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.

Screening and Analysis of Possible Drugs Binding to PDGFRα: A Molecular Modeling Study.

The platelet-derived growth factor receptor (PDGFR) is a membrane tyrosine kinase receptor involved in several metabolic pathways, not only physiological but also pathological, as in tumor progression, immune-mediated diseases, and viral diseases. Considering this macromolecule as a druggable target for modulation/inhibition of these conditions, the aim of this work was to find new ligands or new information to design novel effective drugs. We performed an initial interaction screening with the human intracellular PDGFRα of about 7200 drugs and natural compounds contained in 5 independent databases/libraries implemented in the MTiOpenScreen web server. After the selection of 27 compounds, a structural analysis of the obtained complexes was performed. Three-dimensional quantitative structure-activity relationship (3D-QSAR) and absorption, distribution, metabolism, excretion, and toxicity (ADMET) analyses were also performed to understand the physicochemical properties of identified compounds to increase affinity and selectivity for PDGFRα. Among these 27 compounds, the drugs Bafetinib, Radotinib, Flumatinib, and Imatinib showed higher affinity for this tyrosine kinase receptor, lying in the nanomolar order, while the natural products included in this group, such as curcumin, luteolin, and epigallocatechin gallate (EGCG), showed sub-micromolar affinities. Although experimental studies are mandatory to fully understand the mechanisms behind PDGFRα inhibitors, the structural information obtained through this study could provide useful insight into the future development of more effective and targeted treatments for PDGFRα-related diseases, such as cancer and fibrosis.

Assessment of sST2 Behaviors to Evaluate Severity/Clinical Impact of Acute Pulmonary Embolism.

Pulmonary embolism (PE) is a potentially life-threatening disorder. Beyond its usefulness in the prognostic stratification of heart failure, sST2 can represent a biomarker with high utility in several acute conditions. Our study was aimed to investigate whether sST2 can be used as a clinical marker of severity and prognostic outcome in acute PE. We enrolled 72 patients with documented PE and 38 healthy subjects; we measured the plasma concentrations of sST2 to evaluate the prognostic and severity performance of different levels of sST2 according to its association with the pulmonary embolism severity index (PESI) score and several parameters of respiratory function. PE patients had significantly higher levels of sST2 compared with healthy subjects (87.74 ± 17.1 vs. 17.1 ± 0.4 ng/mL, p < 0.001); we found higher PESI scores and serum lactate values in the group of patients with sST2 > 35 ng/mL compared with patients with sST2 < 35 ng/mL (138.7 ± 14.9 vs. 103.7 ± 15.1 and 2.43 ± 0.69 vs. 1.025 ± 0.05 mmol/L, respectively; p < 0.05). Patients with sST2 > 35 ng/mL showed higher radiological severity of PE compared with patients with sST2 < 35 ng/mL. Moreover, sST2 was the strongest parameter with a discriminative capacity for the development of acute respiratory failure and a PESI score >106 with respect to C reactive protein (CRP), creatinine, d-dimer, and serum lactate. We clearly demonstrated that sST2 significantly increased in PE and that its elevation was associated with disease severity. Therefore, sST2 may be used as a clinical marker in the evaluation of PE severity. However, further studies with larger patient populations are required to confirm these findings.

Role of Intestinal Inflammation and Permeability in Patients with Acute Heart Failure.

Background and Objectives: Heart failure (HF) represents a major health burden. Although several treatment regimens are available, their effectiveness is often unsatisfactory. Growing evidence suggests a pivotal role of the gut in HF. Our study evaluated the prognostic role of intestinal inflammation and permeability in older patients with acute HF (AHF), and their correlation with the common parameters traditionally used in the diagnostic-therapeutic management of HF. Materials and Methods: In a single-center observational, prospective, longitudinal study, we enrolled 59 patients admitted to the Emergency Department (ED) and then hospitalized with a diagnosis of AHF, from April 2022 to April 2023. Serum routine laboratory parameters and transthoracic echocardiogram were assayed within the first 48 h of ED admission. Fecal calprotectin (FC) and both serum and fecal levels of zonulin were measured, respectively, as markers of intestinal inflammation and intestinal permeability. The combined clinical outcome included rehospitalizations for AHF and/or death within 90 days. Results: Patients with increased FC values (>50 µg/g) showed significantly worse clinical outcomes (p < 0.001) and higher median levels of NT-proBNP (p < 0.05). No significant correlation was found between the values of fecal and serum zonulin and the clinical outcome. Median values of TAPSE were lower in those patients with higher values of fecal calprotectin (p < 0.05). After multivariate analysis, NT-proBNP and FC values > 50 µg/g resulted as independent predictors of a worse clinical outcome. Conclusions: Our preliminary finding supports the hypothesis of a close relationship between the gut and heart, recognizing in a specific marker of intestinal inflammation such as FC, an independent predictive prognostic role in patients admitted for AHF. Further studies are needed to confirm these results, as well as investigate the reliability of new strategies targeted at modulation of the intestinal inflammatory response, and which are able to significantly impact the course of diseases, mainly in older and frail patients.

Use of an innovative cuff pressure control and subglottic secretions drainage system in COVID-19 ARDS patients undergoing pronation.

We conducted a proof of concept study where Anapnoguard endotracheal tubes and its control unit were used in 15 patients with COVID-19 acute respiratory distress syndrome. Anapnoguard system provides suction, venting, rinsing of subglottic space and controls cuff pressure detecting air leakage through the cuff. Alpha-amylase and pepsin levels, as oropharyngeal and gastric microaspiration markers, were assessed from 85 tracheal aspirates in the first 72 h after connection to the system. Oropharyngeal microaspiration occurred in 47 cases (55%). Episodes of gastric microaspiration were not detected. Patient positioning, either prone or supine, did not affect alpha-amylase and pepsin concentration in tracheal secretions. Ventilator-associated pneumonia (VAP) rate was 40%. The use of the AG system provided effective cuff pressure control and subglottic secretions drainage. Despite this, no reduction in the incidence of VAP has been demonstrated, compared to data reported in the current COVID-19 literature. The value of this new technology is worth of being evaluated for the prevention of ventilator-associated respiratory tract infections.

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.

Impact of bile acids on the severity of laryngo-pharyngeal reflux.

OBJECTIVES: The primary end point of this study was to evaluate the impact of bile acids on severity of laryngo-pharyngeal reflux (LPR) and the possible correlation with esophagitis and upper airway malignancies. The second end point was to evaluate if salivary bile acids and molecules other than pepsin might serve as diagnostic biomarkers of LPR. DESIGN: Observational prospective comparative study. SETTING: Otorhinolaryngology unit of a tertiary hospital. PARTICIPANTS: Sixty-two consecutive adult outpatients suspected of LPR. MAIN OUTCOME MEASURES: Bile acids, bilirubin and pepsinogen I-II were measured in saliva. Patients underwent pH metry and based on the results of bile acids were subdivided as acid, mixed and alkaline LPR. RESULTS: Significantly higher Reflux Findings Score (RFS) and Reflux Symptoms Index (RSI) were seen in patients with alkaline and mixed LPR compared to acid LPR. Salivary bile acids >1 µmol/L seem to be a reliable indicator of the severity of LPR. Compared to those without, patients with esophagitis or a history of upper airway malignancy have high concentrations of bile acids in saliva. Among the molecules studied, bile acids were the most suitable for diagnosis of LPR, with a sensitivity of 86% and a positive predictive value of 80.7%. CONCLUSIONS: Our data suggest that high concentrations of bile acids are associated with higher values of RSI and RFS in LPR as well as a higher risk of esophagitis and history of upper airway malignancies. We finally observed that bile acids provided the best biometric parameters for diagnosis of LPR among the molecules tested.

Untreated Psoriasis Impairs Male Fertility: A Case-Control Study.

BACKGROUND: Recent evidence indicates that a systemic state of inflammation may impair fertility, but data about psoriatic males are scarce. OBJECTIVES: The aim of this study was to assess gonadal function in psoriatic males implementing our knowledge about fertility in these subjects. METHODS: Male psoriatic patients, aged between 18 and 55 years, and a group of healthy subjects matched for age, BMI and geographic origin were enrolled. All subjects underwent a complete physical and andrological examination, standard semen analysis, complete microbiological analysis and ultrasound evaluation of sexual glands. Seminal levels of soluble urokinase-type plasminogen activator receptor (suPAR) and serum levels of testosterone, estradiol (E2), sex hormone-binding globulin (SHBG), luteinizing hormone and follicle-stimulating hormone were also assessed. RESULTS: Fifty patients and 50 controls fulfilled the inclusion criteria and were enrolled in our study. Testosterone and SHBG were found to be significantly decreased in patients with psoriasis compared with the control group. Higher levels of E2 were also reported in psoriatic patients. Total sperm count, sperm motility and percent of spermatozoa with normal morphology were significantly reduced in patients compared to controls. suPAR levels were significantly increased in patients compared to controls and found to be above the reference limits. Ultrasound signs of inflammation of the accessory glands were observed in 35/50 patients with psoriasis and in none of the controls. CONCLUSION: Our study suggests that untreated psoriasis may impair male fertility. We also found that this might be due to an impact of systemic inflammation on the hormonal profile and on sexual accessory gland inflammation.

Multi-Marker Approach in Patients with Acute Chest Pain in the Emergency Department.

BACKGROUND: Chest pain is a prevalent reason for emergency room referrals and presents diagnostic challenges. The physician must carefully differentiate between cardiac and noncardiac causes, including various vascular and extracardiovascular conditions. However, it is crucial not to overlook serious conditions such as acute coronary syndrome (ACS). Diagnosis of acute myocardial infarction (AMI) and early discharge management become difficult when traditional clinical criteria, ECG, and troponin values are insufficient. Recently, the focus has shifted to a "multi-marker" approach to improve diagnostic accuracy and prognosis in patients with chest pain. METHODS: This observational, prospective, single-center study involved, with informed consent, 360 patients presenting to the emergency department with typical chest pain and included a control group of 120 healthy subjects. In addition to routine examinations, including tests for hsTnI (Siemens TNIH kit), according to the 0-1 h algorithm, biochemical markers sST2 (tumorigenicity suppression-2) and suPAR (soluble urokinase plasminogen activator receptor) were also evaluated for each patient. A 12-month follow-up was conducted to monitor outcomes and adverse events. RESULTS: We identified two groups of patients: a positive one (112 patients) with high levels of hsTnI, sST2 > 24.19 ng/mL, and suPAR > 2.9 ng/mL, diagnosed with ACS; and a negative one (136 patients) with low levels of hsTnI, suPAR < 2.9 ng/mL, and sST2 < 24.19 ng/mL. During the 12-month follow-up, no adverse events were observed in the negative group. In the intermediate group, patients with hsTnI between 6 ng/L and the ischemic limit, sST2 > 29.1 ng/mL and suPAR > 2.9 ng/mL, showed the highest probability of adverse events during follow-up, while those with sST2 < 24.19 ng/mL and suPAR < 2.9 ng/mL had a better outcome with no adverse events at 12 months. CONCLUSION: Our data suggest that sST2 and suPAR, together with hsTnI, may be useful in the prognosis of cardiovascular patients with ACS, providing additional information on endothelial damage. These biomarkers could guide the clinical decision on further diagnostic investigations. In addition, suPAR and sST2 emerge as promising for event prediction in patients with chest pain. Their integration into the standard approach in PS could facilitate more efficient patient management, allowing safe release or timely admission based on individual risk.

Diagnostic Accuracy of Fecal Calprotectin in Discriminating Organic-Inflammatory Gastrointestinal Diseases and Functional Gastrointestinal Disorders in Older Patients.

Fecal calprotectin (FC) has been largely recognized as a surrogate marker of intestinal neutrophilic inflammation, very reliable in distinguishing between inflammatory bowel diseases and functional gastrointestinal (GI) disorders. Aging has been suggested to influence FC results and their diagnostic accuracy; however, no studies are specifically targeted on this focus. In a retrospective study, we evaluated the eventual age-differences of the diagnostic accuracy of FC in discriminating between organic-inflammatory GI diseases and functional GI disorders. In 573 younger and 172 older (≥65 years) subjects undergoing an FC assay, we found that the latter showed higher median FC values, 72 (25-260) µg/g vs. 47 (25-165) µg/g (p < 0.01). Younger patients were more commonly affected by IBDs, while colorectal cancer and high-risk polyps, infective colitis, and diverticular disease represented the most common findings in the older subgroup. However, the estimated optimum FC threshold in discriminating between organic-inflammatory GI diseases and functional GI disorders was quite similar between the two groups (109 µg/g for the younger subgroup and 98 µg/g for the older subgroup), maintaining a very high specificity. In conclusion, we show that FC also represents a very specific test for intestinal inflammation in older patients, at similar threshold levels to younger subjects.

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.

Association between Plasma HLA-DR+ Placental Vesicles and Preeclampsia: A Pilot Longitudinal Cohort Study.

(1) Background: Preeclampsia (PE) usually presents with hypertension and proteinuria, related to poor placentation. Reduced maternal-fetal immunological tolerance is a possible trigger of inadequate placentation. Aberrant antigen expression of HLA-DR has been observed in the syncytiotrophoblast of PE patients. In this study, we analyzed plasma levels of Human Leukocyte Antigen (HLA)-DR+ syncytiotrophoblast-derived extracellular vesicles (STEVs) during the three trimesters of pregnancy in relation to PE onset. (2) Methods: Pregnant women underwent venous blood sampling during the three trimesters. STEVs were collected from plasma via ultracentrifugation (120,000 g) and characterized by Western blot, nanotracking analysis and flow cytometry for the expression of Placental Alkaline Phosphatase (PLAP), a placental-derived marker, and HLA-DR. (3) Results: Out of 107 women recruited, 10 developed PE. STEVs were detected in all three trimesters of pregnancy with a zenith in the second trimester. A significant difference was found between the non-PE and PE groups in terms of plasma levels of HLA-DR+ STEVs during all three trimesters of pregnancy. (4) Conclusions: More research is needed to investigate HLA-DR+ as a potential early marker of PE.

Predicting Role of GFAP and UCH-L1 biomarkers in Spontaneous Subarachnoid Hemorrhage: a preliminary study to evaluate in the short-term their correlation with severity of bleeding and prognosis.

BACKGROUND: Spontaneous non-traumatic subarachnoid hemorrhage (sSAH) is a severe brain vascular accident. Glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) can be theoretically assayed to predict a patient's progression, picturing different aspects of clinical failure after sSAH. The study aims to: a) explore the correlation between sSAH blood volume and biomarkers variation; b) evaluate if these can be predictive of the neurogenic response after sSAH and be prognostic of patient outcome; c) establish eventual threshold levels of biomarkers to define patients' clinical outcome. METHODS: Blood volumetry at CT scan upon admission, GFAP and UCH-L1 were collected at 24 h, at 72 h, and after 7 days from hemorrhage. Trends and cut-off serum sampling were determined. Clinical outcome was assessed with mRS scale at 14 days. RESULTS: A strong correlation between GFAP and UCH-L1 and blood diffusion volume in all explored serum intervals related to unfavorable outcome. GFAP and UCH-L1 were very early predictors of unfavorable outcomes at 24 h from sSAH (p = 0.002 and 0.011 respectively). Threshold levels of UCH-L1 apparently revealed a very early, early and late predictor of unfavorable outcomes. CONCLUSION: GFAP and UCH-L1 represent a potential tool for prompt monitoring and customization of therapies in neurosurgical patients.

Pulmonary embolism post-Covid-19 infection: physiopathological mechanisms and vascular damage biomarkers.

Covid-19 infection is characterized by several acute complications, as well long-term sequelae, mostly sustained by endothelial dysfunction; several studies show that complications as pulmonary embolism (PE) are described both in the acute phase and after negativization. Aim of research was to evaluate anthropometric, bio-humoral, instrumental parameters in a group of patients affected by PE after recent Covid-19 infection compared to PE patients without previous Covid-19 infection. We enrolled 72 consecutive patients (35M, 37F) with acute PE, distinguished in relation to previous acute Covid-19 infection: 54 pts without previous acute Covid-19 infection and 18 pts with previous Covid-19 infection within negativity at least 2 months before PE diagnosis; 44 healthy subjects (21M, 23F) were recruited as control group. Patients who had previously developed Covid-19 needed hospitalization in high percentage (84%); this group showed significantly higher prevalence of diabetes mellitus than Covid-19-free PE patients, reduced serum levels of C-reactive protein, sST2 and PESI score. In post-Covid-19 PE group, we observed higher mean IMPROVE risk score, whereas in Covid-19-free group lower P/F ratio, higher radiological severity, and worse PESI score and severity index. Covid-19 infection affects not just the lung parenchyma but also other organs; endothelial damage plays pivotal role in long-term alterations; in high thrombotic risk group (recent hospitalization due to acute Covid-19 infection), we have described thrombotic complications characterized by persistent prothrombotic state after recovery, highlighted by well-known markers as PCR and D-Dimer as well as novel vascular marker (sST2).

Relation between high-sensitivity troponin I serum levels and myocardial ischemia in patients with suspected chronic coronary syndrome: The reset-MI study.

BACKGROUND: Previous studies showed that exercise may increase cardiac troponin serum levels; whether the occurrence of myocardial ischemia influences the changes of exercise-induced troponin raise, however, remains debatable. METHODS: We prospectively enrolled consecutive patients undergoing for the first time an elective stress myocardial perfusion scintigraphy (MPS) because of clinical suspicion of obstructive coronary artery disease (CAD). Patients were divided into 3 groups based on the evidence and degree of stress-induced myocardial ischemia at MPS: 1) group 1, no myocardial ischemia (≤4 %); 2) group 2, mild myocardial ischemia (5-10 %); 3) group 3, moderate-to-severe myocardial ischemia (≥10 %). High-sensitivity cardiac troponin I (cTnI) was measured immediately before (T0) and 1 hour (T1) and 4 h (T2) after the stress test. RESULTS: One hundred-seven patients (71 males; age 65.6 ± 9.4 years) were enrolled in the study. Serum hs-cTnI concentrations (logarithmic values) significantly increased after MPS, compared to baseline, in the whole population, from 1.47±1.26 ng/L at T0, to 1.68±1.12 ng/L at T1 (p<0.001) and 2.15±1.02 ng/L at T2 (p<0.001 vs. both T0 and T1). The increase in hs-cTnI did not significantly differ between the 3 groups (p = 0.44). The heart rate achieved during the test was the strongest determinant of cTnI increase (p < 0.001) after the stress test. CONCLUSIONS: In patients with suspected CAD, stress MPS induces an increase of cTnI that is independent of the induction and extension/severity of myocardial ischemia and is mainly related to myocardial work, as indicated by the heart rate achieved during the test.

Mapping of Urinary Volatile Organic Compounds by a Rapid Analytical Method Using Gas Chromatography Coupled to Ion Mobility Spectrometry (GC-IMS).

Volatile organic compounds (VOCs) are a differentiated class of molecules, continuously generated in the human body and released as products of metabolic pathways. Their concentrations vary depending on pathophysiological conditions. They are detectable in a wide variety of biological samples, such as exhaled breath, faeces, and urine. In particular, urine represents an easily accessible specimen widely used in clinics. The most used techniques for VOCs detections are expensive and time-consuming, thus not allowing for rapid clinical analysis. In this perspective, the aim of this study is a comprehensive characterisation of the urine volatilome by the development of an alternative rapid analytical method. Briefly, 115 urine samples are collected; sample treatment is not needed. VOCs are detected in the urine headspace using gas chromatography coupled to ion mobility spectrometry (GC-IMS) by an extremely fast analysis (10 min). The method is analytically validated; the analysis is sensitive and robust with results comparable to those reported with other techniques. Twenty-three molecules are identified, including ketones, aldehydes, alcohols, and sulphur compounds, whose concentration is altered in several pathological states such as cancer and metabolic disorders. Therefore, it opens new perspectives for fast diagnosis and screening, showing great potential for clinical applications.