Laparoscopic peritoneal lavage. Our experience and review of the literature

NTRODUCTION: Over the years various therapeutic techniques for diverticulitis have been developed. Laparoscopic peritoneal lavage (LPL) appears to be a safe and useful treatment, and it could be an effective alternative to colonic resection in emergency surgery. AIM: This prospective observational study aims to assess the safety and benefits of laparoscopic peritoneal lavage in perforated sigmoid diverticulitis. MATERIAL AND METHODS: We surgically treated 70 patients urgently for complicated sigmoid diverticulitis. Thirty-two (45.7%) patients underwent resection of the sigmoid colon and creation of a colostomy (Hartmann technique); 21 (30%) patients underwent peritoneal laparoscopic lavage; 4 (5.7%) patients underwent colostomy by the Mikulicz technique; and the remaining 13 (18.6%) patients underwent resection of the sigmoid colon and creation of a colorectal anastomosis with a protective ileostomy. RESULTS: The 66 patients examined were divided into 3 groups: 32 patients were treated with urgent surgery according to the Hartmann procedure; 13 patients were treated with resection and colorectal anastomosis; 21 patients were treated urgently with laparoscopic peritoneal lavage. We had no intraoperative complications. The overall mortality was 4.3% (3 patients). In the LPL group the morbidity rate was 33.3%. CONCLUSIONS: Currently it cannot be said that LPL is better in terms of mortality and morbidity than colonic resection. These data may, however, be proven wrong by greater attention in the selection of patients to undergo laparoscopic peritoneal lavage

MiRNAs as Potential Prognostic Biomarkers for Metastasis in Thin and Thick Primary Cutaneous Melanomas.

Background/Aim: The identification of novel prognostic biomarkers for melanoma metastasis is essential to improve patient outcomes. To this aim, we characterized miRNA expression profiles in relation to metastasis in melanoma and correlated miRNAs expression with clinicalpathological factors. Materials and Methods: MiR-145-5p, miR-150-5p, miR-182-5p, miR-203-3p, miR-205-5p and miR211-5p expression levels were analyzed in primary cutaneous melanomas, including thin and thick melanomas, and in melanoma metastases by quantitative Real-Time PCR. Results: A significantly lower miR-205-5p expression was found in metastases compared to primary melanomas. Furthermore, a progressive down-regulation of miR-205-5p expression was observed from loco-regional to distant metastasis. Significantly lower miR-145-5p and miR-203-3p expression levels were found in cases with Breslow thickness >1 mm, high Clark level, ulceration and mitotic rate ≥1/mm2. Conclusion: Our findings point to miR-205-5p as potential biomarker of distant metastases and to miR-145-5p and miR-203-3p as markers of aggressiveness in melanoma

Robotic total gastrectomy with intracorporeal robot-sewn anastomosis. A novel approach adopting the double-loop reconstruction method

Gastric cancer constitutes a major health problem. Robotic surgery has been progressively developed in this field. Although the feasibility of robotic procedures has been demonstrated, there are unresolved aspects being debated, including the reproducibility of intracorporeal in place of extracorporeal anastomosis. Difficulties of traditional laparoscopy have been described and there are well-known advantages of robotic systems, but few articles in literature describe a full robotic execution of the reconstructive phase while others do not give a thorough explanation how this phase was run. A new reconstructive approach, not yet described in literature, was recently adopted at our Center. Robotic total gastrectomy with D2 lymphadenectomy and a socalled ‘‘double-loop’’ reconstruction method with intracorporeal robotsewn anastomosis (Parisi’s technique) was performed in all reported cases. Preoperative, intraoperative, and postoperative data were collected and a technical note was documented. All tumors were located at the upper third of the stomach, and no conversions or intraoperative complications occurred. Histopathological analysis showed R0 resection obtained in all specimens. Hospital stay was regular in all patients and discharge was recommended starting from the 4th postoperative day. No major postoperative complications or reoperations occurred. Reconstruction of the digestive tract after total gastrectomy is one of the main areas of surgical research in the treatment of gastric cancer and in the field of minimally invasive surgery. The double-loop method is a valid simplification of the traditional technique of construction of the Roux-limb that could increase the feasibility and safety in performing a full hand-sewn intracorporeal reconstruction and it appears to fit the characteristics of the robotic system thus obtaining excellent postoperative clinical outcome

A game-theoretic approach to computation offloading in mobile cloud computing

We consider a three-tier architecture for mobile and pervasive computing scenarios, consisting of a local tier ofmobile nodes, a middle tier (cloudlets) of nearby computing nodes, typically located at the mobile nodes access points but characterized by a limited amount of resources, and a remote tier of distant cloud servers, which have practically infinite resources. This architecture has been proposed to get the benefits of computation offloading from mobile nodes to external servers while limiting the use of distant servers whose higher latency could negatively impact the user experience. For this architecture, we consider a usage scenario where no central authority exists and multiple non-cooperative mobile users share the limited computing resources of a close-by cloudlet and can selfishly decide to send their computations to any of the three tiers. We define a model to capture the users interaction and to investigate the effects of computation offloading on the users’ perceived performance. We formulate the problem as a generalized Nash equilibrium problem and show existence of an equilibrium.We present a distributed algorithm for the computation of an equilibrium which is tailored to the problem structure and is based on an in-depth analysis of the underlying equilibrium problem. Through numerical examples, we illustrate its behavior and the characteristics of the achieved equilibria

Crohn's Disease Imaging: A Review

Crohn's disease is a chronic granulomatous inflammatory disease of the gastrointestinal tract, which can involve almost any segment from the mouth to the anus. Typically, Crohn's lesions attain segmental and asynchronous distribution with varying levels of seriousness, although the sites most frequently involved are the terminal ileum and the proximal colon. A single gold standard for the diagnosis of CD is not available and the diagnosis of CD is confirmed by clinical evaluation and a combination of endoscopic, histological, radiological, and/or biochemical investigations. In recent years, many studies have been performed to investigate the diagnostic potential of less invasive and more patient-friendly imaging modalities in the evaluation of Crohn's disease including conventional enteroclysis, ultrasonography, color-power Doppler, contrast-enhanced ultrasonography, multidetector CT enteroclysis, MRI enteroclysis, and 99mTc-HMPAO-labeled leukocyte scintigraphy. The potential diagnostic role of each imaging modality has to be considered in different clinical degrees of the disease, because there is no single imaging technique that allows a correct diagnosis and may be performed with similar results in every institution. The aim of this paper is to point out the advantages and limitations of the various imaging techniques in patients with suspected or proven Crohn's disease

Rag defects and thymic stroma: lessons from animal models

Thymocytes and thymic epithelial cells (TECs) cross-talk is essential to support T cell development and preserve thymic architecture and maturation of TECs and Foxp3+ natural regulatory T cells. Accordingly, disruption of thymic lymphostromal cross-talk may have major implications on the thymic mechanisms that govern T cell tolerance. Several genetic defects have been described in humans that affect early stages of T cell development [leading to severe combined immune deficiency (SCID)] or late stages in thymocyte maturation (resulting in combined immunodeficiency). Hypomorphic mutations in SCID-causing genes may allow for generation of a limited pool of T lymphocytes with a restricted repertoire. These conditions are often associated with infiltration of peripheral tissues by activated T cells and immune dysregulation, as best exemplified by Omenn syndrome (OS). In this review, we will discuss our recent findings on abnormalities of thymic microenvironment in OS with a special focus of defective maturation of TECs, altered distribution of thymic dendritic cells and impairment of deletional and non-deletional mechanisms of central tolerance. Here, taking advantage of mouse models of OS and atypical SCID, we will discuss how modifications in stromal compartment impact and shape lymphocyte differentiation, and vice versa how inefficient T cell signaling results in defective stromal maturation. These findings are instrumental to understand the extent to which novel therapeutic strategies should act on thymic stroma to achieve full immune reconstitution

Myelodysplastic syndromes: advantages of a combined cytogenetic and molecular diagnostic workup

In this study we present a new diagnostic workup for the myelodysplastic syndromes (MDS) including FISH, aCGH, and somatic mutation assays in addition to the conventional cytogenetics (CC). We analyzed 61 patients by CC, FISH for chromosome 5, 7, 8 and PDGFR rearrangements, aCGH, and PCR for ASXL1, EZH2, TP53, TET2, RUNX1, DNMT3A, SF3B1 somatic mutations. Moreover, we quantified WT1 and RPS14 gene expression levels, in order to find their possible adjunctive value and their possible clinical impact. CC analysis showed 32% of patients with at least one aberration. FISH analysis detected chromosomal aberrations in 24% of patients and recovered 5 cases (13.5%) at normal karyotype (two 5q- syndromes, one del(7) case, two cases with PDGFR rearrangement). The aGCH detected 10 "new" unbalanced cases in respect of the CC, including one with alteration of the ETV6 gene. After mutational analysis, 33 patients (54%) presented at least one mutation and represented the only marker of clonality in 36% of all patients. The statistical analysis confirmed the prognostic role of CC either on overall or on progression-free-survival. In addition, deletions detected by aCGH and WT1 over-expression negatively conditioned survival. In conclusion, our work showed that 1) the addition of FISH (at least for chr. 5 and 7) can improve the definition of the risk score; 2) mutational analysis, especially for the TP53 and SF3B1, could better define the type of MDS and represent a "clinical warning"; 3) the aCGH use could be probably applied to selected cases (with suboptimal response or failure)

PMN-MDSC frequency discriminates active versus latent tuberculosis and could play a role in counteracting the immune-mediated lung damage in active disease

: Tuberculosis (TB), due to Mycobacterium tuberculosis infection, is still the principal cause of death caused by a single infectious agent. The balance between the bacillus and host defense mechanisms reflects the different manifestations of the pathology. Factors defining this variety are unclear and likely involve both mycobacterial and immunological components. Myeloid derived suppressor cells (MDSC) have been shown to be expanded during TB, but their role in human TB pathogenesis is not clear. We evaluated the frequency of circulating MDSC by flow-cytometry in 19 patients with active TB, 18 with latent TB infection (LTBI), and 12 healthy donors (HD) as control. Moreover, we investigated the capacity of MDSC to modulate the mycobactericidal activity of monocytes. The association between MDSC level and TB chest X-ray severity score was analyzed. We observed that, unlike active TB, polymorphonuclear (PMN)-MDSC are not expanded in LTBI patients, and, by performing a receiver operating characteristic (ROC) curve analysis, we found that PMN-MDSC frequency supported the discrimination between active disease and LTBI. Interestingly, we observed an association between PMN-MDSC levels and the severity of TB disease evaluated by chest X-ray. Specifically, PMN-MDSC frequency was higher in those classified with a low/mild severity score compared to those classified with a high severity score. Moreover, PMN-MDSC can impact mycobacterial growth by inducing ROS production in Bacillus Calmette et Guerin (BCG)-infected monocytes. This effect was lost when tested with M. tuberculosis (MTB), In conclusion, our data indicate that the elevated frequency of PMN-MDSC in IGRA-positive individuals is associated with active TB. Our findings also pointed out a beneficial role of PMN-MDSC during human active TB, most likely associated with the limitation of inflammation-induced tissue damage

Passive immunotherapy for N-truncated tau ameliorates the cognitive deficits in two mouse Alzheimer's disease models

Abstract Clinical and neuropathological studies have shown that tau pathology better correlates with the severity of dementia than amyloid plaque burden, making tau an attractive target for the cure of Alzheimer's disease. We have explored whether passive immunization with the 12A12 monoclonal antibody (26–36aa of tau protein) could improve the Alzheimer's disease phenotype of two well-established mouse models, Tg2576 and 3xTg mice. 12A12 is a cleavage-specific monoclonal antibody which selectively binds the pathologically relevant neurotoxic NH226-230 fragment (i.e. NH2htau) of tau protein without cross-reacting with its full-length physiological form(s). We found out that intravenous administration of 12A12 monoclonal antibody into symptomatic (6 months old) animals: (i) reaches the hippocampus in its biologically active (antigen-binding competent) form and successfully neutralizes its target; (ii) reduces both pathological tau and amyloid precursor protein/amyloidβ metabolisms involved in early disease-associated synaptic deterioration; (iii) improves episodic-like type of learning/memory skills in hippocampal-based novel object recognition and object place recognition behavioural tasks; (iv) restores the specific up-regulation of the activity-regulated cytoskeleton-associated protein involved in consolidation of experience-dependent synaptic plasticity; (v) relieves the loss of dendritic spine connectivity in pyramidal hippocampal CA1 neurons; (vi) rescues the Alzheimer's disease-related electrophysiological deficits in hippocampal long-term potentiation at the CA3-CA1 synapses; and (vii) mitigates the neuroinflammatory response (reactive gliosis). These findings indicate that the 20–22 kDa NH2-terminal tau fragment is crucial target for Alzheimer's disease therapy and prospect immunotherapy with 12A12 monoclonal antibody as safe (normal tau-preserving), beneficial approach in contrasting the early Amyloidβ-dependent and independent neuropathological and cognitive alterations in affected subjects

Extracellular Vesicles Secreted by Mesenchymal Stromal Cells Exert Opposite Effects to Their Cells of Origin in Murine Sodium Dextran Sulfate-Induced Colitis

Several reports have described a beneficial effect of Mesenchymal Stromal Cells (MSCs) and of their secreted extracellular vesicles (EVs) in mice with experimental colitis. However, the effects of the two treatments have not been thoroughly compared in this model. Here, we compared the effects of MSCs and of MSC-EV administration in mice with colitis induced by dextran sulfate sodium (DSS). Since cytokine conditioning was reported to enhance the immune modulatory activity of MSCs, the cells were kept either under standard culture conditions (naïve, nMSCs) or primed with a cocktail of pro-inflammatory cytokines, including IL1β, IL6 and TNFα (induced, iMSCs). In our experimental conditions, nMSCs and iMSCs administration resulted in both clinical and histological worsening and was associated with pro-inflammatory polarization of intestinal macrophages. However, mice treated with iEVs showed clinico-pathological improvement, decreased intestinal fibrosis and angiogenesis and a striking increase in intestinal expression of Mucin 5ac, suggesting improved epithelial function. Moreover, treatment with iEVs resulted in the polarization of intestinal macrophages towards and anti-inflammatory phenotype and in an increased Treg/Teff ratio at the level of the intestinal lymph node. Collectively, these data confirm that MSCs can behave either as anti- or as pro-inflammatory agents depending on the host environment. In contrast, EVs showed a beneficial effect, suggesting a more predictable behavior, a safer therapeutic profile and a higher therapeutic efficacy with respect to their cells of origin.Fil: Tolomeo, Anna Maria. Fondazione Istituto di Ricerca Pediatrica Città della Speranza; Italia. Università di Padova; Italia. Consorzio per la Ricerca Sanitaria; ItaliaFil: Castagliuolo, Ignazio. Università di Padova; ItaliaFil: Piccoli, Martina. Fondazione Istituto di Ricerca Pediatrica Città della Speranza; ItaliaFil: Grassi, Michele. Università di Padova; ItaliaFil: Magarotto, Fabio. Fondazione Istituto di Ricerca Pediatrica Città della Speranza; Italia. Università di Padova; ItaliaFil: De Lazzari, Giada. Fondazione Istituto di Ricerca Pediatrica Città della Speranza; Italia. Consorzio per la Ricerca Sanitaria; Italia. Università di Padova; ItaliaFil: Malvicini, Ricardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; Argentina. Consorzio per la Ricerca Sanitaria; Italia. Fondazione Istituto di Ricerca Pediatrica Città della Speranza; ItaliaFil: Caicci, Federico. Università di Padova; ItaliaFil: Franzin, Chiara. Fondazione Istituto di Ricerca Pediatrica Città della Speranza; ItaliaFil: Scarpa, Melania. Veneto Institute of Oncology; ItaliaFil: Macchi, Veronica. Università di Padova; ItaliaFil: De Caro, Raffaele. Università di Padova; Italia. Consorzio Per la Ricerca Sanitaria; ItaliaFil: Angriman, Imerio. Università di Padova; ItaliaFil: Viola, Antonella. Università di Padova; ItaliaFil: Porzionato, Andrea. Consorzio Per la Ricerca Sanitaria; Italia. Università di Padova; ItaliaFil: Pozzobon, Michela. Fondazione Istituto Di Ricerca Pediatrica Città Della Speranza; Italia. Università di Padova; ItaliaFil: Muraca, Maurizio. Università di Padova; Italia. Consorzio Per la Ricerca Sanitaria; Italia. Fondazione Istituto Di Ricerca Pediatrica Città Della Speranza; Itali