Anomalies of the right hepatic artery in periampullary cancer treatment: are pathological and clinical outcomes different? A single tertiary referral center retrospective analysis.

PURPOSE: Anomalies of the right hepatic artery (RHA) may represent an additional challenge in pancreatoduodenectomy (PD). The aim of this study is to assess the potential impact of variations in hepatic arterial anatomy on perioperative outcomes. METHODS: PDs performed for periampullary malignancies between 2017 and 2022 were retrospectively enrolled and subdivided in two groups: modal pattern of vascularization (MPV) and anomalous pattern of vascularization (APV). A propensity score matching (PSM) analysis was conducted to homogenize the two study populations. The two groups were then compared in terms of perioperative outcomes and pathological findings. RESULTS: Thirty-eight patients (16.3%) out of 232 presented a vascular anomaly: an accessory RHA in 7 cases (3%), a replaced RHA in 26 cases (11.2%), and a replaced HA in 5 cases (2.1%). After PSM, 76 MPV patients were compared to the 38 APV patients. The incidence rate of postoperative complications was comparable between the two study populations (p=0.2). Similarly, no difference was detected in terms of histopathological data, including margin status. No difference was noted in terms of intraoperative hemorrhage and vascular resection. CONCLUSION: When PDs are performed in high-volume centers, the presence of an APV of the RHA does not relate to a significant impact on perioperative complications. Moreover, no influence was noted on histopathological findings.

Is Silver Addition to Scaffolds Based on Polycaprolactone Blended with Calcium Phosphates Able to Inhibit Candida albicans and Candida auris Adhesion and Biofilm Formation?

Candida spp. periprosthetic joint infections are rare but difficult-to-treat events, with a slow onset, unspecific symptoms or signs, and a significant relapse risk. Treatment with antifungals meets with little success, whereas prosthesis removal improves the outcome. In fact, Candida spp. adhere to orthopedic devices and grow forming biofilms that contribute to the persistence of this infection and relapse, and there is insufficient evidence that the use of antifungals has additional benefits for anti-biofilm activity. To date, studies on the direct antifungal activity of silver against Candida spp. are still scanty. Additionally, polycaprolactone (PCL), either pure or blended with calcium phosphate, could be a good candidate for the design of 3D scaffolds as engineered bone graft substitutes. Thus, the present research aimed to assess the antifungal and anti-biofilm activity of PCL-based constructs by the addition of antimicrobials, for instance, silver, against C. albicans and C. auris. The appearance of an inhibition halo around silver-functionalized PCL scaffolds for both C. albicans and C. auris was revealed, and a significant decrease in both adherent and planktonic yeasts further demonstrated the release of Ag+ from the 3D constructs. Due to the combined antifungal, osteoproliferative, and biodegradable properties, PCL-based 3D scaffolds enriched with silver showed good potential for bone tissue engineering and offer a promising strategy as an ideal anti-adhesive and anti-biofilm tool for the reduction in prosthetic joints of infections caused by Candida spp. by using antimicrobial molecule-targeted delivery.

The impact of gastrojejunostomy orientation on delayed gastric emptying after pancreaticoduodenectomy: a single center comparative analysis.

BACKGROUND: Delayed gastric emptying (DGE) represents the most frequent complication after pancreaticoduodenectomy (PD). Aim of this study was to evaluate the impact of gastrojejunostomy (GJ)orientation on DGE incidence after PD. METHODS: One-hundred and twenty-one consecutive PDs were included in the analysis and divided in the horizontal (H-GJ group) and vertical GJ anastomosis groups (V-GJ group). Postoperative data and the value of the flow angle between the efferent jejunal limb and the stomach of the GJ anastomosis at the upper gastrointestinal series were registered. RESULTS: Seventy-five patients (62%)underwent H-GJ, while 46 patients (38%)underwent V-GJ. The incidence of DGE was significantly lower in the V-GJ group as compared to the H-GJ group (23.9%vs45.3%; p = 0.02). V-GJ was also associated to a less severe DGE manifestation (p = 0.006). The flow angle was significantly lower in case of V-GJ as compared to H-GJ (24.5°vs37°; p = 0.002). At the multivariate analysis, ASA score≥3 (p = 0.02), H-GJ (p = 0.03), flow angle>30°(p = 0.004) and Clavien-Dindo≥3 (p = 0.03) were recognized as independent prognostic factors for DGE. These same factors were independent prognostic features also for a more severe DGE manifestation. CONCLUSION: VGJ and the more acute flow angle appear to be associated to a lower incidence rate and severity of DGE. This modified technique should be considered by surgeons in order to reduce postoperative DGE occurrence.

Propensity score-matched comparison of short- and long-term outcomes between surgery and endoscopic submucosal dissection (ESD) for intestinal type early gastric cancer (EGC) of the middle and lower third of the stomach: a European tertiary referral center experience.

BACKGROUND: Despite the comparable results between ESD and gastrectomy reported in multiple Asiatic studies, limited data are currently present on the long-term efficacy of ESD for EGC in Western countries. The aim of this study was to compare the short- and long-term outcomes of the endoscopic submucosal dissection and surgery for non-diffuse early gastric cancer treatment in a Western cohort of patients. METHODS: All patients with a diagnosis of intestinal type EGC located in the middle and lower third of the stomach from 2005 to 2015 were enrolled in the study. All patients completed a 5-year follow-up. Patients were divided according to the procedure performed (ESD/subtotal gastrectomy). The two groups were matched for age, gender, ASA score, tumor dimension, and grade of infiltration (mucosa/submucosa). RESULTS: After matching, 84 patients (42 per group) were included in the analysis. Peri-procedural morbidity rate was 7.1% and no difference was observed between the two groups (4.8% vs 9.5% for ESD and STG groups, respectively; p = 0.3). Similar results in terms of 5-year OS and DFS were observed for ESD and STG (77.7% vs 71.8% ; p = 0.78 and 74.9% vs 72% ; p = 0.7, respectively). At the multivariate analysis, ASA3 score was recognized as the only negative predictor factor for the 5-year OS (OR 6.2; 95% CI 2.2-16.8; p < 0.001). Regarding the DFS, both ASA3 score (OR 4.4; 95% CI 1.7-10.9; p < 0.001) and submucosal infiltration(OR 5.1; 95% CI 1.2-22.4 ; p = 0.02) were identified as independent risk factors for a worse outcome. CONCLUSIONS: Our results confirm the safety and feasibility ESD for EGC treatment in a Western setting. In addition, this is one of the few reports showing comparable results both in terms of short- and long-term outcomes between ESD and surgery for intestinal type ECG treatment in Western countries.

Development and prospective validation of a scoring system for the Basic Endoscopic Skills Training (BEST) box.

AIMS: The increased use of endoscopy as a minimally invasive therapeutic technique has created a great demand for endoscopic training. The Basic Endoscopic Skills Training (BEST) box provides a low-cost solution by adapting the Fundamentals of Laparoscopic Surgery (FLS) box for flexible endoscopic simulation. The BEST box consists of six endoscopic tasks with a 5-min time limit per task. This study aims to develop a scoring system for objective evaluation of user performance. METHODS: A total of 165 participants were tested on the BEST box. Participants were divided into two groups: retrospective analysis (n = 100) and prospective analysis (n = 65). From the retrospective group, 55 individuals were also scored on the Global Assessment of Gastrointestinal Endoscopic Skills-Upper Endoscopy (GAGES-UE). Linear regression between user performance on BEST box and GAGES-UE was performed to develop the scoring system. Receiver Operating Characteristic curve was used to determine a threshold score to help users appreciate their endoscopic expertise. Prospective scoring of 65 individuals was then performed using the formula developed (20 experts and 45 trainees). RESULTS: The minimum and maximum possible scores are 30 and 110, respectively. Retrospective analysis showed that the scoring system was able to distinguish between experts and trainees (p < 0.001), correlated with GAGES-UE (p < 0.001), and had a reliability constant of r = 0.765 (p < 0.001). On prospective testing using the scoring system the expert group received a final average score of 92, whereas the average score for the trainee group was 61 (p < 0.001). CONCLUSIONS: The developed BEST box scoring system correlates with the experience level of the test taker as well as with the GAGES-UE scoring system. The results of this study add further evidence to the validity of the BEST box as an effective, low-cost endoscopic simulator with the scores used by trainees to track their performance level overtime.

Survival advantage of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) for advanced gastric cancer: experience from a Western tertiary referral center.

BACKGROUND: Selection criteria and prognostic factors for patients with advanced gastric cancer (AGC) undergoing cytoreductive surgery (CRS) plus hyperthermic intra-operative peritoneal chemotherapy (HIPEC) have not been well defined and the literature data are not homogeneous. The aim of this study was to compare prognostic factors influencing overall (OS) and disease-free survival (DFS) in a population of patients affected by AGC with surgery alone and surgery plus HIPEC, both with curative (PCI, Peritoneal Carcinomatosis Index >1) and prophylactic (PCI=0) intent. METHODS: A retrospective analysis of a prospectively collected database was conducted in patients affected by AGC from January 2006 to December 2015. Uni- and multivariate analyses of prognostic factors were performed. RESULTS: A total of 85 patients with AGC were analyzed. Five-year OS for surgery alone, CRS plus curative HIPEC, and surgery plus prophylactic HIPEC groups was 9%, 27%, and 33%, respectively. Statistical significance was reached comparing both prophylactic HIPEC vs surgery alone group (p = 0.05), curative HIPEC vs surgery alone group (p = 0.03), and curative vs prophylactic HIPEC (p = 0.04). Five-year DFS for surgery alone, CRS + curative HIPEC, and surgery + prophylactic HIPEC groups was 9%, 20%, and 30%, respectively. Statistical significance was reached comparing both prophylactic HIPEC vs surgery alone group (p < 0.0001), curative HIPEC vs surgery alone group (p = 0.008), and curative vs prophylactic HIPEC (p = 0.05). CONCLUSIONS: Patients with AGC undergoing surgery plus HIPEC had a better OS and DFS with respect to patients treated with surgery alone.

Survival advantage of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) for advanced gastric cancer: experience from a Western tertiary referral center.

BACKGROUND: Selection criteria and prognostic factors for patients with advanced gastric cancer (AGC) undergoing cytoreductive surgery (CRS) plus hyperthermic intra-operative peritoneal chemotherapy (HIPEC) have not been well defined, and the literature data are not homogeneous. The aim of this study was to compare prognostic factors influencing overall (OS) and disease-free survival (DFS) in a population of patients affected by AGC with surgery alone and surgery plus HIPEC, both with curative (PCI, peritoneal carcinomatosis index > 1) and prophylactic (PCI = 0) intent. METHODS: A retrospective analysis of a prospectively collected database was conducted in patients affected by AGC from January 2006 to December 2015. Uni- and multivariate analyses of prognostic factors were performed. RESULTS: A total of 85 patients with AGC were analyzed. A 5-year OS for surgery alone, CRS plus curative HIPEC, and surgery plus prophylactic HIPEC groups was 9%, 27% and 33%, respectively. Statistical significance was reached comparing both prophylactic HIPEC vs surgery alone group (p = 0.05), curative HIPEC vs surgery alone group (p = 0.03), and curative vs prophylactic HIPEC (p = 0.04). A 5-year DFS for surgery alone, CRS + curative HIPEC, and surgery + prophylactic HIPEC groups was 9%, 20%, and 30%, respectively. Statistical significance was reached comparing both prophylactic HIPEC vs surgery alone group (p < 0.0001), curative HIPEC vs surgery alone group (p = 0.008), and curative vs prophylactic HIPEC (p = 0.05). CONCLUSIONS: Patients with AGC undergoing surgery plus HIPEC had a better OS and DFS with respect to patients treated with surgery alone.

HYPerspectral Enhanced Reality (HYPER): a physiology-based surgical guidance tool.

BACKGROUND: HSI is an optical technology allowing for a real-time, contrast-free snapshot of physiological tissue properties, including oxygenation. Hyperspectral imaging (HSI) has the potential to quantify the gastrointestinal perfusion intraoperatively. This experimental study evaluates the accuracy of HSI, in order to quantify bowel perfusion, and to obtain a superposition of the hyperspectral information onto real-time images. METHODS: In 6 pigs, 4 ischemic bowel loops were created (A, B, C, D) and imaged at set time points (from 5 to 360 min). A commercially available HSI system provided pseudo-color maps of the perfusion status (StO2, Near-InfraRed perfusion) and the tissue water index. An ad hoc software was developed to superimpose HSI information onto the live video, creating the HYPerspectral-based Enhanced Reality (HYPER). Seven regions of interest (ROIs) were identified in each bowel loop according to StO2 ranges, i.e., vascular (VASC proximal and distal), marginal vascular (MV proximal and distal), marginal ischemic (MI proximal and distal), and ischemic (ISCH). Local capillary lactates (LCL), reactive oxygen species (ROS), and histopathology were measured at the ROIs. A machine-learning-based prediction algorithm of LCL, based on the HSI-StO2%, was trained in the 6 pigs and tested on 5 additional animals. RESULTS: HSI parameters (StO2 and NIR) were congruent with LCL levels, ROS production, and histopathology damage scores at the ROIs discriminated by HYPER. The global mean error of LCL prediction was 1.18 ± 1.35 mmol/L. For StO2 values > 30%, the mean error was 0.3 ± 0.33. CONCLUSIONS: HYPER imaging could precisely quantify the overtime perfusion changes in this bowel ischemia model.

Three-dimensional imaging improved the laparoscopic performance of inexperienced operators: a prospective trial.

BACKGROUND: Three-dimensional (3-D) high-definition (HD) stereovision and two-dimensional (2-D) ultra-high-resolution (4K) monitors have recently become available for laparoscopic surgery. The aim of this study was to compare laparoscopic performance between inexperienced participants using 3-D/HD and 2-D/4K monitors and those using conventional 2-D/HD monitors. METHODS: The study enrolled 66 participants with no previous surgical experience or medical training. They were randomly divided into three equal groups, each using a different type of monitor (2-D/HD, 2-D/4K, or 3-D/HD), to perform three phantom tasks using a laparoscopic simulator: Task 1, touching markers on a non-flat surface; Task 2, bimanual peg transfer; and Task 3, passing a straight rod through a loop. Each task was performed three times. The performance scores (operative time, path length of the forceps, and technical errors) were compared for each monitor type and by age group (< 30 vs. > 30 years). RESULTS: For all three tasks, scores using the 3-D monitor were significantly better than those using either 2-D monitor, with no difference between the 2-D/4K and 2-D/HD monitors. Using the 2-D monitors, the performance of Task 3 by the participants > 30 years was worse than that by the younger participants; however, there was no difference between the age groups when using the 3-D monitor. CONCLUSION: Participants with no prior experience using a 3-D monitor showed better laparoscopic performance than those using 2-D monitors, even with 4K resolution. This improvement was more marked in older participants, suggesting a greater loss of depth perception in a 2-D environment.

Simultaneous computer-assisted assessment of mucosal and serosal perfusion in a model of segmental colonic ischemia.

BACKGROUND: Fluorescence-based enhanced reality (FLER) enables the quantification of fluorescence signal dynamics, which can be superimposed onto real-time laparoscopic images by using a virtual perfusion cartogram. The current practice of perfusion assessment relies on visualizing the bowel serosa. The aim of this experimental study was to quantify potential differences in mucosal and serosal perfusion levels in an ischemic colon segment. METHODS: An ischemic colon segment was created in 12 pigs. Simultaneous quantitative mucosal and serosal fluorescence imaging was obtained via intravenous indocyanine green injection (0.2 mg/kg), using two near-infrared camera systems, and computer-assisted FLER analysis. Lactate levels were measured in capillary blood of the colonic wall at seven regions of interest (ROIs) as determined with FLER perfusion cartography: the ischemic zone (I), the proximal and distal vascularized areas (PV, DV), and the 50% perfusion threshold proximally and distally at the mucosal and serosal side (P50M, P50S, D50M, D50S). RESULTS: The mean ischemic zone as measured (mm) for the mucosal side was significantly larger than the serosal one (56.3 ± 21.3 vs. 40.8 ± 14.9, p = 0.001) with significantly lower lactate values at the mucosal ROIs. There was a significant weak inverse correlation between lactate and slope values for the defined ROIs (r = - 0.2452, p = 0.0246). CONCLUSIONS: Mucosal ischemic zones were larger than serosal zones. These results suggest that an assessment of bowel perfusion from the serosal side only can underestimate the extent of ischemia. Further studies are required to predict the optimal resection margin and anastomotic site.

Total mesopancreas excision for periampullary malignancy: a single-center propensity score-matched comparison of long-term outcomes.

PURPOSE: Few comparative studies are available on the long-term prognostic role of mesopancreas (MP) excision after pancreaticoduodenectomy (PD). We compared the long-term outcomes of patients undergoing standard PD (sPD) and PD with MP excision (PD-MPe). METHODS: Sixty sPDs were compared to 60 matched PD-MPe patients for intraoperative and postoperative data, histopathological findings, and long-term outcomes. RESULTS: R0 rate was similar in the two groups (p = 0.17). However, PD-MPe related to a lower rate of MP resection margin positivity (16.7% vs 5%; p = 0.04) and to a higher harvested lymph nodes number (19.8 ± 7.6 vs 10.1 ± 5.1; p < 0.0001). Local tumor recurrence was more frequent in the sPD cohort (55.5% vs 26.8% in the PD-MPe group; p = 0.002), with a consequent worse disease-free survival (DFS) (14.8% vs 22.3%; p = 0.04). An inferior 5-year overall survival (OS) was noted in case of MP margin positivity compared with MP margin negativity (0% vs 29%; p < 0.0001). MP positivity resulted as an independent prognostic factor for both a worse OS and DFS at the multivariate analysis. CONCLUSION: PD-MPe offers clinical advantages in terms of MP resection margin status, local recurrence, long-term mortality, and DFS. The lower MP positivity rate, achieved with PD-MPe, leads to better outcomes both in terms of OS and DFS.

Adaptation of the fundamentals of laparoscopic surgery box for endoscopic simulation: performance evaluation of the first 100 participants.

BACKGROUND: The paucity of readily accessible, cost-effective models for the simulation, practice, and evaluation of endoscopic skills present an ongoing barrier for resident training. We have previously described a system for conversion of the Fundamentals of Laparoscopic Surgery box (FLS) for flexible endoscopic simulation. Six endoscopic tasks focusing on scope manipulation, and other clinically relevant endoscopic skills are performed within a 5-min time limit per task. This study describes our experience and validation results with the first 100 participants. METHODS: A total of 100 participants were evaluated on the simulator. Thirty individuals were classified as experts (having done over 200 endoscopic procedures), and 70 were classified as trainees (39 individuals reported having no prior endoscopy experience). Of the 100 participants, 55 individuals were retested on the simulator within a period of 4 months. These 55 individuals were also evaluated using the "Global Assessment of Gastrointestinal Endoscopic Skills" (GAGES). T-tests and Pearson correlations were used where appropriate, values less than 0.05 were considered significant. RESULTS: Experts completed all six tasks significantly faster than trainees. For the 55 participants who were retested on the simulator, all tasks demonstrated evidence of test-retest reliability for both experts and trainees who did not practice in between tests. Moderate correlations between lower completion times and higher GAGES scores were observed for all tasks except the clipping task. CONCLUSIONS: The results from the first 100 participants provide evidence for the simulator's validity. Based on task completion times, we found that experts perform significantly better than trainees. Additionally, preliminary data demonstrate evidence of test-retest reliability, as well as GAGES score correlation. Additional studies to determine and validate a scoring system for this simulator are ongoing.

New intraoperative imaging technologies: Innovating the surgeon's eye toward surgical precision.

Imaging is one of the pillars for the ongoing evolution of surgical oncology toward a precision paradigm. In the present overview, some established or emerging intraoperative imaging technologies are described in light of the vision and experience of our group in image-guided surgery, focusing on digestive surgical oncology.

Thermal ablation of pancreatic cancer: A systematic literature review of clinical practice and pre-clinical studies.

PURPOSE: Pancreatic cancer is a challenging malignancy with low treatment option and poor life expectancy. Thermal ablation techniques were proposed as alternative treatment options, especially in advanced stages and for unfit-for-surgery patients. This systematic review describes the thermal ablative techniques -i.e., Laser (LA), Radiofrequency (RFA), Microwave (MWA) Ablation, High-Intensity Focused Ultrasound (HIFU) and cryoablation- available for pancreatic cancer treatment. Additionally, an analysis of the efficacy, complication rate and overall survival for each technique is conducted. MATERIAL AND METHODS: This review collects the ex vivo, preclinical and clinical studies presenting the use of thermal techniques in the pancreatic cancer treatment, searched up to March 2018 in PubMed and Medline. Abstracts, letters-to-the-editor, expert opinions, reviews and non-English language manuscripts were excluded. RESULTS: Sixty-five papers were included. For the ex vivo and preclinical studies, there are: 12 records for LA, 8 for RFA, 0 for MWA, 6 for HIFU, 1 for cryoablation and 3 for hybrid techniques. For clinical studies, 1 paper for LA, 14 for RFA, 1 for MWA, 17 for HIFU, 1 for cryoablation and 1 for hybrid techniques. CONCLUSIONS: Important technological advances are presented in ex vivo and preclinical studies, as the real-time thermometry, nanotechnology and hybrid techniques to enhance the thermal outcome. Conversely, a lack of standardization in the clinical employment of the procedures emerged, leading to contrasting results on the safety and feasibility of some analyzed techniques. Uniform conclusions on the safety and feasibility of these techniques for pancreatic cancer will require further structured investigation.

Residual fundus or neofundus after laparoscopic sleeve gastrectomy: is fundectomy safe and effective as revision surgery?

INTRODUCTION: Up to 30 % of patients who have undergone laparoscopic sleeve gastrectomy require revision surgery for inadequate weight loss, weight regain, and/or the development of severe upper gastrointestinal symptoms. The aim of this retrospective study was to evaluate the safety and efficacy of laparoscopic fundectomy (LF) in cases of a residual fundus/neofundus development regarding GERD symptoms. METHODS: The study group comprised 19 patients (17 female; mean BMI 35.4 kg/m(2)) divided into 2 groups. Group A (n = 10) patients with severe GERD and evidence of residual fundus/neofundus, Hiatal hernia with good results in terms of weight loss. Group B (n = 9) patients with severe GERD, a residual fundus/neofundus, inadequate weight loss or weight regain. Fundectomy was indicated when a residual fundus/neofundus was associated with severe GERD symptoms. The presence of a residual fundus/neofundus was assessed by a barium swallow and/or multislice computed tomography. RESULTS: No mortality or intra-operative complications occurred. Five postoperative complications occurred: 2 cases of bleeding, 1 mid-gastric stenosis and 2 leaks (10.5 %). All patients experienced improvements in their GERD symptoms and stopped PPI treatment. Group B exhibited an additional %EWL of 53.4 % at 24 months. CONCLUSION: LF and cruroplasty is feasible and has good results in terms of GERD symptoms control and additional weight loss. The high rate of postoperative complications observed in this series remains a matter of concern. A re-sleeve procedure might be considered as an alternative to RYGB/DS conversion restricted to selected patients.

Reinforcement of hiatal defect repair with absorbable mesh fixed with non-permanent devices.

AIM: To report the results of an open label prospective study on a new technique for laparoscopic hiatal hernia (HH) repair with absorbable mesh fixed with absorbable materials Methods: From January 2011 to May 2013, 43 patients were treated; group A, 20 patients submitted to laparoscopic sleeve gastrectomy (LSG); group B, 13 patients submitted to revisional surgery for the diagnosis of HH and symptomatic GERD post-LSG; and group C, ten patients submitted to 360° fundoplication. All patients underwent cruroplasty reinforced with bio-absorbable mesh fixed with absorbable tacks and/or fibrin glue. Conversion rate, intra-operative complications, operative time (tacks vs tacks plus fibrin glue), perioperative complications, perioperative symptoms and radiological control set the criteria for clinical/surgical evaluation. RESULTS: Conversion and mortality rate was 0%. The mean time for mesh fixation with the tacks vs tacks plus fibrin glue was 6.2 ± 2 vs 7.3 ± 3 min. The remission of GERD symptoms was observed in 39 patients, and we did not observe any cases of mesh-related complications at a mean follow-up of 17.4 months. Recurrence rate was 2.3% (one asymptomatic patient of group B). CONCLUSIONS: Reinforcement with absorbable mesh-cancel bio mesh is a safe and effective option for laparoscopic HH repair in normal weight and obese patients.

New Generation of Osteoinductive and Antimicrobial Polycaprolactone-Based Scaffolds in Bone Tissue Engineering: A Review.

With respect to other fields, bone tissue engineering has significantly expanded in recent years, leading not only to relevant advances in biomedical applications but also to innovative perspectives. Polycaprolactone (PCL), produced in the beginning of the 1930s, is a biocompatible and biodegradable polymer. Due to its mechanical and physicochemical features, as well as being easily shapeable, PCL-based constructs can be produced with different shapes and degradation kinetics. Moreover, due to various development processes, PCL can be made as 3D scaffolds or fibres for bone tissue regeneration applications. This outstanding biopolymer is versatile because it can be modified by adding agents with antimicrobial properties, not only antibiotics/antifungals, but also metal ions or natural compounds. In addition, to ameliorate its osteoproliferative features, it can be blended with calcium phosphates. This review is an overview of the current state of our recent investigation into PCL modifications designed to impair microbial adhesive capability and, in parallel, to allow eukaryotic cell viability and integration, in comparison with previous reviews and excellent research papers. Our recent results demonstrated that the developed 3D constructs had a high interconnected porosity, and the addition of biphasic calcium phosphate improved human cell attachment and proliferation. The incorporation of alternative antimicrobials-for instance, silver and essential oils-at tuneable concentrations counteracted microbial growth and biofilm formation, without affecting eukaryotic cells' viability. Notably, this challenging research area needs the multidisciplinary work of material scientists, biologists, and orthopaedic surgeons to determine the most suitable modifications on biomaterials to design favourable 3D scaffolds based on PCL for the targeted healing of damaged bone tissue.

Synergistic Effect of Essential Oils and Antifungal Agents in Fighting Resistant Clinical Isolates of Candida auris.

Recently, a large number of nosocomial infections have been caused by an emerging pathogen that is rising as a worldwide issue in human health: Candida auris. This yeast is considered resistant to antifungals of the first-line therapies, and consequently it is related to morbidity and mortality. Therefore, the aim of this research was to determine the in vitro anti-C. auris activity against twenty-three resistant clinical strains of different essential oils (EOs), pure or in combination with traditional antifungal agents, mainly caspofungin, fluconazole, micafungin and 5-flucytosine. Broth dilution assay was performed to evaluate the fungistatic and fungicidal effectiveness of fifteen EOs towards all the C. auris isolates. The data demonstrated that EOs were able to prevent C. auris growth, with MIC values ranging from 0.03 to 1% for the efficacious EOs (thyme, cinnamon, geranium, clove bud, lemongrass and mentha of Pancalieri), whereas the MICs were >1% for the ineffective ones. Thereafter, the six most effective EOs were used to perform the checkerboard experiments by assaying simultaneously the activity of EOs and traditional antifungals towards two selected strains. The most promising synergic combinations towards C. auris, depending on the isolate, were those with micafungin and geranium, thyme, cinnamon, lemongrass or clove bud EOs, with fluconazole and mentha of Pancalieri EO, and with 5-flucytosine and mentha of Pancalieri EO. These EOs and their combinations with antifungal drugs may provide a useful therapeutic alternative that could reduce the dose of the individual components, limiting the overall side effects. These associations might be a prospective option for the future treatment of infections, thus helping to overcome the challenging issue of resistance in C. auris.

Unveiling the Relationship between Ceftobiprole and High-Molecular-Mass (HMM) Penicillin-Binding Proteins (PBPs) in Enterococcus faecalis.

Low-affinity PBP4, historically linked to penicillin resistance in Enterococcus faecalis, may still have affinity for novel cephalosporins. Ceftobiprole (BPR) is a common therapeutic choice, even with PBP4-related overexpression and amino acid substitution due to mutations. Our study aims to explore the interaction between BPR and High-Molecular-Mass (HMM) low-reactive PBPs in Penicillin-Resistant-Ampicillin-Susceptible/Ceftobiprole Non-Susceptible (PRAS/BPR-NS) E. faecalis clinical isolates. We conducted competition assays examining class A and B HMM PBPs from four PRAS/BPR-NS E. faecalis strains using purified membrane proteins and fluorescent penicillin (Bocillin FL), in treated and untreated conditions. Interaction strength was assessed calculating the 50% inhibitory concentration (IC50) values for ceftobiprole, by analyzing fluorescence intensity trends. Due to its low affinity, PBP4 did not display significant acylation among all strains. Moreover, both PBP1a and PBP1b showed a similar insensitivity trend. Conversely, other PBPs showed IC50 values ranging from 1/2-fold to 4-fold MICs. Upon higher BPR concentrations, increased percentages of PBP4 inhibition were observed in all strains. Our results support the hypothesis that PBP4 is necessary but not sufficient for BPR resistance, changing the paradigm for enterococcal cephalosporin resistance. We hypothesize that cooperation between class B PBP4 and at least one bifunctional class A PBP could be required to synthesize peptidoglycan and promote growth.

The role of procalcitonin as a risk stratification tool of severity, prognosis, and need for surgery in patients with acute left-sided colonic diverticulitis.

BACKGROUND: Imaging-based classifications do not always reflect the clinical severity and prognosis of acute left-sided colonic diverticulitis. This study aims to investigate the role of an early procalcitonin assessment in the emergency department as a risk stratification tool for severity, prognosis, and need for surgery in patients with acute left-sided colonic diverticulitis. METHODS: In this retrospective cohort study, all adult patients consecutively admitted from January 2015 to September 2020 for acute left-sided colonic diverticulitis and having a procalcitonin determination at admission were enrolled. The following data were collected: age, sex, comorbidities, laboratory parameters, level of urgency, clinical presentation, type of treatment, complications, and post-management outcomes. The association between the procalcitonin value at admission and the following endpoints was analyzed: type of treatment, classification of acute left-sided colonic diverticulitis, mortality, and type of surgery. RESULTS: A total of 503 consecutive patients were enrolled. Procalcitonin >0.5 ng/mL emerged as an independent risk factor for complicated acute left-sided colonic diverticulitis (P = .007). Procalcitonin >0.5 ng/mL (P = .033), together with a history of complicated acute left-sided colonic diverticulitis (P < .001), abdominal pain (P = .04), bowel perforation (P < .001), and peritonitis (P < .001), was a significant risk factor for surgery. Procalcitonin >0.5 ng/mL (P = .007) and peritonitis (P = .03) emerged as independent risk factors for sigmoidectomy without colorectal anastomosis. Procalcitonin >0.5 ng/mL (P = .004), a higher level of urgency at admission (P = .005), Hartmann's procedure (P = .002), and the necessity of mechanical ventilation (P = .004) emerged as independent risk factors for mortality. CONCLUSION: Procalcitonin >0.05 ng/mL at emergency department admission is a useful risk stratification tool for severity, prognosis, and need for surgical treatment in patients with acute left-sided colonic diverticulitis.