An algorithm is presented, that provides a fast and robust reconstruction of neutrino induced upward-going muons and a discrimination of these events from downward-going atmospheric muon background ...in data collected by the ANTARES neutrino telescope. The algorithm consists of a hit merging and hit selection procedure followed by fitting steps for a track hypothesis and a point-like light source. It is particularly well-suited for real time applications such as online monitoring and fast triggering of optical follow-up observations for multi-messenger studies. The performance of the algorithm is evaluated with Monte Carlo simulations and various distributions are compared with that obtained in ANTARES data.
Abstract
Objective
To evaluate rates of major bleeding (mBleed) associated with anticoagulant treatments in patients (pts) with age ≥75 years (y), referred to hospital in northwest Tuscany.
Methods
...We analysed 4-y survey; 302,687 visits; catchment area 197,722 inhabitants, of whom 15,267 on Warfarin (W) and 10,397 on direct oral anticoagulants (DOACs). DOACs were available in the catchment area since 4 y (dabigatran and rivaroxaban), 3 y (apixaban), and 2 y (edoxaban). Overall, 3,373 pts received dabigatran, 4,046 rivaroxaban, 2,141 apixaban, and 839 edoxaban. Pts with hemorrhage were submitted to propensity score matching for mBleed and stratified according to age ≥75 y, and W or DOACs. Primary endpoint was one-month death in pts with age ≥75 y.
Results
Out of 1,919 mBleed enrolled, those of pts aged ≥75 y were 1,127 (59%) versus (vs) 792 (41%) aged <75 y, with 77 (4.0%) one-month death vs 20 (1.0%), respectively; p<0.0001.
Patients on W showed higher rate of mBleed (n=175; 9.1%) compared to DOACs (n=53; 2.8%); p<0.0001. One-month death accounted for 14 (0.7%) vs 1 (0.1%), respectively; p=0.0019. Pts aged ≥75 years were more likely to show female gender and comorbidities including atrial fibrillation; p<0.01. Among DOACs, edoxaban presented the lowest absolute rate of hospital admission for mBleed and dabigatran the highest, although without statistical differences within DOACs (p=0.6454). Interestingly, in the subset of pts aged ≥75 y, within DOACs, we found no statistical difference in one-month mortality, although edoxaban showed one death due to brain mBleed; conversely, we found statistical significance in rate of mBleed. Indeed, edoxaban vs dabigatran showed p=0.0008, edoxaban vs apixaban p=0.0242, edoxaban vs rivaroxaban p=0.0058, apixaban vs rivaroxaban p=0.7093, apixaban vs dabigatran p=0.2279, rivaroxaban vs dabigatran p=0.5087.
Warfarin or DOACs and outcomes
Major Bleeding (pts ≥75 y)
p value versus pts <75 y
p value within group
One-month death (pts ≥75 y)
p value versus pts <75 y
p value within group
n=1,127
n=77
Warfarin
175 (9.1%)
0.0001
<0.0001
14 (1.2%)
0.514
0.0019
DOACS
53 (2.8%)
0.0001
1 (0.1%)
0.256
Dabigatran
21 (1.1%)
0.026
0.0088
0 (0%)
0.391
0.8012
Rivaroxaban
16 (0.8%)
0.121
0 (0%)
0.619
Apixaban
13 (0.7%)
0.033
0 (0%)
1
Edoxaban
3 (0.2%)
0.647
1 (0.1%)
0.191
Patients: pts; direct oral anticoagulants: DOACs; p value Yates' correction: p value.
Patients with age >75 years and bleeding
Conclusion
In pts with age ≥75 y, rate of mBleed and short-term mortality were significantly higher than in pts aged <75 y In those pts, DOACs showed significantly lower rate of mBleed, and short-term death. Within DOACs, edoxaban was more likely to show lower rate of mBleed.
(ProQuest: ... denotes formulae and/or non-USASCII text omitted; see image).Atmospheric neutrinos are produced during cascades initiated by the interaction of primary cosmic rays with air nuclei. In ...this paper, a measurement of the atmospheric ... energy spectrum in the energy range 0.1-200 TeV is presented, using data collected by the ANTARES underwater neutrino telescope from 2008 to 2011. Overall, the measured flux is 25 % higher than predicted by the conventional neutrino flux, and compatible with the measurements reported in ice. The flux is compatible with a single power-law dependence with spectral index gamma sub(meas)=3.58 plus or minus 0.12. With the present statistics the contribution of prompt neutrinos cannot be established.
Background
Weight loss is a milestone in the prevention of chronic diseases associated with high morbility and mortality in industrialized countries. Very-low calorie ketogenic diets (VLCKDs) are ...increasingly used in clinical practice for weight loss and management of obesity-related comorbidities. Despite evidence on the clinical benefits of VLCKDs is rapidly emerging, some concern still exists about their potential risks and their use in the long-term, due to paucity of clinical studies. Notably, there is an important lack of guidelines on this topic, and the use and implementation of VLCKDs occurs vastly in the absence of clear evidence-based indications.
Purpose
We describe here the biochemistry, benefits and risks of VLCKDs, and provide recommendations on the correct use of this therapeutic approach for weight loss and management of metabolic diseases at different stages of life.
Objective
Pasireotide LAR (PAS-LAR) was released in Italy in 2017 to treat acromegaly patients resistant to SRLs (Somatostatin Receptors Ligands). The long-term follow-up data of PAS-LAR therapy in ...Italy are limited. This study aimed to evaluate the efficacy and safety of PAS-LAR in acromegaly.
Design
Patients with acromegaly in PAS-LAR treatment were enrolled in three tertiary Italian endocrinological centers and evaluated by a retrospective observational real-life multicentre study.
Methods
Patients have been studied before (baseline) and 1, 6, 12, 24 and > 36 months after PAS-LAR start. Clinical, biochemical, and pituitary magnetic resonance data were collected, along with information on adverse events. Acromegaly disease activity was classified according to the IGF-1 index (normal value < 1.0).
Results
Fifty patients (female 23) were enrolled. PAS-LAR treatment (mean follow-up 24 ± 16 months) significantly decreased IGF-1 levels (IGF-1 index baseline vs last visit: 1.9 ± 0.6 vs 1.2 ± 0.6,
p
< 0.0001). At the last visit, 67% of patients had controlled disease, and 44% showed a decrease in tumor volume. Clinical and biochemical efficacy was observed as early as after 1-month of PAS-LAR treatment (IGF-1 index baseline vs 1-month: 1.9 ± 0.6 vs 1.4 ± 0.7,
p
< 0.0001). Also, 50% of patients referred headache improvement or disappearance. Fifteen patients discontinued PAS-LAR due to failure of treatment and poor glycaemic control. The prevalence of diabetes increased from 33% at the baseline to 54% at the last visit (
p
= 0.0072).
Conclusion
In real-life settings, PAS-LAR significantly decreases symptoms, IGF-1 levels, and the size of adenoma in patients with acromegaly resistant to SRLs. Beneficial effects may occur early after the first injection.
Purpose
Type 2 amiodarone-induced thyrotoxicosis (AIT2) is a form of drug-induced destructive thyroiditis, usually treated with oral glucocorticoids (oGCs). Our objective was to investigate the ...short-term effects of intravenous glucocorticoids (ivGCs) on serum thyroid hormone concentrations in patients with AIT2.
Methods
Exploratory study of three naive AIT2 patients treated with iv methylprednisolone (two pulses of 400 mg with no interpulse oGCs), followed by oGCs, matched 1:3 with AIT2 patients treated with oGCs alone. Changes in serum thyroid hormone concentrations were evaluated in the short-term period (24 h and 7 days) and after a cumulative dosage of 400 and 800 mg equivalents of methylprednisolone; in addition, healing time and duration of exposure to GCs were calculated.
Results
During the first 24 h of treatment, serum FT4 concentrations increased in ivGCs patients, and decreased in oGCs patients (+ 3.3%
vs
− 10.7%, respectively,
p
= 0.025). After 7 days, serum FT4 and FT3 concentrations decreased significantly in both groups, with no statistical difference between them (
p
= 0.439 for FT4 and
p
= 0.071 for FT3), even though the cumulative GCs dose was higher in ivGCs than in oGCs patients (800 mg
vs
280 mg,
p
= 0.008). Furthermore, the iv administration of single 400 mg pulses of methylprednisolone resulted in a less significant decrease in serum thyroid hormone concentrations when compared to equivalent GCs doses fractionated in several consecutive days (
p
= 0.021 for FT4 and
p
= 0.052 for FT3). There were no significant differences in the healing time (
p
= 0.239) and duration of exposure to GCs (
p
= 0.099).
Conclusions
High-dose ivGCs therapy does not offer advantages over standard oGCs therapy in the rapid, short-term control of AIT2.
Objectives
To explore the role of conventional X-ray imaging in detecting vertebral fractures (VFs) in patients with acromegaly, both at diagnosis of disease and at the last clinical visit. The risk ...factors for VFs were also evaluated.
Design and methods
A retrospective cohort study was conducted on 60 consecutive patients with acromegaly, in a tertiary referral centre. Thoracolumbar spine radiography (X-spine) was performed at the last clinical visit during the follow-up in order to detect VFs. Routine chest radiograph, performed as a part of the general evaluation at diagnosis of acromegaly, were retrospectively analysed to screen for baseline VFs.
Results
At diagnosis of acromegaly, chest X-ray revealed that 10 (17%) patients had VFs. Of the 50 patients without VFs at diagnosis of acromegaly, 33 (66%) remained unfractured at the last clinical visit (median IQR time, 144 96–192 months after the diagnosis of acromegaly), whereas 17 (34%) had VFs. Overall, 22 patients (37%) had novel VFs detected on X-spine including five patients with previous VFs. Risk factor for incident VFs was the presence of hypogonadism at diagnosis of acromegaly (
p
= 0.016).
Conclusions
In acromegaly patients, conventional X-rays can detect vertebral fractures early at diagnosis of acromegaly. They can also reveal incident VFs, which may occur several years later even in patients without VFs at diagnosis, above all in relation to hypogonadism.
Background
Autoimmune Polyglandular Syndrome type 1 (APS-1) is a rare recessive inherited disease, caused by AutoImmune Regulator (
AIRE
) gene mutations and characterized by three major ...manifestations: chronic mucocutaneous candidiasis (CMC), chronic hypoparathyroidism (CH) and Addison’s disease (AD).
Methods
Autoimmune conditions and associated autoantibodies (Abs) were analyzed in 158 Italian patients (103 females and 55 males; F/M 1.9/1) at the onset and during a follow-up of 23.7 ± 15.1 years.
AIRE
mutations were determined.
Results
The prevalence of APS-1 was 2.6 cases/million (range 0.5–17 in different regions). At the onset 93% of patients presented with one or more components of the classical triad and 7% with other components. At the end of follow-up, 86.1% had CH, 77.2% AD, 74.7% CMC, 49.5% premature menopause, 29.7% autoimmune intestinal dysfunction, 27.8% autoimmune thyroid diseases, 25.9% autoimmune gastritis/pernicious anemia, 25.3% ectodermal dystrophy, 24% alopecia, 21.5% autoimmune hepatitis, 17% vitiligo, 13.3% cholelithiasis, 5.7% connective diseases, 4.4% asplenia, 2.5% celiac disease and 13.9% cancer. Overall, 991 diseases (6.3 diseases/patient) were found. Interferon-ω Abs (IFNωAbs) were positive in 91.1% of patients. Overall mortality was 14.6%. The
AIRE
mutation R139X was found in 21.3% of tested alleles, R257X in 11.8%, W78R in 11.4%, C322fsX372 in 8.8%, T16M in 6.2%, R203X in 4%, and A21V in 2.9%. Less frequent mutations were present in 12.9%, very rare in 9.6% while no mutations in 11% of the cases.
Conclusions
In Italy, APS-1 is a rare disorder presenting with the three major manifestations and associated with different
AIRE
gene mutations. IFNωAbs are markers of APS-1 and other organ-specific autoantibodies are markers of clinical, subclinical or potential autoimmune conditions.
Summary Pituitary apoplexy (PA) is a medical emergency with complex diagnosis and management. In this study, we describe a case of PA in a 63-year-old male treated with oral anticoagulant therapy for ...atrial fibrillation. In the patient, PA manifested itself with asthenia and severe headache not responsive to common analgesics. Despite the finding of a pituitary mass through CT, and in anticipation of the endocrinological evaluation and pituitary MRI, the patient’s clinical condition worsened with an escalation of headache and asthenia associated with deterioration of the visual field and impairment of consciousness level. The emergency assessments revealed an adrenal failure, whereas MRI showed a haemorrhagic pituitary macroadenoma with compression of the optic chiasm. Intravenous fluids repletion and high-dose hydrocortisone were started with a rapid improvement of the patient’s health and visual field abnormalities. Hydrocortisone was gradually reduced to a replacement dose. During the follow-up, panhypopituitarism was documented, and replacement therapies with l-thyroxine and testosterone were introduced. Three months later, a pituitary MRI showed a 50% reduction in the pituitary adenoma volume. Learning points Pituitary apoplexy (PA) is a medical emergency that can result in haemodynamic instability and abnormalities in the level of consciousness. The management of PA requires a multidisciplinary team that includes endocrinologists, ophthalmologists, neuro-radiologists, and neuro-surgeons. Pituitary MRI with gadolinium is the diagnostic gold standard for PA. PA therapy aims to improve general conditions and treat compression symptoms, especially visual field abnormalities. Adrenocorticotrophic hormone deficiency is a common and severe complication of PA. Thus, all patients with PA must be promptly treated with injective synthetic glucocorticoids (e.g. hydrocortisone 100 mg) and i.v. saline. PA must be taken into consideration in case of sudden headache in patients with a pituitary macroadenoma, especially if other risk factors are recognized.
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