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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.)

Liver biopsy remains the gold standard for the histological assessment of the liver. With clear disadvantages and the rise in the incidences of liver disease, the role of neoadjuvant chemotherapy in colorectal liver metastasis (CRLM) and an explosion of surgical management options available, non-invasive serological and imaging markers of liver histopathology have never been more pertinent in order to assess liver health and stratify patients considered for surgical intervention. Liver MRI is a leading modality in the assessment of hepatic malignancy. Recent technological advancements in multiparametric MRI software such as the LiverMultiScan TM offers an attractive non-invasive assay of anatomy and histopathology in the pre-operative setting, especially in the context of CRLM. This narrative review examines the evidence for the LiverMultiScan TM in the assessment of hepatic fibrosis, steatosis/steatohepatitis, and potential applications for chemotherapy-associated hepatic changes. We postulate its future role and the hurdles it must surpass in order to be implemented in the pre-operative management of patients undergoing hepatic resection for colorectal liver metastasis. Such a role likely extends to other hepatic malignancies planned for resection.

Pancreatic ductal adenocarcinoma (PDAC) accounts for up to 95% of all pancreatic cancer cases and is the seventh-leading cause of cancer death. Poor prognosis is a result of late presentation, a lack of screening tests and the fact some patients develop resistance to chemotherapy and radiotherapy. Novel therapies like immunotherapeutics have been of recent interest in pancreatic cancer. However, this field remains in its infancy with much to unravel. Immunotherapy and other targeted therapies have yet to yield significant progress in treating PDAC, primarily due to our limited understanding of the disease immune mechanisms and its intricate interactions with the tumour microenvironment (TME). In this review we provide an overview of current novel immunotherapies which have been studied in the field of pancreatic cancer. We discuss their mechanisms, evidence available in pancreatic cancer as well as the limitations of such therapies. We showcase the potential role of combining novel therapies in PDAC, postulate their potential clinical implications and the hurdles associated with their use in PDAC. Therapies discussed with include programmed death checkpoint inhibitors, Cytotoxic T-lymphocyte-associated protein 4, Chimeric Antigen Receptor-T cell therapy, oncolytic viral therapy and vaccine therapies including KRAS vaccines, Telomerase vaccines, Gastrin Vaccines, Survivin-targeting vaccines, Heat-shock protein (HSP) peptide complex-based vaccines, MUC-1 targeting vaccines, Listeria based vaccines and Dendritic cell-based vaccines.

Background and Aim of the Work: The Covid-19 pandemic led to an increased demand for healthcare professionals, particularly nurses. The Piacenza Local Health Service, Northern Italy, issued several calls for tenders in order to recruit nurses and the University anticipated graduation sessions, so several new graduates nurses found themselves facing their first work experience in the middle of the pandemic emergency. It is well known that being a first-time employee causes stress, but there are few studies yet investigating the perception of newly employed nurses during the pandemic. The aim of this research is therefore to describe the experience of these nurses., Methods: A descriptive qualitative study was conducted through interviews. The research was approved by the 'Area Vasta Emilia Nord Ethics Committee., Results: 14 nurses were interviewed and nine themes were found. Emotions, awareness, job opportunities, professional liability, organisational aspects and relationship with the other., Conclusions: Our study shows how stress, anxiety and feelings of inadequacy characterise new nurses' entry into the workplace. Emotional support strategies, such as counselling and emergency preparedness training, could help early career professionals to cope with complex and emotionally charged clinical care situations with greater resilience., Study Registration: ClinicalTrials.gov Identifier: NCT05110859.

The Emergency Medical Service team are often the first to arrive in situations that later turned out to be crime scenes. Therefore, multiple responsibilities derive from their actions, as there is the burden of assisting the parties involved by maintaining the integrity of forensic evidence while, at the same time, mitigating further harm or risks. The aforementioned, however, often lack any forensic training with the consequent risk of alteration of the area and loss of fundamental information for the purpose of further investigation. The purpose of this study, born from the interdisciplinary collaboration between nursing and forensic sciences, is aimed to guarantee the correct approach by emergency professionals at the Crime Scene; in the light of the data currently available regarding intervention strategies, a Data Collection Sheet was drawn up, whose non-immediate compilation would inevitably lead to the loss of important informations. This is a tool not intended for medical examiners, already trained in this field and equipped with elaborate survey cards, but rather an easy-to-use tool that is the prerogative of "laymen" that can prevent emergency healthcare professionals from losing crucial elements that will then be provided to the investigative bodies and consequently to the consultants or experts. The working method involved the research in Literature of already existing operational tools and a bibliographic review of texts, articles and protocols relating to the topic, as well as surveys carried out at national level via email with EMS Operations Centres about the use of a Crime Scene Report Card.

The acquisition of languages by children using two languages is a matter of debate as many factors contribute to the success of this type of acquisition. We focus on how the competence of dual-language children changes in their two languages as a function of length of exposure and establish whether there are reciprocal influences during language development. We examined the comprehension of subject and object relative clauses in a group of 6-year-old (younger) and 8-year-old (older) Mandarin-Italian dual-language children. After 3 years of regular and intensive exposure to Italian, the younger group reached the same level of competence in the comprehension of relative clauses in their two languages, and after 5 years of exposure to Italian, the older group had a better comprehension of relative clauses in Italian than in Mandarin. Acquiring two languages leads to bidirectional influence, beyond a reciprocal support. Finally, some penalty may be observed in the acquisition of subject head-final relative clauses, which is not evident in that of subject head-initial relative clauses., (Copyright © 2020 Hu, Costa and Guasti.)

The 66 kDa isoform of the mammalian Shc gene promotes adipogenesis, and p66Shc -/- mice accumulate less body weight than wild-type (WT) mice. As the metabolic consequences of the leaner phenotype of p66Shc -/- mice is debated, we hypothesized that gut microbiota may be involved. We confirmed that p66Shc -/- mice gained less weight than WT mice when on a high-fat diet (HFD), but they were not protected from insulin resistance and glucose intolerance. p66Shc deletion significantly modified the composition of gut microbiota and their modification after an HFD. This was associated with changes in gene expression of Il-1b and regenerating islet-derived protein 3 γ ( Reg3g) in the gut and in systemic trimethylamine N-oxide and branched chain amino acid levels, despite there being no difference in intestinal structure and permeability. Depleting gut microbiota at the end of HFD rendered both strains more glucose tolerant but improved insulin sensitivity only in p66Shc -/- mice. Microbiota-depleted WT mice cohoused with microbiota-competent p66Shc -/- mice became significantly more insulin resistant than WT mice cohoused with WT mice, despite no difference in weight gain. These findings reconcile previous inconsistent observations on the metabolic phenotype of p66Shc -/- mice and illustrate the complex microbiome-host-genotype interplay under metabolic stress.-Ciciliot, S., Albiero, M., Campanaro, S., Poncina, N., Tedesco, S., Scattolini, V., Dalla Costa, F., Cignarella, A., Vettore, M., Di Gangi, I. M., Bogialli, S., Avogaro, A., Fadini, G. P. Interplay between gut microbiota and p66Shc affects obesity-associated insulin resistance.

Background: Improvement in morbidity of pancreatoduodenectomy (PD) largely depends on the reduction in the incidence of clinically relevant (CR) postoperative pancreatic fistula (POPF)., Methods: After internal validation of the clinical risk score (CRS) of POPF, and identification of other predictive factors for POPF, robotic (RPD), and open (OPD) PDs were stratified into risk categories and matched by propensity scores. The primary endpoint of this study was incidence of CR-POPF. Secondary endpoints were 90-day morbidity and mortality, and sample size calculation for randomized controlled trials (RCT)., Results: No patient undergoing RPD was classified at negligible risk for POPF, and no CR-POPF occurred in 7 RPD at low risk. The matching process identified 48 and 11 pairs at intermediate and high risk for POPF, respectively. In the intermediate-risk group, RPD was associated with higher rates of CR-POPF (31.3% vs 12.5%) (p = 0.0026), with equivalent incidence of grade C POPF. In the high-risk group, CR-POPF occurred frequently, but in similar percentages, after either procedures. Starting from an unadjusted point estimate of the effect size of 1.71 (0.91-3.21), the pair-matched odds ratio for CR-POPF after RPD was 2.80 (1.01-7.78) for the intermediate-risk group, and 0.20 (0.01-4.17) for the high-risk group. Overall morbidity and mortality were equivalent in matched study groups. Sample size calculation for a non-inferiority RCT demonstrated that a total of 31,669 PDs would be required to randomize 682 patients at intermediate risk and 1852 patients at high risk., Conclusions: In patients at intermediate risk, RPD is associated with higher rates of CR-POPF. Incidence of grade C POPF is similar in RPD and OPD, making overall morbidity and mortality also equivalent. A RCT, with risk stratification for POPF, would require an enormous number of patients. Implementation of an international registry could be the next step in the assessment of RPD.

Background: Robotic assistance enhances surgical dexterity and could facilitate wider adoption of laparoscopy for pancreatic resections (PR)., Methods: Data were prospectively entered into a database and analyzed retrospectively to assess feasibility and safety of robotic-assisted PR (RAPR). Additionally, robotic-assisted pancreaticoduodenectomy (RAPD) was compared to a contemporary group of open pancreaticoduodenectomies (OPD)., Results: Between October 2008 and October 2014, 200 consecutive patients underwent RAPR. Three procedures were converted to open surgery (1.5 %), despite 14 patients required associated vascular procedures. RAPD was performed in 83 patients (41.5 %), distal pancreatectomy in 83 (41.5 %), total pancreatectomy in 17 (8.5 %), tumor enucleation in 12 (6 %), and central pancreatectomy in 5 (2.5 %). Thirty-day and 90-day mortality rates were 0.5 and 1 %, respectively. Both deaths occurred after RAPD with vein resection. Complications occurred in 63.0 % of the patients (≥Clavien-Dindo grade IIIb in 4 %). Median comprehensive complication index was 20.9 (0-26.2). Incidence of grade B/C pancreatic fistula was 28.0 %. Reoperation was required in 14 patients (7.0 %). The risk of reoperation decreased after post-operative day 20 (OR 0.072) (p = 0.0015). When compared to OPD, RAPD was associated with longer mean operative time (527.2 ± 166.1 vs. 425.3 ± 92.7; <0.0001) but had an equivalent safety profile. The median number of examined lymph nodes (37; 28.8-45.3 vs. 36; 28-52.8) and the rate of margin positivity in patients diagnosed with pancreatic cancer were also similar (12.5 vs. 45.5 %)., Conclusions: RAPR, including RAPD, are safely feasible in selected patients. The results of RAPD in pancreatic cancer are encouraging but deserve further investigation.

Laparoscopic resection of liver tumors located in the posterosuperior segments is a challenging operation that could be facilitated by robotic assistance. Laparoscopic resection of 12 tumors located in posterosuperior segments (IVa: 1; VII: 5; VIII: 6) was carried out under robotic assistance. All patients had a single tumor nodule. Data were collected prospectively and analyzed retrospectively. Surgery required a mean of 260.4 min (115-430) and was completed laparoscopically in all but one patient, who required conversion to mini-laparotomy because of intolerance of pneumoperitoneum (8.3%). Mean estimated blood loss was 252.7 ml (50-600), making transfusion necessary in 3 patients (25.0%). Post-operative complications occurred in 4 patients (33.3%), being of Clavien-Dindo grade II in 3 patients (25.0%) and Clavien-Dindo grade IV in 1 patient (8.3%). Reoperation was required in 1 patient, who subsequently had a long hospital stay, because of decompensated cirrhosis. Median length of hospital stay was 8.5 days (7-96). No patient was readmitted. Pathology showed hepatocellular carcinoma in 7 patients (58.3%), liver metastasis in 2 patients (16.6%), and hepatic adenoma, focal nodular hyperplasia, and hemangioma in one patient each (8.3%). All patients had a margin negative resection. After a mean follow-up period of 21.4 months (±24.4), no patient with malignant histology developed recurrence. Our initial experience confirms that laparoscopic robot-assisted resection of tumors located in the posterosuperior segments is feasible. Further experience is needed before final conclusions can be drawn and meaningful comparison with other surgical techniques becomes possible.

Effective treatment for neuropathic pain is still lacking, because of poor understanding of pathological mechanisms at the molecular level. Chronic pain (inflammatory and neuropathic pain) is believed to be caused by aberrant neuronal responses along the pain transmission pathways. Both peripheral and central origins are likely to be involved in chronic pain, although their contribution may be different depending on the various forms of chronic pain. Glial cells have recently been implicated in neuropathic pain. These cells form close interactions with neurons and thus may modulate nociceptive transmission under pathological conditions. We will first examine the recent progress in the role of glia in neuropathic and inflammatory pain, with particular emphasis on microglia. Finally, we will discuss how the study of the interaction between neuronal and microglial mechanisms can open the door to new therapeutic opportunities, designed to act on the mechanisms underlying the disease ("disease-oriented") using natural endogenous substances.