303 research outputs found
An epidemiological evaluation of pediatric long bone fractures - a retrospective cohort study of 2716 patients from two Swiss tertiary pediatric hospitals.
BACKGROUND: Children and adolescents are at high risk of sustaining fractures during growth. Therefore, epidemiological assessment is crucial for fracture prevention. The AO Comprehensive Injury Automatic Classifier (AO COIAC) was used to evaluate epidemiological data of pediatric long bone fractures in a large cohort.
METHODS: Data from children and adolescents with long bone fractures sustained between 2009 and 2011, treated at either of two tertiary pediatric surgery hospitals in Switzerland, were retrospectively collected. Fractures were classified according to the AO Pediatric Comprehensive Classification of Long Bone Fractures (PCCF).
RESULTS: For a total of 2716 patients (60% boys), 2807 accidents with 2840 long bone fractures (59% radius/ulna; 21% humerus; 15% tibia/fibula; 5% femur) were documented. Children's mean age (SD) was 8.2 (4.0) years (6% infants; 26% preschool children; 40% school children; 28% adolescents). Adolescent boys sustained more fractures than girls (p < 0.001). The leading cause of fractures was falls (27%), followed by accidents occurring during leisure activities (25%), at home (14%), on playgrounds (11%), and traffic (11%) and school accidents (8%). There was boy predominance for all accident types except for playground and at home accidents. The distribution of accident types differed according to age classes (p < 0.001). Twenty-six percent of patients were classed as overweight or obese - higher than data published by the WHO for the corresponding ages - with a higher proportion of overweight and obese boys than in the Swiss population (p < 0.0001).
CONCLUSION: Overall, differences in the fracture distribution were sex and age related. Overweight and obese patients seemed to be at increased risk of sustaining fractures. Our data give valuable input into future development of prevention strategies. The AO PCCF proved to be useful in epidemiological reporting and analysis of pediatric long bone fractures
Pre-treatment comorbidities, C-reactive protein and eosinophil count, and immune-related adverse events as predictors of survival with checkpoint inhibition for multiple tumour entities
BACKGROUND
The development of immune-related adverse events (irAEs) may be associated with clinical efficacy of checkpoint inhibitors (CPIs) in patients with cancer. We therefore investigated the effect of irAEs and pre-treatment parameters on outcome in a large, real-life patient cohort.
METHODS
We performed a single-centre, retrospective, observational study including patients who received CPIs from 2011 to 2018 and followed until 2021. The primary outcome was overall survival, and the secondary outcome was the development of irAEs.
RESULTS
In total, 229 patients with different tumour entities (41% non-small cell lung cancer [NSCLC], 29% melanoma) received a total of 282 CPI treatment courses (ipilimumab, nivolumab, pembrolizumab or atezolizumab). Thirty-four percent of patients developed irAEs (of these 17% had CTCAE Grade ≥3). Factors independently associated with mortality were pre-treatment CRP ≥10 mg/L (hazard ratio [HR] 2.064, p = 0.0003), comorbidity measured by Charlson comorbidity index (HR 1.149, p = 0.014) and irAEs (HR 0.644, p = 0.036) (age-adjusted, n = 216). Baseline eosinophil count ≤0.2 × 10 /L was a further independent predictor of mortality (age-, CRP-, CCI- and irAE-adjusted HR = 2.252, p = 0.002, n = 166). Anti-CTLA-4 use (p < 0.001), and pre-treatment CRP <10 mg/L were independently associated with irAE occurrence (p = 0.037).
CONCLUSIONS
We found an independent association between irAE occurrence and improved overall survival in a real-life cohort spanning multiple tumour entities and treatment regimens. Pre-treatment comorbidities, CRP and eosinophil count represent potential markers for predicting treatment response
A Study of Cosmic Ray Secondaries Induced by the Mir Space Station Using AMS-01
The Alpha Magnetic Spectrometer (AMS-02) is a high energy particle physics
experiment that will study cosmic rays in the to range and will be installed on the International Space Station
(ISS) for at least 3 years. A first version of AMS-02, AMS-01, flew aboard the
space shuttle \emph{Discovery} from June 2 to June 12, 1998, and collected
cosmic ray triggers. Part of the \emph{Mir} space station was within the
AMS-01 field of view during the four day \emph{Mir} docking phase of this
flight. We have reconstructed an image of this part of the \emph{Mir} space
station using secondary and emissions from primary cosmic rays
interacting with \emph{Mir}. This is the first time this reconstruction was
performed in AMS-01, and it is important for understanding potential
backgrounds during the 3 year AMS-02 mission.Comment: To be submitted to NIM B Added material requested by referee. Minor
stylistic and grammer change
Prognostic significance of lymphangiogenesis in pharyngolaryngeal carcinoma patients
<p>Abstract</p> <p>Background</p> <p>Lymphatic vessel spread is considered a major route for head and neck squamous cell carcinoma metastasis. Formation of new lymphatic vessels could facilitate the process, raising the malignant potential of these tumours. Recent identification of lymphatic markers allows the study of the lymphangiogenesis phenomenon. We searched for molecular events involved in the lymphangiogenic process that could have prognostic value in laryngeal/pharyngeal carcinoma patients.</p> <p>Methods</p> <p>104 paraffin-embedded pharyngeal/laryngeal tumour samples were studied. Immunohistochemical analysis of podoplanin and double immunofluorescence analysis of Ki-67 and D2-40 were performed. Lymph vessel density (inside the tumour mass, at its periphery or considered as a whole) and the presence of tumour emboli inside lymphatics were recorded. The proliferative state of endothelial lymphatic cells was evaluated.</p> <p>Results</p> <p>Lymphatic vessels were detected inside the tumour mass (75%) and in the surrounding tissue (80%); some of them in a proliferative state. Tumour emboli were detected in a high proportion of the cases (45%). Lymphatic vessel density was higher in the pharyngeal cases (p = 0.0029), in greater size (p = 0.039), more advanced stage primary tumours (p = 0.006) and in carcinomas of patients with affected nodes (p = 0.019). The presence of tumour emboli and a high global vessel density were indicators of poor prognosis (recorded as death from tumour) in the laryngeal group (p = 0.015 and p = 0.027, respectively), but notably not in the pharyngeal one. Interestingly, high global vessel density showed a negative prognostic value among pathologically staged N0 laryngeal carcinomas (p = 0.03).</p> <p>Conclusions</p> <p>The lymphangiogenic process correlated with aggressive tumour features (pN category, tumour size, tumour stage), but might play different roles in tumours arising from different anatomic sites.</p> <p>Our results suggest that detection of tumour emboli and assessment of global vessel density using the D2-40 antibody, may be useful in the clinical practice, as predictors of reduced survival among pN0 laryngeal carcinoma patients.</p
A multicenter phase II trial of anti-EGFR-immunoliposomes loaded with doxorubicin in patients with advanced triple negative breast cancer
Advanced triple negative breast cancer (TNBC) is an aggressive, but initially chemo-sensitive disease. The prognosis is poor and more than three quarters of patients experience progression 12 months after the initiation of conventional first-line chemotherapy. Approximately two thirds of TNBC express epidermal growth factor receptor 1 (EGFR). We have developed an anti-EGFR targeted nanocontainer drug by inserting anti-EGFR antibody fragments into the membrane of pegylated liposomes (anti-EGFR-ILs-dox). The payload consists of doxorubicin, a standard drug for TNBC. In a first-in-human phase I trial in 26 patients with various advanced solid malignancies, anti-EGFR-ILs-dox has shown little toxicity and encouraging efficacy. In this single-arm phase II trial, we assessed the efficacy of anti-EGFR-ILs-dox as first-line therapy in patients with advanced, EGFR + TNBC. The primary endpoint was progression-free survival at 12 months (PFS12m). Secondary endpoints included overall response rate (ORR), duration of response (DOR), time to progression (TTP), overall survival (OS) and adverse events (AEs). 48 patients received anti-EGFR-ILs-dox 50 mg/m iv, on day one of a 28 days-cycle until progression. The Kaplan-Meier estimate for PFS12m was 13% (one-sided 90% CI 7%, 95% CI [5%, 25%]), median PFS was 3.5 months (95% CI 1.9, 5.4). The trial has not reached its primary endpoint. There were no new toxicity signals. Based on these results, anti-EGFR-ILs-dox should not be further developed for TNBC. It remains an open question whether anti-EGFR-ILs-dox would offer more opportunities in other EGFR-expressing malignancies, where targeting this receptor has already shown anticancer effects.Trial registration: This trial was registered at clinicaltrials.gov: NCT02833766. Registered 14/07/2016
Protons in near earth orbit
The proton spectrum in the kinetic energy range 0.1 to 200 GeV was measured
by the Alpha Magnetic Spectrometer (AMS) during space shuttle flight STS-91 at
an altitude of 380 km. Above the geomagnetic cutoff the observed spectrum is
parameterized by a power law. Below the geomagnetic cutoff a substantial second
spectrum was observed concentrated at equatorial latitudes with a flux ~ 70
m^-2 sec^-1 sr^-1. Most of these second spectrum protons follow a complicated
trajectory and originate from a restricted geographic region.Comment: 19 pages, Latex, 7 .eps figure
Isotopic Composition of Light Nuclei in Cosmic Rays: Results from AMS-01
The variety of isotopes in cosmic rays allows us to study different aspects
of the processes that cosmic rays undergo between the time they are produced
and the time of their arrival in the heliosphere. In this paper we present
measurements of the isotopic ratios 2H/4He, 3He/4He, 6Li/7Li, 7Be/(9Be+10Be)
and 10B/11B in the range 0.2-1.4 GeV of kinetic energy per nucleon. The
measurements are based on the data collected by the Alpha Magnetic
Spectrometer, AMS-01, during the STS-91 flight in 1998 June.Comment: To appear in ApJ. 12 pages, 11 figures, 6 table
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