Lambertmercer2950

The objective of this analysis was to estimate the incremental cost-utility ratio (ICUR) of dupilumab as an add-on treatment to best supportive care (BSC), versus BSC alone, in Italy for severe uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP). A simulation of outcomes and costs was undertaken using a 1-year decision tree, followed by a lifetime horizon Markov model. Clinical data were derived from a pooled analysis of two studies (SINUS-24 NCT02912468 and SINUS-52 NCT02898454). The Italian National Healthcare Service (NHS) perspective was considered. Model robustness was tested through sensitivity analyses. In the base-case analysis, treatment with dupilumab + BSC resulted in an increase in quality of life-adjusted survival (+1.02 quality-adjusted life years (QALY-gained)), compared to the BSC alone. The resulted ICUR was €21,817 per QALY-gained and it is below the acceptability threshold commonly used in Italy. Both one-way deterministic and probabilistic sensitivity analyses confirmed the robustness of base-case results. The cost-utility analysis showed that dupilumab, as an add-on treatment to BSC, is a cost-effective therapeutic alternative to BSC in the treatment of patients with severe uncontrolled chronic rhinosinusitis with nasal polyps, confirming that it is economically sustainable.Dihydropyrimidine dehydrogenase is one of the main pharmacological metabolizers of fluoropyrimidines, a group of drugs widely used in clinical oncology. Around 20 to 30% of patients treated with fluoropyrimidines experience severe toxicity caused by a partial or total decrease in enzymatic activity. This decrease is due to molecular variants in the DPYD gene. Their prevalence and allelic frequencies vary considerably worldwide, so their description in heterogeneous groups such as the Ecuadorian population will allow for the description of pharmacogenetic variants and proper characterization of this population. Thus, we genotyped all the molecular variants with a predictive value for DPYD in a total of 410 Ecuadorian individuals belonging to Mestizo, Afro-Ecuadorian, and Indigenous ethnic groups. Moreover, we developed a genetic ancestry analysis using 46 autosomal ancestry informative markers. We determined 20 genetic variations in 5 amplified regions, including 3 novel single nucleotide variants. The allele frequencies for DPYD variants c.1627G>A (*5, rs1801159), c.1129-15T>C (rs56293913), c.1218G>A (rs61622928), rs1337752, rs141050810, rs2786783, rs2811178, and g.97450142G>A (chr1, GRCh38.p13) are significantly related to Native American and African ancestry proportions. In addition, the FST calculated from these variants demonstrates the closeness between Indigenous and Mestizo populations, and evidences genetic divergence between Afro-Ecuadorian groups when compared with Mestizo and Indigenous ethnic groups. In conclusion, the genetic variability in the DPYD gene is related to the genetic component of ancestral populations in different Ecuadorian ethnic groups. The absence and low frequency of variants with predictive value for fluoropyrimidine toxicity such as DPYD *2A, HapB3, and c.2846A>T (prevalent in populations with European ancestry) is consistent with the genetic background found.Extracellular vesicles (EVs) are abundantly released into the systemic circulation, where they show remarkable stability and harbor molecular constituents that provide biochemical information about their cells of origin. Due to this characteristic, EVs are attracting increasing attention as a source of circulating biomarkers for cancer liquid biopsy and personalized medicine. Despite this potential, none of the discovered biomarkers has entered the clinical practice so far, and novel approaches for the label-free characterization of EVs are highly demanded. In this regard, Fourier Transform Infrared Spectroscopy (FTIR) has great potential as it provides a quick, reproducible, and informative biomolecular fingerprint of EVs. In this pilot study, we investigated, for the first time in the literature, the capability of FTIR spectroscopy to distinguish between EVs extracted from sera of cancer patients and controls based on their mid-IR spectral response. For this purpose, EV-enriched suspensions were obtained fr same groups of subjects, namely alpha-fetoprotein (AFP), and protein induced by the absence of vitamin K or antagonist-II (PIVKA-II).The use of infliximab has completely changed the therapeutic landscape in inflammatory bowel disease. However, despite its proven efficacy to induce and maintain clinical remission, increasing evidence suggests that treatment failure may be associated with inadequate drug blood concentrations. The introduction of biosensors based on different nanostructured materials for the rapid quantification of drugs has been proposed for therapeutic drug monitoring. This study aimed to apply atomic force microscopy (AFM)-based nanoassay for the measurement of infliximab concentration in serum samples of healthy donors and pediatric IBD patients. This assay measured the height signal variation of a nanostructured gold surface covered with a self-assembled monolayer of alkanethiols. Inside this monolayer, we embedded the DNA conjugated with a tumor necrosis factor able to recognize the drug. The system was initially fine-tuned by testing known infliximab concentrations (0, 20, 30, 40, and 50 nM) in buffer and then spiking the same concentrations of infliximab into the sera of healthy donors, followed by testing pediatric IBD patients. A good correlation between height variation and drug concentration was found in the buffer in both healthy donors and pediatric IBD patients (p-value < 0.05), demonstrating the promising use of AFM nanoassay in TDM.Almost half of patients show no primary or secondary response to monoclonal anti-tumor necrosis factor α (anti-TNF) antibody treatment for inflammatory bowel disease (IBD). Thus, the exact mechanisms of a non-durable response (NDR) remain inadequately defined. We used our genome-wide genotype data to impute expression values as features in training machine learning models to predict a NDR. Blood samples from various IBD cohorts were used for genotyping with the Korea Biobank Array. A total of 234 patients with Crohn's disease (CD) who received their first anti-TNF therapy were enrolled. The expression profiles of 6294 genes in whole-blood tissue imputed from the genotype data were combined with clinical parameters to train a logistic model to predict the NDR. The top two and three most significant features were genetic features (DPY19L3, GSTT1, and NUCB1), not clinical features. The logistic regression of the NDR vs. DR status in our cohort by the imputed expression levels showed that the β coefficients were positive for DPY19L3 and GSTT1, and negative for NUCB1, concordant with the known eQTL information. Machine learning models using imputed gene expression features effectively predicted NDR to anti-TNF agents in patients with CD.(1) Background Workers spend most of their days working. One's working environment can be a risk factor for suicide. In this study, we examined whether suicidal ideation can be predicted using individual characteristics, emotional states, and working environments. (2) Methods Nine years of data from the Korean National Health and Nutrition Survey were used. A total of 12,816 data points were analyzed, and 23 variables were selected. The random forest technique was used to predict suicidal thoughts. (3) Results When suicidal ideation cases were predicted using all of the independent variables, 98.9% of cases were predicted, and 97.4% could be predicted using only work-related conditions. (4) Conclusions It was confirmed that suicide risk could be predicted efficiently when machine learning techniques were applied using variables such as working environments.Previous studies have demonstrated that both subcutaneous (SCIT) and sublingual specific immunotherapy (SLIT) are effective in treating allergic rhinitis (AR). Further studies have evaluated the efficacy of allergen-specific immunotherapy (AIT) on different ear, nose, and throat (ENT) manifestations, in which allergy might have an etiopathogenetic role, such as local allergic rhinitis (LAR), rhinosinusitis (RS), otitis media (OM), and adenotonsillar (AT) disease. Nevertheless, the management of allergy in ENT diseases is still debated. To the best of our knowledge, this is the first systematic review assessing the efficacy of AIT in ENT diseases aside from AR. Literature data confirmed that AIT might be an effective therapeutic option in LAR, although its effect is restricted to studies with short-term follow-up. Furthermore, previous research demonstrated that AIT may improve symptoms and surgical outcomes of chronic rhinosinusitis when used as an adjunctive treatment. Few studies supported the hypothesis that AIT may exert positive therapeutic effects on recurrent upper airway infections as adenotonsillar disease. Finally, some clinical observations suggested that AIT may add some benefits in the management of otitis media with effusion (OME). The results of this systematic review allow us to conclude that the efficacy of AIT in ENT disorders has been only slightly investigated and additional studies are needed.The association between serum 25-hydroxyvitamin D [25(OH)D] concentration and breast cancer risk in postmenopausal women is not well understood. The aim of this study was to investigate the association between serum 25(OH)D concentration and breast cancer in postmenopausal women in the United States using nationally representative sample surveys. We used the data from seven cycles of National Health and Nutrition Examination Surveys from 2001 to 2014. Participants were non-institutionalized postmenopausal women (n = 8108). In restricted cubic spline analysis, a significant, nonlinear, invert 'U' relationship was observed between serum 25(OH)D concentrations and breast cancer in postmenopausal women (p = 0.029). Overall, breast cancer risk was highest (OR = 1.5) between 70 nmol/L and 80 nmol/L of serum 25(OH)D concentration. Then after serum 25(OH)D 80 nmol/L concentration, the breast cancer risk declined. In multivariate-adjusted logistic regression, the risk of having breast cancer was significantly higher in serum 25(OH)D 75-˂100 nmol/L category compared to the 25(OH)D < 30 nmol/L category [OR and 95% CI 2.4 (1.4-4.0)]. In conclusion, serum vitamin D concentrations ≥ 100 nmol/L are associated with reduced risk of breast cancer in postmenopausal women. Controlled trials are required to verify if serum 25(OH)D ≥ 100 nmol/L offers protection against breast cancer in postmenopausal women.Xanthogranuloma of the sellar region is a rare chronic inflammatory lesion resulting from secondary hemorrhage, inflammation, infarction, and necrosis of an existing Rathke's cleft cyst, craniopharyngioma, or pituitary adenoma. Sellar xanthogranulomas are challenging to differentiate from other cystic lesions preoperatively due to the lack of characteristic imaging features. We performed a literature overview of the clinical and paraclinical features, treatment options, and long-term outcomes of patients with sellar xanthogranuloma, focusing on the preoperative radiological diagnosis. The hyperintense signal in both T1- and T2-weighted sequences, cystic or partially cystic morphology, ovoid shape, sellar epicenter, intra- and suprasellar location, intratumoral calcifications, linear rim contrast enhancement, and the absence of cavernous sinus invasion suggest xanthogranuloma in the preoperative differential diagnosis. An endoscopic endonasal gross total resection without radiotherapy is the preferred first-line treatment.