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Background: Autosomal dominant polycystic kidney disease (ADPKD) is a hereditary kidney disorder that may progress to kidney failure, accounting for 5-10% of all patients with end-stage kidney disease (ESKD). Clinical data, as well as molecular genetics and advanced imaging techniques have provided surrogate prognostic biomarkers to predict rapid decline in kidney function, nonetheless enhanced tools for assessing prognosis for ADPKD are still needed. The aim of this study was to analyze specific microRNAs involved in the pathogenesis of ADPKD and in the development of renal fibrosis, evaluating their potential role as predictors of renal function loss., Methods: We evaluated kidney function by estimated glomerular filtration rate (eGFR) in 32 ADPKD patients in different stages of kidney disease at T0 and after a 24-month follow up (T1). Patients were divided into two groups: Rapid disease progression ([RP], n 15) and Non-rapid disease progression ([NRP], n 17), according to the Mayo Clinic classification criteria. At T0, ADPKD patients underwent plasma sampling for quantitative analysis of h-miR-17-5p, h-miR-21-5p and h-miR-199a-5p microRNA expression, using the quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) method and a 3 T magnetic resonance imaging (MRI), using an advanced MRI imaging protocol, for the quantification of total kidney volume (TKV), total perfusion volume (TPV) and total fibrotic volume (TFV)., Results: The expression of h-miR17-5p was higher (p < 0.05) in ADPKD patients with rapid disease progression. h-miR-17-5p, h-miR-21-5p and h-mir-199-5p showed a positive and significant correlation with the eGFR slope (mL/min/1.73 m 2 /year) (p < 0.05) but not with the eGFR at both T0 and T1. Both total fibrotic volume (cm 3 ) and height-adjusted total fibrotic volume (cm 3 /m) were positively and significantly correlated to h-miR 21-5p and h-miR 199-5p (p < 0.05), but not to total kidney volume (cm 3 ) and height-adjusted total kidney volume (cm 3 /m)., Conclusions: The microRNAs we studied were associated with fibrosis and renal damage, suggesting their possible role as biomarkers able to identify ADPKD patients at high risk of disease progression regardless of the degree of kidney function, and therefore suitable for medical therapy, and may help uncovering new molecular mechanisms underlying cystogenesis., (© 2024. The Author(s).)

Introduction: the COVID-19 pandemic has brought to light the intricate interplay between viral infections and preexisting health conditions. In the field of kidney diseases, patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD) and Chronic Kidney Disease (CKD) face unique challenges when exposed to the SARS-CoV-2 virus. This study aims to evaluate whether SARS-CoV-2 virus infection impacts renal function differently in patients suffering from ADPKD and CKD when compared to patients suffering only from CKD., Materials and Methods: clinical data from 103 patients were collected and retrospectively analyzed. We compared the renal function of ADPKD and CKD patients at two distinct time points: before COVID-19 infection (T0) and 1 year after the infection (T1). We studied also a subpopulation of 37 patients with an estimated glomerular filtration rate (eGFR) < 60 mL/min and affected by ADPKD and CKD., Results: clinical data were obtained from 59 (57.3%) ADPKD patients and 44 (42.7%) CKD patients. At T1, ADPKD patients had significantly higher serum creatinine levels compared to CKD patients, and a significantly lower eGFR was observed only in ADPKD patients with eGFR < 60 mL/min compared to CKD patients ( p < 0.01, p < 0.05; respectively). Following COVID-19 infection, ADPKD-CKD patients exhibited significantly higher variation in both median serum creatinine ( p < 0.001) and median eGFR ( p < 0.001) compared to CKD patients., Conclusion: the interplay between COVID-19 and kidney disease is complex. In CKD patients, the relationship between COVID-19 and kidney disease progression is more established, while limited studies exist on the specific impact of COVID-19 on ADPKD patients. Current evidence does not suggest that ADPKD patients are at a higher risk of SARS-CoV-2 infection; however, in our study we showed a significant worsening of the renal function among ADPKD patients, particularly those with an eGFR < 60 mL/min, in comparison to patients with only CKD after a one-year follow-up from COVID-19 infection.

Aim: Varicose veins, while frequently perceived as a cosmetic concern, should be evaluated within the broader context of chronic venous insufficiency (CVI) affecting the lower extremities. The Mappa Emodinamica Venosa Condivisa, Italian for Shared Venous Hemodynamics Map (MEVeC) project aims to provide an objective method for assessing the hemodynamic disorders underlying CVI and standardizing the evaluation of therapeutic interventions for lower extremity CVI. To achieve objective treatment assessment, it is essential to ensure uniform expertise among phlebologists and the ability to replicate comparable clinical outcomes., Methods: The study focused on patients with internal saphenous vein varices due to saphenous-femoral junction incompetence. Cases exhibiting non-saphenous reflux or incontinence perforating veins were excluded from the study cohort. Experienced medical practitioners conducted ultrasound Doppler scans and interventions on patients meeting specific inclusion criteria. These criteria included age, varix status, lifestyle, and Clinical Etiology Anatomy Pathophysiology (CEAP) classification. The study involved 40 limbs of patients in two groups, one undergoing traditional surgery and the other ablative laser treatment, with a six-month follow-up., Results: Group A (surgical intervention) exhibited a 5% incidence of ostial reflux and no saphenous vein reflux. In contrast, Group B (laser ablation) showed a 15% incidence of ostial reflux and a 20% incidence of saphenous vein reflux, with only one instance exceeding 0.5 seconds. The reflux observed in Group A was attributed to a previously undisclosed incontinent pudendal sub-ostial vein. In Group B, two instances of ostial refluxes resulted from a common incontinent confluence of the epigastric vein with other collateral vessels, while the third case presented sub-ostial incontinence., Conclusions: Despite the absence of a standardized protocol for assessing the efficacy of diverse therapeutic interventions for Chronic Venous Disease (CVD), the MEVeC technique may offer a methodology to reproduce comparable clinical outcomes regardless of the treatment used. The primary objective of MEVeC is to quantitatively evaluate the hemodynamic disorders that are fundamental to the pathogenesis of chronic venous insufficiency, thereby facilitating standardized comparative analyses of outcomes across various Multidisciplinary Vascular Clinic (MVC) treatment strategies.

Aim: Primary hepatic neuroendocrine carcinomas (PHNECs) are rare tumors with limited understanding and management. Diagnosing and treating these tumors pose significant challenges due to the lack of clinical experience. Surgery is often considered an effective therapeutic strategy for early-stage PHNECs. This case report describes an advanced metastatic PHNEC managed primarily with chemotherapy., Case Presentation: The medical records of the patient and diagnostic imaging findings were reviewed. A multidisciplinary team of specialists discussed the case and determined the treatment plan. The patient received a chemotherapy regimen tailored to PHNEC, which included specific neuroendocrine tumor-targeting agents., Results: Despite the advanced stage of the disease, the patient responded well to chemotherapy, with a notable reduction in tumor size and improvement in symptoms. The treatment was well-tolerated, and the patient showed a favorable overall response. The survival duration from the time of diagnosis was 18 months., Conclusions: In this case of advanced metastatic PHNEC, a primarily chemotherapy-based approach yielded positive outcomes. Although surgery is typically preferred for early-stage cases, this case highlights the potential efficacy of chemotherapy in managing advanced PHNECs. Further research and clinical experience are warranted to better understand the optimal treatment strategies for these rare tumors.

Background: The gold standard for sentinel lymph node staging in melanoma is the use of the combined technique of radioisotope plus blue dye. New techniques and alternative methods have been proposed, with the promise of achieving comparable efficacy. We then carried out a literature search., Methods: We conducted a literature search using the "sentinel lymph node biopsy" and "melanoma" keywords, then selected the case-control studies (the quality of which was assessed using the STROBE criteria)., Results: Twelve studies of 13,017 were selected, concerning the identification rate of indocyanine green fluorescence and indocyanine green-99mtc-nanocolloid techniques. We have found a comparable identification rate between the various techniques, even if given the small population present for some techniques, the results did not reach statistical significance., Conclusions: The use of new techniques in sentinel lymph node detection promises results comparable to the gold standard techniques, but further studies are needed to validate these methods in the context of melanoma surgery., Competing Interests: The authors have no financial interest to declare in relation to the content of this article., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Background: Diabetes mellitus is a prevalent chronic condition that significantly impacts global health. Diabetic foot complications, such as foot ulcers, pose a substantial burden on individuals with diabetes and can lead to serious consequences, including amputation. Platelet-rich plasma (PRP) has emerged as a promising therapeutic approach for enhancing the healing of diabetic foot ulcers., Methods: In our study, we treated 12 patients with chronic diabetic ulcers using PRP injections administered at three-week intervals. Our objective was to assess the reduction in wound size and the rate of complete healing at 6 months after the start of the treatment. Additionally, we conducted a comprehensive literature review to contextualize our findings., Results: Out of the 12 patients, 8 achieved complete healing of their diabetic foot ulcers, while the remaining four showed significant improvement with more than 50% reduction in the initial lesion size. 3 patients developed mild irritation at the inoculation site. These outcomes, combined with the evidence from published studies, highlight the effectiveness of PRP in promoting the healing of diabetic foot ulcers., Conclusion: In conclusion, our study demonstrates the potential of platelet-rich plasma (PRP) as a successful therapeutic option for enhancing the healing process of chronic diabetic foot ulcers. The favorable outcomes observed, including a high rate of complete healing and significant wound size reduction, underscore the value of PRP treatment in managing this challenging complication. Further research and larger studies may provide additional insights into the mechanisms and long-term benefits of PRP in diabetic wound healing., 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 Izzo, De Intinis, Molle, Polistena, Sibio, Codacci-Pisanelli, Biacchi, Di Cello, Santini, Izzo and Izzo.)

(1) Background: Sentinel lymph node biopsy is important in the search for metastases, especially in patients with malignant breast disease. Our study proposed new techniques to prevent complications such as possible postoperative seroma formation, pain or hypoesthesia of the axillary cord and medial arm surface, as well as motor deficits, to avoid disabling outcomes and presents initial data from our experience with the sentinel lymph node biopsy technique. (2) Methods: We mainly used two radioactive tracer detection techniques and a new technique using a radiotracer called Sentimag-magtrace. The positive lymph node was located and removed to perform histologic analysis. In our study, we evaluate 100 patients who underwent breast cancer surgery. (3) Results: We calculated the identification rates of the different methods of sentinel lymph node detection and found that it was 88.9% using radioactive tracers vs. 89.5% using the magnetic tracer technology (Sentimag). (4) Conclusions: Thus, this technique avoids radiation exposure for both patients and health care providers, and can reduce costs and time.

The candidate Adjuvant System AS37 contains a synthetic toll-like receptor agonist (TLR7a) adsorbed to alum. In a phase I study (NCT02639351), healthy adults were randomised to receive one dose of licensed alum-adjuvanted meningococcal serogroup C (MenC-CRM 197 ) conjugate vaccine (control) or MenC-CRM 197 conjugate vaccine adjuvanted with AS37 (TLR7a dose 12.5, 25, 50 or 100 µg). A subset of 66 participants consented to characterisation of peripheral whole blood transcriptomic responses, systemic cytokine/chemokine responses and multiple myeloid and lymphoid cell responses as exploratory study endpoints. Blood samples were collected pre-vaccination, 6 and 24 h post-vaccination, and 3, 7, 28 and 180 days post-vaccination. The gene expression profile in whole blood showed an early, AS37-specific transcriptome response that peaked at 24 h, increased with TLR7a dose up to 50 µg and generally resolved within one week. Five clusters of differentially expressed genes were identified, including those involved in the interferon-mediated antiviral response. Evaluation of 30 cytokines/chemokines by multiplex assay showed an increased level of interferon-induced chemokine CXCL10 (IP-10) at 24 h and 3 days post-vaccination in the AS37-adjuvanted vaccine groups. Increases in activated plasmacytoid dendritic cells (pDC) and intermediate monocytes were detected 3 days post-vaccination in the AS37-adjuvanted vaccine groups. T follicular helper (Tfh) cells increased 7 days post-vaccination and were maintained at 28 days post-vaccination, particularly in the AS37-adjuvanted vaccine groups. Moreover, most of the subjects that received vaccine containing 25, 50 and 100 µg TLR7a showed an increased MenC-specific memory B cell responses versus baseline. These data show that the adsorption of TLR7a to alum promotes an immune signature consistent with TLR7 engagement, with up-regulation of interferon-inducible genes, cytokines and frequency of activated pDC, intermediate monocytes, MenC-specific memory B cells and Tfh cells. TLR7a 25-50 µg can be considered the optimal dose for AS37, particularly for the adjuvanted MenC-CRM 197 conjugate vaccine., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Emilio Siena reports financial support was provided by GSK. Francesca Schiavetti reports financial support was provided by GSK group of companies. Erica Borgogni reports financial support was provided by GSK. Marianna Taccone reports financial support was provided by GSK. Elisa Faenzi reports financial support was provided by GSK. Michela Brazzoli reports financial support was provided by GSK. Susanna Aprea reports financial support was provided by GSK. Monia Bardelli reports financial support was provided by GSK group of companies. Gianfranco Volpini reports financial support was provided by GSK. Francesca Buricchi reports financial support was provided by GSK. Chiara Sammicheli reports financial support was provided by GSK. Simona Tavarini reports financial support was provided by GSK. Viviane Bechtold reports financial support was provided by GSK. Christoph J. Blohmke reports financial support was provided by GSK. Carlo De Intinis reports financial support was provided by GSK. Antonio Gonzalez-Lopez reports financial support was provided by GSK. Derek T. O Hagan reports financial support was provided by GSK. Sandra Nuti reports financial support was provided by GSK. Claudia Seidl reports financial support was provided by GSK. Arnaud M Didierlaurent reports financial support was provided by GSK. Sylvie Bertholet reports financial support was provided by GSK. Ugo D Oro reports financial support was provided by GSK. Duccio Medini reports financial support was provided by GSK. Oretta Finco reports financial support was provided by GSK. Ugo D Oro reports a relationship with GSK that includes: equity or stocks. Christoph J. Blohmke reports a relationship with GSK that includes: equity or stocks. Derek T. O Hagan reports a relationship with GSK that includes: equity or stocks. Sylvie Bertholet reports a relationship with GSK that includes: equity or stocks. Derek T O Hagan has patent issued to Alum/TLR7. Ugo D Oro and Sylvie Bertholet are listed as inventor on patents owned by the GSK. Arnaud M Didierlaurent reports personal fees from Speranza and Lubrizol for consultancy, outside the submitted work. All authors declare no other financial or non-financial relationships and activities., (Copyright © 2022 GlaxoSmithKline Biologicals S.A. Published by Elsevier Ltd.. All rights reserved.)

The suture thread used in digestive surgery must have several characteristics, including resistance to tension until the anastomosis coalescence, rapid absorption to avoid complications, biocompatibility and ease of handling. The preference is for monofilament polymers as they offer greater guarantees in biliary-digestive anastomoses. Suturing with synthetic polymers and mechanical devices such as staplers are the most suitable techniques. It is believed that staplers may become the gold standard technique in robotic surgery based on their experience and experimental data. In general, the goal is to use materials that minimize the risk of post-operative complications and offer maximum reliability in the anastomosis. KEY WORD: Suture material, Stapler.

Understanding immune responses to SARS-CoV-2 messenger RNA (mRNA) vaccines is of great interest, principally because of the poor knowledge about the mechanisms of protection. In the present study, we analyzed longitudinally B cell and T cell memory programs against the spike (S) protein derived from ancestral SARS-CoV-2 (Wuhan-1), B.1.351 (beta), B.1.617.2 (delta) and B.1.1.529 (omicron) variants of concern (VOCs) after immunization with an mRNA-based vaccine (Pfizer). According to the magnitude of humoral responses 3 months after the first dose, we identified high and low responders. Opposite to low responders, high responders were characterized by enhanced antibody-neutralizing activity, increased frequency of central memory T cells and durable S-specific CD8 + T cell responses. Reduced binding antibodies titers combined with long-term specific memory T cells that had distinct polyreactive properties were found associated with subsequent breakthrough with VOCs in low responders. These results have important implications for the design of new vaccines and new strategies for booster follow-up., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Upon chronic antigen exposure, CD8 + T cells become exhausted, acquiring a dysfunctional state correlated with the inability to control infection or tumor progression. In contrast, stem-like CD8 + T progenitors maintain the ability to promote and sustain effective immunity. Adenovirus (Ad)-vectored vaccines encoding tumor neoantigens have been shown to eradicate large tumors when combined with anti-programmed cell death protein 1 (αPD-1) in murine models; however, the mechanisms and translational potential have not yet been elucidated. Here, we show that gorilla Ad vaccine targeting tumor neoepitopes enhances responses to αPD-1 therapy by improving immunogenicity and antitumor efficacy. Single-cell RNA sequencing demonstrated that the combination of Ad vaccine and αPD-1 increased the number of murine polyfunctional neoantigen-specific CD8 + T cells over αPD-1 monotherapy, with an accumulation of Tcf1 + stem-like progenitors in draining lymph nodes and effector CD8 + T cells in tumors. Combined T cell receptor (TCR) sequencing analysis highlighted a broader spectrum of neoantigen-specific CD8 + T cells upon vaccination compared to αPD-1 monotherapy. The translational relevance of these data is supported by results obtained in the first 12 patients with metastatic deficient mismatch repair (dMMR) tumors vaccinated with an Ad vaccine encoding shared neoantigens. Expansion and diversification of TCRs were observed in post-treatment biopsies of patients with clinical response, as well as an increase in tumor-infiltrating T cells with an effector memory signature. These findings indicate a promising mechanism to overcome resistance to PD-1 blockade by promoting immunogenicity and broadening the spectrum and magnitude of neoantigen-specific T cells infiltrating tumors.

Single-cell multi-omics is a rapidly evolving field, thanks to a fast technological improvement and the growing accuracy of dedicated computational tools for data analysis. Its importance is highlighted by the possibility to distinguish apparently identical cells based on their pattern of gene expression. In this review, the mostly used methodological pipelines for single-cell analysis, as well as the advantages and potential limitations of several analytical steps, are presented and discussed, with specific sections focusing on crucial parts of this procedure, their bioinformatic tools, as well as their advantages and potential drawbacks. The current bioinformatic approaches for T-cell receptor (TCR) reconstruction are also introduced, as well as a comparison of single-cell sequencing technologies. Critical points that may introduce analytical biases and potential inaccuracies in data interpretation are also highlighted., (Copyright © 2022 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.)

Gene expression data is commonly used in vaccine studies to characterize differences between treatment groups or sampling time points. Group-wise comparisons of the transcriptional perturbations induced by vaccination have been applied extensively for investigating the mechanisms of action of vaccines. Such approaches, however, may not be sensitive enough for detecting changes occurring within a minority of the population under investigation or in single individuals. In this study, we developed a data analysis framework to characterize individual subject response profiles in the context of repeated measure experiments, which are typical of vaccine mode of action studies. Following the definition of the methodology, this was applied to the analysis of human transcriptome responses induced by vaccination with a subunit influenza vaccine. Results highlighted a substantial heterogeneity in how different subjects respond to vaccination. Moreover, the extent of transcriptional modulation experienced by each individual subject was found to be associated with the magnitude of vaccine-specific functional antibody response, pointing to a mechanistic link between genes involved in protein production and innate antiviral response. Overall, we propose that the improved characterization of the intersubject heterogeneity, enabled by our approach, can help driving the improvement and optimization of current and next-generation vaccines., (© 2021. The Author(s).)

Recent improvements in cost-effectiveness of high-throughput technologies has allowed RNA sequencing of total transcriptomes suitable for evaluating the expression and regulation of circRNAs, a relatively novel class of transcript isoforms with suggested roles in transcriptional and post-transcriptional gene expression regulation, as well as their possible use as biomarkers, due to their deregulation in various human diseases. A limited number of integrated workflows exists for prediction, characterization, and differential expression analysis of circRNAs, none of them complying with computational reproducibility requirements. We developed Docker4Circ for the complete analysis of circRNAs from RNA-Seq data. Docker4Circ runs a comprehensive analysis of circRNAs in human and model organisms, including: circRNAs prediction; classification and annotation using six public databases; back-splice sequence reconstruction; internal alternative splicing of circularizing exons; alignment-free circRNAs quantification from RNA-Seq reads; and differential expression analysis. Docker4Circ makes circRNAs analysis easier and more accessible thanks to: (i) its R interface; (ii) encapsulation of computational tasks into docker images; (iii) user-friendly Java GUI Interface availability; and (iv) no need of advanced bash scripting skills for correct use. Furthermore, Docker4Circ ensures a reproducible analysis since all its tasks are embedded into a docker image following the guidelines provided by Reproducible Bioinformatics Project.

Circular RNAs are highly stable molecules present in all eukaryotes generated by distinct transcript processing. We have exploited poly(A-) RNA-Seq data generated in our lab in MCF-7 breast cancer cells to define a compilation of exonic circRNAs more comprehensive than previously existing lists. Development of a novel computational tool, named CircHunter , allowed us to more accurately characterize circRNAs and to quantitatively evaluate their expression in publicly available RNA-Seq data from breast cancer cell lines and tumor tissues. We observed and confirmed, by ChIP analysis, that exons involved in circularization events display significantly higher levels of the histone post-transcriptional modification H3K36me3 than non-circularizing exons. This result has potential impact on circRNA biogenesis since H3K36me3 has been involved in alternative splicing mechanisms. By analyzing an Ago-HITS-CLIP dataset we also found that circularizing exons overlapped with an unexpectedly higher number of Ago binding sites than non-circularizing exons. Finally, we observed that a subset of MCF-7 circRNAs are specific to tumor versus normal tissue, while others can distinguish Luminal from other tumor subtypes, thus suggesting that circRNAs can be exploited as novel biomarkers and drug targets for breast cancer., Competing Interests: CONFLICTS OF INTEREST The authors declare that they have no competing interests.

The aim of this survey was to describe the incidence, epidemiology, microbiology, risk factors and outcome of medical care related laboratory-confirmed bloodstream infections (LCBIs) observed during a twelve-month prospective study in a Paediatric Teaching Hospital in Turin, Italy. Inclusion criteria were clinical signs of sepsis and positivity of one or more of the following tests: blood culture, polymerase chain reaction for bacterial and fungal DNA on blood, and culture on intravascular device tips. In all, 140 episodes of sepsis were documented in 131 children: 37 (26.4%) were healthcare outpatient-associated, 91 (65.0%) healthcare-associated and 12 (8.6%) community-acquired. The overall incidence of healthcare-associated LCBIs was 13.6/1,000 hospitalized patients and incidence density 1.4/1,000 inpatient days. The overall mortality was 3.9%. Forty-seven (36.7%) episodes involved newborns and 107 (83.6%) episodes were observed in children with an indwelling central venous catheter. Coagulase-negative staphylococci (26.8%), Staphylococcus aureus (15.2%), Escherichia coli (8.7%) and Candida spp. (7.2%) were responsible for the majority of cases. 9.5% of S. aureus isolates were methicillin-resistant and 6.5% of Gram negatives were extended-spectrum beta-lactamase-producing. Incidence and epidemiology of medical care related LCBIs were similar to the existing literature data. LCBIs caused by antibiotic-resistant microorganisms were fewer and mortality rate was lower. Most of the LCBIs recorded involved newborns and oncological children.