Video-assisted anal fistula treatment (VAAFT) combined with ozonide oil dressing: standardization of technique in pediatric patients.

BACKGROUND: Anal fistula and perianal abscess are commonly acquired anorectal pathologies in children. Surgical treatment options commonly adopted are fistulotomy, fistulectomy, cutting seton placement, and more recently video-assisted anal fistula treatment (VAAFT). Optimal postoperative wound dressing remains debated. This study aimed to report our series of pediatric patients, who received VAAFT and postoperative wound dressing using ozonide oil. METHODS: All patients who underwent VAAFT between August 2018 and May 2023 were included in the study. Demographics, clinical features, pre-operative imaging, surgical details, outcome, and mid-term outcome data were retrospectively reviewed for each patient. All VAAFT procedures were performed under general anesthesia and using a 10-Ch fistuloscope. RESULTS: Thirty-three VAAFT procedures were performed in 30 patients over the study period. The median patient age was 5.7 years (range 1.75-14). Anal fistula was idiopathic in 26/30 (86.6%), iatrogenic in 2/30 (6.7%), and secondary to Crohn's disease in 2/30 (6.7%). The median duration of surgery was 23 min (range 18-40). All patients received ozonide oil dressing twice a day for 5 weeks postoperatively. The median hospital stay was 24 h (range 9-36). The median healing time was 28 days (range 17-39). With a median follow-up of 2 years (range 0.5-5), disease recurrence occurred in 3/30 (10%) patients with idiopathic fistula, who were re-operated using the same technique, with no further recurrence. No fecal incontinence or soiling was observed. CONCLUSION: Our series confirmed that VAAFT is a safe and effective technique to treat children with perianal fistula. The technique is versatile, allowing to treat fistulae of different etiologies. Postoperative course was painless and fast. Future comparative prospective studies are needed to better establish these conclusions.

Indocyanine green fluorescent cholangiography: The new standard practice to perform laparoscopic cholecystectomy in pediatric patients. A comparative study with conventional laparoscopic technique.

BACKGROUND: This study aimed to compare outcomes of standard laparoscopic cholecystectomy and indocyanine green fluorescent cholangiography laparoscopic cholecystectomy over a 10-year period. METHODS: From 2013 to 2023, 173 laparoscopic cholecystectomies were performed in 2 pediatric surgery units: 83 using standard technique (G1) and 90 using indocyanine green fluorescent cholangiography (G2). Patients included 96 girls and 77 boys, with a median age of 12.3 years (range 4-17) and a median weight of 51 kg (range 19-114). The 2 groups were compared regarding the following: (1) perioperative complications rate; (2) overall length of surgery (T1); (3) length of cystic duct isolation, clipping, and sectioning (T2); (4) time of gallbladder removal (T3); (5) degree of visualization of biliary tree; (6) safety and feasibility of indocyanine green fluorescent cholangiography; (7) incidence of anatomical anomalies detected intraoperatively. RESULTS: All laparoscopic cholecystectomies were accomplished without conversion to open. The perioperative complications rate was significantly higher in G1 compared with G2 (12% vs 0%; P = .0007). Median T1, T2, and T3 were significantly longer in G1 (90, 37, 35 minutes) compared with G2 (55, 17, 19 minutes) (P = .0001), respectively. The visualization rate of the complete biliary tree was significantly higher in G2 (98.8%) than in G1 (80.7%) (P = .0001). No adverse reactions to indocyanine green were recorded. The incidence of biliary anomalies detected intraoperatively was significantly higher in G2 (7.8%) than in G1 (1.2%) (P = .03). CONCLUSION: Indocyanine green fluorescent cholangiography can be considered the new standard practice to perform laparoscopic cholecystectomy in pediatrics. Indocyanine green fluorescence provided superior visualization of biliary anatomy, increased detection of anatomic variants, faster procedure, and fewer complications compared with conventional technique. Indocyanine green fluorescent cholangiography was safe, feasible, simple, inexpensive, and a timesaving tool.

Indocyanine green (ICG)-GUIDED lymphatic sparing laparoscopic varicocelectomy in children and adolescents. Is intratesticular injection of the dye safe? A mid-term follow-up study.

BACKGROUND: Laparoscopic Palomo varicocelectomy using indocyanine green (ICG) fluorescent lymphography (FL) is standardized technique to perform lymphatic sparing and avoid post-operative hydrocele. No data regarding the safety of intratesticular injection of ICG are currently available. OBJECTIVE: The study aimed to assess the safety and efficacy of this procedure at mid-term follow-up. STUDY DESIGN: Seventy-two patients (median age 14.5 years) undergoing laparoscopic Palomo varicocelectomy using ICG-FL from January 2019 to July 2022, were enrolled. Operative indication was high-grade varicocele in all patients, associated symptoms in 30/72 (41.7 %) and left testicular hypotrophy in 42/72 (58.3 %). Follow-up included clinical examination at 1, 6, 12 months and scrotal Doppler ultrasonography (US) at 12 months postoperatively to assess varicocele persistence, hydrocele, and injections-related complications. RESULTS: Lymphatic sparing was achieved using ICG-FL in all cases. No intra-operative complications or adverse reactions secondary to ICG occurred. The median follow-up was 22.8 months (range 11-49). Self-limited scrotal hematoma at the injection site occurred in 1/72 (1.4 %). Intratesticular hypoechoic millimetric area was detected at the injection site in 3/72 (4.2 %) on US. This finding disappeared after 1-year observation in 2/3 cases (66.7 %) (Figure). Persistent grade II varicocele was observed in 4/72 (5.5 %), not requiring re-intervention. No hydrocele occurred and 14/22 (63.6 %) with pre-operative hypotrophy showed catch-up growth. DISCUSSION: ICG-FL was clinically safe, with no allergy or systemic adverse reactions to the dye reported in this series. No injury directly related to the injection of the dye was clinically observed, except for self-limiting scrotal hematoma in one patient. A millimetric hypoechoic and avascular area in the body of the left testicle at the injection site was found on scrotal US at 1-year follow-up in 3 patients of our series. This finding does not seem to be clinically relevant as patients were asymptomatic and serum tumor markers were normal in all cases. Furthermore, the hypoechoic area with calcifications resolved 1 year later in 2/3 patients. The absence of evolution of this finding seems to exclude the heteroplastic nature. We hypothesized that this finding may be linked to elevated volume and/or pressure of intratesticular injection. Future prospective study with larger series and longer follow-up is needed to assess long-term testicular outcomes. CONCLUSION: Laparoscopic Palomo varicocelectomy using ICG-FL reported excellent outcomes with low incidence of varicocele persistence and no post-operative hydrocele. These preliminary data also confirmed safety of intratesticular injection of ICG at mid-term follow-up, without specific risks for both testis and patient.

Fantastic Needles and Where to Find Them During a Laparoscopic Nissen Fundoplication: Review of Safety Measures to Avoid Needle Loss During Minimally Invasive Surgery.

BACKGROUND: Losing a needle during laparoscopic surgery may be a dramatic moment for the surgeon and potentially have clinical and medico-legal consequences. This case report aims to describe an unusual case of needle loss that occurred during laparoscopic Nissen fundoplication and how to prevent its further occurrence. METHODS: The patient is an 11-year-old boy with a body mass index of 32.4 kg/m 2 . He suffered from severe gastroesophageal reflux disease not responding to medical therapy and hiatal hernia. A laparoscopic Nissen fundoplication was performed. RESULTS: At the closure of the Nissen wrap, CO 2 leakage through the umbilical trocar caused the needle lost during the introduction of the thread. We attempted to find the needle by exploring the entire abdominal cavity without success. Therefore, we decided to complete the surgical procedure. Another 2/0 nonresorbable thread was inserted in the same way as before. But this suture also disappeared. Hence, we manually straightened the needle and introduced it under vision. The operation was accomplished successfully. An intraoperative x-ray was obtained, showing the 2 needles at the level of the 12th rib, near the working port used for the liver retractor. A peritoneal window was created using a monopolar hook, allowing to finally extract the 2 hidden needles. CONCLUSION: The loss of needles, although a rare event, can occur during laparoscopic surgery. Based on our experience, we suggest that needle insertion during laparoscopic operations should be performed under direct vision, especially in obese patients, to reduce the likelihood of such complications.

Applications of indocyanine green (ICG) fluorescence technology in open surgery: preliminary experience in pediatric surgery.

Background: Indocyanine green fluorescence technology (ICG) in pediatric minimally invasive surgery has undergone an important improvement in the last 5 years. However, its use in open surgery is still limited. In this paper, we aim to report our preliminary experience with Rubina® lens ICG fluorescence technology in combination with the IMAGE1 S™ system from KARL STORZ in open excision of masses in children. Methods: The records of 18 patients undergoing open surgery for head, neck and thorax masses between September and November 2022 were retrospectively reviewed. Rubina® lens ICG fluorescence technology system was used in all the cases. In 10 cases we adopted the holding arm system and in 8 cases the hand-held technique. Data about patients' demographics, surgery and outcomes were collected and analyzed through the following criteria: mass localization, intraoperative time (min), ICG administration (ml), intraoperative complications, postoperative complications. Results: A total of 18 patients were operated: 4 thyroglossal duct cysts, 3 supraorbital cysts, 2 neck masses, 2 pre-auricular and 2 scalp cysts, 2 gynecomastias, 2 lymphangiomas, 1 nose mass. In all the cases, intralesional injection of 0.5-1 ml of ICG solution was performed peri-operatively. Mean operative time was 58.4 min (35-134 min). Postoperative complications included seroma formation in 2 cases. Surgical pathology reports confirmed complete mass excision in all the cases. Conclusion: Based on our preliminary experience, ICG fluorescence guided surgery using Rubina® lens system was very helpful also in open surgery procedures. Rubina® lens system permits to have a very low complication rate, a time-saving surgery, a real time reliability of anatomic structures and an excellent clinical safety. In our experience, holding arm system seems more comfortable than hand-held system. However, further cases need to be performed to evaluate the exact role and to identify new indications of this technique in open pediatric surgical procedures.

A novel auxin-inducible degron system for rapid, cell cycle-specific targeted proteolysis.

The discrimination of protein biological functions in different phases of the cell cycle is limited by the lack of experimental approaches that do not require pre-treatment with compounds affecting the cell cycle progression. Therefore, potential cycle-specific biological functions of a protein of interest could be biased by the effects of cell treatments. The OsTIR1/auxin-inducible degron (AID) system allows "on demand" selective and reversible protein degradation upon exposure to the phytohormone auxin. In the current format, this technology does not allow to study the effect of acute protein depletion selectively in one phase of the cell cycle, as auxin similarly affects all the treated cells irrespectively of their proliferation status. Therefore, the AID system requires coupling with cell synchronization techniques, which can alter the basal biological status of the studied cell population, as with previously available approaches. Here, we introduce a new AID system to Regulate OsTIR1 Levels based on the Cell Cycle Status (ROLECCS system), which induces proteolysis of both exogenously transfected and endogenous gene-edited targets in specific phases of the cell cycle. We validated the ROLECCS technology by down regulating the protein levels of TP53, one of the most studied tumor suppressor genes, with a widely known role in cell cycle progression. By using our novel tool, we observed that TP53 degradation is associated with increased number of micronuclei, and this phenotype is specifically achieved when TP53 is lost in S/G2/M phases of the cell cycle, but not in G1. Therefore, we propose the use of the ROLECCS system as a new improved way of studying the differential roles that target proteins may have in specific phases of the cell cycle.

Increased renal elimination of endogenous and synthetic pyrimidine nucleosides in concentrative nucleoside transporter 1 deficient mice.

Concentrative nucleoside transporters (CNTs) are active nucleoside influx systems, but their in vivo roles are poorly defined. By generating CNT1 knockout (KO) mice, here we identify a role of CNT1 in the renal reabsorption of nucleosides. Deletion of CNT1 in mice increases the urinary excretion of endogenous pyrimidine nucleosides with compensatory alterations in purine nucleoside metabolism. In addition, CNT1 KO mice exhibits high urinary excretion of the nucleoside analog gemcitabine (dFdC), which results in poor tumor growth control in CNT1 KO mice harboring syngeneic pancreatic tumors. Interestingly, increasing the dFdC dose to attain an area under the concentration-time curve level equivalent to that achieved by wild-type (WT) mice rescues antitumor efficacy. The findings provide new insights into how CNT1 regulates reabsorption of endogenous and synthetic nucleosides in murine kidneys and suggest that the functional status of CNTs may account for the optimal action of pyrimidine nucleoside analog therapeutics in humans.

Generation of a Yeast Cell Model Potentially Useful to Identify the Mammalian Mitochondrial N-Acetylglutamate Transporter.

The human mitochondrial carrier family (MCF) consists of 53 members. Approximately one-fifth of them are still orphans of a function. Most mitochondrial transporters have been functionally characterized by reconstituting the bacterially expressed protein into liposomes and transport assays with radiolabeled compounds. The efficacy of this experimental approach is constrained to the commercial availability of the radiolabeled substrate to be used in the transport assays. A striking example is that of N-acetylglutamate (NAG), an essential regulator of the carbamoyl synthetase I activity and the entire urea cycle. Mammals cannot modulate mitochondrial NAG synthesis but can regulate the levels of NAG in the matrix by exporting it to the cytosol, where it is degraded. The mitochondrial NAG transporter is still unknown. Here, we report the generation of a yeast cell model suitable for identifying the putative mammalian mitochondrial NAG transporter. In yeast, the arginine biosynthesis starts in the mitochondria from NAG which is converted to ornithine that, once transported into cytosol, is metabolized to arginine. The deletion of ARG8 makes yeast cells unable to grow in the absence of arginine since they cannot synthetize ornithine but can still produce NAG. To make yeast cells dependent on a mitochondrial NAG exporter, we moved most of the yeast mitochondrial biosynthetic pathway to the cytosol by expressing four E. coli enzymes, argB-E, able to convert cytosolic NAG to ornithine. Although argB-E rescued the arginine auxotrophy of arg8∆ strain very poorly, the expression of the bacterial NAG synthase (argA), which would mimic the function of a putative NAG transporter increasing the cytosolic levels of NAG, fully rescued the growth defect of arg8∆ strain in the absence of arginine, demonstrating the potential suitability of the model generated.

Correlation between FLACC scale score and analgesic requirement in children undergoing Minimally Invasive Surgery.

Postoperative pain presents several challenges in pediatric Minimally Invasive Surgery. The Faces, Legs, Activity, Cry, and Consolability (FLACC) scale is a valid scale for pediatric postoperative pain. The aim of our study was to assess postoperative pain using FLACC scale and to analyze the correlation between FLACC scale score and analgesic requirement in children underwent Minimally Invasive Surgery. We retrospectively analyzed data of 153 children aged 2 months-3 years who underwent Minimally Invasive Surgery in our unit from January 2019 and December 2019. Postoperative pain assessment was established using FLACC scale. In each patient were analyzed the correlation between FLACC score and analgesic requirement. Pain evaluation was assigned immediately after surgery and at 15 and 60 minutes. 36.6% of patients (56 children) were asleep so considered pain free; 21.6% of patients (33 children) had a FLACC score more than 7 so they required analgesics and the pain assessment 15 and 60 minutes after was significantly lower. 41.8% of patients (64 children) had a postoperative FLACC score less than 3, so they didn't require any analgesic treatment. On the basis of our results, we recommend FLACC scale for postoperative pain assessment in children underwent MIS aged 2 months-3 years. FLACC scale is an effective and precise scale in detection of postoperative analgesic requirement in children and it could be extended in different age groups with further research.

Endoscopic Treatment of Pilonidal Sinus Disease in Children: A Systematic Review.

Background: Pilonidal sinus disease (PSD) is a common inflammatory disease. PSD management in pediatric patients changed dramatically in the last few years especially when concerning the latest minimally invasive techniques. This article aims to identify clinical evidence about the reliability of the different techniques in managing PSD in children. Materials and Methods: We performed a PubMed search for articles published during the last 10 years, using the keywords "pilonidal," "sinus," "disease," "pediatric," "surgery," and "children." Results: We pooled 38 studies, 18 of these were excluded because they were either not relevant or concerned an adult population. Conclusions: Literature analysis shows that endoscopic techniques for PSD are superior to excision and primary closure (EPC) in terms of tolerance and postoperative conditions and, with the growing number of studies in the matter, important endpoints such as wound healing time and length of hospital stay will be proved to be superior. Pediatric Endoscopic pilonidal disease treatment showed to be a very promising alternative even from a statistical point of view, especially when considered that in this group, studies seemed to be more solid. Literature analysis showed that minimally invasive techniques were statistically superior to EPC in terms of recurrence and complications.

Robotic-assisted pyeloplasty in children: a systematic review of the literature.

Robotic pyeloplasty has become a natural progression from the development of open, then laparoscopic procedures to treat pediatric patients with ureteropelvic junction obstruction (UPJO). Robotic-assisted pyeloplasty (RALP) is now considered a new gold standard in pediatric MIS. A systematic review of the literature retrieved from PubMed and published in the last 10 years (2012-2022) was performed. This review underlines that in all children except the smallest infants, where the open procedure has benefits in terms of duration of general anesthetic and there are limitations in the size of instruments, robotic pyeloplasty is becoming the preferred procedure to perform in patients with UPJO. Results for the robotic approach are extremely promising, with shorter operative times than laparoscopy and equal success rates, length of stay and complications. In case of redo pyeloplasty, RALP is easier to perform than other open or MIS procedures. By 2009, robotic surgery became the most used modality to treat all UPJO and continues to grow in popularity. Robot-assisted laparoscopic pyeloplasty in children is safe and effective with excellent outcomes, even in redo pyeloplasty or challenging anatomical cases. Moreover, robotic approach shortens the learning curve for junior surgeons, who can readily achieve levels of expertise comparable to senior practitioners. However, there are still concerns regarding the cost associated with this procedure. Further high-quality prospective observational studies and clinical trials, as well as new technologies specific for the pediatric population, are advisable for RALP to reach the level of gold standard.

Role of Mitochondrial Transporters on Metabolic Rewiring of Pancreatic Adenocarcinoma: A Comprehensive Review.

Pancreatic cancer is among the deadliest cancers worldwide and commonly presents as pancreatic ductal adenocarcinoma (PDAC). Metabolic reprogramming is a hallmark of PDAC. Glucose and glutamine metabolism are extensively rewired in order to fulfil both energetic and synthetic demands of this aggressive tumour and maintain favorable redox homeostasis. The mitochondrial pyruvate carrier (MPC), the glutamine carrier (SLC1A5_Var), the glutamate carrier (GC), the aspartate/glutamate carrier (AGC), and the uncoupling protein 2 (UCP2) have all been shown to influence PDAC cell growth and progression. The expression of MPC is downregulated in PDAC and its overexpression reduces cell growth rate, whereas the other four transporters are usually overexpressed and the loss of one or more of them renders PDAC cells unable to grow and proliferate by altering the levels of crucial metabolites such as aspartate. The aim of this review is to comprehensively evaluate the current experimental evidence about the function of these carriers in PDAC metabolic rewiring. Dissecting the precise role of these transporters in the context of the tumour microenvironment is necessary for targeted drug development.

Dysregulation of PRMT5 in chronic lymphocytic leukemia promotes progression with high risk of Richter's transformation.

Richter's Transformation (RT) is a poorly understood and fatal progression of chronic lymphocytic leukemia (CLL) manifesting histologically as diffuse large B-cell lymphoma. Protein arginine methyltransferase 5 (PRMT5) is implicated in lymphomagenesis, but its role in CLL or RT progression is unknown. We demonstrate herein that tumors uniformly overexpress PRMT5 in patients with progression to RT. Furthermore, mice with B-specific overexpression of hPRMT5 develop a B-lymphoid expansion with increased risk of death, and Eµ-PRMT5/TCL1 double transgenic mice develop a highly aggressive disease with transformation that histologically resembles RT; where large-scale transcriptional profiling identifies oncogenic pathways mediating PRMT5-driven disease progression. Lastly, we report the development of a SAM-competitive PRMT5 inhibitor, PRT382, with exclusive selectivity and optimal in vitro and in vivo activity compared to available PRMT5 inhibitors. Taken together, the discovery that PRMT5 drives oncogenic pathways promoting RT provides a compelling rationale for clinical investigation of PRMT5 inhibitors such as PRT382 in aggressive CLL/RT cases.

Quality of life of pediatric patients operated for pilonidal sinus disease.

Quality of life (QOL) outcome is an ideal method for determining the efficacy of a surgical treatment. In children operated for pilonidal sinus disease (PSD), open procedures imply prolonged wound care, significant morbidity, and high recurrence rates. Endoscopic treatment (PEPSIT) overcomes these limitations. We report our experience in the management of PSD to evaluate the QOL of patients undergoing open and endoscopic treatment. The records of 177 patients undergoing surgery for PSD from 2008 to 2021 were retrospectively reviewed. Twenty patients were operated with open surgery (G1) and 157 with PEPSIT (G2). We analyzed QOL through the following criteria: hospital stay (HS), healing time (HT), return to sport (RTSp), return to school (RTSc), resumption of social life (RSL), and recurrence rate and reoperation (RRR). Moreover, we used Pediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q) for a more subjective evaluation of life satisfaction. We found significant differences in all the analyzed criteria: HS varied from 3 to 7 days in G1 and from 1 to 2 days in G2; HT from 40 to 75 days in G1 while from 20 to 41 days in G2; RTSp from 50 to 80 days in G1 while from 7 to 21 days in G2; RTSc from 9 to 15 days in G1 while from 2 to 4 days in G2; RSL from 13 to 20 days in G1 while from 2 to 5 days in G2; RRR was 25% in G1 and 4.4% in G2. CONCLUSION: Endoscopic treatment (PEPSIT) significantly improves the quality of life of patients operated for PSD. Compared to open surgery, PEPSIT presents shorter hospital stay, faster healing time, return to sport activities, return to school and resumption of a normal social life, and lower rates of recurrence and reoperation. In addition, PQ-LES-Q demonstrated a good overall quality of life and life satisfaction. Further prospective studies should be obtained to consider PEPSIT as the gold standard for the treatment of PSD in pediatric patients. WHAT IS KNOWN: • Many techniques have been proposed in the last 20 years for the surgical treatment of PSD. • PEPSIT is showing promising results in terms of safety and long-term efficacy. WHAT IS NEW: • The main impact in QOL of patients operated with PEPSIT is on their daily activity, including a shorter hospital stay, faster healing time, return to sport activities, return to school and resumption of a normal social life, lower rates of recurrence and reoperation. • After PEPSIT, children maintain a satisfactory quality of life according to the analysis of PQ-LES-Q.

Indocyanine Green (ICG) Fluorescence-Assisted Open Surgery Using the Rubina® Lens System in the Pediatric Population: A Single-Center Prospective Case Series.

INTRODUCTION: There are scarce papers about the use of fluorescence-guided surgery (FGS) in the open surgical field. This study aimed to assess the usefulness of FGS in an open setting in the pediatric population and to report our preliminary experience using the Rubina® Lens system. METHODS: All patients undergoing ICG fluorescence-assisted open surgery over the period September 2022-September 2023 were enrolled. Each surgical procedure was performed using the Rubina® Lens for ICG fluorescence visualization. RESULTS: A total of 25 patients, 14 boys and 11 girls with a median age at surgery of 5.8 years-old (range 0-15), were enrolled. Surgical indications were dermoid/epidermoid cysts of the head (n = 7), lymphangiomas of the head/neck (n = 2), thyroglossal duct cysts (n = 7), gynecomastia (n = 3), preauricular fistula (n = 2), second branchial cleft fistula (n = 1), fibrolipoma of the shoulder (n = 1) and myofibroma of the gluteal/perineal region (n = 2). In all procedures, an intralesional injection of 2.5 mg/mL ICG solution using a 30-gauge needle was administered. No adverse reactions to ICG occurred. Median operative time was 68.6 min (range 35-189). The visualization of ICG-NIRF with the Rubina® Lens was achieved in all cases. No intraoperative complications were reported. Postoperative complications occurred in 3/25 patients (12%), with gynecomastia (n = 1), thyroglossal duct cyst (n = 1) and neck lymphangioma (n = 1), who developed a fluid collection in the surgical site, requiring needle aspiration in outpatient care (Clavien-Dindo 2). Complete mass excision was confirmed with pathology reports. CONCLUSIONS: Based on this initial experience, FGS using the Rubina® Lens was very helpful in open surgery, providing enhanced visualization of anatomy and identification of margins, real-time reliability and low complication rate. It was easy to use, time saving, feasible and clinically safe. Previous experience in MIS is necessary to adopt this technology. The accuracy of the injection phase is important to avoid diffusion of the ICG into the perilesional tissue.

Effectiveness of a Laparoscopic Training Model for Pediatric Surgeons During COVID-19 Pandemic: A Single-Center Experience.

Background: During COVID-19 pandemic, many restrictions were applied in the field of health care. For this reason, we decided to adopt the laparoscopic simulator Laparo® Analytic to allow the trainees of our pediatric surgery training program to continue their training activity, and we determined its impact on their surgical education. Methods: We used Laparo Analytic Simulator for laparoscopic surgery training among the residents of our center. Fifteen residents from different years of the pediatric surgery program participated in this study. Each participant performed a 2-hour training session per week, consisting of three different exercises: Rubber Bands, Knotting, and Suturing. For each training session, the following parameters were analyzed: training time, economy of movement, smoothness, instrument activity (IA), instrument visibility (IV), and instrument symmetry. Results: Results were collected after the first training session (T0), at 3 months after the beginning of the study (T1) and at 6 months after the beginning of the study (T2). At T2 of training with Laparo Analytic Simulator, residents were able to complete their tasks significantly faster (P = .001) and had a significant improvement in smoothness of movements, IA, IV, and instrument symmetric movements during the tasks analyzed. Conclusion: On the basis of our results, we believe that Laparo analytic is an excellent system to adopt in minimally invasive surgery (MIS) training programs, in particular, during periods of surgical restrictions, as COVID-19 pandemic, or in centers with a limited MIS activity.

Enhanced BRAF engagement by NRAS mutants capable of promoting melanoma initiation.

A distinct profile of NRAS mutants is observed in each tumor type. It is unclear whether these profiles are determined by mutagenic events or functional differences between NRAS oncoproteins. Here, we establish functional hallmarks of NRAS mutants enriched in human melanoma. We generate eight conditional, knock-in mouse models and show that rare melanoma mutants (NRAS G12D, G13D, G13R, Q61H, and Q61P) are poor drivers of spontaneous melanoma formation, whereas common melanoma mutants (NRAS Q61R, Q61K, or Q61L) induce rapid tumor onset with high penetrance. Molecular dynamics simulations, combined with cell-based protein-protein interaction studies, reveal that melanomagenic NRAS mutants form intramolecular contacts that enhance BRAF binding affinity, BRAF-CRAF heterodimer formation, and MAPK > ERK signaling. Along with the allelic series of conditional mouse models we describe, these results establish a mechanistic basis for the enrichment of specific NRAS mutants in human melanoma.

Efficacy of a Virtual Reality Program in Pediatric Surgery to Reduce Anxiety and Distress Symptoms in the Preoperative Phase: A Prospective Randomized Clinical Trial.

Background: Virtual reality (VR) experience is the most adopted form of video-gaming to reduce preoperative anxiety. This prospective randomized clinical trial aimed to examine the feasibility and efficacy of preoperative VR experience in children undergoing elective surgery. Materials and Methods: All patients older than 13 years and scheduled for elective surgery between March and June 2021 were enrolled. Preoperative VR experience consisted in watching a 5-minute video using a head-mounted display. Four parameters were evaluated and compared between the two groups: (1) patient heart rate (HR) before anesthesia; (2) patient evaluation of preoperative anxiety using facial affective scale (FAS); (3) anesthesiologist evaluation of preoperative anxiety using FAS; and (4) subjective stress scoring using a 5-item Likert-type scale. Results: A total of 40 patients (23 boys) with a median age of 14.5 years (range 12-17) participated in the study. The patients were randomized in two groups, each of 20 patients, according to preoperative VR experience: VR group (G1) and control group (G2). No adverse events related to VR occurred. The patient median HR was significantly lower in G1 (72 bpm) than in G2 (101 bpm) (P = .001). The very relaxed/relaxed face selection rate using FAS was significantly higher in G1 than in G2, in both patient and anesthesiologist evaluations (P = .001). Finally, the subjective patient scoring of operating room experience was significantly greater in G1 [4.6 ± 0.4] than in G2 [2.15 ± 1.07] (P = .001). Conclusions: Our preliminary results showed that VR is safe and effective to relieve anxiety and improve relaxation in the preoperative period in pediatric patients undergoing elective surgery. The VR experience resulted in decreased overall anxiety and increased overall positive affect during the preoperative period in VR group compared with the control group. Further studies are needed to investigate this technology in the postoperative phase and on a larger patient cohort.