Publications by authors named "Giuseppe Grande"

56 Publications

Dilation assisted stone extraction for complex biliary lithiasis: Technical aspects and practical principles.

World J Gastrointest Endosc 2021 Feb;13(2):33-44

Gastroenterology and Digestive Endoscopy Unit, Azienda Ospedaliero Universitaria di Modena, Modena 41126, Italy.

Common bile duct stones are frequently diagnosed worldwide and are one of the main indications for endoscopic retrograde cholangio-pancreatography. Endoscopic sphincterotomy (EST) has been used for the removal of bile duct stones for the past 40 years, providing a wide opening to allow extraction. Up to 15% of patients present with complicated choledocholithiasis. In this context, additional therapeutic approaches have been proposed such as endoscopic mechanical lithotripsy, intraductal or extracorporeal lithotripsy, or endoscopic papillary large balloon dilation (EPLBD). EPLBD combined with EST was introduced in 2003 to facilitate the passage of large or multiple bile duct stones using a balloon greater than 12 mm in diameter. EPLBD without EST was introduced as a simplified technique in 2009. Dilation-assisted stone extraction (DASE) is the combination of two techniques: EPLBD and sub-maximal EST. Several studies have reported this technique as safe and effective in patients with large bile duct stones, without any increased risk of adverse events such as pancreatitis, bleeding, or perforation. Nevertheless, it is difficult to analyze the outcomes of DASE because there are no standard techniques and definitions between studies. The purpose of this paper is to provide technical guidance and specific information about the main issues regarding DASE, based on current literature and daily clinical experience in biliary referral centers.
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http://dx.doi.org/10.4253/wjge.v13.i2.33DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890407PMC
February 2021

Too big to go out: gastric endoscopic submucosal dissection of giant lipoma complicated by intestinal obstruction.

Endoscopy 2021 Feb 4. Epub 2021 Feb 4.

Gastroenterology and Digestive Endoscopy Unit, Azienda Ospedaliero-Universitaria di Modena, Baggiovara, Modena, Italy.

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http://dx.doi.org/10.1055/a-1346-8122DOI Listing
February 2021

Large iatrogenic sigmoid colon perforation treated with endoloop-assisted clip closure and over-the-scope clip: a case report.

Endoscopy 2021 Jan 27. Epub 2021 Jan 27.

Azienda Ospedaliero-Universitaria di Modena, Gastroenterology and Digestive Endoscopy Unit.

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http://dx.doi.org/10.1055/a-1333-0620DOI Listing
January 2021

Lps-Stimulated Sertoli Cells Pre-Loaded With Microparticles: Intracellular Activation Pathways.

Front Endocrinol (Lausanne) 2020 7;11:611932. Epub 2021 Jan 7.

Department of Experimental Medicine, University of Perugia, Perugia, Italy.

Sertoli cells (SC) are immune privileged cells with the capacity of modulating the immune response by expressing several immune-regulatory factors. SC have the capacity to respond to external stimuli through innate phagocytic and antibacterial activities. This evidence evoked a potential role of SC as drug carriers and therapeutic agents. Such stimuli drive SC towards a still unknown evolution, the clinical relevance of which as yet remains undisclosed. This study sought to investigate the effects of external stimuli in the form of polymeric microparticles (MP) and bacteria derived endotoxins, such as lipopolysaccharides (LPS), in order to identify the pathways potentially involved in cell phenotype modifications. Compared to single stimulation, when combined, MP and LPS provoked a significant increase in the gene expression of IDO, PD-L1, FAS-L, TLR-3, TLR-4, MHC-II, ICAM-1, TFGβ1, BDF123, BDF129, BDF3 and pEP2C. Western Blotting analysis demonstrated up-regulation of the ERK 1-2 and NF-kB p65 phosphorylation ratios. Our study, showing the exponential increase of these mediators upon combined MP and LPS stimulation, suggests a "switch" of SC function from typical cells of the blood-testicular barrier to nonprofessional tolerogenic antigen-presenting cells. Further studies should target the clinical and technological implications of such stimuli-induced SC transformation.
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http://dx.doi.org/10.3389/fendo.2020.611932DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817811PMC
January 2021

Nuclear Localization of PTTG1 Promotes Migration and Invasion of Seminoma Tumor through Activation of MMP-2.

Cancers (Basel) 2021 Jan 8;13(2). Epub 2021 Jan 8.

International Scientific Institute "Paul VI", ISI, Fondazione Policlinico 'A. Gemelli' IRCCS, 00100 Rome, Italy.

(1) Background: PTTG1 sustains the invasiveness of several cancer types. We previously reported that in seminomas, PTTG1 was detected in the peripheral area of the tumor and in the leading infiltrative edge. Here, we investigate the PTTG1 role on the invasive properties of seminoma. (2) Methods: three seminoma cell lines were used as in vitro model. PTTG1 levels and localization were investigated by biochemical and immunofluorescence analyses. Wound-healing, Matrigel invasion assays, and zymography were applied to study migratory and invasive capability of the cell lines. RNA interference and overexpression experiments were performed to address the PTTG1 role in seminoma invasiveness. PTTG1 and its target MMP-2 were analyzed in human testicular tumors using the Atlas database. (3) Results: PTTG1 was highly and differentially expressed in the seminoma cell lines. Nuclear PTTG1 was positively correlated to the aggressive phenotype. Its modulation confirms these results. Atlas database analysis revealed that PTTG1 was localized in the nucleus in seminoma compared with non-seminoma tumors, and that MMP-2 levels were significantly higher in seminomas. (4) Conclusions: nuclear PTTG1 promotes invasiveness of seminoma cell lines. Atlas database supported these results. These data lead to the hypothesis that nuclear PTTG1 is an eligible prognostic factor in seminomas.
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http://dx.doi.org/10.3390/cancers13020212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7826632PMC
January 2021

Common bile duct lesions - how cholangioscopy helps rule out intraductal papillary neoplasms of the bile duct: A case report.

World J Gastrointest Endosc 2020 Dec;12(12):555-559

Endoscopy Unit, Azienda Ospedaliero-Universitaria di Modena, Modena 41121, MO, Italy.

Background: Intraductal papillary neoplasm of the bile duct (IPNB) is a rare variant of bile duct tumors, characterized by an exophytic growth exhibiting a papillary mass within the bile duct lumen and it can be localized anywhere along the biliary tree, with morphological variations and occasional invasion.

Case Summary: We present a patient with obstructive jaundice who was diagnosed with IPNB using cholangioscopy during endoscopic retrograde cholangio-pancreatography. Using the SpyGlass DS II technology, we were able to define tumor extension and obtain targeted Spy-byte biopsies. After multidisciplinary evaluation, the patient was scheduled for surgical resection of the tumor, which was radically removed.

Conclusion: Cholangioscopy appears to be crucial for the rapid and clear diagnosis of lesions in the bile duct to achieve radical surgical resection.
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http://dx.doi.org/10.4253/wjge.v12.i12.555DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7739144PMC
December 2020

Protein and Peptide Markers in Endocrine Diseases.

Protein Pept Lett 2020 ;27(12):1179-1180

Division of Endocrinology Fondazione Policlinico "A. Gemelli" Rome, Italy.

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http://dx.doi.org/10.2174/092986652712201202094908DOI Listing
January 2020

COVID-19 and the Gastrointestinal System: Lesions Beyond the Symptoms?

ACG Case Rep J 2020 Sep 24;7(9):e00464. Epub 2020 Sep 24.

Gastroenterology and Digestive Endoscopy Unit, Azienda Ospedaliero, Universitaria di Modena, Modena, Italy.

The outbreak of the COVID-19 pandemic has radically changed the daily hospital care activity for all medical specialists. Although the predominant symptoms of this new coronavirus infection are respiratory, the gastrointestinal tract is also significantly involved. In this short report, we will discuss a new and unexpected clinical presentation related to COVID-19 colonization of upper gastrointestinal tract.
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http://dx.doi.org/10.14309/crj.0000000000000464DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7523829PMC
September 2020

"" Effect of Different Follicle-Stimulating Hormone Preparations on Sertoli Cells: Toward a Personalized Treatment for Male Infertility.

Front Endocrinol (Lausanne) 2020 18;11:401. Epub 2020 Jun 18.

Research Unit on Human Reproduction, International Scientific Institute Paul VI, Rome, Italy.

Follicle-stimulating hormone (FSH), a major regulator of spermatogenesis, has a crucial function in the development and function of the testis and it is extensively given as a fertility treatment to stimulate spermatogenesis. We analyzed the effects of different FSH preparations (α-follitropin, β-follitropin, and urofollitropin) in combination with testosterone on porcine pre-pubertal Sertoli cells. To study the effect of the different FSH treatments in the Sertoli cell function we performed Real Time PCR analysis of AMH, inhibin B, and FSH-r, an ELISA assay for AMH and inhibin B, and a high-throughput comparative proteomic analysis. We verified that all three preparations induced a reduction of AMH in terms of mRNA and secreted proteins, and an increase of inhibin B in terms of mRNA in all the FSH formulations, while solely α-follitropin produced an increase of secreted inhibin B in the culture medium. Comparative proteomic analysis of the three FSH preparations identified 46 proteins, 11 up-regulated and 2 down-regulated. Surprisingly, the combination of testosterone with β-follitropin specifically induced an up-regulation of eight specific secreted proteins. Our study, showing that the three different FSH preparations induce different effects, could offer the opportunity to shed light inside new applications to a personalized reproductive medicine.
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http://dx.doi.org/10.3389/fendo.2020.00401DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7314925PMC
May 2021

Why Do We Need New Markers for Male Hypogonadism and How Seminal Proteomics Might Solve the Problem?

Protein Pept Lett 2020 ;27(12):1186-1191

International Scientific Institute “Paul VI”, Rome, Italy

Male hypogonadism is "a clinical syndrome that results from failure of the testis to produce physiological concentrations of testosterone and/or a normal number of spermatozoa due to pathology at one or more levels of the hypothalamic- pituitary-testicular axis". The diagnostic protocol of male hypogonadism includes accurate medical history, physical exam, as well as hormone assays and instrumental evaluation. Basal hormonal evaluation of serum testosterone, LH, and FSH is important in the evaluation of diseases of the hypothalamus-pituitary-testis axis. Total testosterone levels < 8 nmol/l profoundly suggest the diagnosis of hypogonadism. An inadequate androgen status is moreover possible if the total testosterone levels are 8-12 nmol/L. In this "grey zone" the diagnosis of hypogonadism is debated and the appropriateness for treating these patients with testosterone should be fostered by symptoms, although often non-specific. Up to now, no markers of androgen tissue action can be used in clinical practice. The identification of markers of androgens action might be useful in supporting diagnosis, Testosterone Replacement Treatment (TRT) and clinical follow-up. The aim of this review is to analyze the main findings of recent studies in the field of discovering putative diagnostic markers of male hypogonadism in seminal plasma by proteomic techniques. The identified proteins might represent a "molecular androtest" useful as a seminal fingerprint of male hypogonadism, for the diagnosis of patients with moderate grades of testosterone reduction and in the follow-up of testosterone replacement treatment.
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http://dx.doi.org/10.2174/0929866527666200505214021DOI Listing
February 2021

Factors affecting serum lactate in patients with intracranial tumors - A report of our series and review of the literature.

Surg Neurol Int 2020 6;11:39. Epub 2020 Mar 6.

Departments of Neurosurgery, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Rome.

Background: A hyperlactemia may occur in the presence of tissue hypoperfusion, in diseases affecting metabolism and in cases of malignant neoplasm. However, the factors affecting the serum lactate levels in patients submitted to craniotomy for the resection of an intracranial tumor have been investigated only marginally. Here, we assessed the factors possibly affecting the levels of serum lactate in intracranial tumors and carried out a thorough literature review on this topic.

Methods: All patients submitted to elective craniotomy from January 2017 to August 2018 for the resection of a glioblastoma (GBM; 101 cases) and a benign meningioma (WHO I; 105 cases) were included in this study. The sex, age, histological diagnosis, body mass index (BMI), and diabetes were assessed as possible factors affecting the level of the preoperative and postoperative serum lactate in these patients.

Results: We found that preoperative hyperlactemia (> 2 mmol/l) was more frequent in patients with GBM than in patients with meningioma ( = 0.0003). Moreover, a strong correlation between a preoperative lactemia and postoperative lactemia ( < 0.0001) was observed. On univariate analysis, we found increased preoperative serum lactate levels in GBM patients ( = 0.0022) and in patients with a BMI ≥30 ( = 0.0068). Postoperative serum lactate levels were significantly higher in GBM patients ( = 0.0003). On multivariate logistic regression analysis, a diagnosis of GBM was an independent factor for higher level of preoperative ( = 0.0005) and postoperative ( < 0.0001) serum lactate.

Conclusion: The malignant phenotype of GBM is the strongest factor associated with a pre- and postoperative hyperlactemia in patients submitted to craniotomy for the resection of an intracranial tumor.
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http://dx.doi.org/10.25259/SNI_552_2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7110274PMC
March 2020

Endoscopic full-thickness resection in a recurrent perianastomotic esophagojejunal cancer followed by fully covered metal stent placement for lumen occlusion.

Endoscopy 2020 09 18;52(9):E337-E338. Epub 2020 Mar 18.

Azienda Ospedaliero-Universitaria di Modena, Ospedale Civile di Baggiovara, Endoscopia Digestiva, Baggiovara, Italy.

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http://dx.doi.org/10.1055/a-1113-7001DOI Listing
September 2020

Over-the-scope clip vs epinephrine with clip for first-line hemostasis in non-variceal upper gastrointestinal bleeding: a propensity score match analysis.

Endosc Int Open 2020 Jan 8;8(1):E50-E58. Epub 2020 Jan 8.

Azienda Ospedaliero-Universitaria di Modena Ospedale Civile di Baggiovara, Gastroenterology and Digestive Endoscopy Unit, Modena, Italy.

 The over-the-scope clip (OTSC) is a novel tool used to improve the maintenance of hemostasis for non-variceal upper gastrointestinal bleeding (NVUGIB); however, studies on the comparison with "conventional" techniques are lacking. In this study, we aimed to compare first-line endoscopic hemostasis achieved using conventional techniques with that achieved using OTSC placement for NVUGIB.  From January 2007 to March 2018, 793 consecutive patients underwent upper endoscopy with the hemostasis procedure. Among them, 327 patients were eligible for inclusion (112 patients had OTSC placement and 215 underwent conventional hemostasis). After propensity score matching and adjustment for confounding factors, 84 patients were stratified into the "conventional" group and 84 into the OTSC group. Patient characteristics and outcomes (rebleeding rate, mortality rate within 30 days, and adverse events) were compared between the two groups.  In the unmatched cohort, hemostasis with OTSC was more frequent in cases of duodenal ulcers with Forrest Ia to IIa and in patients with a higher Rockall score compared with the "conventional group". In the matched cohort, 93 % of the patients in the "conventional group" underwent hemostasis with epinephrine + through-the-scope clip. Rebleeding events were significantly less frequent in the OTSC group (8 % vs 20 %, 95 %CI 3 - 16 vs 12 - 30;  = 0.02); however, the mortality rate in the two groups was not significantly different (6 % vs 2 %, 95 %CI 1 - 8 vs 2 - 13;  = 0.4).  OTSC is a safe and effective tool for achieving hemostasis, and we recommend its use as the first-line therapy for lesions with a high risk of rebleeding and in patients with a high risk Rockall score.
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http://dx.doi.org/10.1055/a-1005-6401DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6949178PMC
January 2020

Quantitative Analysis of the Seminal Plasma Proteome in Secondary Hypogonadism.

J Clin Med 2019 Dec 3;8(12). Epub 2019 Dec 3.

International Scientific Institute "Paul VI", 100168 Rome, Italy.

In the grey zone of testosterone levels between 8 and 12 nmol/L, the usefulness of therapy is controversial; as such, markers of tissue action of androgens may be helpful in adjusting clinical decisions. To better understand the effect of the hypothalamic-pituitary-testicular axis on male accessory secretion, we performed a proteomic quantitative analysis of seminal plasma in patients with secondary hypogonadism, before and after testosterone replacement therapy (TRT). Ten male patients with postsurgical hypogonadotrophic hypogonadism were enrolled in this study, and five of these patients were evaluated after testosterone treatment. Ten men with proven fertility were selected as a control group. An aliquot of seminal plasma from each individual was subjected to an in-solution digestion protocol and analyzed using an Ultimate 3000 RSLC-nano HPLC apparatus coupled to a LTQ Orbitrap Elite mass spectrometer. The label-free quantitative analysis was performed via Precursor Ions Area Detector Node. Eleven proteins were identified as decreased in hypogonadic patients versus controls, which are primarily included in hydrolase activity and protein binding activity. The comparison of the proteome before and after TRT comes about within the discovery of six increased proteins. This is the primary application of quantitative proteomics pointed to uncover a cluster of proteins reflecting an impairment not only of spermatogenesis but of the epididymal and prostate epithelial cell secretory function in male hypogonadism. The identified proteins might represent putative clinical markers valuable within the follow-up of patients with distinctive grades of male hypogonadism.
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http://dx.doi.org/10.3390/jcm8122128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6947469PMC
December 2019

Protein Expression of PTTG-1, OCT-4, and KLF-4 in Seminoma: A Pilot Study.

Front Endocrinol (Lausanne) 2019 11;10:619. Epub 2019 Sep 11.

Division of Anatomic Pathology and Histology, School of Medicine, Catholic University of Rome, Rome, Italy.

Seminomas are the most frequent kind of testicular germ cell tumors (TGCTs), accounting for 50% of tumor diagnosis in young men, whereas non-seminomas account for 40% and mixed forms for 10% of cases. It is currently supposed that TGCTs evolve from a pre-invasive stage of carcinoma (CIS). Octamer-binding transcription factor 4 (OCT4) is essential for self-renewal of stem cells. It is considered as a major regulator of cell pluripotency. Prior studies have shown that seminoma expresses OCT4. Transcription factor Krüppel-like factor 4 (KLF4) has moreover associated with embryonic stem cell maintenance. Finally, we previously demonstrated the expression of PTTG1 in CIS and seminomas. In this pilot study, we compared the combined expression of PTTG1 with KLF4 and OCT4 in seminoma, in order to validate our hypotesis that PTTG1 marks a specific population of stem cells in neoplastic tissue, strictly related with tumor. Formalin-fixed and paraffin-embedded testicular tissues by 5 patients who underwent an orchidectomy for seminoma have been collected and immunofluorescence analysis was performed using antibody rabbit monoclonal PTTG-1 and mouse monoclonal OCT4 or mouse monoclonal KLF4 antibody. In seminoma we observed that tumor cells strongly express OCT-4 in all seminomas and in the intratubular areas of seminoma. Expression of KLF-4 was observed in many tumor cells. PTTG1 marks some specific OCT4- and KLF4-positive tumor cells, mainly localized at the periphery of the neoplasm. In the intertubular infiltration areas nests of cells expressing both OCT4/KLF4 and PTTG1 have been observed. This is the first identification of a cell population in seminoma characterized for being OCT4, KLF4, and PTTG1 positive cells in seminoma, associated with cancer invasiveness. Further investigation is needed to elucidate if a functional abrogation of PTTG1 might be used in order to offer new therapeutic approaches in the clinical workout of seminoma.
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http://dx.doi.org/10.3389/fendo.2019.00619DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6749154PMC
September 2019

Underwater endoscopic submucosal dissection of an obstructing giant colonic lipoma.

Endoscopy 2020 03 27;52(3):E90-E91. Epub 2019 Sep 27.

Digestive Endoscopy Unit, Ospedale Civile di Baggiovara, Azienda Ospedaliero-Universitaria di Modena, Baggiovara, Italy.

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http://dx.doi.org/10.1055/a-1011-3617DOI Listing
March 2020

Germ Cell Neoplasia (GCNIS) in Testis-Sparing Surgery (TSS) for Small Testicular Masses (STMs).

Front Endocrinol (Lausanne) 2019 7;10:512. Epub 2019 Aug 7.

Division of Endocrinology, Istituto Scientifico Internazionale "Paolo VI", Fondazione Policlinico Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy.

The testis-sparing surgery (TSS) is surgical technique accepted for small testicular masses (STMs). Frozen section examination (FSE) is an essential assessment at the time of TSS. The aim of this study is to measure the maximum distance of the foci of ITGCN from STMs. In our hospital between June 2010 and October 2017 a total of 68 patients with STM underwent a TSS. All the testis specimens were totally embedded and processed via the whole-mount method and a diagnosis of germ cell tumor with GCNIS were made. The distance between STMs and GCNIS were calculated by two pathologists directly on the slides considering for the third dimension the number of the paraffin blocks in which the foci of GCNIS were found. The STMs were classic seminoma in 62 out 68 cases, embryonal carcinoma in 4 cases, while in 2 case a diagnose of mixed germ cell tumor were made. The size of the STMs was between 0.5 and 2 cm and the foci of GCNIS were observed in seminiferous tubules very closed to SMTs or as skip lesions in the surrounding testicular parenchyma, dispersed in normal testis. In 48 out of 68 cases (70.5%) foci of GCNIS were at the distance from SMTS of 1.5 cm or below and in 60 out of 68 cases (88%) at the distance of 2 cm or below The distance of GCNIS from the STMs was not related to the histological subtype of the germ cell tumor, while there is a linear correlation between size of the STMs and the distance of foci of GCNIS ( = 0.0105; = 0.9167). Our data showed that foci of ITGCN were not observed beyond 2.5 cm from the STM. In particular we demonstrated that exist a linear correlation between size of STMs and distance of the foci of GCNIS from STMs ( = 0.0105; = 0.9167). In conclusion mapping the tissue around the tumor not randomly but in targeted areas could reduce the false negative biopsies of the testis with GCNIS, increasing the radicality of the TSS procedure.
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http://dx.doi.org/10.3389/fendo.2019.00512DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6692875PMC
August 2019

Proteomics for the Identification of Biomarkers in Testicular Cancer-Review.

Front Endocrinol (Lausanne) 2019 12;10:462. Epub 2019 Jul 12.

International Scientific Institute "Paul VI", Rome, Italy.

A large number of biomarkers have been proposed for the diagnosis of testicular cancer, representing putative molecular targets for anticancer treatments. However, no conclusive data have been provided. Proteomics represents a research field recently developed. It evaluates the large-scale analysis of the full protein components of a single cell, of a specific tissue, or of biological fluids. In the last decades, proteomics has been applied in clinical fields, thanks to modern technology and new bioinformatic tools, to identify novel molecular markers of diseases. The aim of this review is to argue the findings of recent studies in the discoveries of putative prognostic and diagnostic markers of testis cancer by proteomic techniques. We present here a panel of proteins identified by proteomics which might be used after validation for early detection and the prognostic evaluation of testicular tumors. In addition, the molecular mechanisms revealed by these proteomic studies might also guide the development of novel treatments in future.
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http://dx.doi.org/10.3389/fendo.2019.00462DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6639829PMC
July 2019

First Case of Mature Teratoma and Yolk Sac Testis Tumor Associated to Inherited MEN-1 Syndrome.

Front Endocrinol (Lausanne) 2019 12;10:365. Epub 2019 Jun 12.

UOC di Endocrinologia e Diabetologia, Fondazione Policlinico Universitario A. Gemelli, IRCCS, ENETS Center of Excellence, Istituto di Patologia Speciale Medica, Università Cattolica del Sacro Cuore, Rome, Italy.

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominantly inherited endocrine tumor syndrome characterized by the development of cancer in various endocrine organs, particularly in the pituitary, parathyroid and pancreas. Moreover, in some cases, also non-endocrine tumors can be diagnosed, developing atypical phenotypes. We report herein the clinical history of a patient affected by MEN-1 syndrome who developed atypical features for this disease. The patient's clinical history started in August 2015 when he was referred, at the age of 23 years, to the Emergency Department of our Hospital for the occurrence of progressive asthenia, weakness, tremors and syncope. The biochemical test documented hyper-calcemia and severe hypoglycemia. The patient was referred to our Neuroendocrine Tumor and Pituitary Unit and he was diagnosed with pancreatic insulinoma, hypercalcemic hyperparathyroidism, and a prolactin secreting pituitary adenoma. The MEN-1 syndrome was suspected and genetic tests for mutation of resulted positive for the pathogenic variant c1548dupG. In January 2016, the patient was diagnosed with intratubular germ cell neoplasia, consisting of a mature teratoma and yolk sac tumor and he underwent a right orchiectomy. This is the first case report showing the clear association of MEN-1 syndrome with yolk sac tumors and teratomas, as in our case, the c1548dupG represents a pathogenic variant rather than a SNP. This case suggests the opportunity of an accurate evaluation of the testis particularly in young MEN-1 affected patients and that a prompt screening for neoplastic disease should involve all the endocrine glands.
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http://dx.doi.org/10.3389/fendo.2019.00365DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6582702PMC
June 2019

Covered metal stent as a rescue therapy for impacted Dormia basket in the biliary tract.

Turk J Gastroenterol 2019 03;30(3):305-306

Gastrointestinal and Digestive Endoscopy Unit, Sant'Agostino Estense Hospital, AOU Modena, Italy.

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http://dx.doi.org/10.5152/tjg.2018.18028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6428518PMC
March 2019

First-line endoscopic treatment with over-the-scope clips in patients with either upper or lower gastrointestinal bleeding: a multicenter study.

Endosc Int Open 2018 Nov 7;6(11):E1317-E1321. Epub 2018 Nov 7.

Surgical Digestive Endoscopy, Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy.

Endoscopic treatment is the mainstay approach for gastrointestinal bleeding, in either upper (UGIB) or lower (LGIB) tract. The over-the-scope clip (OTSC) may overcome limitations of standard clips or thermocoagulation in high-risk bleeding lesions. We evaluate the main clinically relevant outcomes following endoscopic hemostasis with OTSC in high-risk lesions and/or patients. This was a retrospective analysis of prospectively collected databases including all patients with UGIB and LGIB who underwent OTCS placement as first-line treatment in eleven tertiary endoscopic referral centers. Technical success, primary hemostasis, rebleeding, blood transfusion, hospital stay, and hemorrhage-related mortality rates were evaluated.  Data from 286 patients, with either UGIB (N = 214) or LGIB (N = 72) were available. Overall, 112 patients (39.2 %) were receiving antithrombotic therapy. Technical success and primary hemostasis rates were 97.9 % and 96.4 %, respectively. Early rebleeding occurred in 4.4 %, more frequently in those on antithrombotic therapy, and no late rebleeding was observed. Following a successful primary haemostasis, only 5.2 % patients needed blood transfusions, and the median hospital stay was 4 days (range: 3 - 11). Eighteen patients with either technical failure (N = 6) or rebleeding (N = 12) underwent radiological or surgical approaches. Overall, bleeding-related deaths occurred in 5 (1.7 %) patients, including 3 patients with technical procedural failure, and 2 in the rebleeding group.   Data from our large, multicenter study show that OTSC placement is an effective first-line treatment for hemostasis in high-risk patients and/or lesions both in upper and lower gastrointestinal tract.
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http://dx.doi.org/10.1055/a-0746-8435DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6221819PMC
November 2018

Identification of seminal markers of male accessory gland inflammation: From molecules to proteome.

Am J Reprod Immunol 2018 08 10;80(2):e12992. Epub 2018 Jul 10.

Division of Endocrinology and Metabolic Diseases, Fondazione Policlinico Universitario "A. Gemelli", Rome, Italy.

Male accessory gland infection/inflammation (MAGI) is a frequent disease, mostly with a chronic course, involving 1 or more sexual accessory glands. Majority of the MAGIs remain asymptomatic, thereby leading to a dilemma whether to treat these patients or not. It is moreover noteworthy that the diagnosis of MAGI is difficult, since patients are frequently asymptomatic and semen samples or prostatic secretions are often free from bacteria. As a consequence the identification of novel and reliable markers of inflammation in seminal plasma is an open challenge. If leukocytospermia and polymorphonuclear elastase and the analysis of the secretory products of male accessory glands have been widely used in the past, their diagnostic significance is discussed. Some cytokines (IL-6 and IL-8) and protein markers (suPAR) have been reported in the last years as the most promising markers for the diagnosis and the follow-up of MAGI. Recent advances in proteomic techniques undoubtedly represent a real promise in the future for the identification of novel markers of MAGI. This article provides an overview of key seminal biomarkers of MAGI, including the novel perspectives of the putative markers deriving by the most recent proteomic approaches.
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http://dx.doi.org/10.1111/aji.12992DOI Listing
August 2018

The "three-in-one" formulation of bismuth quadruple therapy for Helicobacter pylori eradication with or without probiotics supplementation: Efficacy and safety in daily clinical practice.

Helicobacter 2018 Aug 20;23(4):e12502. Epub 2018 Jun 20.

Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy.

Background: Clinical trials have shown a good efficacy of the "three-in-one" formulation of bismuth quadruple therapy (BQT) for Helicobacter (H.) pylori eradication. We aimed to assess the efficacy and safety of the three-in-one BQT in clinical practice, and investigate the effect of probiotic supplementation, in Italy.

Materials And Methods: A retrospective database, multicentre observational study was conducted in seven Italian Hospitals. Consecutive H. pylori-positive patients who received the three-in-one BQT for 10 days were included in the analysis. H. pylori eradication was assessed by histology, C-urea breath test, or stool antigen test. Compliance and adverse events were evaluated by interview.

Results: A total of 376 patients were included in the intention-to-treat (ITT) and 352 in the per protocol (PP) analyses. One hundred and ninety-three subjects received probiotics supplementation. Overall, eradication rates were 90.2% (95% Confidence Interval (CI):86.7-93.0) in ITT and 94.6% (95% CI: 91.7-96.7) in PP analyses. The compliance was good (≥90% of treatment taken) in 94.9% of patients. The proportion of patients with a good compliance was not different with and without probiotics supplementation (94.8% vs 95.1%). Eradication rates were equally high for first-line (91.4%), second-line (87.5%), and third-line treatments (91.7%) in the ITT analysis (P = .48). Adverse events were reported by 32.4% of patients, but only 6.1% of patients discontinued treatment.

Conclusions: The three-in-one BQT is highly effective and well tolerated for H. pylori eradication in daily clinical practice. Probiotics supplementation fails to improve compliance.
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http://dx.doi.org/10.1111/hel.12502DOI Listing
August 2018

Endoscopic papillary large balloon dilation in patients with large biliary stones and periampullary diverticula: Results of a multicentric series.

Dig Liver Dis 2018 Aug 6;50(8):828-832. Epub 2018 Apr 6.

Digestive Endoscopy Unit, University Hospital G. Fucito, Ruggi d'Aragona, Salerno, Italy.

Introduction: Stone extraction represents the most frequent indication for endoscopic retrograde cholangiopancreatography (ERCP). Endoscopic papillary large balloon dilation (EPLBD) is a recent introduced approach consisting of an endoscopic papillary large balloon dilation following limited endoscopic sphyncterotomy (ES), which has been proven to be safe and effective for extraction of large common bile duct (CBD) stones. Peri-ampullary diverticula (PAD) are described in 10-20% of patients undergoing ERCP. Aim of our study is to evaluate efficacy and safety of EPLBD for the extraction of large biliary stones in patients with PAD.

Methods: The prospectively collected endoscopy databases of 4 Italian ERCP high-volume centers were reviewed retrospectively, and all consecutive patients with an instrumental diagnosis of large biliary stones and PAD, between September 2014 and October 2016, were included in this study.

Results: Eighty-one patients (36 males, median age 75 years) were treated between September 2014 and October 2016. Deep biliary cannulation was reached in 78/80 patients. Successful extraction was achieved in 74/78 patients at the first attempt. AEs occurred in 8 patients (1 severe). Younger age, stone size and incomplete stone extraction were significantly associated with AEs.

Conclusions: EPLBD is an effective and safe technique in patients with PAD and large biliary stones, which avoids the need of other techniques, thereby reducing the risks of adverse events.
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http://dx.doi.org/10.1016/j.dld.2018.03.034DOI Listing
August 2018

Testosterone and FSH modulate Sertoli cell extracellular secretion: Proteomic analysis.

Mol Cell Endocrinol 2018 11 25;476:1-7. Epub 2018 Apr 25.

Department of Experimental Medicine, University of Perugia, Perugia, 06100, Italy; Division of Medical Andrology and Endocrinology of Reproduction, University of Perugia and Saint Mary Hospital, Terni, 05100, Italy. Electronic address:

Spermatogenesis is a highly complicated biological process that occurs in the epithelium of the seminiferous tubules. It is regulated by a complex network of endocrine and paracrine factors and by juxtacrine testicular cross-talk. Sertoli cells (SC) play a key role in spermatogenesis due to their production of trophic, differentiation and immune-modulating factors, but many of the molecular pathways of SC action remain controversial and unclear. Over the last two decades, research has focused on extracellular vesicles as an important mechanism of intercellular communication. The aim of this study was to investigate the presence of extracellular vesicles (EVs) in SC and the modulation of their content in SC after FSH and testosterone stimulation. Highly purified porcine pre-pubertal Sertoli cells were isolated according to previously established methods. After 48 h of culture with FSH or FSH + testosterone stimulation, we identified sertolian EVs containing specific mRNAs. Proteomic analysis of EVs content identified 29 proteins under non-stimulatory conditions, most of which were related to receptor binding activity. FSH stimulation induced increases in inhibin-alpha, inhibin-beta, plakoglobin, haptoglobin, D-3-phosphoglycerate dehydrogenase and sodium/potassium-transporting ATPase in sertolian EVs. Testosterone stimulation enhanced the abundance of inhibin-alpha, inhibin-beta, tissue-type plasminogen activator, epidermal growth factor-like protein 8, elongating factor 1-gamma and D-3-phosphoglycerate dehydrogenase. These results are likely to help determine the unknown molecular secretion of Sertoli cells.
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http://dx.doi.org/10.1016/j.mce.2018.04.001DOI Listing
November 2018

Seminal suPAR Levels as Marker of Abacterial Male Accessory Gland Inflammation in Hypogonadism.

Protein Pept Lett 2018 ;25(5):478-482

Institute of Chemistry and Clinical Biochemistry, Catholic University, Rome, Italy.

Background: Recent evidences suggest that hypogonadism is an important risk factor for lower urinary tract symptoms and benign prostatic hyperplasia. Several papers have discussed the role of chronic inflammation in the development of BPH, which may be modulated by the hypogonadal state. Soluble Urokinase-type Plasminogen Activator Receptor (suPAR), known protein marker of systemic inflammation, can be assayed in the seminal plasma and represents a reliable and sensitive marker of inflammation for the Male Accessory Gland Inflammation (MAGI).

Objective: The aim of this study has been to investigate if seminal suPAR is elevated in MAGI with hypogonadism and if suPAR represent a useful marker of abacterial inflammation in hypogonadism.

Methods: We included in the study twenty male patients aged between 25 and 55 year-old with secondary postsurgical hypogonadism. The same patients were also evaluated after a 3-month of Testosterone Replacement Therapy (TRT), to evaluate the effect of androgen replacement therapy on suPAR. Ten fertile men have been enrolled as a control group in the protocol. SuPAR concentrations were assayed on seminal plasma using an Enzyme-Linked Immunosorbent Assay (ELISA) kit.

Results: Hypogonadic patients presented significantly increased levels of seminal suPAR respect to controls (86.1±36.8 vs 55.2±20.0 ng/mL, p<0.05). TRT in hypogonadic patients has been associated with a significant reduction of suPAR levels as reported in the control group (50.9±22.91 vs 86.1±36.8 ng/ml p<0.05).

Conclusions: These results confirm the role of suPAR as a protein marker of MAGI and support the hypothesis that hypogonadism induces a state of inflammation in male accessory glands which is involved in male infertility. Moreover demonstrated that testosterone treatment probably exerts a positive effect on MAGI and infertility as documented by reduction of suPAR levels in hypogonadic treated patients.
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http://dx.doi.org/10.2174/0929866525666180418121421DOI Listing
August 2018

Proteomic Markers in Cervical Mucus.

Protein Pept Lett 2018 ;25(5):463-471

Department of Medicine, Faculty of Medicine, Universidad Autónoma de Barcelona, Barcelona, Spain.

Background: Cervical Mucus (CM) is a viscous fluid produced by the secretory cells of the cervical crypts. The CM undergoes modifications throughout the cycle that make it have different biochemical and biophysical characteristics, becoming a crucial element for the identification of ovulation. Since CM is rich in secreted proteins, it may represent moreover a source of biomarkers for female reproductive tract diseases.

Objective: This review is an attempt to collect relevant knowledge about the physicochemical properties and functions of the cervical mucus, including its important role as a clinical marker of female fertility, and draws attention to CM as a source of potential proteomic biomarkers.

Findings: All the assessed studies evidenced that the observation of the CM allows the identification of the days with the highest probability of pregnancy. CM proteome changes throughout the menstrual cycle have been revealed. Few proteomic studies on the constitutive protein composition of CM of fertile women have been conducted to date. In the CM of patients affected by endometriosis have been identified some proteins that could represent potential biomarkers of the disease.

Conclusion: There is still limited knowledge about the physicochemical properties and functions of the CM and how these undergo to changes during menstrual cycle. CM is a reliable predictor of fertility. Further characterization of CM proteins would contribute to a better understanding of the key role they have on fertility, reproduction and biological regulation. CM may represent moreover a source of biomarkers for gynecological diseases.
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http://dx.doi.org/10.2174/0929866525666180418122705DOI Listing
August 2018

Semen Proteomics Reveals the Impact of Enterococcus faecalis on male Fertility.

Protein Pept Lett 2018 ;25(5):472-477

International Scientific Institute "Paul VI", Catholic University, Rome, Italy.

Background: Infectious etiologies contribute to 15% of male factor infertility. Enterococcus faecalis (E. faecalis) is commonly identified in semen culture of infertile men and it is associated with significantly poorer semen quality.

Objective: Aim of this study was to identify new seminal biomarkers for the male tract infection by E. faecalis, using proteomic profiling, in order to understand the effect of E. faecalis on the physiopathology of male reproduction.

Methods: We included in the study ten patients seeking medical care for primary infertility with prostate-vesicular-epidydimitis and with microbiological analysis on semen and/or prostatic secretions positive for E. faecalis. Ten fertile men have been enrolled as a control group in the protocol. An aliquot of each seminal plasma was subjected to an in-solution digestion protocol and analyzed using an Ultimate 3000 RSLCnano HPLC apparatus coupled to a LTQ Orbitrap Elite mass spectrometer.

Results: Eight proteins have not been identified in the group of controls and have been observed in a remarkable proportion of patients, mainly involved in immune system activity (CD177, Swiprosin-1 and 2-oxoglutarate dehydrogenase). Arylsulfatase has been identified in the group of controls and was absent in all patients with infection. Three proteins (TIMP-1, WFDC domain protein 2 and Carboxypeptidase E) have been observed significantly different in patients versus controls, mainly related with inflammation.

Conclusions: This is the first application of MS-based proteomics aimed to reveal an array of proteins in the seminal plasma and reflecting the effect of the infection by E. faecalis on semen composition.
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http://dx.doi.org/10.2174/0929866525666180412161818DOI Listing
August 2018

[Errors in Medicine: perceptions of nursing students in Rome].

Prof Inferm 2017 Oct-Dec;70(4):206-213

Dipartimento di Sanità Pubblica e Malattie Infettive, Sapienza Università di Roma.

Introduction: The error in medicine has long been discussed in scientific debates. The purpose of this study is to evaluate the degree knowledge, attitude and behavior of students in Nursing for the failure in the health sector.

Methods: It was administered to 231 students of Nursing of the Sapienza University of Rome (171 females and 60 males), aged between 21 and 45 years, a structured questionnaire in three questions that explore the experiences and opinions about the errors found in medical practice, the causes underlying them and the mistakes that should never be committed. Data were collected, stratified by sex, age, marital status, and analyzed using the χ2 test. Significance was set at p≤0.05.

Results: The 5 errors found more frequently in clinical practice by the students were the following: Errors that favors the onset of hospital infections (58.9%); Non adherence to protocols (50.2%); Patient care (45.9%); Errors due to the administration of therapies and drugs (45.9%); Errors relating to the execution of withdrawals (35.9%). The five cases considered most frequently responsible for such errors were: the rush (70.1%), followed by neglect / superficial (55%); disorganization (51.5%); not hygienically / infertility (50.6%) and inattention (42.9%). With regard to the errors that you should never commit, students have shown more frequently: the errors of administration of therapies / medications (69.3%); errors of prescription therapies / medications (58.9%); errors related to surgery (52.8%); the exchange of patient or misidentification of the patient (50.6%); errors that favor the occurrence of hospital infections (48.1%).

Conclusions: The results of this study shows the importance of a culture of error in medicine, also as part of undergraduate education, in order to train and educate future health professionals to this issue in order to promoting patient safety and quality of health.
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http://dx.doi.org/10.7429/pi.2017.704206DOI Listing
June 2018

Olfactory Receptors in Semen and in the Male Tract: From Proteome to Proteins.

Front Endocrinol (Lausanne) 2017 23;8:379. Epub 2018 Jan 23.

Division of Endocrinology, Fondazione Policlinico Universitario Agostino Gemelli, Rome, Italy.

The estimated number of testicular olfactory receptors (ORs) in mammals range between 20 and 66. Previous data reported the role of hOR17-4 and mOR23 in sperm-oocyte chemiotaxis. Proteomic analysis was performed to understand which are the ORs expressed in seminal plasma. Seminal samples by four fertile men were analyzed by an Ultimate 3000Nano/Micro-HPLC apparatus coupled with an LTQ-Orbitrap XL hybrid mass spectrometer. Western blot analysis confirmed the expression of three identified ORs. The expression of ORs in sperm cells, testis, and epididymis was evaluated by confocal microscopy analysis. In seminal plasma eight different ORs were identified by proteomics and three ORs have been confirmed by western blot. Confocal microscopy analysis revealed that OR4S1, OR4C13, and OR1I1 are expressed on the surface of sperm cells. In testicular tissue, OR4S1 and OR1I1 are expressed in spermatocytes and spermatids and OR4C13 is expressed throughout all the tubules. In patients with spermatocyte maturation arrest OR4S1 and OR1I1 expression was reduced and a weak positivity for OR4C13 was detected in the spermatogonia. OR4S1, OR4C13, and OR1I1 had intense and diffuse staining in the epididymis. This study initiated a new methodology for screening OR repertoire in sperms, testis and epididymis. Our results open new insights into OR involvement in sperm maturation and migration.
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http://dx.doi.org/10.3389/fendo.2017.00379DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5787142PMC
January 2018