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According to the FAO/WHO guidelines, selection of probiotics requires the assessment of survival under gastrointestinal stress and adhesion to human epithelial cells. These attributes were evaluated on Akkermansia muciniphila ATCC BAA-835 simulating the gastrointestinal transit (GIT) immediately followed by adhesion to human intestinal cell lines (CaCo2, HT-29, and HT-29-MTX) as an alternative approach to in vitro methods performed with fresh cells in each trial. The survival rate after GIT, as determined by plate counts and fluorescent probes, was significantly higher for A. muciniphila (about 8 Log CFU/mL) than for the probiotic Lacticaseibacillus rhamnosus GG ATCC 53103 (about 3 Log CFU/mL). The use of Live/Dead assay highlighted that A. muciniphila forms cell aggregates in the gastric phase as protective mechanism, explaining its high viability in the intestine. The rate of adhesion to human cell lines was always lower for strains tested after simulated GIT than for strains that did not undergo simulated GIT. Akkermansia muciniphila exhibited significantly higher adhesion than Lbs. rhamnosus GG, particularly to the mucus-secreting HT-29-MTX cells across a range of concentrations (2-8 Log CFU/mL). Finally, the bioinformatic analysis of A. muciniphila proteome confirmed the Amuc_1434 as a potential factor in binding to the human MUC2 protein., 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 Vergalito, Bagnoli, Maiuro, Pannella, Palombo, Testa, Coppola, Di Marco, Tremonte, Lombardi, Iorizzo, Coppola and Succi.)

The present study aimed to find solutions based on the use of plant-based ingredients that would improve the nutritional quality of meat products as well as ensure sensory and microbiological quality. Two fat replacers, lemon albedo ( Citrus lemon ) and carob seed gum ( Ceratonia siliqua ), were investigated by chemical analysis and panel testing to evaluate their effect on the nutritional and sensory quality of beef burgers. The antimicrobial activity of two plant extracts, from nettle ( Urtica dioica ) leaves and medlar ( Eriobotrya japonica ) seeds, was studied, evaluating the intensity of inhibitory action and the minimum inhibitory concentration against Pseudomonas spp. and Listeria innocua strains by plate test. In addition, the antioxidant activity of both extracts was evaluated. Based on the results, lemon albedo and medlar seed extracts were validated in a food model (beef burger) by a storage test and a challenge test. The storage test results highlight that medlar seed extract prevents the formation of thiobarbituric acid reactive substances (TBARSs) and ensures microbiological quality, inhibiting Enterobacteriaceae and Pseudomonas spp. Anti- Listeria efficacy was confirmed in situ by challenge test results. In conclusion, although fat replacers ensure nutritional and sensory quality, they do not satisfy microbiological quality. This study clearly demonstrates that the safety of low-fat burgers can only be achieved through the combination of appropriate fat replacers with well-selected natural antimicrobial extracts.

Our work investigated the antimicrobial and prebiotic properties of basil, mint, oregano, rosemary, savory, and thyme honey. The potential antimicrobial action, assessed against the pathogens Acinetobacter baumannii , Escherichia coli , Listeria monocytogenes , Pseudomonas aeruginosa , and Staphylococcus aureus , evidenced the capacity of the honey to influence the pathogenic hydrophobicity and hemolytic activities. Honey inhibited pathogen biofilms, acting especially on the mature biofilms, with inhibition rates of up to 81.62% (caused by the presence of mint honey on L. monocytogenes ). S. aureus biofilms were the most susceptible to the presence of honey, with inhibition rates up of to 67.38% in the immature form (caused by basil honey) and up to 80.32% in the mature form (caused by mint honey). In some cases, the amount of nuclear and proteic material, evaluated by spectrophotometric readings, if also related to the honey's biofilm inhibitory activity, let us hypothesize a defective capacity of building the biofilm scaffold or bacterial membrane damage or an incapability of producing them for the biofilm scaffold. The prebiotic potentiality of the honey was assessed on Lacticaseibacillus casei Shirota, Lactobacillus gasseri , Lacticaseibacillus paracasei subsp. paracasei , and Lacticaseibacillus rhamnosus and indicated their capacity to affect the whole probiotic growth and in vitro adhesive capacity, as well as the antioxidant and cytotoxic abilities, and to inhibit, mainly in the test performed with the L. casei Shirota, L. gasseri , and L. paracasei supernatants, the immature biofilm of the pathogens mentioned above.

Pancreas units represent new organizational models of care that are now at the center of the European debate. The PUECOF study, endorsed by the European-African Hepato-Pancreato-Biliary Association (E-AHPBA), aims to reach an expert consensus by enquiring surgical leaders about the Pancreas Units' most relevant organizational factors, with 30 surgical leaders from 14 countries participating in the Delphi survey. Results underline that surgeons believe in the need to organize multidisciplinary meetings, nurture team leadership, and create metrics. Clinical professionals and patients are considered the most relevant stakeholders, while the debate is open when considering different subjects like industry leaders and patient associations. Non-technical skills such as ethics, teamwork, professionalism, and leadership are highly considered, with mentoring, clinical cases, and training as the most appreciated facilitating factors. Surgeons show trust in functional leaders, key performance indicators, and the facilitating role played by nurse navigators and case managers. Pancreas units have a high potential to improve patients' outcomes. While the pancreas unit model of care will not change the technical content of pancreatic surgery, it may bring surgeons several benefits, including more cases, professional development, easier coordination, less stress, and opportunities to create fruitful connections with research institutions and industry leaders., (© 2024. The Author(s).)

Background and Aims: We aimed to characterize the epidemiologic and comorbidities profiles of patients with chronic Hepatitis D (CHD) followed in clinical practice in Italy and explored their interferon (IFN) eligibility., Methods: This was a cross-sectional study of the PITER cohort consisting of consecutive HBsAg-positive patients from 59 centers over the period 2019-2023. Multivariable analysis was performed by logistic regression model., Results: Of 5492 HBsAg-positive enrolled patients, 4152 (75.6%) were screened for HDV, 422 (10.2%) were anti-HDV positive. Compared with HBsAg mono-infected, anti-HDV positive patients were more often younger, non-Italians, with a history of drug use, had elevated alanine transaminase (ALT), cirrhosis, or hepatocellular carcinoma (HCC). Compared with Italians, anti-HDV positive non-Italians were younger (42.2% age ≤ 40 years vs. 2.1%; P < 0.001), more often females (males 43.0% vs. 68.6%; P < 0.001) with less frequent cirrhosis and HCC. HDV-RNA was detected in 63.2% of anti-HDV-positive patients, who were more likely to have elevated ALT, cirrhosis, and HCC. Extrahepatic comorbidities were present in 47.4% of anti-HDV positive patients and could affect the eligibility of IFN-containing therapies in at least 53.0% of patients in care., Conclusions: CHD affects young, foreign-born patients and older Italians, of whom two-thirds had cirrhosis or HCC. Comorbidities were frequent in both Italians and non-Italians and impacted eligibility for IFN., 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 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background/Objectives : The textbook outcome (TO) is a composite tool introduced to uniform surgical units and regulate surgical quality and outcomes. A patient is considered TO only if all predetermined items are met. In colorectal surgery, TO represents a new tool that can achieve important results given the prevalence of colorectal cancers. However, at present, there is a lack of uniformity in the TO's definition. This study utilized the Delphi process to define an Italian version of the TO in colorectal cancer. Methods : The survey consisted of two rounds of online questionnaires submitted to an expert panel in colorectal oncological surgery, renowned academic surgeons, who had attended multiple scientific conferences and who were authors of papers on this specific topic. Five main topics with 26 questions were investigated through an online modified Delphi method. Items with almost 75% agreement achieved consensus. Results : Twenty-eight Italian experts were selected and participated in the two rounds. The Italian version of the textbook outcome in colorectal surgery was defined as the presence of 90-day postoperative survival, negative margins and at least 12 lymph nodes, a minimally invasive approach, ostomy fashioning if preoperatively planned, postoperative complication < Clavien-Dindo 3b, at least 10 ERAS items, no readmission, proper CHT and RT regimens, complete colonoscopy after or before surgery and Tumor Board Evaluation. Conclusions : The textbook outcome in colorectal cancer patients is a quality instrument providing a complete overview of the care of such patients, from diagnosis to treatment. We hereby propose an Italian version of the TO with outcomes chosen by an expert panel.

Backgrounds: Rectal robotic surgery gained momentum in the last decade, but it is still associated with not-negligible costs. In order to reduce costs, recently different robotic systems have received approval for clinical use. This study aims to present the first case series of rectal resection with the novel cost-effective platform Robotic Assisted Surgery (RAS) Hugo™. Tips for effective set up of the system and detailed configuration of tilt and docking angles are also provided., Methods: Three cases of rectal resection with Hugo RAS™ system are reported. After the first two cases of resection with partial mesorectal excision in which surgeries were performed with the setup proposed by the vendor company, in the third case we tested a novel setup that allowed a full robotic low rectal resection performing vascular ligations, TME and colonic splenic flexure mobilization without the need of any de-docking., Results: Our first three robotic rectal resections with the Hugo RAS™ system were completed without complications with a median docking time of 12 min (range 8-15) and a median console time of 345 minutes (range 271-475). In the first two cases, hybrid robotic and laparoscopic surgeries were performed to obtain an adequate haemostasis and traction during the pelvic phase. In the third case, a full robotic TME was successfully accomplished., Conclusion: Our experience demonstrates that a full robotic low rectal resection with TME with Hugo™ RAS system is feasible, safe and associated with satisfactory postoperative outcomes., (© 2024 Royal Australasian College of Surgeons.)

Objective: The REDISCOVER consensus conference aimed at developing and validating guidelines on the perioperative care of patients with borderline-resectable (BR-) and locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC)., Background: Coupled with improvements in chemotherapy and radiation, the contemporary approach to pancreatic surgery supports the resection of BR-PDAC and, to a lesser extent, LA-PDAC. Guidelines outlining the selection and perioperative care for these patients are lacking., Methods: The Scottish Intercollegiate Guidelines Network (SIGN) methodology was used to develop the REDISCOVER guidelines and create recommendations. The Delphi approach was used to reach a consensus (agreement ≥80%) among experts. Recommendations were approved after a debate and vote among international experts in pancreatic surgery and pancreatic cancer management. A Validation Committee used the AGREE II-GRS tool to assess the methodological quality of the guidelines. Moreover, an independent multidisciplinary advisory group revised the statements to ensure adherence to nonsurgical guidelines., Results: Overall, 34 recommendations were created targeting centralization, training, staging, patient selection for surgery, possibility of surgery in uncommon scenarios, timing of surgery, avoidance of vascular reconstruction, details of vascular resection/reconstruction, arterial divestment, frozen section histology of perivascular tissue, extent of lymphadenectomy, anticoagulation prophylaxis, and role of minimally invasive surgery. The level of evidence was however low for 29 of 34 clinical questions. Participants agreed that the most conducive means to promptly advance our understanding in this field is to establish an international registry addressing this patient population ( https://rediscover.unipi.it/ )., Conclusions: The REDISCOVER guidelines provide clinical recommendations pertaining to pancreatectomy with vascular resection for patients with BR-PDAC and LA-PDAC, and serve as the basis of a new international registry for this patient population., Competing Interests: S.G.B.: support from Flinders Foundation grant: 49358025, NHMRC Ideas Grant: 2021009, Pankind 21.R7.INV.CB.UOSA.6.2. F.M.: Tsumura, Inc., Scientific Advisory Board. M.D.C. is a co-PI of a Boston Scientific–sponsored study and he has been awarded an industry grant by Haemonetics, Inc. M.H.: Intuitive Surgical—teaches courses and proctors. The remaining authors report no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: This was an observational, retrospective, multicenter study, enrolling elderly patients (>65 years old) treated with ixekizumab with a diagnosis of psoriasis (PsO) and/or psoriatic arthritis (PsA) during the period 2020 to 2023., Objectives: Efficacy of ixekizumab in elderly patients in the treatment of moderate to severe psoriasis., Methods: We included 73 patients with psoriasis (32.9%), psoriatic arthritis (1.4%) and both of them (PsO-PsA 65.8%), attending the outpatient clinics of seven Italian referral center for psoriasis in Lazio region: Policlinico Umberto I Università Roma La Sapienza, Sant'Andrea Università di Roma La Sapienza, Polo Pontino Università Roma La Sapienza, Fondazione Policlinico Universitario A. Gemelli, Università Campus Biomedico Roma, Istituto Dermopatico dell'Immacolata - IDI and Policlinico Tor Vergata. We collected data related to the characteristics of the patients (age, sex, body mass index) and of the disease (age at onset, duration of psoriasis, previous treatments). The severity of psoriasis was measured with the Psoriasis Area and Severity Index (PASI) score at baseline and after 16, 24, 52, 104 and 156 weeks of treatment., Results: PASI90 was achieved by all the patients in week 16 and remained stable until the end of the study. PASI100 has been achieved by 55.1% of patients at weeks 16 and by 81.3% at week 104. A statistically significant difference has been showed between baseline and all the other time points (P < 0.0001) for PASI score. A similar trend was observed for Visual Analogue Scale score and Dermatology Life Quality Index score., Conclusions: Ixekizumab was effective and with a good safety profile in psoriatic patients over 65 years. No significant adverse events were reported.

In this study, two Mediterranean coastal lagoons (Lesina and Varano) of southern Italy, located in the north of the Apulia region, were investigated for the presence of Shiga toxin Escherichia coli (STEC) and potentially enteropathogenic Vibrio species in parallel with norovirus (NoV), hepatitis A virus (HAV), hepatitis E virus (HEV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study aimed to evaluate the presence of potentially pathogenic bacteria and viruses in the water and sediments of these ecosystems. From March 2022 to February 2023, a total of 98 samples were collected: 49 water samples and 49 sediment samples. STEC strains were isolated in three samples (3.1%), of which one (2%) was water ( stx1 and stx2 positive) and two (4.1%) were sediment (both stx2 positive) samples. Vibrio spp. were detected in twenty samples (20.4%), of which nine were water (18.4%) and eleven were sediment (22.4%) samples. The species detected included V. parahaemolyticus , V. cholerae , and V. vulnificus . NoV was detected in 25 (25.5%) samples, while none of the water or sediment samples were positive for HAV, HEV, and SARS-CoV-2. The results of this study provide an overview of the presence of potentially pathogenic microorganisms in areas influenced by anthropogenic pressure. Monitoring the circulation of these pathogens could be useful to evaluate the water flowing into the lagoons, in particular discharge waters ( i.e. , urban, agricultural, and livestock runoff), considering the presence of fish and shellfish farms in these sites., Competing Interests: Conflict of interest: the authors declare no potential conflict of interest., (Copyright © 2024, the Author(s).)

Grape-associated microbial community is influenced by a combination of viticultural, climatic, pedological and anthropological factors, collectively known as terroir . Therefore, grapes of the same cultivar grown in different areas can be appreciated for their distinctive biogeographic characteristics. In our previous study, we showed that the phenotypic response of Aglianico and Cabernet grapevines from Molise and Sicily regions is significantly influenced by the prevailing pedoclimatic conditions, particularly soil physical properties. However, the scale at which microbial communities differ could be important in clarifying the concept of terroir , including whether it is linked to the grape variety present in a particular vineyard. To explore this further, in the research presented here, a comparative study on the fungal communities inhabiting the berry surfaces of Cabernet and Aglianico cultivars was conducted on different vineyards located in Southern Italy (Molise, Sicily and Campania regions, the first two of which had been involved in our previous study) by using high-throughput sequencing (HTS) and multivariate data analysis. The descriptive approach through relative abundance analysis showed the most abundant phyla (Ascomycota, Basidiomycota, and Chytridiomycota), families ( Cladosporiaceae , Saccotheciaceae , Pleosporaceae , Saccharomycodaceae , Sporidiobolaceae , Didymellaceae , Filobasidiaceae , Bulleribasidiaceae , and Saccharomycetaceae ) and genera ( Cladosporium , Aureobasidium , Alternaria , Stemphylium and Filobasidium ) detected on grape berries. The multivariate data analysis performed by using different packages (phyloseq, Vegan, mixOmics, microbiomeMarker and ggplot2) highlighted that the variable "vineyard location" significantly affect the fungal community, while the variable "grape variety" has no significant effect. Thus, some taxa are found to be part of specific vineyard ecosystems rather than specific grape varieties, giving additional information on the microbial contribution to wine quality, thanks to the presence of fermentative yeasts or, conversely, to the involvement in negative or detrimental roles, due to the presence of grape-deriving fungi implied in the spoilage of wine or in grapevine pathogenesis. In this connection, the main functions of core taxa fungi, whose role in the vineyard environment is still poorly understood, are also described., 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 Iorizzo, Bagnoli, Vergalito, Testa, Tremonte, Succi, Pannella, Letizia, Albanese, Lombardi and Coppola.)

Background: The Hugo RAS™ system (Medtronic, Minneapolis, MN, USA), approved for gynaecological and urological procedures, has been recently certified for the use in few general surgeries. Only bariatric and colorectal procedures have been described so far., Methods: Here, we report the first worldwide experience with three cases of full-robotic cholecystectomies with the Hugo RAS™ system., Results: A description of the operative room setup, of the docking angles and details of the procedures is reported. Docking time was 12, 10, and 6 min, respectively. The total operative time was 105 min in the first case, 100 min in the second and 88 in the third case. Intra- and post-operative courses were uneventful., Conclusions: With this pre-defined set up, the innovative conformation of Hugo RAS™ system can safely allow performing full robotic cholecystectomy avoiding the need for additional ports., (© 2023 The Authors. ANZ Journal of Surgery published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Surgeons.)

Objectives: The purpose of this study was to analyze the drug survival rate of dupilumab up to 2 years in a large real-world cohort of adult patients affected by moderate/severe atopic dermatitis (AD), and to investigate the clinical, demographic and predictive factors influencing the patients' treatment persistence., Material and Methods: This study included adult patients affected by moderate-to-severe AD treated with dupilumab for at least 16 weeks who visited 7 dermatologic outpatient clinics in Lazio, Italy, from January 2019 until August 2021., Results: A total of 659 adult patients (345 male [52.3%], mean age: 42.8 years) with an average treatment duration of 23.3 months were enrolled in the study. Overall, 88.6% and 76.1% of patients were still on treatment after 12 and 24 months, respectively. The drug survival rate for discontinuation due to AEs and dupilumab ineffectiveness was 95.0% at 12 months and 90.0% at 24 months. The main reasons for drug discontinuation included inefficacy (29.6%), failed compliance (17.4%), persistent efficacy (20.4%) and adverse events (7.8%). Adult AD onset (≥18 years) and EASI score severity measured at the last follow-up visit were the only factors significantly associated with lower drug survival., Conclusion: This study revealed an increased cumulative probability of dupilumab survival at 2 years, reflected by a sustained effectiveness and a favorable safety profile of the drug.

HCV infection is still a major burden worldwide, and most countries are not on track to meet the WHO 2030 elimination goal. The current challenge is to identify individuals to be treated. In this study, we will describe the trend of new DAA prescriptions and the changes over time in terms of the characteristics of patients starting antiviral therapy in our unit. Data of 1646 hepatitis C patients who started therapy during the period of 2015-2022 regarding annual number of prescriptions, age, gender, nationality, HCV genotype, provenance, and liver disease severity were analyzed. We observed a peak in the number of new prescriptions in 2018 and a downward trend starting in 2019. Patients from the general population, centers for addictions, and prison differed significantly. The mean age in the general population remained above 60 years, the percentage of patients from centers for addictions and prison increased and, after 2016, there was no significant change in the percentage of patients with F3-F4 fibrosis. As HCV screening and linkage-to-care pathways seem to be already well implemented and successful in centers for addictions and in prisons, efforts need to be focused on those of older age in the general population. To carry this out, the more structured involvement of different health professionals must be figured out.

Background: Pancreatoduodenectomy (PD) is a complex surgical procedure known for its significant morbidity rates, and the presence of an aberrant hepatic artery (AHA) introduces additional challenges. The impact of AHA on post-PD outcomes has been a subject of conflicting findings in the medical literature. This study aimed to investigate how variations in hepatic arterial anatomy influence intra-operative variables and postoperative morbidity., Methods: A retrospective analysis was conducted on 113 PD cases. Patients with variant hepatic arterial anatomy (n=38) were categorized as Group 1, while those without vascular abnormalities comprised Group 2. Perioperative and postoperative outcomes were examined., Results: Patients in Groups 1 and 2 exhibited similar characteristics, and no notable differences in surgical complications were observed. There was, however, a noticeable trend towards a higher incidence of postpancreatectomy hemorrhage (PPH) in Group 1 (31.6% vs. 20.0%; P=0.17). Furthermore, a statistically significant increase in the rate of arterial resections was noted in patients with vascular anomalies (10.5% vs. 1.33%; P=0.02)., Conclusions: The prevalence of vascular abnormalities in the hepatic arterial circulation is more frequent than initially anticipated. These anomalies present additional complexities to the already intricate PD procedure, leading to a heightened necessity for arterial resection, albeit without any discernible impact on postoperative complications., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-23-191/coif). The authors have no conflicts of interest to declare., (2023 Journal of Gastrointestinal Oncology. All rights reserved.)

Hepatitis E virus (HEV) is an important cause of acute viral hepatitis in humans worldwide. The food-borne transmission of HEV appears to be a major route in Europe through the consumption of pork and wild boar meat. HEV epidemiology in wild boars has been investigated mainly in Northern and Central Italian regions, whilst information from Southern Italy is limited. We investigated the occurrence of HEV in wild boar in the Apulia and Basilicata regions (Southern Italy). Thirteen (10.4%) out of one hundred and twenty-five wild boar samples tested positive for HEV using a quantitative reverse transcription PCR. HEV prevalence was 12% in Apulia and 9.3% in Basilicata. Seven samples were genotyped, and different subtypes (c, f, m) of genotype 3 were identified. The complete genome of a 3m strain was determined, and the virus showed the highest nucleotide identity to a human HEV strain identified in France in 2017. These findings demonstrate the substantial circulation of HEV in the wild boar population in Italian Southern regions. Gathering information on the HEV strains circulating in different geographical areas is useful for tracking the origin of HEV outbreaks and assessing the epidemiological role of wild boar as a potential virus reservoir for domestic pigs.

Aim: To investigate the use of comprehensive pre-treatment staging with multiple diagnostic modalities, including functional imaging and minimally invasive surgical procedures, in locally advanced pancreatic cancer (LAPC) patients. The primary objective was to detect occult metastatic disease using staging laparoscopy and 18FFDG-PET/CT scan. The study also evaluated treatment efficacy and outcomes in LAPC patients treated with combined therapies., Materials and Methods: This study was a secondary analysis of three prospective studies of chemoradiotherapy (CRT) with or without induction chemotherapy (IC). The inclusion period was from December 2009 until February 2023. An intensified pretreatment staging was conducted for all LAPC patients. Patients without distant disease at initial staging, with borderline resectable or unresectable LAPC, were enrolled in chemoradiotherapy combination protocols (CRT with or without IC). IC regimens included GemOx or FOLFIRINOX for four cycles, followed by concurrent CRT with gemcitabine. The primary endpoint was the detection of occult metastatic disease, and secondary objectives included resection rate, treatment toxicity, overall survival (OS), progression-free survival (PFS), local control (LC), and metastasis-free survival (MFS)., Results: Out of the 134 LAPC patients, 33.5% were identified with metastatic disease. Of these, 23.1% had a positive exploratory laparoscopy. Additionally, 13.4% were identified as having distant metastases by 18-FDG PET/CT. The median PFS for all patients who completed CRT was 14.3 months, and the median OS was 17.2 months. Resected patients after the combined therapies demonstrated significantly improved outcomes compared to non-resected patients (median PFS, 22.5 mo vs. 9.5 mo, P<0.001; median OS, 38.2 mo vs. 13 mo, P<0.001). Moreover, patients treated with IC followed by CRT showed significantly better outcomes compared to upfront CRT group (median PFS, 19 mo vs. 9.9 mo, P<0.001; median OS, 19.3 mo vs. 14.6 mo, P<0.001). At univariate logistic regression analysis, the adding of IC was the only predictor for resection rate (95% CI 0.12-1.02, P=0.05), and this data was confirmed at multivariate analysis (95% CI 0.09-0.98, P=0.04). Haematological and gastrointestinal toxicities were observed during treatment, with manageable adverse events., Conclusions: The use of comprehensive pre-treatment staging, including laparoscopy and 18F-FDG-PET/CT scan, is an effective approach in identifying occult metastatic disease in LAPC patients. Our findings offer valuable insights into accurate staging and treatment efficacy, providing evidence-based support for optimal management strategies in LAPC patients., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Lymph-nodal involvement (N+) represents an adverse prognostic factor after pancreatoduodenectomy (PD) for pancreatic adenocarcinoma (PDAC). Preoperative diagnostic and staging modalities lack sensitivity for identifying N+. This study aimed to investigate preoperative CA19.9 in predicting the N+ stage in resectable-PDAC (R-PDAC)., Methods: Patients included in a multi-institutional retrospective database of PDs performed for R-PDAC from January 2000 to June 2021 were analyzed. A preoperative laboratory value of CA19.9 >37 U/L was used in univariate and multivariate logistic regression analysis to determine a possible association with N+. Additionally, different cut-offs of CA19.9 related to the preoperative clinical T (cT) stage was assessed to evaluate the risk of N+., Results: A total of 2034 PDs from thirteen centers were included in the study. CA19.9>37 U/L was significantly associated with higher N+ at univariate and multivariate analysis (P<0.001). CA19.9 levels >37 U/L were associated with N+ in 75.9%, 81.3%, and 85.7% of patients, respectively, in cT1, cT2, and cT3 tumors and with higher cut-off values for all cT stages., Conclusion: Lymph nodal involvement is strongly related to preoperative CA19.9 levels. Specially in patients staged as cT3 the CA 19.9 could represent a valid and easy tool to suspect nodal involvement. Due to these findings, R-PDAC patients with elevated CA19.9 values should be considered in a more biologically advanced stage., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

The cultivated grapevine, Vitis vinifera subsp. vinifera , possesses a rich biodiversity with numerous varieties. Each variety adapts differently to varying pedoclimatic conditions, which greatly influence the terroir expression of wine regions. These conditions impact vine growth, physiology, and berry composition, ultimately shaping the unique characteristics and typicity of the wines produced. Nowadays, the potential of the different adaptation capacities of grape varieties has not yet been thoroughly investigated. We addressed this issue by studying two grape varieties, Aglianico and Cabernet Sauvignon, in two different pedoclimatic conditions of Southern Italy. We evaluated and compared the effect of different pedoclimatic conditions on plant physiology, the microbial quality of grapes using Next-Generation Sequencing (NGS) technology, the expression trends of key genes in ripe berries and the concentration of phenolic compounds in grapes and wines by HPLC-MS, HPLC-DAD, NMR and spectrophotometric analyses. Metabolomic and microbiome data were integrated with quantitative gene expression analyses to examine varietal differences and plasticity of genes involved in important oenological pathways. The data collected showed that the phenotypic response of studied grapes in terms of vigor, production, and fruit quality is strongly influenced by the pedoclimatic conditions and, in particular, by soil physical properties. Furthermore, Aglianico grape variety was more influenced than the Cabernet Sauvignon by environmental conditions. In conclusion, the obtained findings not only reinforce the terroir concept and our comprehension of grape's ability to adapt to climate variations but can also have implications for the future usage of grape genetic resources., 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 Iorizzo, Sicilia, Nicolosi, Forino, Picariello, Lo Piero, Vitale, Monaco, Ferlito, Succi, Tremonte, Gambuti, Villano, Bonfante, Aversano and Coppola.)

Honey is a natural remedy for various health conditions. It exhibits a prebiotic effect on the gut microbiome, including lactobacilli, essential for maintaining gut health and regulating the im-mune system. In addition, monofloral honey can show peculiar therapeutic properties. We in-vestigated some legumes honey's prebiotic properties and potential antimicrobial action against different pathogens. We assessed the prebiotic potentiality of honey by evaluating the antioxidant activity, the growth, and the in vitro adhesion of Lacticaseibacillus casei , Lactobacillus gasseri , Lacticaseibacillus paracasei subsp. paracasei , Lactiplantibacillus plantarum , and Lacticaseibacillus rhamnosus intact cells. We also tested the honey's capacity to inhibit or limit the biofilm produced by five pathogenic strains. Finally, we assessed the anti-biofilm activity of the growth medium of probiotics cultured with honey as an energy source. Most probiotics increased their growth or the in vitro adhesion ability to 84.13% and 48.67%, respectively. Overall, alfalfa honey best influenced the probiotic strains' growth and in vitro adhesion properties. Their radical-scavenging activity arrived at 83.7%. All types of honey increased the antioxidant activity of the probiotic cells, except for the less sensitive L. plantarum . Except for a few cases, we observed a bio-film-inhibitory action of all legumes' honey, with percentages up to 81.71%. Carob honey was the most effective in inhibiting the biofilm of Escherichia coli , Listeria monocytogenes , Pseudomonas aeruginosa , and Staphylococcus aureus ; it retained almost entirely the ability to act against the bio-film of E. coli , L. monocytogenes , and S. aureus also when added to the bacterial growth medium instead of glucose. On the other hand, alfalfa and astragalus honey exhibited greater efficacy in acting against the biofilm of Acinetobacter baumannii . Indigo honey, whose biofilm-inhibitory action was fragile per se, was very effective when we added it to the culture broth of L. casei , whose supernatant exhibited an anti-biofilm activity against all the pathogenic strains tested. Conclusions: the five kinds of honey in different ways can improve some prebiotic properties and have an inhibitory biofilm effect when consumed.

This retrospective analysis of the prospective IGOMIPS registry reports on 1191 minimally invasive pancreatic resections (MIPR) performed in Italy between 2019 and 2022, including 668 distal pancreatectomies (DP) (55.7%), 435 pancreatoduodenectomies (PD) (36.3%), 44 total pancreatectomies (3.7%), 36 tumor enucleations (3.0%), and 8 central pancreatectomies (0.7%). Spleen-preserving DP was performed in 109 patients (16.3%). Overall incidence of severe complications (Clavien-Dindo ≥ 3) was 17.6% with a 90-day mortality of 1.9%. This registry analysis provided some important information. First, robotic assistance was preferred for all MIPR but DP with splenectomy. Second, robotic assistance reduced conversion to open surgery and blood loss in comparison to laparoscopy. Robotic PD was also associated with lower incidence of severe postoperative complications and a trend toward lower mortality. Fourth, the annual cut-off of ≥ 20 MIPR and ≥ 20 MIPD improved selected outcome measures. Fifth, most MIPR were performed by a single surgeon. Sixth, only two-thirds of the centers performed spleen-preserving DP. Seventh, DP with splenectomy was associated with higher conversion rate when compared to spleen-preserving DP. Eighth, the use of pancreatojejunostomy was the prevalent reconstruction in PD. Ninth, final histology was similar for MIPR performed at high- and low-volume centers, but neoadjuvant chemotherapy was used more frequently at high-volume centers. Finally, this registry analysis raises important concerns about the reliability of R1 assessment underscoring the importance of standardized pathology of pancreatic specimens. In conclusion, MIPR can be safely implemented on a national scale. Further analyses are required to understand nuances of implementation of MIPR in Italy., (© 2023. The Author(s).)

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease, for which mortality closely parallels incidence. So far, the available techniques for PDAC detection are either too invasive or not sensitive enough. To overcome this limitation, here we present a multiplexed point-of-care test that provides a " risk score " for each subject under investigation, by combining systemic inflammatory response biomarkers, standard laboratory tests, and the most recent nanoparticle-enabled blood (NEB) tests. The former parameters are routinely evaluated in clinical practice, whereas NEB tests have been recently proven as promising tools to assist in PDAC diagnosis. Our results revealed that PDAC patients and healthy subjects can be distinguished accurately (i.e., 88.9% specificity, 93.6% sensitivity) by the presented multiplexed point-of-care test, in a quick, non-invasive, and highly cost-efficient way. Furthermore, the test allows for the definition of a " risk threshold ", which can help clinicians to trace the optimal diagnostic and therapeutic care pathway for each patient. For these reasons, we envision that this work may accelerate progress in the early detection of PDAC and contribute to the design of screening programs for high-risk populations.

Background: Pancreatic ductal adenocarcinoma (PDAC) represents a challenging disease for the surgeon, oncologist, and radiation oncologist in both diagnostic and therapeutic settings. Surgery is currently the gold standard treatment, but the role of neoadjuvant treatment (NAD) is constantly evolving and gaining importance in resectable PDACs. The aim of this narrative review is to report the state of the art and future perspectives of neoadjuvant therapy in patients with PDAC., Methods: A PubMed database search of articles published up to September 2022 was carried out., Results: Many studies showed that FOLFIRINOX or Gemcitabine-nab-paclitaxel in a neoadjuvant setting had a relevant impact on overall survival (OS) for patients with locally advanced and borderline resectable PDAC without increasing post-operative complications. To date, there have not been many published multicentre randomised trials comparing upfront surgery with NAD in resectable PDAC patients, but the results obtained are promising. NAD in resectable PDAC showed long-term effective benefits in terms of median OS (5-year OS rate 20.5% in NAD group vs. 6.5% in upfront surgery). NAD could play a role in the treatment of micro-metastatic disease and lymph nodal involvement. In this scenario, given the low sensitivity and specificity for lymph-node metastases of radiological investigations, CA 19-9 could be an additional tool in the decision-making process., Conclusions: The future challenge could be to identify only selected patients who will really benefit from upfront surgery despite a combination of NAD and surgery.

Background and Hypothesis: We used the uniquely high combined spatial and temporal resolution of magnetoencephalography to characterize working memory (WM)-related modulation of beta band activity in neuroleptic-free patients with schizophrenia in comparison to a large sample of performance-matched healthy controls. We also tested for effects of antipsychotic medication on identified differences in these same patients., Study Design: Inpatients with schizophrenia (n = 21) or psychotic disorder not otherwise specified (n = 4) completed N-back and control tasks during magnetoencephalography while on placebo and during antipsychotic medication treatment, in a blinded, randomized, counterbalanced manner. Healthy, performance-matched controls (N = 100) completed the same tasks. WM-related neural activation was estimated as beta band (14-30 Hz) desynchronization throughout the brain in successive 400 ms time windows. Voxel-wise statistical comparisons were performed between controls and patients while off-medication at each time window. Significant clusters resulting from this between-groups analysis were then used as regions-of-interest, the activations of which were compared between on- and off-medication conditions in patients., Study Results: Controls showed beta-band desynchronization (activation) of a fronto-parietal network immediately preceding correct button press responses-the time associated with WM updating and task execution. Altered activation in medication-free patients occurred largely during this time, in prefrontal, parietal, and visual cortices. Medication altered patients' neural responses such that the activation time courses in these regions-of-interest more closely resembled those of controls., Conclusions: These findings demonstrate that WM-related beta band alterations in schizophrenia are time-specific and associated with neural systems targeted by antipsychotic medications. Future studies may investigate this association by examining its potential neurochemical basis., (Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center 2023.)

Background: Early detection and therapy of pancreatic fistula after pancreaticoduodenectomy is crucial to improve outcomes of this surgery. Since it is not clear if procalcitonin (PCT), can predict the onset of clinically relevant post-operative pancreatic fistula (CR-POPF), we aimed to investigate this ability., Methods: One-hundred-thirty pancreaticoduodenectomies (PD) were analyzed. Receiver Operating Characteristic curves analysis defined the optimal cut-offs for PCT and drains amylase levels (DAL). Complications were compared using chi-square for proportions test., Results: DAL ≥2,000 U/L in postoperative day (POD) 2 had 71% positive predictive value (PPV) and 91% negative predictive value (NPV) for CR-POPF (P<0.001). In POD2, PCT ≥0.5 ng/mL showed NPV 91% (P<0.045) and increased DAL PPV for CR-POPF to 81%. In POD3, POD4 and POD5, DAL (cut-offs 780, 157 and 330 U/L, respectively) showed NPV for CR-POPF >90% (P<0.0001). PCT ≥0.5 ng/mL showed NPV for CR-POPF of about 90%. In POD5, combining DAL (cut-off 330 U/L) and PCT (cut-off 0.5 ng/mL), a PPV for CR-POPF of 81% was detected. A progressive increased risk of CR-POPF from POD2 [odds ratio (OR) =3.05; P=0.0348] to POD5 (OR =4.589; P=0.0082) was observed. In POD2 and 5, PCT ≥0.5 ng/mL, alone and in combination with DAL, may be a reliable marker for identifying patients at highest risk of CR-POPF after PD., Conclusions: This association could be proposed to select high risk patients that could benefit of "intensive" postoperative management., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-22-803/coif). The series “Pancreas Surgery” was commissioned by the editorial office without any funding or sponsorship. AC served as the unpaid Guest Editor of the series. The authors have no other conflicts of interest to declare., (2023 Journal of Gastrointestinal Oncology. All rights reserved.)

Background and Objective: Despite advances in the multidisciplinary management of pancreatic cancer, overall prognosis remains poor, due to early progression of the disease. There is a need to also take action in staging, to make it increasingly accurate and complete, to define the setting of the therapeutic strategy. This review was planned to update the current status of pre-treatment evaluation for pancreatic cancer., Methods: We conducted an extensive review, including relevant articles dealing with traditional imaging, functional imaging and minimally invasive surgical procedures before treatment for pancreatic cancer. We searched articles written in English only. Data in the PubMed database, published in the period between January 2000 and January 2022, were retrieved. Prospective observational studies, retrospective analyses and meta-analyses were reviewed and analysed., Key Content and Findings: Each imaging modality (endoscopic ultrasonography, endoscopic retrograde cholangiopancreatography, computed tomography, positron emission tomography/computed tomography, staging laparoscopy) has its own diagnostic advantages and limitations. The sensitivity, specificity and accuracy for each image set are reported. Data that support the increasing role of neoadjuvant therapy (radiotherapy and chemotherapy) and the meaning of a patient-tailored treatment selection, based on tumour staging, are also discussed., Conclusions: A multimodal pre-treatment workup should be searched as it improves staging accuracy, orienting patients with resectable tumors towards surgery, optimizing patient selection with locally advanced tumors to neoadjuvant or definite therapy and avoiding surgical resection or curative radiotherapy in those with metastatic disease., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-22-1034/coif). The series “Pancreas Surgery” was commissioned by the editorial office without any funding or sponsorship. AC served as the unpaid Guest Editor of the series. The authors have no other conflicts of interest to declare., (2023 Journal of Gastrointestinal Oncology. All rights reserved.)

Introduction: Seed oils are versatile in the food sector and for pharmaceutical purposes. In recent years, their biological properties aroused the interest of the scientific world., Materials and Methods: We studied the composition of fatty acids (FAs) and some in vitro potential therapeutic benefits of five cold-pressed commercial oils obtained from broccoli, coffee, green coffee, pumpkin, and watermelon seeds. In particular, we assayed the antioxidant activity (using diphenyl-1-picrylhydrazyl (DPPH) and azino-bis (3-ethylbenzothiazoline-6-sulfonic acid (ABTS) assays). In addition, through the fatty acid composition, we calculated the atherogenicity index (AI) and thrombogenicity index (TI) to evaluate the potential impact of such oils on cardiovascular diseases. Furthermore, we assessed the in vitro anti-inflammatory capacity of the oils (evaluated through their effectiveness in preventing protein degradation, using bovine serum albumin as protein standard) and the ability of the oils to inhibit in vitro activity of three among the essential enzymes, cholinesterases and tyrosinase, involved in the Alzheimer's and Parkinson's neurodegenerative diseases. Finally, we evaluated the capacity of the oils to inhibit the biofilm of some pathogenic bacteria., Results: The unsaturated fatty acids greatly predominated in broccoli seed oil (84.3%), with erucic acid as the main constituent (33.1%). Other unsaturated fatty acids were linolenic (20.6%) and linoleic (16.1%) acids. The saturated fatty acids fraction comprised the palmitic (6.8%) and stearic acids (0.2%). Broccoli seed oil showed the best AI (0.080) and TI (0.16) indexes. The oils expressed a good antioxidant ability. Except for the watermelon seed oil, the oils exhibited a generally good in vitro anti-inflammatory activity, with IC 50 values not exceeding 8.73 micrograms. Broccoli seed oil and green coffee seed oil showed the best acetylcholinesterase inhibitory activity; coffee seed oil and broccoli seed oil were the most effective in inhibiting butyrylcholinesterase (IC 50 = 15.7 μg and 20.7 μg, respectively). Pumpkin and green coffee seed oil showed the best inhibitory activity against tyrosinase (IC 50 = 2 μg and 2.77 μg, respectively). In several cases, the seed oils inhibited the biofilm formation and the mature biofilm of some gram-positive and gram-negative bacteria, with Staphylococcus aureus resulting in the most sensitive strain. Such activity seemed related only in some cases to the capacity of the oils to act on the sessile bacterial cells' metabolism, as indicated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric method., 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 Fratianni, Amato, De Feo, d'Acierno, Coppola and Nazzaro.)

Coppa Piacentina is considered a peculiar dry cured salami, since it is manufactured by the entire neck muscles stuffed and matured in natural casings, the same as dry cured ham and fermented dry cured sausages. In this work the proteolysis of external and internal portions was investigated by a proteomic approach and by amino acids analysis. Samples of "Coppa Piacentina" were analyzed at 0 days and after 5 and 8 months of ripening through mono- and two-dimensional gel electrophoresis. Image analysis of 2D electrophoretic maps indicated a more intense enzyme activity on the external part, mainly due to endogenous enzymes. They favored, respectively, myofibrillar or sarcoplasmic proteins at 5 or 8 months of ripening. Free amino acids determination proved that lysine and glutamic acid were the most represented ones, followed by a free amino acids sequence like that of dry cured ham. The peculiarities of "Coppa Piacentina" were characterized by a slow proteolysis, due to sacking and binding of the whole cut of the pork neck., 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 © 2023 Elsevier Ltd. All rights reserved.)

Pancreatic ductal adenocarcinoma (PDAC) represents an unmet medical need. Difficult/late diagnosis as well as the poor efficacy and high toxicity of chemotherapeutic drugs result in dismal prognosis. With the aim of improving the treatment outcome of PDAC, we tested the effect of combining Gemcitabine with a novel single chain bispecific antibody (scDb) targeting the cancer-specific hERG1/β1 integrin complex. First, using the scDb (scDb-hERG1-β1) in immunohistochemistry (IHC), Western blot (WB) analysis and immunofluorescence (IF), we confirmed the presence of the hERG1/β1 integrin complex in primary PDAC samples and PDAC cell lines. Combining Gemcitabine with scDb-hERG1-β1 improved its cytotoxicity on all PDAC cells tested in vitro. We also tested the combination treatment in vivo, using an orthotopic xenograft mouse model involving ultrasound-guided injection of PDAC cells. We first demonstrated good penetration of the scDb-hERG1-β1 conjugated with indocyanine green (ICG) into tumour masses by photoacoustic (PA) imaging. Next, we tested the effects of the combination at either therapeutic or sub-optimal doses of Gemcitabine (25 or 5 mg/kg, respectively). The combination of scDb-hERG1-β1 and sub-optimal doses of Gemcitabine reduced the tumour masses to the same extent as the therapeutic doses of Gemcitabine administrated alone; yielded increased survival; and was accompanied by minimised side effects (toxicity). These data pave the way for a novel therapeutic approach to PDAC, based on the combination of low doses of a chemotherapeutic drug (to minimize adverse side effects and the onset of resistance) and the novel scDb-hERG1-β1 targeting the hERG1/β1 integrin complex as neoantigen.

Background: Studies reporting on the outcome of 90-year-old patients undergoing cardiac surgery are scant in literature; and currently, those regarding the implementation of trans-catheter techniques number even fewer., Methods: We compared patients aged >89 years operated on between 1998 and 2008 at 8 Italian cardiac surgery centers, with patients of the same age operated on between 2009 and 2021. All of the patients were operated on with "open" surgery, with the exclusion of percutaneous valve repair/implantation procedures., Results: The patients of the two groups (group 98-08-127 patients, and group 09-21-101 patients) had comparable preoperative risk factors in terms of the LogEuroSCORE (98-08: 21.3 ± 6.1 vs. 09-21: 20.9 ± 11.1, p = 0.12). There was a considerable difference in the type of surgery (isolated valve, isolated coronary, and combined surgery, 46.5, 38.5, and 15% vs. 52, 13, and 35% in 98-08 and 09-21, respectively, p = 0.01). Analogous operating durations were recorded (cross-clamp time: 98-08: 46 ± 28 min vs. 09-21: 51 ± 28 min, p = 0.06). The number of packed bypasses was lower in 09-21 (1.3 ± 0.6 vs. 2.4 ± 1.2, p = 0.001). In the postoperative period, there was a statistically significant difference in the 30-day survival in favor of the "more recent" patients (98-08: 17 deaths (13.4%) versus 09-21: 6(5.9%); p = 0.001), also confirmed in the subgroups (12.2% vs. 0% in isolated coronary surgery, p < 0.001; and 12.3% vs. 0% in isolated valve surgery, p < 0.001)., Conclusions: Accurate pre-, intra-, and post-operative evaluation/management to reduce biological impacts facilitate significant improvements in the outcomes in nonagenarian patients when compared to the results recorded in previous years.

The emergence of antimicrobial resistance (AMR) is increasingly common across the globe and aquatic ecosystems could be considered a reservoir of antibiotic-resistant bacteria. This study aimed to determine prevalence and antibiotic susceptibility of the potential pathogenic bacteria Salmonella spp. and Vibrio spp. in bivalve molluscs intended for human consumption, collected over a period of 19 months along the northern coast of Apulia region. The AMR profile was also determined in non-pathogenic Vibrio species, common natural inhabitants of seawater and a useful indicator for the surveillance of AMR in the environment. The current study presents data on the AMR of 5 Salmonella and 126 Vibrio isolates by broth microdilution MIC. Multidrug resistance (MDR) was observed in one S. Typhimurium strain towards sulfamethoxazole, trimethoprim, tetracycline, gentamicin, and ampicillin and in 41.3% of the Vibrio strains, mostly towards sulphonamides, penicillin, and cephems. All Vibrio isolates were sensitive to azithromycin, chloramphenicol, tetracycline, amoxicillin/clavulanic acid, gentamicin, streptomycin, amikacin, and levofloxacin. The AMR phenomenon in the investigated area is not highly worrying but not entirely negligible; therefore, in-depth continuous monitoring is suggested. Results concerning the antibiotic agents without available specific clinical breakpoints could be useful to upgrade the MIC distribution for Vibrio spp. but, also, the establishment of interpretative criteria for environmental species is necessary to obtain a more complete view of this issue.

We studied the total polyphenols, flavonoids, vitamin C, the antioxidant and anti-inflammatory activity of six Citrus monofloral honey, and the in vitro inhibitory effect against cholinesterases and tyrosinase. Finally, we assessed their effect against the biofilm of some pathogenic bacteria. Lime honey showed the best antioxidant activity and the highest content of polyphenols and vitamin C. Lemon and tangerine honey contained almost exclusively flavonoids. Lemon honey better preserved the bovine serum albumin against denaturation (IC 50  = 48.47 mg). Honeys inhibited acetylcholinesterase, butyrylcholinesterase, and tyrosinase up to 12.04% (tangerine), 19.11% (bergamot), and 94.1% (lemon), respectively. Lime and clementine honey better inhibited the Listeria monocytogenes biofilm. Bergamot honey acted mainly against the Staphylococcus aureus and Acinetobacter baumannii biofilm; bergamot and tangerine honey inhibited the Pseudomonas aeruginosa biofilm particularly. Bergamot, clementine, and tangerine honey acted against Escherichia coli sessile cell metabolism. This Citrus honey exhibited in vitro prospective health benefits and is applicable for future in vivo studies., (© 2023. The Author(s).)

Aim: The aim of this monocentric retrospective study was to investigate the relation between sarcopenia, postoperative complications and survival in patients undergoing radical surgery for pancreatic ductal adenocarcinoma (PDAC)., Material of Study: From a prospective collected database of 230 consecutive pancreatoduodenectomies (PD), data regarding patient's body composition, evaluated on diagnostic preoperative CT scans and defined as Skeletal Muscle Index (SMI) and Intramuscular Adipose Tissue Content (IMAC), postoperative complications and long-term outcomes were retrospectively analysed. Descriptive and survival analyses were performed., Results: Sarcopenia was found in 66% of study population. The majority of patients who developed at least one postoperative complication was sarcopenic. However, sarcopenia did not statistically significantly relate with the development of postoperative complications. However, all pancreatic fistula C occurs in sarcopenic patients. Moreover, there was no significant difference in median Overall Survival (OS) and Disease Free Survival (DFS) between sarcopenic and nonsarcopenic patients (31 versus 31.8 months and 12.9 and 11.1 months respectively)., Discussion: Our results showed that sarcopenia was not related to short- and long-term outcomes in PDAC patients undergoing PD. However, the quantitative and qualitative radiological parameters are probably not enough to study the sarcopenia alone., Conclusions: The majority of early stage PDAC patients undergoing PD were sarcopenic. Cancer stage was a determinant factor of sarcopenia while BMI seems less important. In our study, sarcopenia was associated with postoperative complications and in particular with pancreatic fistula. Further studies will need to demonstrated that sarcopenia can be considered an objective measure of patient frailty and strongly associated with short- and long-term outcomes., Key Words: Pancreatic ductal adenocarcinoma, Pancretoduodenectomy, Sarcopenia.

The development of new tools for the early detection of pancreatic ductal adenocarcinoma (PDAC) represents an area of intense research. Recently, the concept has emerged that multiplexed detection of different signatures from a single biospecimen (e.g., saliva, blood, etc.) may exhibit better diagnostic capability than single biomarkers. In this work, we develop a multiplexed strategy for detecting PDAC by combining characterization of the nanoparticle (NP)-protein corona, i.e., the protein layer that surrounds NPs upon exposure to biological fluids and circulating levels of plasma proteins belonging to the acute phase protein (APPs) family. As a first step, we developed a nanoparticle-enabled blood (NEB) test that employed 600 nm graphene oxide (GO) nanosheets and human plasma (HP) (5% vol/vol) to produce 75 personalized protein coronas (25 from healthy subjects and 50 from PDAC patients). Isolation and characterization of protein corona patterns by 1-dimensional (1D) SDS-PAGE identified significant differences in the abundance of low-molecular-weight corona proteins (20-30 kDa) between healthy subjects and PDAC patients. Coupling the outcomes of the NEB test with the circulating levels of alpha 2 globulins, we detected PDAC with a global capacity of 83.3%. Notably, a version of the multiplexed detection strategy run on sex-disaggregated data provided substantially better classification accuracy for men (93.1% vs. 77.8%). Nanoliquid chromatography tandem mass spectrometry (nano-LC MS/MS) experiments allowed to correlate PDAC with an altered enrichment of Apolipoprotein A-I, Apolipoprotein D, Complement factor D, Alpha-1-antichymotrypsin and Alpha-1-antitrypsin in the personalized protein corona. Moreover, other significant changes in the protein corona of PDAC patients were found. Overall, the developed multiplexed strategy is a valid tool for PDAC detection and paves the way for the identification of new potential PDAC biomarkers.

hERG1 potassium channels are widely expressed in human cancers of different origins, where they affect several key aspects of cellular behaviour. The present study was designed to evaluate the expression and clinical relevance of hERG1 protein in cancer tissues from patients suffering from neuroendocrine tumours (NETs) of ileal (iNETs) and pancreatic (pNETs) origin, with available clinicopathological history and follow-up. The study was carried out by immunohistochemistry with an anti-hERG1 monoclonal antibody. In a subset of samples, a different antibody directed against the hERG1/β1 integrin complex was also used. The analysis showed for the first time that hERG1 is expressed in human NETs originating from either the ileum or the pancreas. hERG1 turned out to have a prognostic value in NETs, showing (i) a statistically significant positive impact on OS of patients affected by ileal NETs, regardless the TNM stage; (ii) a statistically significant positive impact on OS of patients affected by aggressive (TNM stage IV) disease, either ileal or pancreatic; (iii) a trend to a negative impact on OS of patients affected by less aggressive (TNM stage I-III) disease, either ileal or pancreatic. Moreover, in order to evaluate whether ERG1 was functionally expressed in a cellular model of pNET, the INS1E rat insulinoma cell line was used, and it emerged that blocking ERG1 with a specific inhibitor of the channel (E4031) turned out in a significant reduction in cell proliferation.

Colistin is a last-resort drug for the treatment of infections by carbapenem-resistant Enterobacteriaceae , and the emergence of colistin resistance poses a serious clinical challenge. The aim of this study was to investigate the occurrence of colistin-resistant Escherichia coli in retail meat in Southern Italy in 2018-2020. Of 570 samples, 147 contained E. coli . Two out of 147 (1.4%) E. coli showed a non-wild-type phenotype to colistin and harboured mcr-1 . mcr-1 was also detected in a wild-type isolate, resulting in a 2% mcr prevalence. mcr-1 -positive isolates originated from turkey meat collected in Apulia (n = 2) and Basilicata (n = 1). A whole-genome sequencing analysis confirmed mcr-1.2 and mcr-1.1 in two and one isolate, respectively. The strains were diverse, belonging to three multi-locus sequence types (ST354, ST410, SLV of ST10) and harbouring genes mediating resistance to antimicrobials in two, six and seven classes. mcr-1 was carried by IncX4 plasmids with high nucleotide similarity to IncX4 plasmids harbouring mcr-1.2 and mcr-1.1 in Enterobacterales from different sources and geographical regions. This is the first study reporting updates on E. coli non-wild-type to colistin from retail meat in Southern Italy, highlighting the importance of phenotypic and genotypic antimicrobial resistance surveillance to contain the dissemination of mcr among E. coli .

Background: Surgery still represents the gold standard of treatment for resectable pancreatic ductal adenocarcinoma (PDAC). Neoadjuvant treatments (NAT), currently proposed for borderline and locally advanced PDACs, are gaining momentum even in resectable tumors due to the recent interesting concept of "biological resectability". In this scenario, CA 19.9 is having increasing importance in preoperative staging and in the choice of therapeutic strategies. We aimed to assess the state of the art and to highlight the future perspectives of CA 19.9 use in the management of patients with resectable pancreatic cancer., Methods: A PubMed database search of articles published up to December 2021 has been carried out., Results: Elevated pre-operative levels of CA 19.9 have been associated with reduced overall survival, nodal involvement, and margin status positivity after surgery. These abilities of CA 19.9 increase when combined with radiological or different biological criteria. Unfortunately, due to strong limitations of previously published articles, CA 19.9 alone cannot be yet considered as a key player in resectable pancreatic cancer patient management., Conclusion: The potential of CA 19.9 must be fully explored in order to standardize its role in the "biological staging" of patients with resectable pancreatic cancer.

This work aimed to evaluate the chemical composition of the essential oils (EOs) of two cultivars of Allium sativum and their antibiofilm activity against the food pathogens Acinetobacter baumannii , Escherichia coli , Listeria monocytogenes , and Staphylococcus aureus . The crystal violet assay ascertained the susceptibility of the bacterial biofilms, while the MTT assay let to evaluations of the metabolic changes occurring in the bacterial cells within biofilms. Their chemical composition indicated some sulfuric compounds (i.e., allicin, diallyl disulfide, and allyl propyl disulfide), and decene as some of the main components of the EOs. The aerial parts and bulbs' EOs from the two cultivars showed chemical differences, which seemed to affect the antibiofilm activity. The EOs from aerial parts of 'Bianco del Veneto' inhibited the biofilm formation of L. monocytogenes and E. coli (60.55% and 40.33%, respectively). In comparison, the 'Staravec' EO inhibited the cellular metabolism of E. coli (62.44%) and S. aureus (51.52%) sessile cells. These results indicate their possible use as preserving agents in the food industry and suggest their potential exploitation in the development of new formulations to avoid or limit nosocomial infections.

In recent years, alongside the conventional screening procedures for the evaluation of probiotics for human usage, the pharmaceutical and food industries have encouraged scientific research towards the selection of new probiotic bacterial strains with particular functional features. Therefore, this study intended to explore novel functional properties of five Lactiplantibacillus plantarum strains isolated from bee bread. Specifically, antioxidant, antimicrobial and β-glucosidase activities, exopolysaccharides (EPS) production and the ability to synthesize γ-aminobutyric acid (GABA) were evaluated. The results demonstrated that the investigated L. plantarum strains were effective in inhibiting the growth of some human opportunistic pathogens in vitro ( Pseudomonas aeruginosa , Escherichia coli , Proteus mirabilis , Enterococcus faecalis and Staphylococcus aureus ). Moreover, the evaluation of antioxidant and β-glucosidase activity and of EPS and GABA production, revealed a different behavior among the strains, testifying how these properties are strongly strain-dependent. This suggests that a careful selection within a given species is important in order to identify appropriate strains for specific biotechnological applications. The results highlighted that the five strains of L. plantarum are promising candidates for application as dietary supplements in the human diet and as microbial cultures in specific food productions.

The present study evaluated the fungal contamination of ready-to-eat dried hazelnuts considering for the first time the application of the same condition drying process of several hazelnut cultivars from different boreal hemisphere areas. Fifty lots of hazelnuts ( Corylus avellana ), belonging to eight cultivars from seven regions in four countries, were analyzed for fungal microbiota, describing both load levels and species diversity. For this purpose, a polyphasic approach consisting of morphological examination (optical and scanning electron microscope observation) and molecular characterization [PCR-DGGE analysis and sequence analyses of the internal transcribed spacer (ITS)] was performed. The results show that different fungal populations occur in dried hazelnuts regardless of their geographical area of production. Although some varieties appear to be relatively less susceptible, species related to Aspergillus , such as A. commune and A. ochraceus , Penicillium , including P. commune, P. solitum , and P. expansum , and Rhizopus , for instance, R. stolonifer and R. oryzae , have generally been found. A related character "hazelnut cultivar-fungi" was found for species related to the genera Trichoderma and Fusarium , including F. oxyxporum , F. solani , and F. falciforme . All 14 species found are known to host pathogenic strains. Therefore, their presence in a ready-to-eat product, such as dried hazelnuts, can pose a real danger to the consumer. Based on these considerations, the development of new protective strategies seems highly desirable. The species-level description of the contaminating fungal community acquired through this study is the starting point for the development of tailor-made protective biotechnologies., 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 © 2022 Lombardi, Pannella, Tremonte, Mercurio, Vergalito, Caturano, Maiuro, Iorizzo, Succi, Sorrentino and Coppola.)

Coxiella burnetii is a Gram-negative obligate intracellular bacterium that is responsible for Q fever, a common zoonosis which is present virtually worldwide. This microorganism infects a wide range of wild and domestic mammals, but the main reservoirs are cattle, goats and sheep, which also represent sources of human infection. A potential route of transmission of this pathogen to humans is the consumption of C. burnetii-contaminated raw milk or dairy products derived from contaminated raw milk, although the role of these foods as possible infection sources is controversial. The aims of this study were (i) to apply two ddPCR based assays targeting the C. burnetii IS1111 and icd genes for the detection and quantification of C. burnetii DNA, and (ii) to evaluate the occurrence of C. burnetii DNA in raw milk and raw milk products from sheep and goats in Apulia and Basilicata regions of Southern Italy. Of 413 milk and cheese samples tested, 78 were positive for the presence of C. burnetii DNA (18.9%), specifically, 68 of 285 milk samples (23.9%) and 10 of 128 cheese samples (7.8%) The presence of both IS1111 and icd genes was detected in only 2 (2.6%) of the 78 positive samples, while the remaining 76 (97.4%) were positive only for IS1111. C. burnetii DNA was specifically detected by the ddPCR method, whereas no cross-amplification was observed with the DNA of other foodborne bacterial pathogens. The sensitivity of the ddPCR method was determined as 0.35 and 0.56 copies/μL for IS1111 and icd genes, respectively. The findings of this study demonstrate the presence of C. burnetii DNA in a significant proportion of raw milk and dairy products. Although there is no conclusive epidemiological evidence that C. burnetii infection occurs via food, the presence of this organism in raw milk and dairy products made of raw milk should be considered a potential hazard. ddPCR is a useful tool to investigate the quality and safety of food products due to its sensitivity and precision, and could be applied to routine testing., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Pancreatic surgery is one of the surgeries burdened with the highest mortality and morbidity rate. This is due both to the aggressive biological nature of the pathology affecting the organ and to the technical difficulties associated with surgery. A further aspect on which research is focusing is represented by inflammation related to oncological pathology. Inflammation plays an important role in tumor progression, and growing evidence has confirmed that the fibrinogen-to-albumin ratio (FAR) is an important prognostic factor for overall survival (OS) in malignant tumors. Inflammatory markers had demonstrated also a role in the prediction of postoperative complication after pancreatic surgery. We speculate that FAR, as an easily available, cost-effective, and non-invasive prognostic indicator for pancreatic cancer patients, could help to identify patients at increased risk of postoperative pancreatic fistula (POPF). We therefore retrospectively analyzed the data relating to 117 pancreatic resections relating direct and indirect markers of inflammation with the incidence of post-operative complications., 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., (© 2022 The Authors. Published by Elsevier Inc.)

Background: The objectives of the study were to investigate the organizational characteristics of acute care facilities worldwide in preventing and managing infections in surgery; assess participants' perception regarding infection prevention and control (IPC) measures, antibiotic prescribing practices, and source control; describe awareness about the global burden of antimicrobial resistance (AMR) and IPC measures; and determine the role of the Coronavirus Disease 2019 pandemic on said awareness., Methods: A cross-sectional web-based survey was conducted contacting 1432 health care workers (HCWs) belonging to a mailing list provided by the Global Alliance for Infections in Surgery. The self-administered questionnaire was developed by a multidisciplinary team. The survey was open from May 22, 2021, and June 22, 2021. Three reminders were sent, after 7, 14, and 21 days., Results: Three hundred four respondents from 72 countries returned a questionnaire, with an overall response rate of 21.2%. Respectively, 90.4% and 68.8% of participants stated their hospital had a multidisciplinary IPC team or a multidisciplinary antimicrobial stewardship team. Local protocols for antimicrobial therapy of surgical infections and protocols for surgical antibiotic prophylaxis were present in 76.6% and 90.8% of hospitals, respectively. In 23.4% and 24.0% of hospitals no surveillance systems for surgical site infections and no monitoring systems of used antimicrobials were implemented. Patient and family involvement in IPC management was considered to be slightly or not important in their hospital by the majority of respondents (65.1%). Awareness of the global burden of AMR among HCWs was considered very important or important by 54.6% of participants. The COVID-19 pandemic was considered by 80.3% of respondents as a very important or important factor in raising HCWs awareness of the IPC programs in their hospital. Based on the survey results, the authors developed 15 statements for several questions regarding the prevention and management of infections in surgery. The statements may be the starting point for designing future evidence-based recommendations., Conclusion: Adequacy of prevention and management of infections in acute care facilities depends on HCWs behaviours and on the organizational characteristics of acute health care facilities to support best practices and promote behavioural change. Patient involvement in the implementation of IPC is still little considered. A debate on how operationalising a fundamental change to IPC, from being solely the HCWs responsibility to one that involves a collaborative relationship between HCWs and patients, should be opened., (© 2022. The Author(s).)

Dietary probiotic supplementation has the potential to enhance the health of fish and their disease resistance. In this study, some properties of ten Lactiplantibacillus plantarum strains have been evaluated, for their potential use as probiotics in freshwater fish diet. In particular, antimicrobial activity, antioxidant activity, the potentiality to survive the gastrointestinal transit and persist in the intestine, were evaluated in vitro. The experimental tests were carried out at 15 °C and 30 °C to determine the suitability of these lactic acid bacteria to be used as probiotics in the diet of fish grown at different temperatures. The results demonstrated that the evaluated Lp. plantarum strains, which often have significant differences among themselves, are characterized by important functional characteristics such as cell surface properties (auto-aggregation and hydrophobicity), ability to produce antioxidant substances, capacity to survive in the presence of 0.3% bile salts and acidic environment (2.5 pH), antagonistic activity against some fish opportunistic pathogens ( A. salmonicida , Ps. aeruginosa , E. coli and C. freundii ) and other unwanted bacteria present in fish products ( S. aureus and L. innocua ). The outcomes suggest that these Lp. plantarum strains may be candidates as probiotics in warm- and cold-water aquaculture.

Campania is the most important region of Italy in the apricot cultivation, present mostly in the Vesuvio area. At least to the best of our knowledge, no studies are reporting the biochemical characterization of the considerable number of traditional apricot varieties present on this territory, including the qualitative and quantitative profile of the polyphenols present. Our work evaluated the content of β-carotene, total phenolics, phenolic profiles, ascorbic acid and antioxidant activity of 23 traditional varieties of apricots of the Campania region. Principal component analysis (PCA) highlighted that, in the two main groups, the antioxidant activity was strongly affected by the content of ascorbic acid (-0.89), or slightly affected by the content of total polyphenols (-0.67), respect to the content of ascorbic acid (-0.55), never by β-carotene. Chlorogenic acid (up to 55.07 μg g -1 ) and catechin (up to 96.15 μg g -1 ) resulted the most abundant polyphenols recognized through the chromatographic analysis. PCA, extended to the polyphenol profile, confirmed the distribution of the varieties in two large groups, evidencing once again the hierarchical distance of four varieties ("Panzona", "Paolona" "Baracca" and "Boccucia Eboli") compared to the others.