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Staphylococcus aureus is a predominant cause of infections in individuals with spinal cord stimulation (SCS) devices. Biofilm formation complicates these infections, commonly requiring both surgical and antibiotic treatments. This study explored the biofilm matrix composition and antimicrobial susceptibility of planktonic and biofilm-growing S. aureus isolates from individuals with SCS-related infections. Whole-genome sequencing (WGS) examined genotypes, virulome, resistome, and the pan-genome structure. The study also analyzed biofilm matrix composition, early surface adhesion, hemolytic activity, and antibiotic-susceptibility testing. WGS revealed genetic diversity among isolates. One isolate, though oxacillin susceptible, contained the mec A gene. The median number of virulence factor genes per isolate was 58. All isolates harbored the biofilm-related ica A/D genes. When assessing phenotypic characteristics, all strains demonstrated the ability to form biofilms in vitro . The antimicrobial susceptibility profile indicated that oxacillin, rifampin, and teicoplanin showed the highest efficacy against S. aureus biofilm. Conversely, high biofilm tolerance was observed for vancomycin, trimethoprim/sulfamethoxazole, and levofloxacin. These findings suggest that S. aureus isolates are highly virulent and produce robust biofilms. In cases of suspected biofilm infections caused by S. aureus , vancomycin should not be the primary choice due to its low activity against biofilm. Instead, oxacillin, rifampin, and teicoplanin appear to be more effective options to manage SCS infections.IMPORTANCESCS devices are increasingly used to manage chronic pain, but infections associated with these devices, particularly those caused by Staphylococcus aureus , present significant clinical challenges. These infections are often complicated by biofilm formation, which protects bacteria from immune responses and antibiotic treatments, making them difficult to eradicate. Understanding the genetic diversity, virulence, and biofilm characteristics of S. aureus isolates from SCS infections is critical to improving treatment strategies. Our study highlights the need to reconsider commonly used antibiotics like vancomycin, which shows reduced activity against biofilm-growing cells. Identifying more effective alternatives, such as oxacillin, rifampin, and teicoplanin, provides valuable insight for clinicians when managing biofilm-related S. aureus infections in patients with SCS implants. This research contributes to the growing evidence that biofilm formation is crucial in treating device-related infections, emphasizing the importance of tailoring antimicrobial strategies to the biofilm phenotype.

Atopic dermatitis (AD) is a chronic inflammatory skin disorder exacerbated by Staphylococcus aureus colonization. The specific factors that drive S. aureus overgrowth and persistence in AD remain poorly understood. This study analyzed skin barrier functions and microbiome diversity in lesional (LE) and non-lesional (NL) forearm sites of individuals with severe AD compared to healthy control subjects (HS). Notable differences were found in transepidermal water loss, stratum corneum hydration, and microbiome composition. Cutibacterium was more prevalent in HS, while S. aureus and S. lugdunensis were predominantly found in AD LE skin. The results highlighted that microbial balance depends on inter-species competition. Specifically, network analysis at the genus level demonstrated that overall bacterial correlations were higher in HS, indicating a more stable microbial community. Notably, network analysis at the species level revealed that S. aureus engaged in competitive interactions in NL and LE but not in HS. Whole-genome sequencing (WGS) showed considerable genetic diversity among S. aureus strains from AD. Despite this variability, the isolates exhibited convergence in key phenotypic traits such as adhesion and biofilm formation, which are crucial for microbial persistence. These common phenotypes suggest an adaptive evolution, driven by competition in the AD skin microenvironment, of S. aureus and underscoring the interplay between genetic diversity and phenotypic convergence in microbial adaptation., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Sodium hypochlorite (NaOCl) is widely recognized for its broad-spectrum antimicrobial efficacy in skin wound care. This study investigates the effectiveness of NaOCl against a range of bacterial and fungal isolates from pressure ulcer (PU) patients. We analyzed 20 bacterial isolates from PU patients, comprising carbapenem-resistant Klebsiella pneumoniae (CRKP), multidrug-resistant Acinetobacter baumannii (MDRAB), methicillin-resistant Staphylococcus aureus (MRSA), methicillin-susceptible Staphylococcus aureus (MSSA), along with 5 Candida albicans isolates. Antibiotic resistance profiles were determined using standard susceptibility testing. Whole-genome sequencing (WGS) was employed to identify antimicrobial resistance genes (ARGs) and disinfectant resistance genes (DRGs). Genetic determinants of biofilm formation were also assessed. The antimicrobial activity of NaOCl was evaluated by determining the minimum inhibitory concentration (MIC) and the minimal biofilm eradication concentration (MBEC) for both planktonic and biofilm-associated cells. CRKP and MDRAB showed resistance to fluoroquinolones and carbapenems, while MRSA exhibited resistance to β-lactams and levofloxacin. MSSA displayed a comparatively lower resistance profile. WGS identified significant numbers of ARGs in CRKP and MDRAB, with fewer DRGs compared to MRSA and MSSA. All isolates possessed genes associated with fimbriae production and adhesion, correlating with pronounced biofilm biomass production. NaOCl demonstrated substantial antimicrobial activity against both planktonic cells and biofilms. The MIC 90 for planktonic bacterial cells was 0.125 mg/mL, and the MBEC 90 ranged from 0.225 to 0.5 mg/mL. For planktonic C. albicans , the MIC 90 was 0.150 mg/mL, and the MBEC 90 was 0.250 mg/mL. These results highlight the challenge in treating biofilm-associated infections and underscore the potential of NaOCl as a robust antimicrobial agent against difficult-to-treat biofilm infections at concentrations lower than those typically found in commercial disinfectants., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Fabrizio, Sivori, Cavallo, Truglio, Toma, Sperati, Francalancia, Obregon, Pamparau, Kovacs, Pimpinelli and Di Domenico.)

Radical cystectomy (RC) is the gold standard treatment for patients with organ-confined bladder cancer. However, despite the success of this treatment, many men who undergo orthotopic neobladder substitution develop significant erectile dysfunction and urinary symptoms, including daytime and nighttime urinary incontinence. Prostate-capsule-sparing radical cystectomy (PCS-RC) with orthotopic neobladder (ONB) has been described in the literature as a surgical technique to improve functional outcomes in appropriately selected patients. We performed a systematic review and meta-analysis of manuscripts on PCS-RC with ONB published after 2000. We included retrospective and prospective studies with more than 25 patients and compared PCS-RC with nerve-sparing or conventional RC. Studies in which the entire prostate was spared (including the transitional zone) were excluded. Comparative studies were analyzed to assess rates of daytime continence, nighttime continence, and satisfactory erectile function in patients undergoing PCS-RC compared with those undergoing conventional RC. Fourteen reports were included in the final review. Our data identify high rates of daytime (83%-97%) and nighttime continence (60%-80%) in patients undergoing PCS-RC with ONB. In comparative studies, meta-analysis results demonstrate no difference in daytime continence (RR:1.12; 95% CI: 0.72-1.73) in those undergoing PCS-RC compared to those undergoing conventional RC. Similarly, nighttime continence was similar between the 2 groups (RR:1.85; 95% CI: 0.57-6.00. Erectile function was improved in those undergoing PCS-RC (RR 5.35; 95% CI: 1.82-15.74) in the PCS-RC series. Bladder cancer margin positivity and recurrence rates were similar to those reported in the literature with conventional RC with an average weighted follow-up of 52.2 months. While several studies utilized different prostate cancer (CaP) screening techniques, the rates of CaP were low (incidence 0.02; 95% CI:0.01-0.04), and oncologic outcomes were similar to standard RC. PCS-RC is associated with improved nighttime continence and erectile function compared to conventional RC techniques. Further work is needed to standardize CaP screening before surgery, but the data suggest low rates of CaP with similar oncologic outcomes when compared to RC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Seborrheic dermatitis (SD) affects 2-5% of the global population, with imbalances in the skin microbiome implicated in its development. This study assessed the impact of an oily suspension containing Lactobacillus crispatus P17631 and Lacticaseibacillus paracasei I1688 (termed EUTOPLAC) on SD symptoms and the skin mycobiome-bacteriome modulation. 25 SD patients were treated with EUTOPLAC for a week. Symptom severity and skin mycobiome-bacteriome changes were measured at the start of the treatment (T0), after seven days (T8), and three weeks post-treatment (T28). Results indicated symptom improvement post-EUTOPLAC, with notable reductions in the Malassezia genus. Concurrently, bacterial shifts were observed, including a decrease in Staphylococcus and an increase in Lactobacillus and Lacticaseibacillus. Network analysis highlighted post-EUTOPLAC instability in fungal and bacterial interactions, with increased negative correlations between Malassezia and Lactobacillus and Lacticaseibacillus genera. The study suggests EUTOPLAC's potential as a targeted SD treatment, reducing symptoms and modulating the mycobiome-bacteriome composition., (© 2024. The Author(s).)

Acinetobacter baumannii is increasingly associated with various epidemics, representing a serious concern due to the broad level of antimicrobial resistance and clinical manifestations. During the last decades, A. baumannii has emerged as a major pathogen in vulnerable and critically ill patients. Bacteremia, pneumonia, urinary tract, and skin and soft tissue infections are the most common presentations of A. baumannii , with attributable mortality rates approaching 35%. Carbapenems have been considered the first choice to treat A. baumannii infections. However, due to the widespread prevalence of carbapenem-resistant A. baumannii (CRAB), colistin represents the main therapeutic option, while the role of the new siderophore cephalosporin cefiderocol still needs to be ascertained. Furthermore, high clinical failure rates have been reported for colistin monotherapy when used to treat CRAB infections. Thus, the most effective antibiotic combination remains disputed. In addition to its ability to develop antibiotic resistance, A. baumannii is also known to form biofilm on medical devices, including central venous catheters or endotracheal tubes. Thus, the worrisome spread of biofilm-producing strains in multidrug-resistant populations of A. baumannii poses a significant treatment challenge. This review provides an updated account of antimicrobial resistance patterns and biofilm-mediated tolerance in A. baumannii infections with a special focus on fragile and critically ill patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Cavallo, Oliva, Pages, Sivori, Truglio, Fabrizio, Pasqua, Pimpinelli and Di Domenico.)

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Mono-ADP-ribosylation is a reversible post-translational protein modification that modulates the function of proteins involved in different cellular processes, including signal transduction, protein transport, transcription, cell cycle regulation, DNA repair and apoptosis. In mammals, mono-ADP-ribosylation is mainly catalyzed by members of two different classes of enzymes: ARTCs and ARTDs. The human ARTC family is composed of four structurally related ecto-mono-ARTs, expressed at the cell surface or secreted into the extracellular compartment that are either active mono-ARTs (hARTC1, hARTC5) or inactive proteins (hARTC3, hARTC4). The human ARTD enzyme family consists of 17 multidomain proteins that can be divided on the basis of their catalytic activity into polymerases (ARTD1-6), mono-ART (ARTD7-17), and the inactive ARTD13. In recent years, ADP-ribosylation was intensively studied, and research was dominated by studies focusing on the role of this modification and its implication on various cellular processes. The aim of this review is to provide a general overview of the ARTC enzymes. In the following sections, we will report the mono-ADP-ribosylation reactions that are catalysed by the active ARTC enzymes, with a particular focus on hARTC1 that recently has been intensively studied with the discovery of new targets and functions., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Development of anti-human leukocyte antigen donor-specific antibodies (DSAs) is associated with antibody-mediated rejection (AMR) and reduced allograft survival in kidney transplant recipients. Whether changes in circulating lymphocytes anticipate DSA or AMR development is unclear., Methods: We used time-of-flight mass cytometry to analyze prospectively collected peripheral blood mononuclear cells (PBMC) from pediatric kidney transplant recipients who developed DSA (DSA-positive recipients [DSA POS ], n = 10). PBMC were obtained at 2 months posttransplant, 3 months before DSA development, and at DSA detection. PBMC collected at the same time points posttransplant from recipients who did not develop DSA (DSA-negative recipients [DSA NEG ], n = 11) were used as controls., Results: DSA POS and DSA NEG recipients had similar baseline characteristics and comparable frequencies of total B and T cells. Within DSA POS recipients, there was no difference in DSA levels (mean fluorescence intensity [MFI]: 13 687 ± 4159 vs 11 375 ± 1894 in DSA POS AMR-positive recipients (AMR POS ) vs DSA POS AMR-negative recipients (AMR NEG ), respectively; P = 0.630), C1q binding (5 DSA POS AMR POS [100%] vs 4 DSA POS AMR NEG [80%]; P = 1.000), or C3d binding (3 DSA POS AMR POS [60%] vs 1 DSA POS AMR NEG [20%]; P = 0.520) between patients who developed AMR and those who did not. However, DSA POS patients who developed AMR (n = 5; 18.0 ± 3.6 mo post-DSA detection) had increased B cells with antibody-secreting (IgD - CD27 + CD38 + ; P = 0.002) and memory (IgD - CD27 + CD38 - ; P = 0.003) phenotypes compared with DSA NEG and DSA POS AMR NEG recipients at DSA detection., Conclusions: Despite the small sample size, our comprehensive phenotypic analyses show that circulating B cells with memory and antibody-secreting phenotypes are present at DSA onset, >1 year before biopsy-proven AMR in pediatric kidney transplant recipients., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2019 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

Protein mono-ADP-ribosylation is a reversible post-translational modification of cellular proteins. This scheme of amino-acid modification is used not only by bacterial toxins to attack host cells, but also by endogenous ADP-ribosyltransferases (ARTs) in mammalian cells. These latter ARTs include members of three different families of proteins: the well characterised arginine-specific ecto-enzymes (ARTCs), two sirtuins, and some members of the poly(ADP-ribose) polymerase (PARP/ARTD) family. In the present study, we demonstrate that human ARTC1 is localised to the endoplasmic reticulum (ER), in contrast to the previously characterised ARTC proteins, which are typical GPI-anchored ecto-enzymes. Moreover, using the "macro domain" cognitive binding module to identify ADP-ribosylated proteins, we show here that the ER luminal chaperone GRP78/BiP (glucose-regulated protein of 78 kDa/immunoglobulin heavy-chain-binding protein) is a cellular target of human ARTC1 and hamster ARTC2. We further developed a procedure to visualise ADP-ribosylated proteins using immunofluorescence. With this approach, in cells overexpressing ARTC1, we detected staining of the ER that co-localises with GRP78/BiP, thus confirming that this modification occurs in living cells. In line with the key role of GRP78/BiP in the ER stress response system, we provide evidence here that ARTC1 is activated during the ER stress response, which results in acute ADP-ribosylation of GRP78/BiP paralleling translational inhibition. Thus, this identification of ARTC1 as a regulator of GRP78/BiP defines a novel, previously unsuspected, player in GRP78-mediated ER stress responses.

Mono-ADP-ribosylation is a post-translational modification that was discovered more than five decades ago, and it consists of the enzymatic transfer of ADP-ribose from NAD⁺ to acceptor proteins. In viruses and prokaryotes, mono-ADP-ribosylation is mainly, but not exclusively, a mechanism used to take control of the host cell. In mammals, mono-ADP-ribosylation serves to regulate protein functions, and it is catalysed by two families of toxin-related cellular ADP-ribosyltransferases: ecto-enzymes that modify various cell-surface proteins, like integrins and receptors, and intracellular enzymes that act on a variety of nuclear and cytosolic proteins. These two families have been recently renamed the ARTCs (clostridia toxin like) and ARTDs (diphtheria toxin like), depending on their conserved structural features, and in terms of their relationships to the bacterial toxins. In addition, two members of the structurally non-related sirtuin family can also modify cellular proteins by mono-ADP-ribosylation. Recently, new examples of ADP-ribosylation of proteins involved in signal transduction and intracellular trafficking have been discovered, thus opening the route to the better molecular understanding of this reaction and of its role in human cell physiology and pathology.

During the development, progression and dissemination of neoplastic lesions, cancer cells can hijack normal pathways and mechanisms. This includes the control of the function of cellular proteins through reversible post-translational modifications, such as ADP-ribosylation, phosphorylation, and acetylation. In the case of mono-ADP-ribosylation and poly-ADP-ribosylation, the addition of one or several units of ADP-ribose to target proteins occurs via two families of enzymes that can generate ADP-ribosylated proteins: the diphtheria toxin-like ADP-ribosyltransferase (ARTD) family, comprising 17 different proteins that are either poly-ADP-ribosyltransferases or mono-ADP-ribosyltransferases or inactive enzymes; and the clostridial toxin-like ADP-ribosyltransferase family, with four human members, two of which are active mono-ADP-ribosyltransferases, and two of which are enzymatically inactive. In line with a central role for poly-ADP-ribose polymerase 1 in response to DNA damage, specific inhibitors of this enzyme have been developed as anticancer therapeutics and evaluated in several clinical trials. Recently, in combination with the discovery of a large number of enzymes that can catalyse mono-ADP-ribosylation, the role of this modification has been linked to human diseases, such as inflammation, diabetes, neurodegeneration, and cancer, thus revealing the need for the development of specific ARTD inhibitors. This will provide a better understanding of the roles of these enzymes in human physiology and pathology, so that they can be targeted in the future to generate new and efficacious drugs. This review summarizes our present knowledge of the ARTD enzymes that are involved in mono-ADP-ribosylation reactions and that have roles in cancer biology. In particular, the well-documented role of macro-containing ARTD8 in lymphoma and the putative role of ARTD15 in cancer are discussed., (© 2013 The Authors Journal compilation © 2013 FEBS.)

Background: To determine the repeatability and reproducibility of optical coherence tomography (OCT) Spectralis retinal thickness measurements in diabetic patients with clinically significant macular edema (CSME)., Methods: Twelve eyes of 12 volunteers (without macular pathology - control group) and 21 eyes of 21 diabetic patients with CSME were included in the study. Reproducibility, repeatability, intraclass correlation coefficients (ICCs) and intrasession correlation coefficients were tested with 20 × 15 degree raster scans consisting of 19 high-resolution line scans that were repeated three times by two experienced examiners., Results: In the control group, examining all regions, coefficient of repeatability was less than 1.1%, while coefficient of reproducibility was less than 2.2%. In diabetic patients, examining all regions, coefficient of repeatability was less than 2.6%, while coefficient of reproducibility was less than 2.4%. ICCs were, respectively, greater than or equal to 0.98 in the control group and 0.99 in diabetic patients. Intrasession coefficients of variation were less than 0.4% in the control group and less than 0.5% in diabetic patients., Conclusion: Retinal thickness measurements are repeatable and reproducible with OCT Spectralis in both the control group and diabetic patients. The results indicate that a change in central subfield thickness exceeding 12 µm and 3% in the diabetic patients is likely to be real.

The post-translational modifications of proteins by mono- and poly-ADP-ribosylation involve the cleavage of βNAD⁺, with the release of its nicotinamide moiety, accompanied by the transfer of a single (mono) or several (poly) ADP-ribose molecules from βNAD⁺ to a specific amino-acid residue of various cellular proteins. Thus, both mono- and poly-ADP-ribosylation are NAD⁺-consuming reactions. ADP-ribosylation reactions have been reported to have important roles in the nucleus, and in mitochondrial activity. Distinct subcellular NAD⁺ pools have been identified, not only in the nucleus and the mitochondria, but also in the endoplasmic reticulum and peroxisomes. Recent reports have shed new light on the correlation between NAD⁺-dependent ADP-ribosylation reactions and the endoplasmic reticulum. We have demonstrated that ARTD15/PARP16 is a novel mono-ADP-ribosyltransferase with a new intracellular location, as it is associated with the endoplasmic reticulum. The endoplasmic reticulum is a membranous network of tubules, vesicles, and cisternae that are interconnected in the cytoplasm of eukaryotic cells. This intracellular compartment is responsible for many cellular functions, including facilitation of protein folding and assembly, biosynthesis of lipids, storage of intracellular Ca²⁺, and transport of proteins. ARTD15 might have a role in both the nucleo-cytoplasmic shuttling, through importinβ1 mono-ADP-ribosylation, and in the unfolded protein response through its ability to ADP-ribosylate two components of this pathway: PERK and IRE1. This review summarizes our present knowledge of the enzymes and targets involved in ADP-ribosylation reactions, with special regard to the novel regulatory reactions that occurs at the level of the endoplasmic reticulum, and that can affect the function of this organelle.

Objectives: To determine the maximal and safely dose of preoperative radiotherapy and concurrently intensified chemotherapy regimen (raltitrexed plus oxaliplatin) in locally advanced rectal cancer patients., Methods: Patients with cT3-T4 and/or cN≥1 or locally recurrent rectal cancer were sequentially assigned to 4 treatment schedules of chemoradiation: standard radiotherapy (50.4 Gy/5.5 wk) plus raltitrexed (cohort A), accelerated radiotherapy (55 Gy/5 wk) plus raltitrexed (cohort B), standard radiotherapy plus raltitrexed and oxaliplatin (cohort C), accelerated radiotherapy plus raltitrexed and oxaliplatin (cohort D). Patients were treated in cohorts of 6 to 12 per group. The maximal tolerated dose was exceeded if more than one-third of patients in a given cohort experienced dose-limiting toxicity (DLT). DLT was defined as any grade ≥3 toxicity according to the Radiation Therapy Oncology Group criteria., Results: Forty-six consecutive patients were enrolled. In cohort A, 6 patients received the planned treatment with no DLT. In cohort B, 1 of 8 patients experienced a DLT. In cohort C, a DLT occurred in 2 of 6 patients and therefore, a cohort expansion was required. Three of 16 patients treated at this dose level experienced a DLT. In addition, cohort D was expanded and DLT was found in 4 of 16 patients. Therefore, the maximal tolerated dose was not exceeded at any treatment level., Conclusions: An intensified regimen of chemoradiotherapy delivering raltitrexed and oxaliplatin concurrently with concomitant boost radiotherapy (55 Gy/5 wk) can be safely administered in patients with locally advanced rectal cancer. On the basis of these results, this intensified regimen could be tested in a phase II study.

Our laboratory has developed a process for generating mAbs with selectivity to unique peptides in the context of MHC molecules. Recently, we reported that RL4B, an mAb that we have called a TCR mimic (TCRm) because it recognizes peptide in the context of MHC, has cytotoxic activity in vitro and prevented growth of tumor cells in a prophylactic setting. When presented in the context of HLA-A2, RL4B TCRm recognizes the peptide GVLPALPQV derived from human chorionic gonadotropin (hCG)-beta. In this study, we show that RL4B TCRm has strong binding affinity for the GVLPALPQV peptide/HLA-A2 epitope and fine binding specificity for cells that express endogenous hCGbeta Ag and HLA-A2. In addition, suppression of tumor growth with RL4B TCRm was observed in orthotopic models for breast cancer. Using two aggressive human tumor cell lines, MDA-MB-231 and MCF-7, we provide evidence that RL4B TCRm significantly retards tumor growth, supporting a possible role for TCRm agents in therapeutic settings. Moreover, tumors in mice responded to RL4B TCRm therapy in a dose-dependent manner, eliminating tumors at the highest dose. RL4B TCRm strongly detects the hCGbeta peptide/HLA-A2 epitope in human primary breast tumor tissue, but does not react or reacts weakly with normal breast tissue from the same patient. These results further illustrate the selective nature of TCRm Abs and the clinical relevance of the GVLPALPQV peptide/HLA-A2 epitope expression in tumor cells, because they provide the first evidence that Abs that mimic the TCR can be used to markedly reduce and suppress tumor growth.

Objective: Nm23-H1 and CD44v6 expression has been shown to be correlated with the metastatic potential of colorectal cancer (CRC) in some studies but not in others. The present study was undertaken to evaluate immunohistochemically the expression of these markers and to correlate them with clinicopathological variables., Materials and Methods: Archival tissues of 41 non metastatic colorectal cancers were histopathologically evaluated and stained with monoclonal antibodies versus Nm23-H1 and CD44v6., Results: Expression of Nm23-H1 was detected in 73% (n = 30) of all CRC, and CD44v6 in 37% (n = 15) of all CRC. CD44v6 was found to be statistically associated with tumour grading differentiation (p < 0.03), but no correlation emerged between Nm23-H1 and CD44v6 and Dukes stage, site, peritumoral lymphocytic infiltration, venous infiltrating, perineural infiltrating, tumour budding, pushing and infiltrating tumour growth., Conclusion: Even if the results are not statistically significant, the authors noticed that the expression of Nm23-H1 was correlated with those histopathological parameters that indicate local disease progression and metastases.

Objective: To assess the use of testicular needle aspiration techniques to evaluate fertility potential in azoospermic, formerly cryptorchid men., Study Design: Fifteen consecutive adult azoospermic, formerly cryptorchid patients (eight unilateral and seven bilateral) were examined by needle aspiration techniques, fine (FNA) and large needle (LNAB) testicular aspiration biopsy, for cytologic and histologic analysis. Five of the 15 subsequently underwent surgical biopsy for attempted assisted fertilization., Results: Spermatozoa or spermatids were detected by FNA cytology or LNAB histology in one or both testicles in 87.5% of the unilateral and 28.6% of the bilaterally affected, formerly cryptorchid patients (P = .041, Fisher's exact test). The addition of LNAB to FNA identified spermatids in one patient with unilateral cryptorchidism and only Sertoli cells on FNA cytology. Furthermore, LNAB differentiated testicles with the cytologic finding of only Sertoli cells into those with or without diffuse fibrosis. In the five patients in whom assisted fertilization was attempted, the needle aspiration techniques predicted the presence or absence of spermatozoa in the subsequent surgical biopsy., Conclusion: The two needle aspiration techniques can be used to assess the fertility potential of azoospermic, formerly cryptorchid men and to select patients for assisted fertilization.

The authors, on the basis of 3 cases of complicated diverticular disease, discuss the indications to surgery, considering the advantages and disadvantages of the various surgical techniques and examining in particular the rules for a correct operation with resection and primary or secondary anastomosis. As they performed a rectosigmoidectomy with primary high colorectal anastomosis, they report the reasons why they adopted the preservation and peeling of the inferior mesenteric artery (IMA).