Correlation between inflammatory biomarkers and disease control in chronic rhinosinusitis with nasal polyps.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) may have a heterogeneous response to medical/surgical treatments based on endotypes. Data correlating biomarkers and severity of the disease are lacking. We aimed to determine if IL-5 and calprotectin may be useful in defining severity of disease and identifying uncontrolled patients. METHODS: This was a case-control study including 81 patients with diffuse CRSwNP who underwent at least one previous surgery and treated with intranasal steroids. We enrolled 39 uncontrolled patients (SNOT-22 ≥ 40 and two or more cycles of systemic corticosteroids in last year) (Group A) and 42 controlled one (SNOT-22 < 40 and less than two cycles of systemic corticosteroids in last year) (Group B). We analyzed IL-5 and calprotectin in both nasal secretions and nasal polyp tissue. RESULTS: Calprotectin and IL-5 were significantly higher in Group A in both secretions and tissue, and the higher the number of previous surgeries, the higher the levels detected in nasal secretions. At univariate analyses, smoking, asthma, non-steroidal anti-inflammatory drugs-exacerbated respiratory disease (NSAID-ERD), blood eosinophilia, neutrophils, and eosinophils at nasal cytology were significantly associated with uncontrolled disease. Multivariate analyses showed that asthma, NSAID-ERD, and IL-5 in nasal secretion/polyp tissue were significantly related to the risk of uncontrolled disease. CONCLUSIONS: Our data suggest that asthma, NSAID-ERD, and IL-5 in nasal secretions/tissue may be helpful to identify more severe patients, as they are related to the risk of uncontrolled disease. Nonetheless, high levels of calprotectin and neutrophilia were also observed in uncontrolled patients, especially after multiple surgeries.

Temporal trends of blood eosinophilia in severe uncontrolled CRSwNP treated with dupilumab: a real-life study.

PURPOSE: Induced eosinophilia is commonly related to dupilumab treatment. We analysed the temporal trends of blood eosinophilia in patients with severe uncontrolled CRSwNP during the first year of treatment with dupilumab in real-life setting to evaluate its correlation with outcomes of response and adverse events (AEs). METHODS: Seventy-four patients with severe uncontrolled CRSwNP treated with dupilumab at our institution were enrolled. At each visit, we evaluated AEC, outcomes of response to treatment and AEs. RESULTS: A significant increase in AEC was observed since the first month with a peak at 3 months; at 12 months, the values returned comparable to those at baseline. A ≥ 50% increase of the baseline AEC with a value greater than 500 cells/mm3 was documented in 38/74 patients (Group A) regardless of the time of observation, whereas in 36/74 patients (Group B), no changes were observed. Analysing the blood eosinophilia trend over time in group A, we observed a temporary eosinophilia with early onset (within 6 months), persistent eosinophilia with early onset, and eosinophilia with late onset. No differences in terms of outcomes of response to treatment or AEs were found between Group A and Group B, or between patients who developed an AEC ≥ 1500 cells/mm3 or not. CONCLUSION: In our series, we observed that an increase in AEC with different temporal trends may be observed in CRSwNP patients during the first year of treatment with dupilumab. In our series, eosinophilia is not correlated with a negative outcome of response to treatment or a risk of AEs.

CSF neuron-specific enolase as a biomarker of neurovascular conflict severity in drug-resistant trigeminal neuralgia: a prospective study in patients submitted to microvascular decompression.

BACKGROUND: Although neurovascular conflict (NVC) is the most widely accepted cause of trigeminal neuralgia (TN), few articles have analyzed molecular and biochemical mechanisms underlying TN. In the present study, we dosed neuron-specific enolase (NSE) on serum and CSF samples of 20 patients submitted to microvascular decompression (MVD) and correlated these findings with the type of NVC. METHODS: Blood samples were obtained preoperatively and 48 h after MVD. CSF from trigeminal cistern was intraoperatively obtained. NSE levels were measured using the Diasorin kit (LIAISON®NSE). NVC was classified as "contact" or "trigeminal nerve distortion/indentation" or "trigeminal root atrophy" based on MRI and intraoperative findings. Clinical outcome was measured by acute pain relief (APR) and Barrow Neurological Institute (BNI) scale at last available follow-up (FU; 6.40 ± 5.38 months). RESULTS: APR was obtained in all patients. A statistically significant BNI reduction was obtained at latest FU (p < 0.0001). Serum NSE levels significantly decreased following MVD (from 12.15 ± 3.02 ng/mL to 8.95 ± 2.83 ng/mL, p = 0.001). The mean CSF NSE value was 48.94 ng/mL, and the mean CSF/serum NSE rate was 4.18 with a strong correlation between these two variables (p = 0.0008). CSF NSE level in "trigeminal root atrophy" group was significantly higher compared to "contact" (p = 0.0045) and "distortion/indentation" (p = 0.010) groups. CONCLUSION: NSE levels seem to be related to the etiopathology and severity of NVC. A significant reduction of serum NSE levels could be related to the resolution of the NVC and clinical TN improvement.

The role of biomarkers in drug-resistant trigeminal neuralgia: a prospective study in patients submitted to surgical treatment.

BACKGROUND: Molecular mechanisms underlying trigeminal neuralgia (TN) have been poorly understood. Recently, different biomarkers have been studied in several chronic neuropathic diseases or in neuronal damage, but their role in TN has not yet been investigated. Here, we firstly analyzed the serum levels of the neuron-specific enolase (NSE) (as an index of neuronal tissue damage) in TN patients submitted to surgical treatment. Different cytokines and interleukins related to inflammation were also studied. METHODS: Blood samples from 40 patients were prospectively collected preoperatively and after the surgical procedure, namely microvascular decompression (MVD) and percutaneous balloon compression (PBC). Serum levels of uric acid, NSE, ferritin, CRP, IL-2R, and IL-6 were studied. The acute pain relief (APR) and the pre- and postoperative BNI were used to evaluate the clinical outcome. RESULTS: Overall, we obtained an APR in 87.5% of patients and a significant reduction of BNI after surgery (p < 0.0001). We observed a significant reduction of postoperative NSE values in the group of patients undergoing MVD (p = 0.0055) and a significant increase of postoperative NSE values in patients undergoing PBC (p < 0.05). Furthermore, in the group of patients undergoing MVD, we found a significant postoperative increase of CRP (p < 0.0001), ferritin (p = 0.001), and IL-6 (p = 0.01) values. The only patient who did not respond to MVD had NSE levels unchanged. CONCLUSION: Our results suggest the hypothesis that TN would be related to the neural damage instead of the systemic inflammatory status and indicate NSE as a possible biomarker of response in patients submitted to MVD.

Analytical Performance Evaluation of a New Calcitonin Assay.

BACKGROUND: The use of efficient laboratory calcitonin (CT) testing is required for optimal management of medullary thyroid carcinoma. Several pitfalls are related to the calcitonin laboratory assays and a careful evaluation is needed. We report the analytical performances of the new Siemens ADVIA-Centaur-CALCT (CT-XPT) assay and its comparison with our standard method DiaSorin-Calcitonin-II-Gen (CT-LIA) assay. METHODS: Analytical performance of the CT-XPT-assay, limit of blank (LOB), limit of detection (LOD), and limit of quantification (LOQ), were determined. We also evaluated the in vitro stability of the sample, together with the linearity and percentage recovery. RESULTS: The CT-XPT-assay showed a better detection limit than the CT-LIA assay, with lower values of LOB (0.86 pg/mL vs 1.00 pg/mL) and LOQ (1.65 pg/mL vs 3.00 pg/mL). Both values were in agreement with those reported by the manufacturer. Within- and between-run precision demonstrated a good concordance of results. Regarding the in vitro stability of CT, the low CT concentration sera showed a much greater decrease in CT levels compared to the high concentration sera. Correlation studies showed a good correlation between the two methods (Kappa Cohen coefficent, KC: 0.68, agreement % for male: 89.58%; KC: 0.63; agreement % for female: 88.33%). CONCLUSIONS: Our findings showed a good correlation between the CT-LIA and CT-XPT methods. Moreover, we demonstrated that the analytical performance of the CT-XPT assay, together with its technical specifications, could represent major features of the CT-XPT method. Collectively, the technical evaluation and the analytical results described in the presented paper highlight that the novel CT-XPT is a valid method for CT testing in a clinical diagnostic setting.

Evaluation of Intra-Renal Stiffness in Patients with Primary Aldosteronism.

INTORDUCTION: Aldosterone is known to play important role in developing cardiovascular, metabolic, renal damage in hypertensive patients. AIM: Aim of study was to evaluate parameters obtained by eco-color Doppler study, as non-invasive and easly performed method in asyntomatic patients with Essential Hypertension (EH) and Primary Aldosteronism (PA), without overt organ damage. METHODS: From April 2019 to March 2020 we consecutively enrolled 73 hypertensive subjects (48 males, 25 women), distinguished in two groups: 30 EH patients (mean age 49.5 ± 18.7 years) and 43 PA patients (mean age 53.1 ± 11.6 years)] [23 with aldosterone-secreting adrenal adenoma (APA), 20 with idiopathic aldosteronism (IHA)]. RESULTS: PA group showed higher renal filtration rate and 24-h urinary excretion of albumin respect to EH; moreover, in PA we found higher Pulsatility Index, altered percentage of Renale Resistance Index, Atrophy Index, and reducted parietal thickness than EH. The correlation study showed that plasma aldosterone were positively correlated with pulsatility index in PA group (right r = 0.35; p < 0.05; left r = 0.36; p < 0.05). CONCLUSION: parameters obtained through the intra-renal eco-color Doppler examination, easly performed and non-invasive, can be useful in the early-stage identification of subclinical microvascular alterations, especially in PA, condition characterized by increased risk of cardio-vascular remodelling and metabolic alterations.

New obesity classification criteria as a tool for bariatric surgery indication.

Obesity plays relevant pathophysiological role in the development of health problems, arising as result of complex interaction of genetic, nutritional, and metabolic factors. Due to the role of adipose tissue in lipid and glucose metabolism, and low grade inflammation, it is necessary to classify obesity on the basis of body fat composition and distribution, rather than the simply increase of body weight, and the Body Mass Index. The new term of adiposopathy (''sick fat'') clearly defines the pathogenic role of adipose tissue. Four phenotypes of obese individuals have been described: (1) normal weight obese (NWO); (2) metabolically obese normal weight; (3) metabolically healthy obese; and (4) metabolically unhealthy obese or "at risk" obese. Moreover, sarcopenic obesity has been related to all the phenotypes. The category of normal weight lean, represented by metabolically healthy normal weight has been classified to distinguish from NWO. It is crucial to recommend a bariatric surgery taking into account adiposopathy and sick fat that occurs with the expansion of fat mass, changing the inflammatory and metabolic profile of the patient. Body fat percentage and genetic polymorphism have to be evaluated to personalize the best bariatric surgery intervention.

Individually tailored screening of susceptibility to sarcopenia using p53 codon 72 polymorphism, phenotypes, and conventional risk factors.

BACKGROUND AND AIM: p53 activity plays a role in muscle homeostasis and skeletal muscle differentiation; all pathways that lead to sarcopenia are related to p53 activities. We investigate the allelic frequency of the TP53 codon 72 in exon 4 polymorphism in the Italian female population and the association with appendicular skeletal muscle mass index in normal weight (NW), normal weight obese (NWO), and preobese-obese (Preob-Ob) subjects. METHODS: We evaluated anthropometry, body composition, and p53 polymorphism in 140 women distinguished in NW, NWO, and Preob-Ob. RESULTS: *Arg/*Arg genotype increases sarcopenia risk up to 20% (*Arg/*Arg genotype OR = 1.20; 95% CI = 0.48-2.9; *proallele carriers OR = 0.83; 95% CI = 0.83-2.06). The risk of being sarcopenic for *Arg/*Arg genotype in NWO and Preob-Ob is 31% higher than NW carriers of *proallele (RR = 0,31, 95% CI = 0,15-0,66, P = 0,0079). We developed a model able to predict sarcopenia risk based on age, body fat, and p53 polymorphism. CONCLUSION: Our study evidences that genotyping TP53 polymorphism could be a useful new genetic approach, in association with body composition evaluations, to assess sarcopenia risk.