Can Metformin Exert as an Active Drug on Endothelial Dysfunction in Diabetic Subjects?

Abstract: Cardiovascular mortality is a major cause of death among in type 2 diabetes (T2DM). Endothelial dysfunction (ED) is a well-known important risk factor for the development of diabetes cardiovascular complications. Therefore, the prevention of diabetic macroangiopathies by preserving endothelial function represents a major therapeutic concern for all National Health Systems. Several complex mechanisms support ED in diabetic patients, frequently cross-talking each other: uncoupling of eNOS with impaired endothelium-dependent vascular response, increased ROS production, mitochondrial dysfunction, activation of polyol pathway, generation of advanced glycation end-products (AGEs), activation of protein kinase C (PKC), endothelial inflammation, endothelial apoptosis and senescence, and dysregulation of microRNAs (miRNAs). Metformin is a milestone in T2DM treatment. To date, according to most recent EASD/ADA guidelines, it still represents the first-choice drug in these patients. Intriguingly, several extraglycemic effects of metformin have been recently observed, among which large preclinical and clinical evidence support metformin’s efficacy against ED in T2DM. Metformin seems effective thanks to its favorable action on all the aforementioned pathophysiological ED mechanisms. AMPK pharmacological activation plays a key role, with metformin inhibiting inflammation and improving ED. Therefore, aim of this review is to assess metformin’s beneficial effects on endothelial dysfunction in T2DM, which could preempt development of atherosclerosis

WHATSAPP MESSENGER AS A REAL-TIME TOOL FOR A LONG-DISTANCE ACTIVITY OF A MULTIDISCIPLINARY

Introduction: Communication between doctors is traditionally conducted by written clinical charts. Mobile health is becoming an integral part of modern medical systems, improving accessibility and quality of medical care. Recent papers suggest that an increasing number of doctors are using in their clinical practice mobile tools to communicate clinical informations (1, 2). The aim of our study was to verify the adoption of WhatsApp Messenger in everyday clinical practice to obtain a real-time multidisciplinary collaboration among medical centers located in different areas of the city. Materials and Methods: In January 2016 a WhatsApp Messenger group was created among 25 specialists: 9 urologists, 9 oncologists, 3 urology residents, 3 radiotherapists and 1 general practitioner. A general coordinator and a group coordinator for each specialty was monthly appointed. The participants were invited to interact within the group clinical cases of genitourinary tumors of particular complexity requiring a multidisciplinary approach. All the chats were registered. A preliminary analysis of the activity of the group was planned after the first 10 entered patients. An evaluation questionnaire was sent after 6 months to evaluate the level of appreciation. The questionnaire was composed of a first section investigating the appreciation among the members of the group and a second section analyzing the impact in their everyday clinical practice of whatsapp multidisciplinary consultation. Results: In 10 (91%) out of 11 patients the WhatsApp consultation was completed, one case was not of oncological interest. An average of 8 (range=2-13) specialists joined the chat for each patient. An average of 17.6 (range: 4-43) interventions for each clinical case was recorded. On the average, 27%, 54% and 19% of the interventions for each clinical case were provided by oncologists, urologists and radiotherapists respectively. In 9 (81.8%) cases a final agreement on the patient's management was reached. At the evaluation questionnaire in a scale 1-10, the average rating score of appreciation was 7.8 (range=4-10). Relevant suggestions to improve the Whatsapp Messenger consultation were obtained and will be considered for future application the ameliorate the tool. Discussion: WhatsApp is a useful alternative and powerful complementary communication tool because of its capability to rapidly transfer large amount of clinical and radiological data. In our experience this new approach for multidisciplinary consultations improved collaboration among different specialist in different areas of the city through an easier and more informal change of opinions. In difficult and complex cases a rapid multidisciplinary approach allowed to offer the patient a personalized and tailored therapy management. GSTU Foundation. 1Sidhoum N, Dast S, Abdulshakoor A, Assaf N, Herlin C and Sinna R: WhatsApp: Improvement tool for surgical team communication. J Plast Reconstr Aesthet Surg 69: 1562-1563, 2016. 2 Gould G and Nilforooshan R: WhatsApp Doc? BMJ Innov 2(3): 109-110, 201

Molecular detection of TP53, Ki-Ras and p16INK4A promoter methylation in plasma of patients with colorectal cancer and its association with prognosis. Results of a 3-year GOIM (Gruppo Oncologico dell'Italia Meridionale) prospective study.

BACKGROUND:Despite the improvement in detection and surgical therapy in the last years, the outcome of patients affected by colorectal carcinoma (CRC) remains limited by metastatic relapse. The aim of this study was to investigate the presence of free tumor DNA in the plasma of CRC patients in order to understand its possible prognostic role. PATIENTS AND METHODS: Ki-Ras, TP53 mutations and p16(INK4A) methylation status were prospectively evaluated in tumor tissues and plasma of 66 CRC patients. RESULTS: In 50 of the 66 primitive tumor cases (76%) at least one significant alteration was identified in Ki-Ras and/or TP53 and/or p16(INK4A) genes. Eighteen of the 50 patients presented the same alteration both in the plasma and in the tumor tissue. At univariate analysis, Ki-Ras mutations proved to be significantly related to quicker relapse (P <0.01), whereas only a trend towards statistical significance (P = 0.083) was observed for the TP53 mutations CONCLUSIONS: Detection of Ki-Ras and TP53 mutation in plasma should be significantly related to disease recurrence. These data suggest that patients with a high risk of recurrence can be identified by means of the analysis of tumor-derived plasma DNA with the use of fairly non-invasive techniques

Detection and quantification of mammaglobin in the blood of breast cancer patients: can it be useful as a potential clinical marker? Preliminary results of a GOIM (Gruppo Oncologico dell'Italia Meridionale) prospective study.

BACKGROUND: Mammaglobin is expressed mainly in mammary tissue, overexpressed in breast cancer (BC) and rarely in other tissue. The aim of this study was to assess the sensitivity and specificity of transcript MGB1 detection and to evaluate the role of MGB1 as potential clinical marker for the detection of disseminated cancer cells in the blood of BC patients. PATIENTS AND METHODS: A consecutive series of 23 BC tissues, 36 peripheral blood BC samples and 35 healthy peripheral blood samples was prospectively recruited to investigate MGB1 expression by means of a quantitative Real Time RT-PCR assay. RESULTS: MGB1 overexpression in tissue samples of BC patients is significantly associated only with high level of Ki67 (P <0.05). None of the samples from peripheral blood of 35 healthy female individuals were positive for MGB1 transcript. In contrast MGB1 mRNA expression was detected in three of 36 (8%) peripheral blood of BC patients. CONCLUSIONS: Our preliminary results demonstrate that the detection of MGB1 transcript in peripheral blood of BC patients was specific but with low sensitivity. MGB1 overexpression by itself or in combination with Ki67 might be considered an index of BC progression

Clinical, histopathological and molecular features of dedifferentiated melanomas:An EORTC Melanoma Group Retrospective Analysis

PURPOSE: Dedifferentiated melanoma (DedM) poses significant diagnostic challenges. We aimed to investigate the clinical, histopathological and molecular features of DedM. Methylation signature (MS) and copy number profiling (CNP) were carried out in a subgroup of cases.PATIENTS AND METHODS: A retrospective series of 78 DedM tissue samples from 61 patients retrieved from EORTC (European Organisation for Research and Treatment of Cancer) Melanoma Group centres were centrally reviewed. Clinical and histopathological features were retrieved. In a subgroup of patients, genotyping through Infinium Methylation microarray and CNP analysis was carried out.RESULTS: Most patients (60/61) had a metastatic DedM showing most frequently an unclassified pleomorphic, spindle cell, or small round cell morphology akin to undifferentiated soft tissue sarcoma, rarely associated with heterologous elements. Overall, among 20 successfully analysed tissue samples from 16 patients, we found retained melanoma-like MS in only 7 tissue samples while a non-melanoma-like MS was observed in 13 tissue samples. In two patients from whom multiple specimens were analysed, some of the samples had a preserved cutaneous melanoma MS while other specimens exhibited an epigenetic shift towards a mesenchymal/sarcoma-like profile, matching the histological features. In these two patients, CNP was largely identical across all analysed specimens, in line with their common clonal origin, despite significant modification of their epigenome.CONCLUSIONS: Our study further highlights that DedM represents a real diagnostic challenge. While MS and genomic CNP may help pathologists to diagnose DedM, we provide proof-of-concept that dedifferentiation in melanoma is frequently associated with epigenetic modifications.</p