The upcoming 5th edition of the World Health Organization (WHO) Classification of Haematolymphoid Tumours is part of an effort to hierarchically catalogue human cancers arising in various organ ...systems within a single relational database. This paper summarizes the new WHO classification scheme for myeloid and histiocytic/dendritic neoplasms and provides an overview of the principles and rationale underpinning changes from the prior edition. The definition and diagnosis of disease types continues to be based on multiple clinicopathologic parameters, but with refinement of diagnostic criteria and emphasis on therapeutically and/or prognostically actionable biomarkers. While a genetic basis for defining diseases is sought where possible, the classification strives to keep practical worldwide applicability in perspective. The result is an enhanced, contemporary, evidence-based classification of myeloid and histiocytic/dendritic neoplasms, rooted in molecular biology and an organizational structure that permits future scalability as new discoveries continue to inexorably inform future editions.
Abstract
We analyse observations of eight quiescent low-mass X-ray binaries in globular clusters and combine them to determine the neutron star mass–radius curve and the equation of state of dense ...matter. We determine the effect that several uncertainties may have on our results, including uncertainties in the distance, the atmosphere composition, the neutron star maximum mass, the neutron star mass distribution, the possible presence of a hotspot on the neutron star surface, and the prior choice for the equation of state of dense matter. The distance uncertainty is implemented in a new Gaussian blurring method that can be directly applied to the probability distribution over mass and radius. We find that the radius of a 1.4 solar mass neutron star is most likely from 10 to 14 km and that tighter constraints are only possible with stronger assumptions about the nature of the neutron stars, the systematics of the observations, or the nature of dense matter. Strong phase transitions in the equation of state are preferred, and in this case, the radius is likely smaller than 12 km. However, radii larger than 12 km are preferred if the neutron stars have uneven temperature distributions.
Abstract
Recent studies raised concerns about the increasing use of gabapentinoids in different countries. With their potential for misuse and addiction, understanding the global consumption of ...gabapentinoids will offer us a platform to examine the need for any interventional policies. This longitudinal trend study utilised pharmaceutical sales data from 65 countries and regions across the world to evaluate the global trends in gabapentinoid consumption between 2008-2018. The multinational average annual percentage change of gabapentinoid consumption was +17.20%, increased from 4.17 defined daily dose per ten thousand inhabitants per day (DDD/TID) in 2008 to 18.26 DDD/TID in 2018. High-income countries had the highest pooled gabapentinoid consumption rate (39.92 DDD/TID) in 2018, which was more than six times higher than the lower-middle income countries (6.11 DDD/TID). The study shows that despite differences in healthcare system and culture, a consistent increase in gabapentinoid consumption is observed worldwide, with high-income countries remaining the largest consumers.
The phase III, randomized, open-label ENSURE study (NCT01342965) evaluated first-line erlotinib versus gemcitabine/cisplatin (GP) in patients from China, Malaysia and the Philippines with epidermal ...growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC).
Patients ≥18 years old with histologically/cytologically confirmed stage IIIB/IV EGFR mutation-positive NSCLC and Eastern Cooperative Oncology Group performance status 0-2 were randomized 1:1 to receive erlotinib (oral; 150 mg once daily until progression/unacceptable toxicity) or GP G 1250 mg/m(2) i.v. days 1 and 8 (3-weekly cycle); P 75 mg/m(2) i.v. day 1, (3-weekly cycle) for up to four cycles. Primary end point: investigator-assessed progression-free survival (PFS). Other end points include objective response rate (ORR), overall survival (OS), and safety.
A total of 217 patients were randomized: 110 to erlotinib and 107 to GP. Investigator-assessed median PFS was 11.0 months versus 5.5 months, erlotinib versus GP, respectively hazard ratio (HR), 0.34, 95% confidence interval (CI) 0.22-0.51; log-rank P < 0.0001. Independent Review Committee-assessed median PFS was consistent (HR, 0.42). Median OS was 26.3 versus 25.5 months, erlotinib versus GP, respectively (HR, 0.91, 95% CI 0.63-1.31; log-rank P = .607). ORR was 62.7% for erlotinib and 33.6% for GP. Treatment-related serious adverse events (AEs) occurred in 2.7% versus 10.6% of erlotinib and GP patients, respectively. The most common grade ≥3 AEs were rash (6.4%) with erlotinib, and neutropenia (25.0%), leukopenia (14.4%), and anemia (12.5%) with GP.
These analyses demonstrate that first-line erlotinib provides a statistically significant improvement in PFS versus GP in Asian patients with EGFR mutation-positive NSCLC (NCT01342965).
We present the drastic transformation of the X-ray properties of the active galactic nucleus (AGN) 1ES 1927+654, following a changing-look event. After the optical/ultraviolet outburst the power-law ...component, produced in the X-ray corona, disappeared, and the spectrum of 1ES 1927+65 instead became dominated by a blackbody component (kT ∼ 80-120 eV). This implies that the X-ray corona, ubiquitously found in AGNs, was destroyed in the event. Our dense ∼450 days long X-ray monitoring shows that the source is extremely variable in the X-ray band. On long timescales the source varies up to ∼4 dex in ∼100 days, while on short timescales up to ∼2 dex in ∼8 hr. The luminosity of the source is found to first show a strong dip down to , and then a constant increase in luminosity to levels exceeding the pre-outburst level 300 days after the optical event detection, rising up asymptotically to . As the X-ray luminosity of the source increases, the X-ray corona is recreated, and a very steep power-law component (Γ 3) reappears, and dominates the emission for 0.3-2 keV luminosities , ∼300 days after the beginning of the event. We discuss possible origins of this event, and speculate that our observations could be explained by the interaction between the accretion flow and debris from a tidally disrupted star. Our results show that changing-look events can be associated with dramatic and rapid transformations of the innermost regions of accreting supermassive black holes.
Summary
Background Chronic hepatitis B (CHB) infection leads to development of hepatocellular carcinoma (HCC), but the effects of treatment in preventing HCC are not clear.
Aim To study the effects ...of interferon (IFN) or nucleoside/tide analogue (NA) on the risk of developing HCC in CHB patients.
Methods Randomized trials, case–control and cohort studies were retrieved from five electronic databases and international conferences over the past 10 years. Relative risks (RRs) of HCC with or without treatment were studied.
Results Twelve studies (n = 2742) enrolling patients treated by IFN vs. control showed that the risk of HCC after treatment was reduced by 34% (RR: 0.66, 95% CI: 0.48–0.89). Benefit is more significant among patients with early cirrhosis than among those without cirrhosis. Five studies (n = 2289) compared patients treated by NA with control. The risk of HCC after treatment was reduced by 78% (RR: 0.22, 95% CI: 0.10–0.50). HBeAg‐positive patients showed more significantly reduced HCC risk with treatment. Patients without cirrhosis benefited more from NA than those with cirrhosis. Resistance to NA has obviated the benefit of the treatment.
Conclusions IFN or NA treatment significantly reduces risk of HCC. While IFN benefited patients with cirrhosis, NA benefited patients with no cirrhosis and HBeAg‐positive CHB infection.
Of 682 antiretroviral-naïve patients initiating antiretroviral therapy in a prospective, multicenter human immunodeficiency virus type 1 (HIV-1) drug resistance monitoring study involving 8 sites in ...Hong Kong, Malaysia, and Thailand, the prevalence of patients with ⩾ 1 drug resistance mutation was 13.8%. Primary HIV drug resistance is emerging after rapid scaling-up of antiretroviral therapy use in Asia.
A previous study investigated robustness of manual flash (MF) and robust optimized (RO) volumetric modulated arc therapy plans for breast radiotherapy based on five patients in 2020 and indicated ...that the RO was more robust than the MF, although the MF is still current standard practice. The purpose of this study was to compare their plan robustness in terms of dose variation to clinical target volume (CTV) and organs at risk (OARs) based on a larger sample size. This was a retrospective study involving 34 female patients. Their plan robustness was evaluated based on measured volume/dose difference between nominal and worst scenarios (ΔV/ΔD) for each CTV and OARs parameter, with a smaller difference representing greater robustness. Paired sample t-test was used to compare their robustness values. All parameters (except CTV ΔD98%) of the RO approach had smaller ΔV/ΔD values than those of the MF. Also, the RO approach had statistically significantly smaller ΔV/ΔD values (p < 0.001–0.012) for all CTV parameters except the CTV ΔV95% and ΔD98% and heart ΔDmean. This study’s results confirm that the RO approach was more robust than the MF in general. Although both techniques were able to generate clinically acceptable plans for breast radiotherapy, the RO could potentially improve workflow efficiency due to its simpler planning process.
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