Leda Marina Pomes

Bio: Leda Marina Pomes is an academic researcher from Sapienza University of Rome. The author has contributed to research in topics: Pharmacogenomics & Multiple chemical sensitivity. The author has an hindex of 6, co-authored 10 publications receiving 116 citations. Previous affiliations of Leda Marina Pomes include University of Chieti-Pescara.

Optimising migraine treatment: from drug-drug interactions to personalized medicine

Abstract: Migraine is the most disabling and expensive chronic disorders, the etiology of which is still not fully known. The neuronal systems, (glutammatergic, dopaminergic, serotoninergic and GABA-ergic) whose functionality is partly attributable to genetically determined factors, has been suggested to play an important role. The treatment of acute attacks and the prophylactic management of chronic forms include the use of different category of drugs, and it is demonstrated that not each subject has the same clinical answer to them. The reason of this is to be searched in different functional capacity and quantity of phase I enzymes (such as different isoforms of CYP P450), phase II enzymes (such as UDP-glucuronosyltransferases), receptors (such as OPRM1 for opioids) and transporters (such as ABCB1) involved in the metabolic destiny of each drug, all of these dictated by DNA and RNA variations. The general picture is further exacerbated by the need for polytherapies, often also to treat comorbidities, which may interfere with the pharmacological action of anti-migraine drugs. Personalized medicine has the objective of setting the optimal therapies in the light of the functional biochemical asset and of the comorbidities of the individual patient, in order to obtain the best clinical response. Novel therapeutic perspectives in migraine includes biotechnological drugs directed against molecules (such as CGRP and its receptor) that cause vasodilatation at the peripheral level of the meningeal blood vessels and reflex stimulation of the parasympathetic system. Drug-drug interactions and the possible competitive metabolic destiny should be studied by the application of pharmacogenomics in large scale. Drug-drug interactions and their possible competitive metabolic destiny should be studied by the application of pharmacogenomics in large scale.

Long-term results after resection of bronchial carcinoid tumour: evaluation of survival and prognostic factors

Abstract: OBJECTIVES: We retrospectively analysed morbidity, mortality and oncological results of patients who had undergone surgery for bronchial carcinoid tumours. METHODS: Between 2002 and 2012, 65 patients with bronchial carcinoids underwent lobectomy (n= 34), sublobar resection (segmentectomy/wedge) (n= 18), sleeve lobectomy (n= 5) (reconstruction of the pulmonary artery was associated in 1 case), sleeve resection of the main bronchus (n= 4) or pneumonectomy (n= 4) (reconstruction of the carina was associated in 1 case). RESULTS: Resection was radical with histologically negative margins in all patients (R0). Histology showed typical carcinoid (TC) in 55 (84.6%) patients and atypical carcinoid (AC) in 10 (15.4%) patients. Final pathological stages were Stage I in 42 (64.6%) patients, Stage II in 18 (27.7%) and Stage III in 5 (7.7%). No postoperative mortality was observed. The postoperative morbidity rate was 15.4% (no bronchial and/or vascular reconstructive-related complications occurred). The median follow-up was 58 (range 2–121) months. The overall recurrence rate was 12.3% (n= 8). The survival rate at 5 years was 100% for TC and 87% for AC. Disease-free survival rates at 3 and 5 years were 95 and 93% for TC and 78 and 44% for AC, respectively (P= 0.004). Pathological nodal involvement (pN1–N2) did not affect overall survival or recurrence. CONCLUSIONS: The surgical treatment of bronchial carcinoids provides high long-term survival rates. Low postoperative morbidity and mortality can be expected even after bronchial reconstruction. The AC appears to be the main factor that determines the risk of recurrence. Bronchial reconstructive lung sparing operations are not related to an increased recurrence rate.

Bilateral Single-Port Sympathectomy: Long-Term Results and Quality of Life

Abstract: Object. Video-assisted thoracoscopic sympathectomy is a safe, effective, and minimally invasive procedure for primary hyperhidrosis. This study aims to evaluate long-term results and patients' quality of life and investigate potential variables responsible for compensatory sweating after one-stage bilateral single-port thoracoscopic sympathectomy. Methods. Between 2005 and 2011, 260 consecutive bilateral thoracoscopic sympathectomies were performed in 130 patients for primary palmar and axillary hyperidrosis through one-port access. Residual pain, postoperative complications, recurrence of symptoms, heart rate adjustment, and quality of life were analyzed. Multivariate analysis was performed. Results. No operative mortality and conversion to open surgery were recorded. Mean operative time was 38 ± 5 minutes. Mean hospital stay was 1.1 ± 0.6 days. Eight patients (6%) had unilateral pneumothorax. Twenty-five cases (19%) were complicated by compensatory sweating. Winter and fall were identified as protective factors for compensatory sweating occurrence. Decreased heart rate was observed 1 year after surgery and permanently over the time. No recurrence during the follow-up period (31.5 months) was observed and 90% of patients showed improved quality of life. Conclusions. One-stage bilateral miniuniportal thoracoscopic sympathectomy is a valid and safe treatment for primary hyperhidrosis, achieving definitive and esthetic results, with excellent patients' satisfaction. Compensatory sweating may potentially occur in a season-dependent manner.

Persistent Post-Traumatic Headache and Migraine: Pre-Clinical Comparisons

Abstract: Background: Oftentimes, persistent post traumatic headache (PPTH) and migraine are phenotypically similar and the only clinical feature that differentiate them is the presence of a mild or moderate traumatic brain injury (mTBI). The aim of this study is to describe the differences in brain area and in biochemical cascade after concussion and to define the efficacy and safety of treatments in use. Methods: Sources were chosen in according to the International Classification of Headache Disorder (ICHD) criteria. Results: The articles demonstrated a significant difference between PPTH and migraine regarding static functional connectivity (sFC) and dynamic functional connectivity (dFC) in brain structure that could be used for exploring the pathophysiological mechanisms in PPTH. Many studies described a cascade of neuro-metabolic changes that occur after traumatic brain injury. These variations are associated to the mechanism occurring when developing a PPTH. Conclusions: The state of art of this important topic show how although the mechanisms underlying the development of the two different diseases are different, the treatment of common migraine is efficacious in patients that have developed a post traumatic form.

Current and emerging evidence-based treatment options in chronic migraine: a narrative review

Abstract: Chronic migraine is a disabling condition that is currently underdiagnosed and undertreated. In this narrative review, we discuss the future of chronic migraine management in relation to recent progress in evidence-based pharmacological treatment. Patients with chronic migraine require prophylactic therapy to reduce the frequency of migraine attacks, but the only currently available evidence-based prophylactic treatment options for chronic migraine are topiramate and onabotulinumtoxinA. Improved prophylactic therapy is needed to reduce the high burden of chronic migraine in Italy. Monoclonal antibodies that target the calcitonin gene-related peptide (CGRP) pathway of migraine pathogenesis have been specifically developed for the prophylactic treatment of chronic migraine. These anti-CGRP/R monoclonal antibodies have demonstrated good efficacy and excellent tolerability in phase II and III clinical trials, and offer new hope to patients who are currently not taking any prophylactic therapy or not benefitting from their current treatment. Treatment of chronic migraine is a dynamic and rapidly advancing area of research. New developments in this field have the potential to improve the diagnosis and provide more individualised treatments for this condition. Establishing a culture of prevention is essential for reducing the personal, social and economic burden of chronic migraine.

Incomplete Systemic Recovery and Metabolic Phenoreversion in Post-Acute-Phase Nonhospitalized COVID-19 Patients: Implications for Assessment of Post-Acute COVID-19 Syndrome.

Abstract: We present a multivariate metabotyping approach to assess the functional recovery of nonhospitalized COVID-19 patients and the possible biochemical sequelae of "Post-Acute COVID-19 Syndrome", colloquially known as long-COVID. Blood samples were taken from patients ca. 3 months after acute COVID-19 infection with further assessment of symptoms at 6 months. Some 57% of the patients had one or more persistent symptoms including respiratory-related symptoms like cough, dyspnea, and rhinorrhea or other nonrespiratory symptoms including chronic fatigue, anosmia, myalgia, or joint pain. Plasma samples were quantitatively analyzed for lipoproteins, glycoproteins, amino acids, biogenic amines, and tryptophan pathway intermediates using Nuclear Magnetic Resonance (NMR) spectroscopy and mass spectrometry. Metabolic data for the follow-up patients (n = 27) were compared with controls (n = 41) and hospitalized severe acute respiratory syndrome SARS-CoV-2 positive patients (n = 18, with multiple time-points). Univariate and multivariate statistics revealed variable patterns of functional recovery with many patients exhibiting residual COVID-19 biomarker signatures. Several parameters were persistently perturbed, e.g., elevated taurine (p = 3.6 × 10-3 versus controls) and reduced glutamine/glutamate ratio (p = 6.95 × 10-8 versus controls), indicative of possible liver and muscle damage and a high energy demand linked to more generalized tissue repair or immune function. Some parameters showed near-complete normalization, e.g., the plasma apolipoprotein B100/A1 ratio was similar to that of healthy controls but significantly lower (p = 4.2 × 10-3) than post-acute COVID-19 patients, reflecting partial reversion of the metabolic phenotype (phenoreversion) toward the healthy metabolic state. Plasma neopterin was normalized in all follow-up patients, indicative of a reduction in the adaptive immune activity that has been previously detected in active SARS-CoV-2 infection. Other systemic inflammatory biomarkers such as GlycA and the kynurenine/tryptophan ratio remained elevated in some, but not all, patients. Correlation analysis, principal component analysis (PCA), and orthogonal-partial least-squares discriminant analysis (O-PLS-DA) showed that the follow-up patients were, as a group, metabolically distinct from controls and partially comapped with the acute-phase patients. Significant systematic metabolic differences between asymptomatic and symptomatic follow-up patients were also observed for multiple metabolites. The overall metabolic variance of the symptomatic patients was significantly greater than that of nonsymptomatic patients for multiple parameters (χ2 p = 0.014). Thus, asymptomatic follow-up patients including those with post-acute COVID-19 Syndrome displayed a spectrum of multiple persistent biochemical pathophysiology, suggesting that the metabolic phenotyping approach may be deployed for multisystem functional assessment of individual post-acute COVID-19 patients.

Distinctive pathological and clinical features of lung carcinoids with high proliferation index.

Abstract: Typical (TCs) and atypical carcinoids (ACs) are defined based on morphological criteria, and no grading system is currently accepted to further stratify these entities. The 2015 WHO classification restricts the Ki-67 role to biopsy or cytology samples, rather than for prognostic prediction. We aimed to investigate whether values and patterns of Ki-67 alone would allow for a clinically meaningful stratification of lung carcinoids, regardless of histological typing. Ki-67 proliferation index and pattern (homogeneous versus heterogeneous expression) were assessed in a cohort of 171 TCs and 68 ACs. Cases were subdivided into three Ki-67 ranges (<4/4–9/≥10%). Correlations with clinicopathological data, univariate and multivariate survival analyses were performed. The majority of cases (61.5%) belonged to the <4% Ki-67 range; 25.1 and 13.4% had a proliferation index of 4–9% and ≥10%, respectively. The <4% Ki-67 subgroup was significantly enriched for TCs (83%, p < 0.0001); ACs were more frequent in the subgroup showing Ki-67 ≥ 10% (75%, p < 0.0001). A heterogeneous Ki-67 pattern was preferentially seen in carcinoids with a Ki-67 ≥10% (38%, p < 0.02). Mean Ki-67 values ≥4 and ≥10% identified categories of poor prognosis both in terms of disease-free and overall survival (p = 0.003 and <0.0001). At multivariate analysis, the two thresholds did not retain statistical significance; however, a Ki-67 ≥ 10% identified a subgroup of dismal prognosis even within ACs (p = 0.03) at univariate analysis. Here, we describe a subgroup of lung carcinoids showing brisk proliferation activity within the necrosis and/or mitotic count-based categories. These patients were associated with specific clinicopathological characteristics, to some extent regardless of histological subtyping.

EHF-LTB Aids to management of headache disorders in primary care (2nd edition)

Abstract: The Aids to Management are a product of the Global Campaign against Headache, a worldwide programme of action conducted in official relations with the World Health Organization. Developed in partnership with the European Headache Federation, they update the first edition published 11 years ago.The common headache disorders (migraine, tension-type headache and medication-overuse headache) are major causes of ill health. They should be managed in primary care, firstly because their management is generally not difficult, and secondly because they are so common. These Aids to Management, with the European principles of management of headache disorders in primary care as the core of their content, combine educational materials with practical management aids. They are supplemented by translation protocols, to ensure that translations are unchanged in meaning from the English-language originals.The Aids to Management may be individually downloaded and, as is the case for all products of the Global Campaign against Headache, are available without restriction for non-commercial use.