The Master athlete: An extraordinary physiological model of aging study, a delicate issue for cardiologists and sports physicians

The prolongation of average life in the industrialized countries and the definitive demonstration of preventive and therapeutic role of regular physical exercise and sport, have greatly increased the number of middle-aged and older subjects engaged in the regular practice of sports activities, not only for fun or healthy purposes, but also at competitive level. The creation by sports federations of age categories (five years in five years) has strengthened the agonistic nature of the activity. Master athletes compete not only against adversaries of the same age group but even against themselves and the Time flowing inexorably. At the scientific and clinical level, two are the fundamental implications of this phenomenon. The first is the positive effect of a regular and intense performance training, both anaerobic and aerobic power. In the latter, regular and intense training is able to slow down significantly (even 50%) the natural, progressive decline of cardiorespiratory functions observed in healthy sedentary subjects of the same age. The second, the reverse of the medal, is the difficulty encountered by sports physician and cardiologist to correctly interpret the clinical/instrumental features of the Master athlete who undergoes pre-participation screening for competitive sports. It is not always easy to differentiate the physiological, adaptive, changes of a middle-aged and older athlete from the pathological ones, related to cardiovascular disease, typical of aging, such as ischemic heart disease, arrhythmias, hypertension, valvular diseases. These difficulties can only be solved by having an adequate knowledge of the clinical and instrumental manifestations of the Master Athlete’s Heart and individual cardiopathies, and with the careful use of all modern cardiological instrumental investigations. In addition to echocardiography and maximal ECG stress-test (preferably cardio-pulmonary test), the magnetic resonance imaging with Gadolinium, and coronary tomography (TC) are playing a decisive role. [1

Polymorphic variants of IGF2BP3 and SENCR have an impact on predisposition and/or progression of Ewing sarcoma

Ewing sarcoma (EWS), the second most common malignant bone tumor in children and adolescents, occurs abruptly without clear evidence of tumor history or progression. Previous association studies have identified some inherited variants associated with the risk of developing EWS but a common picture of the germline susceptibility to this tumor remains largely unclear. Here, we examine the association between thirty single nucleotide polymorphisms (SNPs) of the IGF2BP3, a gene that codes for an oncofetal RNA-binding protein demonstrated to be important for EWS patient's risk stratification, and five SNPs of SENCR, a long non-coding RNA shown to regulate IGF2BP3. An association between polymorphisms and EWS susceptibility was observed for three IGF2BP3 SNPs - rs112316332, rs13242065, rs12700421 - and for four SENCR SNPs - rs10893909, rs11221437, rs12420823, rs4526784 -. In addition, IGF2BP3 rs34033684 and SENCR rs10893909 variants increased the risk for female respect to male subgroup when carried together, while IGF2BP3 rs13242065 or rs76983703 variants reduced the probability of a disease later onset (> 14 years). Moreover, the absence of IGF2BP3 rs10488282 variant and the presence of rs199653 or rs35875486 variant were significantly associated with a worse survival in EWS patients with localized disease at diagnosis. Overall, our data provide the first evidence linking genetic variants of IGF2BP3 and its modulator SENCR to the risk of EWS development and to disease progression, thus supporting the concept that heritable factors can influence susceptibility to EWS and may help to predict patient prognosis

Adult IDH wild-type glioblastoma ultrastructural investigation suggests a possible correlation between morphological biomarkers and Ki-67 index

Glioblastoma is an aggressive brain tumor with an average life expectancy between 14 and 16 months after diagnosis. The Ki-67 labeling index (LI), a measure of cellular proliferation, is emerging as a prognostic marker in GBM. In this study, we investigated the ultrastructure of glioblastoma tissue from 9 patients with the same molecular profile (adult IDH wild-type glioblastoma, wild-type ATRX, and positive for TP53 expression, GFAP expression, and EGFR overexpression) to find possible ultrastructural features to be used as biomarkers and correlated with the only parameter that differs among our samples, the Ki-67 LI. Our main results were the visualization of the anatomical basis of astrocyte-endothelial cells crosstalk; the ultrastructural in situ imaging of clusters of hyperactivated microglia cells (MsEVs); the ultrastructural in situ imaging of microglia cells storing lipid vesicles (MsLVs); the ultrastructural in situ imaging of neoplastic cells mitophagy (NCsM). The statistical analysis of our data indicated that MsEVs and MsLVs correlate with the Ki-67 LI value. We can thus assume they are good candidates to be considered morphological biomarkers correlating to Ki-67 LI. The role of NCsM instead must be further evaluated. Our study findings demonstrate that by combining ultrastructural characteristics with molecular information, we can discover biomarkers that have the potential to enhance diagnostic precision, aid in treatment decision-making, identify targets for therapy, and enable personalized treatment plans tailored to each patient. However, further research with larger sample sizes is needed to validate these findings and fully utilize the potential of ultrastructural analysis in managing glioblastoma

Role of 1p/19q Codeletion in Diffuse Low-grade Glioma Tumour Prognosis

Background/Aim: In the latest 2021 WHO classification of central nervous system tumours (CNS), gliomas that present isocitrate dehydrogenase (IDH) mutations are defined as diffuse low-grade gliomas (DLGGs). IDH mutations are commonly observed in this tumour type. The Extent of Resection (EOR) positively influence survival; however, it is still debated whether the predictive value of EOR is independent of the 1p/19q co-deletion. We carried out a retrospective analysis on patients operated on for DLGG at the Sant’Andrea University Hospital Sapienza University of Rome, correlating the outcome with the presence of 1p/19q co-deletion and EOR. Patients and Methods: The study examined 66 patients with DLGG who had undergone surgery for tumour resection between 2008 and 2018. Patients with DLGG were divided into two groups; diffuse astrocytoma (DA) in which 1p/19q codeletion is absent and oligodendroglioma (OG) in which 1p/19q codeletion is present. According to EOR, both groups were divided into two subgroups: subtotal resection (STR) and gross total resection (GTR). Three end-point variables were considered: overall survival (OS), progression-free survival (PFS) and time to malignant transformation (TMT). Results: In the DA group, the GTR subgroup had an average OS of 81.6 months, an average PFS of 45.9 months and an average TMT of 63.6 months. After surgery, these patients had an average Karnofsky Performance Score (KPS) of 83.4. The STR subgroup had an average OS of 60.4 months, PFS was 38.7 months, and TMT was 46.4 months, post-operative KPS was 83.4. In contrast, in the OG group, the GTR averagely had 101.7 months of OS, 64.9 months of PFS, 80.3 months of TMT and an average post-operative KPS of 84.2, and the STR subgroup had an average of OS of 73.3 months, PFS of 48.2 months, TMT of 57.3 and an average postoperative KPS of 96.2. Conclusion: In patients affected by DLGGs, 1p/19q codeletion is significantly associated with prolonged survival and longer time-to-malignant transformation (TMT) compared to the absence of 1p/19q codeletion. Also, the extent of surgical resection (EOR) in DLGG patients has been confirmed as one of the main prognostic factors. However, its predictive value is substantially influenced by the presence of the 1p/19q codeletion

Clinical care pathway program versus open-access system: a study on appropriateness, quality, and efficiency in the delivery of colonoscopy in the colorectal cancer

Open-access colonoscopy (OAC), whereby the colonoscopy is performed without a prior office visit with a gastroenterologist, is affected by inappropriateness which leads to overprescription and reduced availability of the procedure in case of alarming symptoms. The clinical care pathway (CCP) is a healthcare management tool promoted by national health systems to organize work-up of various morbidities. Recently, we started a CCP dedicated to colorectal cancer (CRC), including a colonoscopy session for CRC diagnosis and prevention. We aimed to evaluate the appropriateness, the quality, and the efficiency in the delivery of colonoscopy with the open-access system and a CCP program in the CRC. Quality indicators for colonoscopy in subjects in the CCP were compared to referrals by general practitioners (OAC) or by non-gastroenterologist physicians (non-gastroenterologist physician colonoscopy, NGPC). Attendance rate to colonoscopy was greater in the CCP group and NGPC group than in the OAC group (99%, 99%, and 86%, respectively). Waiting time in the CCP group was shorter than in the OAC group (3.88 ± 2.27 vs. 32 ± 22.31 weeks, respectively). Appropriateness of colonoscopy prescription was better in the CCP group than in the OAC group (92 vs. 50%, respectively). OAC is affected by the lack of timeliness and low appropriateness of prescription. A CCP reduces the number of inappropriate colonoscopies, especially for post-polypectomy surveillance, and improves the delivery of colonoscopy in patients requiring a fast-track examination. The high rate of inappropriate OAC suggests that this modality of healthcare should be widely reviewed

Impact of protein domains on PE_PGRS30 polar localization in Mycobacteria

PE_PGRS proteins are unique to the Mycobacterium tuberculosis complex and a number of other pathogenic mycobacteria. PE_PGRS30, which is required for the full virulence of M. tuberculosis (Mtb), has three main domains, i.e. an N-terminal PE domain, repetitive PGRS domain and the unique C-terminal domain. To investigate the role of these domains, we expressed a GFP-tagged PE_PGRS30 protein and a series of its functional deletion mutants in different mycobacterial species (Mtb, Mycobacterium bovis BCG and Mycobacterium smegmatis) and analysed protein localization by confocal microscopy. We show that PE_PGRS30 localizes at the mycobacterial cell poles in Mtb and M. bovis BCG but not in M. smegmatis and that the PGRS domain of the protein strongly contributes to protein cellular localization in Mtb. Immunofluorescence studies further showed that the unique C-terminal domain of PE_PGRS30 is not available on the surface, except when the PGRS domain is missing. Immunoblot demonstrated that the PGRS domain is required to maintain the protein strongly associated with the non-soluble cellular fraction. These results suggest that the repetitive GGA-GGN repeats of the PGRS domain contain specific sequences that contribute to protein cellular localization and that polar localization might be a key step in the PE_PGRS30-dependent virulence mechanism

PATZ1 acts as a tumor suppressor in thyroid cancer via targeting p53-dependent genes involved in EMT and cell migration

PATZ1, a POZ-Zinc finger protein, is emerging as an important regulator of development and cancer, but its cancer-related function as oncogene or tumor-suppressor is still debated. Here, we investigated its possible role in thyroid carcinogenesis. We demonstrated PATZ1 is down-regulated in thyroid carcinomas compared to normal thyroid tissues, with an inverse correlation to the degree of cell differentiation. In fact, PATZ1 expression was significantly further down-regulated in poorly differentiated and anaplastic thyroid cancers compared to the papillary histotype, and it resulted increasingly delocalized from the nucleus to the cytoplasm proceeding from differentiated to undifferentiated thyroid carcinomas. Restoration of PATZ1 expression in three thyroid cancer-derived cell lines, all characterized by fully dedifferentiated cells, significantly inhibited their malignant behaviors, including in vitro proliferation, anchorage-independent growth, migration and invasion, as well as in vivo tumor growth. Consistent with recent studies showing a role for PATZ1 in the p53 pathway, we showed that ectopic expression of PATZ1 in thyroid cancer cells activates p53-dependent pathways opposing epithelial-mesenchymal transition and cell migration to prevent invasiveness. These results provide insights into a potential tumor-suppressor role of PATZ1 in thyroid cancer progression, and thus may have potential clinical relevance for the prognosis and therapy of thyroid cancer

Lower dose rituximab is active in adults patients with idiopathic thrombocytopenic purpura

Rituximab 375 mg/m2weekly for four weeks has significant activity in patients with immune thrombocytopenia. We evaluated the activity of lower dose rituximab (100 mg iv weekly for 4 weeks) in 28 adults with idiopathic thrombocytopenic purpura. Overall (platelet count > 50×109/L) and complete responses (platelet count > 100×109/L) were achieved in 21/28 (75%) and 12/28 (43%) patients respectively. The median time to response and time to complete response were 31 and 44 days respectively. After a median follow-up of 11 months (range 3-18), 7/21 (33%) patients relapsed and 3 needed further treatments. In patients with idiopathic thrombocytopenic purpura, lower dose rituximab seems to show similar activity to standard dose. ©2008 Ferrata Storti Foundation

First molecular identification of the zoonotic parasite Anisakis pegreffii (Nematoda: Anisakidae) in a paraffin-embedded granuloma taken from a case of human intestinal anisakiasis in Italy

<p>Abstract</p> <p>Background</p> <p>Anisakiasis is an important fish-borne zoonosis provoked by larval stages of nematodes belonging to the genus <it>Anisakis</it>. The detection and identification of human infections is difficult. This is due to: a) the low specificity of the clinical features and symptomatology related to human infections; b) the paucity of diagnostic features of larvae found in granulomatous lesions characteristic of "invasive anisakiasis"; and c) the lack morphological characters diagnostic at the specific level when larvae of <it>Anisakis </it>are detected. Thus, molecular-based diagnostic approaches are warranted.</p> <p>Method</p> <p>We have developed a PCR method that amplifies the DNA of <it>Anisakis </it>spp. in fixed paraffin-embedded tissues. This method was applied to a granuloma removed from a human case of intestinal anisakiasis in Italy. Specific primers of the mtDNA <it>cox2 </it>gene were used and sequence analysis was performed according to the procedures already established for species of <it>Anisakis</it>.</p> <p>Results</p> <p>The sequence obtained (629 bp) was compared with those of the other species of <it>Anisakis </it>which have so far been genetically characterized and with sequences obtained from larval stages of <it>Anisakis </it>collected from the Mediterranean fish <it>Engraulis encrasicolus</it>. This enabled the genetic identification of the larva in the human tissue as <it>A. pegreffii</it>. This is the first instance of human intestinal anisakiasis diagnosed using PCR of DNA purified from a fixed eosinophilic granuloma embedded in paraffin.</p> <p>Conclusion</p> <p>The case of human anisakiasis presented reinforces the pathological significance of the species <it>A. pegreffii </it>to humans. The molecular/genetic methodological approach based on mtDNA <it>cox2 </it>sequence analysis, described here, can allow easy and rapid identification of <it>Anisakis </it>spp. in formalin-fixed and paraffin embedded tissues removed from cases of either gastric or intestinal human anisakiasis.</p