Purpose
Current smoking is a risk factor for osteoporosis (Op), but few data are available regarding the passive smoke impact on Op susceptibility. This cross-sectional study aimed to evaluate the ...association between the smoking habits and Op in community-dwelling women undergoing dual-energy X-ray absorptiometry (DXA).
Methods
On 01/06/2018, general practitioners from “COMEGEN” Medical Cooperative, Naples, Italy, selected the medical records from the last 10 years of women who had a measurement of bone mineral density performed and simultaneously completed a questionnaire about their smoking behaviour and their cohabiters’. The binary logistic regression analysis was used to estimate the role of passive smoke on the risk of Op, adjusting for age and body mass index (BMI).
Results
Among 10,616 subjects, 3942 were currently smokers CS; mean age 69.4 ± 10.4 years; BMI 27.0 ± 4.9 kg/m
2
, 873 were passive smokers (PS; mean age 67.8 ± 11.6 years; BMI 27.0 ± 4.9 kg/m
2
) and 5781 were never smokers (NS; mean age 67.8 ± 11.6 years; body mass index (BMI) 27.0 ± 4.9 kg/m
2
). Of all, 8562 women (mean age 70.3 ± 10.2 yrs; BMI 27.0 ± 4.9 kg/m
2
) received the Op diagnosis. PS showed an increased Op risk compared to NS odds ratio (OR) 1.38 (1.14–1.67) and comparable to CS OR 1.02 (0.84–1.24).
Conclusion
The study results demonstrate an association between passive smoke and Op in community-dwelling women already presenting with susceptibility to Op according to Italian essential assistance levels, suggesting that passive and active smoke are equivalent Op risk factors in women.
Purpose
Osteoporosis (Op) and metabolic syndrome (MetS) are two common disorders showing common pathogenic patterns. This cross-sectional study was performed to evaluate if MetS and its constitutive ...elements are associated to an increased risk of low bone mineral density (BMD) in free-living women examined by Dual-energy X-ray absorptiometry (DXA) for suspected Op.
Methods
13,182 free-living Caucasian women referring to “COMEGEN” general practitioners cooperative operating in Naples, Italy, performed a contextual evaluation of BMD by DXA and all MetS constitutive elements (systolic and diastolic blood pressure, waist circumference, serum levels of triglycerides, high-density lipoprotein cholesterol, and fasting glucose) between June 1st 2008 and May 31st 2018. Subjects aged less than 40 years or with signs or symptoms suggestive of secondary Op were excluded from the study.
Results
MetS is associated to an increased risk of low BMD (Odds Ratio 1.19; 95% Confidence Interval 1.08–1.31). Among MetS constitutive elements, hypertension was associated to increased risk of low BMD, whereas high fasting glucose level/diabetes were associated to reduced risk of low BMD.
Conclusions
The significant association between Op and MetS in free-living women examined by DXA for suspected Op suggests the advisability of a contextual evaluation of both disorders in this setting.
Purpose
We have recently demonstrated a significant association between osteoporosis (Op) and metabolic syndrome (MetS) in Caucasian women examined by Dual-energy X-ray absorptiometry (DXA) for ...suspected Op. This cross-sectional study was performed to evaluate the association between MetS and Op in Caucasian men enrolled in the same geographical area, with identical criteria and in the same time range.
Methods
Among subjects enrolled in the SIMON study, we selected the medical records of all free-living men who performed a contextual evaluation of both bone mineral density (BMD) by DXA and MetS constitutive elements (arterial blood pressure, waist circumference, serum levels of triglycerides, high-density lipoprotein cholesterol, and fasting glucose). All enrolled subjects refer to “COMEGEN” general practitioners’ cooperative operating in Naples, Southern Italy.
Results
Overall, the medical records of 880 men were examined. No significant association between MetS and Op was observed. Among MetS constitutive elements, waist circumference was inversely related to Op risk.
Conclusion
In Caucasian men examined by DXA for suspected Op, no significant association was observed between Op and MetS. The study results contrast to those observed in women enrolled in the same geographical area, with identical criteria and in the same time range and may be related to sexual dimorphism occurring in clinical expressiveness of both MetS and Op.
Entrectinib, a potent oral inhibitor of the tyrosine kinases TRKA/B/C, ROS1, and ALK, was evaluated in two phase I studies in patients with advanced or metastatic solid tumors, including patients ...with active central nervous system (CNS) disease. Here, we summarize the overall safety and report the antitumor activity of entrectinib in a cohort of patients with tumors harboring
, or
gene fusions, naïve to prior TKI treatment targeting the specific gene, and who were treated at doses that achieved therapeutic exposures consistent with the recommended phase II dose. Entrectinib was well tolerated, with predominantly Grades 1/2 adverse events that were reversible with dose modification. Responses were observed in non-small cell lung cancer, colorectal cancer, mammary analogue secretory carcinoma, melanoma, and renal cell carcinoma, as early as 4 weeks after starting treatment and lasting as long as >2 years. Notably, a complete CNS response was achieved in a patient with
-rearranged lung cancer.
Gene fusions of
, and
(encoding TRKA/B/C, ROS1, and ALK, respectively) lead to constitutive activation of oncogenic pathways. Entrectinib was shown to be well tolerated and active against those gene fusions in solid tumors, including in patients with primary or secondary CNS disease.
.
The European hare (Lepus europaeus) is cosmopolitan species, living in a variety of habitats and showing a diversified diet, that has been described mainly from agricultural meadows and crops, with ...little information available for extreme environments. Here, we describe, for the first time, the diet of the European hare from Mount Vesuvius, using DNA metabarcoding and high-throughput sequencing on DNA extracted from faecal pellets, a proxy for a population living in a volcanic environment. The DNA from pellets was first genetically assigned to European hare using high-resolution melting analysis. The diet of the hare on Vesuvius is mainly composed of herbaceous species belonging to Fabaceae (86.26% of total diet). The most frequent plant items ingested by the species are Galega officinalis and Lupinus angustifolius (67.10% of total diet), although these are detected only sporadically in the study area. Indeed, the spectrum of available plants also includes other easily accessible wild (i.e. Lolium sp., Bromus sp., Rumex sp.) and cultivated (i.e. Solanum lycopersicum, Cucumis melo, Pisum sativum) plant items, found only in traces in the diet of the hares. Our contribution adds information on the trophic ecology of the European hare, exploring its ability to live in an extreme environment. This could be useful to set a management strategy for conservation of the species, which is ecologically relevant on Vesuvius as prey for birds and mammals, as well as a vegetation modulator via selective grazing by endozoochory. Furthermore, our study represents the latest information on the diet of the hare living in an environment that no longer exists: an extensive fire destroyed about 80% of the woody area after our sampling. The post-fire regrowth is transforming the original environment and consequently the trophic availability for the European hare.
Conservation of biodiversity in a national park
Ecosystem service of the European hare
Management of a Lagomorpha game species
The pathways leading to female sexual determination in mammals are incompletely defined. Loss-of-function mutations in the WNT4 gene appear to cause developmental abnormalities of sexual ...differentiation in women and mice. We recruited six patients with different degrees of Müllerian abnormalities, with or without renal aberrations and a normal female 46,XX karyotype. A clear androgen excess was found only in one patient. This 19-year-old woman was affected by primary amenorrhoea, absence of Müllerian ducts derivatives, clinical (acne and hirsutism) and biochemical (repeatedly high levels of testosterone) signs of androgen excess. Direct sequencing of her WNT4 gene followed by functional studies in human ovarian cells (OVCAR3) was performed. This patient carried the novel R83C loss-of-function dominant negative mutation in her WNT4, confirming the role of WNT4 in the development and maintenance of the female phenotype in women. Our study can also help refine the phenotype of WNT4 deficiency in humans. In fact, it appears that at least in this limited casuistic small group of patients, the absence of a uterus (and not other Müllerian abnormalities) and the androgen excess are the pathognomonic signs of WNT4 defects, suggesting that this might be a clinical entity distinct from the classic Mayer–Rokitansky–Kuster–Hauser syndrome.
(1) Background: In advanced non-small cell lung cancer (aNSCLC), programmed death ligand 1 (PD-L1) remains the only biomarker for candidate patients to immunotherapy (IO). This study aimed at using ...artificial intelligence (AI) and machine learning (ML) tools to improve response and efficacy predictions in aNSCLC patients treated with IO. (2) Methods: Real world data and the blood microRNA signature classifier (MSC) were used. Patients were divided into responders (R) and non-responders (NR) to determine if the overall survival of the patients was likely to be shorter or longer than 24 months from baseline IO. (3) Results: One-hundred sixty-four out of 200 patients (i.e., only those ones with PD-L1 data available) were considered in the model, 73 (44.5%) were R and 91 (55.5%) NR. Overall, the best model was the linear regression (RL) and included 5 features. The model predicting R/NR of patients achieved accuracy ACC = 0.756, F1 score F1 = 0.722, and area under the ROC curve AUC = 0.82. LR was also the best-performing model in predicting patients with long survival (24 months OS), achieving ACC = 0.839, F1 = 0.908, and AUC = 0.87. (4) Conclusions: The results suggest that the integration of multifactorial data provided by ML techniques is a useful tool to select NSCLC patients as candidates for IO.
Circulating microRNA (ct-miRNAs) are able to identify patients with differential response to HER2-targeted therapy. However, their dynamics are largely unknown. We assessed 752 miRNAs from 52 ...NeoALTTO patients with plasma pairs prior and two weeks after trastuzumab. Increased levels of ct-miR-148a-3p and ct-miR-374a-5p were significantly associated with pathological complete response (pCR) (
= 0.008 and 0.048, respectively). At a threshold ≥ the upper limit of the 95%CI of the mean difference, pCR resulted 45% (95%CI 24%-68%), and 44% (95%CI 22%-69%) for ct-miR-148a-3p and ct-miR-374a-5p, respectively. Notably, ct-miR-148a-3p retained its predictive value (OR 3.42, 95%CI 1.23-9.46,
= 0.018) in bivariate analysis along with estrogen receptor status. Combined information from ct-miR-148a-3p and ct-miR140-5p, which we previously reported to identify trastuzumab-responsive patients, resulted in greater predictive capability over each other, with pCR of 54% (95%CI 25%-81%) and 0% (95%CI 0%-31%) in ct-miR-148a/ct-miR-140-5p high/present and low/absent, respectively. GO and KEGG analyses showed common enriched terms between the targets of these ct-miRNAs, including cell metabolism regulation, AMPK and MAPK signaling, and HCC progression. In conclusion, early modulated ct-miR-148-3p may inform on the functional processes underlying treatment response, integrate the information from already available predictive biomarkers, and identify patients likely to respond to single agent trastuzumab-based neoadjuvant therapy.
NGR-hTNF consists of human tumor necrosis factor alpha (hTNF-alpha) fused to the tumor-homing peptide asparagine-glycine-arginine (NGR) able to selectively bind an aminopeptidase N isoform ...overexpressed on tumor blood vessels. Hypervascularity is a prominent and poor-prognosis feature of malignant pleural mesothelioma (MPM). Currently, there are no standard options for patients with MPM who are failing a front-line pemetrexed-based regimen. We explored safety and efficacy of NGR-hTNF in this setting.
Eligible patients had radiologically documented tumor progression and performance status < or = 2. Primary study aim was progression-free survival (PFS). NGR-hTNF 0.8 microg/m(2) was given intravenously every 3 weeks. A subsequent cohort of patients received 0.8 microg/m(2) on a weekly basis.
In the triweekly cohort (n = 43), only one grade 3 drug-related toxicity was noted, and the most common grades 1 to 2 were short-lived chills (71%). The median PFS was 2.8 months (95% CI, 2.3 to 3.3 months). Nineteen patients (44%) had disease control (one had partial response, and 18 had stable diseases) and experienced a median progression-free time of 4.4 months. In the weekly cohort (n = 14), there was no higher toxicity, and median PFS was 3.0 months (95% CI, 1.9 to 4.1 months). Seven patients (50%) had disease control (all stable diseases) and had a median progression-free interval of 9.1 months. In the overall study population (N = 57), median PFS was 2.8 months. Median progression-free time was 4.7 months in twenty-six patients (46%) who achieved disease control. Median survival was 12.1 months.
The tolerability and disease control of NGR-hTNF 0.8 microg/m(2) weekly warrant additional evaluation in patients with advanced MPM.
Background:
Previous data, mostly from clinical trials, reported that HER2-low status is associated with low pathological complete response (pCR), and favourable prognosis. Since these findings ...suggest the existence of an additional breast cancer subtype, we questioned if the predictive/prognostic value of HER2-low was also relevant in the real world.
Methods:
Data from non-metastatic breast cancer patients treated with neoadjuvant chemotherapy and surgery (2009–2020) were retrieved from our institutional prospectively-maintained registry. Univariable and multivariable logistic models were implemented to study the association between pCR and baseline HER2 status. Univariable analysis of disease-free survival (DFS) was performed through Kaplan-Meier survival curves and log-rank tests.
Results:
Starting from a total of 790 consecutive cases, we identified 444 newly-diagnosed breast cancer patients featuring HER2 immunohistochemistry (IHC) 0 (HER2-0,
n
= 109), and 1 + or IHC 2+/
in situ
hybridization negative (HER2-low,
n
= 335) receiving anthracycline and taxane-based regimens in 88.9% of cases. Most of the patients were diagnosed with stage II (67.3%) and there was no difference of disease presentation according to HER2-status. pCR was attained by 71 (16.0%) patients and was significantly associated with increased DFS (
p
= 0.031). Compared to HER2-0, HER2-low cases were more likely hormone receptor-positive (81.2% vs. 43.1%,
p
< 0.001), well-differentiated (47.5% vs. 26.6%,
p
= 0.001), less proliferative (21.5% vs. 8.3%,
p
= 0.001) and less responsive to treatment (pCR 11.6% vs. 29.4%,
p
< 0.0001). There was no difference in DFS according to HER2 status, though hormone-receptor (HR) negative/HER2-low cases tended to have a worse prognosis compared to HR-negative/HER2-0. By pCR achievement, 3-years DFS was 87.5.% (75.1–100%) vs. 71.6% (65.9–77.8%) (
p
= 0.161) in HER2-low and 89.1% (75.8–100%) vs. 72.1% (59.7–87.0%) (
p
= 0.092) in HER2-0.
Conclusion:
Our real-world data show that HER2-low breast cancer patients represent roughly a half of the cases treated with neoadjuvant therapy, and have poor treatment response. In absence of pCR, HER2-low breast cancer patients have a dismal prognosis, especially when primary tumor hormone receptor status is negative. Studies are therefore needed to define the biology of these tumors for new therapeutic targets and to incorporate HER2-targeting agents in early-stage treatment.
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