studies are needed, caution may be required in utilizing particular anticancer therapies.
NCT04354701
•Among 4966 patients with COVID-19 and a history of or active cancer, 58% were hospitalized and 14% died within 30 days.•Older age, male sex, obesity, comorbidities, non-Hispanic black race, and Hispanic ethnicity were associated with higher COVID-19 severity.•Worse performance status, hematologic malignancy, and recent cytotoxic chemotherapy were associated with more severe COVID-19.•Low or high absolute lymphocyte count, high absolute neutrophil count, low platelets, abnormal creatinine, troponin, lactate dehydrogenase, or C-reactive protein were associated with more severe COVID-19.•Specific anticancer therapies were associated with high 30-day all-cause mortality.
Active galactic nuclei, which are powered by long-term accretion onto central supermassive black holes, produce relativistic jets with lifetimes of at least one million years, and the observation of ...the birth of such a jet is therefore unlikely. Transient accretion onto a supermassive black hole, for example through the tidal disruption of a stray star, thus offers a rare opportunity to study the birth of a relativistic jet. On 25 March 2011, an unusual transient source (Swift J164449.3+573451) was found, potentially representing such an accretion event. Here we report observations spanning centimetre to millimetre wavelengths and covering the first month of evolution of a luminous radio transient associated with Swift J164449.3+573451. The radio transient coincides with the nucleus of an inactive galaxy. We conclude that we are seeing a newly formed relativistic outflow, launched by transient accretion onto a million-solar-mass black hole. A relativistic outflow is not predicted in this situation, but we show that the tidal disruption of a star naturally explains the observed high-energy properties and radio luminosity and the inferred rate of such events. The weaker beaming in the radio-frequency spectrum relative to γ-rays or X-rays suggests that radio searches may uncover similar events out to redshifts of z ≈ 6.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Anti-programmed cell death protein 1 (PD-1) antibodies (PD1) prolong recurrence-free survival in high-risk resected melanoma; however, approximately 25%–30% of patients recur within 1 year. This ...study describes the pattern of recurrence, management and outcomes of patients who recur with adjuvant PD1 therapy.
Consecutive patients from 16 centres who recurred having received adjuvant PD1 therapy for resected stage III/IV melanoma were studied. Recurrence characteristics, management and outcomes were examined; patients with mucosal melanoma were analysed separately.
Melanoma recurrence occurred in 147 (17%) of ∼850 patients treated with adjuvant PD1. In those with cutaneous melanoma (n = 136), median time to recurrence was 4.6 months (range 0.3–35.7); 104 (76%) recurred during (ON) adjuvant PD1 after a median 3.2 months and 32 (24%) following (OFF) treatment cessation after a median 12.5 months, including in 21 (15%) who ceased early for toxicity. Fifty-nine (43%) recurred with locoregional disease only and 77 (57%) with distant disease. Of those who recurred locally, 22/59 (37%) subsequently recurred distantly. Eighty-nine (65%) patients received systemic therapy after recurrence. Of those who recurred ON adjuvant PD1, none (0/6) responded to PD1 alone; 8/33 assessable patients (24%) responded to ipilimumab (alone or in combination with PD1) and 18/23 (78%) responded to BRAF/MEK inhibitors. Of those who recurred OFF adjuvant PD1, two out of five (40%) responded to PD1 monotherapy, two out of five (40%) responded to ipilimumab-based therapy and 9/10 (90%) responded to BRAF/MEK inhibitors.
Most patients who recur early despite adjuvant PD1 develop distant metastases. In those who recur ON adjuvant PD1, there is minimal activity of further PD1 monotherapy, but ipilimumab (alone or in combination with PD1) and BRAF/MEK inhibitors have clinical utility. Retreatment with PD1 may have activity in select patients who recur OFF PD1.
•Melanoma recurrence occurred in 147 (17%) of 850 patients, after a median 4.6 months after starting adjuvant PD1.•At initial recurrence, 57% had distant metastases, mostly detected on imaging while asymptomatic.•Some 38% of patients with initial local recurrence then recurred distantly within short follow-up (median 8.3 months).•PD1 monotherapy was not active in those who recurred ON adjuvant PD1, but had activity in those who recurred OFF adjuvant PD1.•BRAF/MEK inhibitors and ipilimumab (alone or in combination with PD1) had the highest activity in this setting.
The repair of focal cartilage defects remains one of the foremost issues in the field of orthopaedics. Chondral defects may arise from a variety of joint pathologies and left untreated, will likely ...progress to osteoarthritis. Current repair techniques, such as microfracture, result in short-term clinical improvements but have poor long-term outcomes. Emerging scaffold-based repair strategies have reported superior outcomes compared to microfracture and motivate the development of new biomaterials for this purpose. In this study, unique composite implants consisting of a base porous reinforcing component (woven poly(ε-caprolactone)) infiltrated with 1 of 2 hydrogels (self-assembling peptide or thermo-gelling hyaluronan) or bone marrow aspirate were evaluated. The objective was to evaluate cartilage repair with composite scaffold treatment compared to the current standard of care (microfracture) in a translationally relevant large animal model, the Yucatan minipig. While many cartilage-repair studies have shown some success in vivo, most are short term and not clinically relevant. Informed by promising 6-week findings, a 12-month study was carried out and those results are presented here. To aid in comparisons across platforms, several structural and functionally relevant outcome measures were performed. Despite positive early findings, the long-term results indicated less than optimal structural and mechanical results with respect to cartilage repair, with all treatment groups performing worse than the standard of care. This study is important in that it brings much needed attention to the importance of performing translationally relevant long-term studies in an appropriate animal model when developing new clinical cartilage repair approaches.
The discovery of topological insulators, materials with bulk band gaps and protected cross-gap surface states in compounds such as Bi2Se3, has generated much interest in identifying topological ...surface states (TSSs) in other classes of materials. In particular, recent theoretical calculations suggest that TSSs may be found in half-Heusler ternary compounds. If experimentally realizable, this would provide a materials platform for entirely new heterostructure spintronic devices that make use of the structurally identical but electronically varied nature of Heusler compounds. Here we show the presence of a TSS in epitaxially grown thin films of the half-Heusler compound PtLuSb. Spin- and angle-resolved photoemission spectroscopy, complemented by theoretical calculations, reveals a surface state with linear dispersion and a helical tangential spin texture consistent with previous predictions. This experimental verification of topological behaviour is a significant step forward in establishing half-Heusler compounds as a viable material system for future spintronic devices.
The chemical identification of mass spectrometric signals in metabolomic applications is important to provide conversion of analytical data to biological knowledge about metabolic pathways. The ...complexity of electrospray mass spectrometric data acquired from a range of samples (serum, urine, yeast intracellular extracts, yeast metabolic footprints, placental tissue metabolic footprints) has been investigated and has defined the frequency of different ion types routinely detected. Although some ion types were expected (protonated and deprotonated peaks, isotope peaks, multiply charged peaks) others were not expected (sodium formate adduct ions). In parallel, the Manchester Metabolomics Database (MMD) has been constructed with data from genome scale metabolic reconstructions, HMDB, KEGG, Lipid Maps, BioCyc and DrugBank to provide knowledge on 42,687 endogenous and exogenous metabolite species. The combination of accurate mass data for a large collection of metabolites, theoretical isotope abundance data and knowledge of the different ion types detected provided a greater number of electrospray mass spectrometric signals which were putatively identified and with greater confidence in the samples studied. To provide definitive identification metabolite-specific mass spectral libraries for UPLC-MS and GC-MS have been constructed for 1,065 commercially available authentic standards. The MMD data are available at http://dbkgroup.org/MMD/.
The objectives of this tutorial are as follows: 1) to help students and researchers develop a basic understanding of how pulsed-power systems are used to create high-energy-density (HED) matter; 2) ...to develop a basic understanding of a new, compact, and efficient pulsed-power technology called linear transformer drivers (LTDs); 3) to understand why LTDs are an attractive technology for driving HED physics (HEDP) experiments; 4) to contrast LTDs with the more traditional Marx-generator/pulse-forming-line approach to driving HEDP experiments; and 5) to briefly review the history of LTD technology as well as some of the LTD-driven HEDP research presently underway at universities and research laboratories across the globe. This invited tutorial is part of the Mini-Course on Charged Particle Beams and High-Powered Pulsed Sources, held in conjunction with the 44th International Conference on Plasma Science in May of 2017.
Marrow stimulation, including subchondral drilling and microfracture, is the most commonly performed cartilage repair strategy, whereby the subchondral bone plate is perforated to release ...marrow-derived cells into a cartilage defect to initiate repair. Novel scaffolds and therapeutics are being designed to enhance and extend the positive short-term outcomes of this marrow stimulation. However, the translation of these newer treatments is hindered by bony abnormalities, including bone resorption, intralesional osteophytes, and bone cysts, that can arise after marrow stimulation. In this study, three different marrow stimulation approaches - microfracture, subchondral drilling and needle-puncture - were evaluated in a translationally relevant large-animal model, the Yucatan minipig. The objective of the study was to determine which method of marrow access (malleted awl, drilled Kirschner wire or spring-loaded needle) best preserved the underlying subchondral bone. Fluorochrome labels were injected at the time of surgery and 2 weeks post-surgery to capture bone remodelling over the first 4 weeks. Comprehensive outcome measures included cartilage indentation testing, histological grading, microcomputed tomography and fluorochrome imaging. Findings indicated that needle-puncture devices best preserved the underlying subchondral bone relative to other marrow access approaches. This may relate to the degree of bony compaction occurring with marrow access, as the Kirschner wire approach, which consolidated bone the most, induced the most significant bone damage with marrow stimulation. This study provided basic scientific evidence in support of updated marrow stimulation techniques for preclinical and clinical practice.
Selective laser melting (SLM) was used to prepare notched high‐cycle fatigue test specimens made from nickel‐based superalloy Inconel 718. Samples were designed to have 1 of 3 different notch ...geometries, including V notches with Kt of 2.2 or 3.1, a U notch with Kt of 2.0, and were printed in either vertical or horizontal orientations. Samples were tested with as‐printed dimensions and surfaces after heat treatment, but a separate set of SLM samples were printed as plates and machined to final dimensions comporting to the V‐notch specimen with Kt = 3.1. High‐cycle fatigue testing showed that machined SLM specimens behaved similar to wrought Inconel 718 plate specimens, but testing with as‐produced surfaces led to a decrease in fatigue life. The explanation for this difference is based on approximations of linear elastic fracture mechanics solutions for short cracks emanating from notch roots, with intrinsic surface features of SLM materials serving as the cracks. Analysis of the actual notch geometries after SLM fabrication indicates that stress intensity in the presence of these features plays a prominent role in determining number of cycles before fatigue crack initiation and propagation occurs.
Human immunoglobulin prepared for intravenous administration (IGIV) has a number of important uses in the treatment of disease. Some of these are in diseases for which acceptable treatment ...alternatives do not exist. In this review we have evaluated the evidence underlying a wide variety of IGIV uses and make specific recommendations on the basis of these data. Given the potential risks and inherent scarcity of IGIV, careful consideration of the indications for and administration of IGIV is warranted.
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