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Background: Fragile X syndrome, with an approximate incidence rate of 1 in 4000 males to 1 in 8000 females, is the most prevalent genetic cause of heritable intellectual disability and the most common monogenic cause of autism spectrum disorder. The full mutation of the Fragile X Messenger Ribonucleoprotein-1 gene, characterized by an expansion of CGG trinucleotide repeats (>200 CGG repeats), leads to fragile X syndrome. Currently, there are no targeted treatments available for fragile X syndrome. In a recent large multi-site trial, FXLEARN, the effects of the mGluR5 negative allosteric modulator, AFQ056 (mavoglurant), were investigated, but did not show a significant impact of AFQ056 on language development in children with fragile X syndrome aged 3-6 years., Objectives: The current analyses from biospecimens collected in the FXLEARN study aimed to determine whether AFQ056 affects the level of potential biomarkers associated with Akt/mTOR and matrix metalloproteinase 9 signaling in young individuals with fragile X syndrome. Previous research has indicated that these biomarkers play crucial roles in the pathophysiology of fragile X syndrome., Design: A double-blind placebo-controlled parallel-group flexible-dose forced titration design., Methods: Blood samples for biomarkers were collected during the FXLEARN at baseline and subsequent visits (1- and 8-month visits). Biomarker analyses included fragile X messenger ribonucleoprotein-1 genotyping by Southern blot and PCR approaches, fragile X messenger ribonucleoprotein-1 mRNA levels determined by PCR, matrix metalloproteinase 9 levels' detection using a magnetic bead panel, and targets of the Akt/mTOR signaling pathway with their phosphorylation levels detected., Results: This research revealed that administering AFQ056 does not affect the expression levels of the investigated blood biomarkers in young children with fragile X syndrome., Conclusion: Our findings of the lack of association between clinical improvement and biomarkers' levels in the treatment group are in line with the lack of benefit observed in the FXLEARN study. These findings indicate that AFQ056 does not provide benefits as assessed by primary or secondary endpoints., Registration: ClincalTrials.gov NCT02920892., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dragana Protic has received funding from The Science Fund of the Republic of Serbia and the FRAXA Research Foundation for carrying out studies on Fragile X Syndrome. Flora Tassone has received funding from Zynerba and Azrieli Foundation for carrying out studies on Fragile X Syndrome. Elizabeth Berry-Kravis has received funding from Acadia, Biogen, BioMarin, Erydel, GeneTx/Ultragenyx, Ionis, Jaguar, Kisbee, Neuren, Neurogene, Orphazyme/Kempharm/Zevra, PTC Therapeutics, Roche, Taysha, Tetra/Shionogi, Yamo, Zynerba, and Mallinckrodt Pharmaceuticals, for consulting or on clinical trials in genetic neurological disorders, all funds directed to Rush University Medical Center. 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) 2024.)

We study the coupling between time-dependent Darcy-Brinkman and the Darcy equations at the microscale subjected to inhomogeneous body forces and initial conditions to describe a double porosity problem. We derive the homogenized governing equations for this problem using the asymptotic homogenization technique, and as macroscopic results, we obtain a coupling between two Darcy equations, one of which with memory effects, with mass exchange between phases. The memory effects are a consequence of considering the time dependence in the Darcy-Brinkman equation, and they allow us to study in more detail the role of time in the problem under consideration. After the formulation of the model, we solve it in a simplified setting and we use it to describe the movement of fluid within a vascularized lymph node., Competing Interests: We declare we have no competing interests., (© 2024 The Authors.)

Introduction: Total thyroidectomy (TT) and central neck dissection (CND) had a significant effect on the reduction of local recurrence compared with TT alone. Lateral Neck Dissection (LND) was performed in all the cases with therapeutic intent. The suspicion of nodal recurrence is provided by the appearance of one or more enlarged nodes in the central and/or laterocervical compartment during the follow up period., Methods: From January 2018 to November 2023, 16 patients at the University General Surgery unit of the Polyclinic of Foggia underwent reoperation due to nodal recurrence after previously undergoing total thyroidectomy with central and lateral cervical dissection., Results: All surgical interventions were approached with intraoperative ultrasound performed by the operating surgeon. In all cases, ultrasound identification of the suspicious lymph node led to histological confirmation of malignancy. In only two cases it was necessary to carry out an extemporaneous intraoperative histological examination. No complications were recorded during the operations., Conclusions: Surgical reintervention in patients with nodal recurrence is challenging and requires an assessment by members of the interdisciplinary team. The ideal method should be economically convenient, easy to practice, with a quick learning curve, easily reproducible, and safe for patients. Intraoperative, ultrasound-guided, is a safe and effective technique. It facilitates tumor localization and removal, especially in patients requiring re-operative neck surgery., 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., (© 2024 Pacilli, Pavone, Quazzico, Fersini, Ambrosi and Tartaglia.)

Background: Literature suggests colonic resection and primary anastomosis (RPA) instead of Hartmann's procedure (HP) for the treatment of left-sided colonic emergencies. We aim to evaluate the surgical options globally used to treat patients with acute left-sided colonic emergencies and the factors that leading to the choice of treatment, comparing HP and RPA., Methods: This is a prospective, international, multicenter, observational study registered on ClinicalTrials.gov. A total 1215 patients with left-sided colonic emergencies who required surgery were included from 204 centers during the period of March 1, 2020, to May 31, 2020. with a 1-year follow-up., Results: 564 patients (43.1%) were females. The mean age was 65.9 ± 15.6 years. HP was performed in 697 (57.3%) patients and RPA in 384 (31.6%) cases. Complicated acute diverticulitis was the most common cause of left-sided colonic emergencies (40.2%), followed by colorectal malignancy (36.6%). Severe complications (Clavien-Dindo ≥ 3b) were higher in the HP group (P < 0.001). 30-day mortality was higher in HP patients (13.7%), especially in case of bowel perforation and diffused peritonitis. 1-year follow-up showed no differences on ostomy reversal rate between HP and RPA. (P = 0.127). A backward likelihood logistic regression model showed that RPA was preferred in younger patients, having low ASA score (≤ 3), in case of large bowel obstruction, absence of colonic ischemia, longer time from admission to surgery, operating early at the day working hours, by a surgeon who performed more than 50 colorectal resections., Conclusions: After 100 years since the first Hartmann's procedure, HP remains the most common treatment for left-sided colorectal emergencies. Treatment's choice depends on patient characteristics, the time of surgery and the experience of the surgeon. RPA should be considered as the gold standard for surgery, with HP being an exception., (© 2024. The Author(s).)

Background: Robotic bariatric surgery serves as an alternative to laparoscopy. The technology provides the surgeon with an accurate three-dimensional view, allowing complex maneuvers while maintaining full control of the operating room., Hypothesis: We report our experience with this innovative surgery compared with laparoscopy during Roux-en-Y gastric bypass to demonstrate its safety and feasibility. The aim of this study is to evaluate potential differences between the robotic and laparoscopic techniques., Materials and Methods: Our study retrospectively identified 153 consecutive obese patients who underwent either laparoscopic or robotic gastric bypass (RGB) procedures over a 2-year period at the Department of Medical and Surgical Sciences, University of Foggia. Data on demographics, operative time, conversion rate, length of hospital stay, and mortality were collected and compared between two groups of patients: 82 patients who underwent laparoscopic procedures and 71 who underwent robotic procedures., Results: We analyzed 153 patients who underwent gastric bypass with a mean age of 42.58 years, of whom 74 were female; 71 were treated with a robotic approach and 82 with a laparoscopic approach. The mean operative time was 224.75 ± 10.4 min for RGB (including docking time) and 101.22 min for laparoscopic gastric bypass (LGB) ( p  < 0.05), which is statistically significant. The median length of stay was 4.1 days for the RGB group and 3.9 days for the LGB group ( p  = 0.89). There is only one conversion to laparoscopy in the RGB group. We observed only one case of postoperative complications, specifically one episode of endoluminal bleeding in the laparoscopic group, which was successfully managed with medical treatment. No mortality was observed in either group., Conclusion: The statistical analysis shows to support the robotic approach that had a lower incidence of complications but a longer operative duration. Based on our experience, the laparoscopic approach remains a technique with more haptic feedback than the robotic approach, making surgeons feel more confident.This study has been registered on ClinicalTrial.gov Protocol Registration and Results System with this ID: NCT05746936 for the Organization UFoggia (https://clinicaltrials.gov/ct2/show/NCT05746936)., 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., (© 2024 Pavone, Pacilli, Gerundo, Quazzico, Ambrosi and Tartaglia.)

Background: Various factors influence treatment and outcomes in tibial plateau fractures. Bone defects are among them. Many materials have been proposed to address this problem: allograft, bone-cements and various bone substitutes (BSM). Cal-Cemex (β-tricalciophosphate and polymethylmethacrylate) is a new hybrid bi-component BSM. A retrospective multicenter study was conducted based on the clinical experience of three European Hospitals, to demonstrate its clinical effectiveness, versatility and safety., Materials and Methods: From December 2016 to March 2022, 45 displaced tibial plateau fractures were treated with internal fixation and augmentation using Cal-Cemex. The average age was 55.9 years. According to Schatzker classification, we included 13 type II, 24 type III, 3 type V and 4 type VI fractures. The postoperative follow-up (FU) consisted of clinical and radiological examinations at 6 and 12 weeks and 1 year after surgery. A CT scan was performed preoperatively and 1 year after surgery. Full weight bearing was permitted after less than 6 weeks. Clinical data were collected from patient charts, while functional data were evaluated using the Rasmussen knee function score, the KOOS score and the Hospital for Special Surgery knee rating score (HSS), to evaluate the range of motion, axis and functionality of the knee., Results: The average FU was 42.8 months. CT scans taken at 1 year demonstrated a good surface osteointegration without radiolucent lines or osteolysis with good evidence of interdigitation and even bone ingrowth. At 1-year FU, the mean Rasmussen score was 24.7, the mean KOOS score was 90.7 and the mean HSS was 89.9 and the average full weight-bearing period 34.9. No patients had hardware failure or fracture secondary displacement., Discussion: Cal-Cemex combines biological features and good mechanical performances. It guarantees biocompatibility and osteoconductivity, although it is not fully reabsorbable; β-tricalciophosphate component gives macro- and microporosity that allow fluids to penetrate inside the material, to stimulate bone ingrowth., Conclusions: The study suggests that Cal-Cemex is an option for tibial plateau fractures, where augmentation and support are necessary for early full weight bearing. The absence of major complications, ease of application, the possibility to cut and perforate this material support its extensive use in bone augmentation for trauma cases., (© 2023. The Author(s).)

The presence of an additional X or Y chromosome (sex chromosome trisomies, SCT) is associated with an increased risk for neurodevelopmental difficulties, including socio-emotional problems, across the life span. Studying emotion regulation in young children with SCT could signal deviations in emotional development that serve as risk markers to guide clinical care. This study explored the presence and variety of emotion regulation strategies in 75 SCT children and 81 population-based controls, aged 1-7 years, during a frustration-inducing event in which physiological (heart rate) and observational data (behavioral responses) were collected. Children with SCT were equally physiologically aroused by the event as compared to controls. However, they showed more emotion regulation difficulties in terms of behavior compared to controls that were not explicable in terms of differences in general intellectual functioning. Specifically, they had a more limited range of behavioral alternatives and tended to rely longer on inefficient strategies with increasing age. The field of practice should be made aware of these early risk findings regarding emotion regulation in SCT, which may potentially lay the foundation for later socio-emotional problems, given the significant impact of emotion regulation on child and adult mental health outcomes. The current results may help to design tailored interventions to reduce the impact of the additional sex chromosome on adaptive functioning, psychopathology, and quality of life.

Conditions related to cardiometabolic disease, including metabolic syndrome and type 2 diabetes, are common among men with Klinefelter syndrome (KS). The molecular mechanisms underlying this aberrant metabolism in KS are largely unknown, although there is an assumption that chronic testosterone deficiency plays a role. This cross-sectional study compared plasma metabolites in 31 pubertal adolescent males with KS to 32 controls of similar age (14 ± 2 years), pubertal stage, and body mass index z-score of 0.1 ± 1.2 and then between testosterone-treated (n = 16) and untreated males with KS. The plasma metabolome in males with KS was distinctly different from that in controls, with 22% of measured metabolites having a differential abundance and seven metabolites nearly completely separating KS from controls (area under the curve > 0.9, P < 0.0001). Multiple saturated free fatty acids were higher in KS, while mono- and polyunsaturated fatty acids were lower, and the top significantly enriched pathway was mitochondrial β-oxidation of long-chain saturated fatty acids (enrichment ratio 16, P < 0.0001). In contrast, there were no observed differences in metabolite concentrations between testosterone-treated and untreated individuals with KS. In conclusion, the plasma metabolome profile in adolescent males with KS is distinctly different from that in males without KS independent of age, obesity, pubertal development, or testosterone treatment status and is suggestive of differences in mitochondrial β-oxidation.

The 3rd International Workshop on Klinefelter Syndrome, Trisomy X, and 47,XYY syndrome was held in Leiden, the Netherlands, on September 12-14, 2022. Here, we review new data presented at the workshop and discuss scientific and clinical trajectories. We focus on shortcomings in knowledge and therefore point out future areas for research. We focus on the genetics and genomics of supernumerary sex chromosome syndromes with new data being presented. Most knowledge centre specifically on Klinefelter syndrome, where aspects on testosterone deficiency and the relation to bone, muscle and fat were discussed, as was infertility and the treatment thereof. Both trisomy X and 47,XYY syndrome are frequently affected by infertility. Transitioning of males with Klinefelter syndrome was addressed, as this seemingly simple process in practise is often difficult. It is now realized that neurocognitive changes are pervasive in all supernumerary sex chromosome syndromes, which were extensively discussed. New intervention projects were also described, and exciting new data concerning these were presented. Advocacy organizations were present, describing the enormous burden carried by parents when having to explain their child's specific syndrome to most professionals whenever in contact with health care and education systems. It was also pointed out that most countries do not have health care systems that diagnose patients with supernumerary sex chromosome syndromes, thus pinpointing a clear deficiency in the current genetic testing and care models. At the end of the workshop, a roadmap towards the development of new international clinical care guidelines for Klinefelter syndrome was decided.

Introduction: The aim of this study is to analyze the progress of hospitalizations and how the emergency operations in our Department of Medical and Surgical Sciences of the Foggia Hospital have changed qualitatively and quantitatively from pre-Covid-19 to today. Methods: Our cohort-study was conducted by analyzing four groups of patients admitted in emergency to our department from 2019 to 2022. Results: We observed a total of 150 patients for the group 1, 25 patients for the group 2, 71 patients for the group 3 and 110 for the group 4, of these 20 were emergency admission during 2019, 16 during 2020, 31 during 2021 and 10 during 2020 (p 0.05); 130 were elective admission during 2019, 9 during 2020, 40 during 2021 and 100 during 2022 (p 0.05). Of the emergency admissions 11 were operated during the no covid period in 2019, 14 during 2020, 29 during 2021, 6 during 2022. Conclusions: The contraction of hospitalizations for urgent and emergency conditions during the first lockdown has been accompanied by positive implications. The measures employed in hospitals to contain the infection determined a reduction in COVID cases, allowing the nearly complete resumption of the surgical activity provided in the pre-COVID era., (Celsius.)

Background: Fragile X syndrome (FXS) is associated with dysregulated endocannabinoid signaling and may therefore respond to cannabidiol therapy., Design: CONNECT-FX was a double-blind, randomized phase 3 trial assessing efficacy and safety of ZYN002, transdermal cannabidiol gel, for the treatment of behavioral symptoms in children and adolescents with FXS., Methods: Patients were randomized to 12 weeks of ZYN002 (250 mg or 500 mg daily [weight-based]) or placebo, as add-on to standard of care. The primary endpoint assessed change in social avoidance (SA) measured by the Aberrant Behavior Checklist-Community Edition FXS (ABC-C FXS ) SA subscale in a full cohort of patients with a FXS full mutation, regardless of the FMR1 methylation status. Ad hoc analyses assessed efficacy in patients with ≥ 90% and 100% methylation of the promoter region of the FMR1 gene, in whom FMR1 gene silencing is most likely., Results: A total of 212 patients, mean age 9.7 years, 75% males, were enrolled. A total of 169 (79.7%) patients presented with ≥ 90% methylation of the FMR1 promoter and full mutation of FMR1. Although statistical significance for the primary endpoint was not achieved in the full cohort, significant improvement was demonstrated in patients with ≥ 90% methylation of FMR1 (nominal P = 0.020). This group also achieved statistically significant improvements in Caregiver Global Impression-Change in SA and isolation, irritable and disruptive behaviors, and social interactions (nominal P-values: P = 0.038, P = 0.028, and P = 0.002). Similar results were seen in patients with 100% methylation of FMR1. ZYN002 was safe and well tolerated. All treatment-emergent adverse events (TEAEs) were mild or moderate. The most common treatment-related TEAE was application site pain (ZYN002: 6.4%; placebo: 1.0%)., Conclusions: In CONNECT-FX, ZYN002 was well tolerated in patients with FXS and demonstrated evidence of efficacy with a favorable benefit risk relationship in patients with ≥ 90% methylation of the FMR1 gene, in whom gene silencing is most likely, and the impact of FXS is typically most severe., Trial Registration: The CONNECT-FX trial is registered on Clinicaltrials.gov (NCT03614663)., (© 2022. The Author(s).)

Background: Indocyanine green (ICG) can be injected into the human bloodstream and it allows us to show stomach vascularity in real time. The aim of our study is to observe the preliminary results of the application of indocyanine green fluorescence (IGF) during laparoscopic Roux-en-Y Gastric Bypass (RYGB in our center and how the perfusion of the gastro-jejunal anastomosis affects the onset of fistula., Materials and Methods: 30 consecutive patients underwent RYGB with ICG fluorescence angiography at our center from January 2020 to December 2021.5 ml of ICG were then injected intravenously to identify the blood supply of the stomach and the gastro-jejunal anastomosis. The UIN for ClinicalTrial.gov Protocol Registration and Results System is: NCT05476159 for the Organization UFoggia., Results: In the RYGB tested with ICG, we all have adequate perfusion but despite this a methylene blue test was positive and allowed us to reinforce the suture of the gastro-jejunal anastomosis., Conclusion: Intraoperative ICG testing during laparoscopic RYGB may be helpful in determining which patients are at an increased risk for leakage but multiple factors concur to the pathophysiology and the incidence of gastric fistula not only the perfusion., Competing Interests: GIOVANNA PAVONE, ALBERTO FERSINI, MARIO PACILLI, PASQUALE CIANCI, ANTONIO AMBROSI, NICOLA TARTAGLIA. declare no conflict of interests., (© 2022 The Authors.)

Background: Duodenal perforation is a life-threatening condition and ideal approaches for the management of duodenal perforations are nowadays unclear, so numerous variables must be considered. Peptic ulcer disease is the most common disease determining a duodenal perforation, however, there may be other less common causes. Methods: We retrospectively analyzed all the patients who presented at our Division of General Surgery for a Duodenal Perforation, from September 2018 to December 2019. We focused on patients requiring a tube duodenostomy. Five patients were included in this study. Results: Five patients suffering from a duodenal perforation were analyzed and their data collected. All patients were treated with tube duodenostomy, pyloric exclusion and omega loop gastro-enteroanastomosis. The duodenostomy was removed four weeks after surgery. All patients suffered postsurgical complications ranging from wound infection to pneumonitis; the incidence of severe complications was greater in the older patients. We did not record any deaths four months after the operation. Conclusions: The tube duodenostomy is an old and dated procedure but simple to implement, which may require an increase in post-operative hospitalization, but which subsists as an effective and safe way to treat patients in critical conditions., (Celsius.)

Bleeding after total thyroidectomy remains a rare event that affects early postoperative morbidity, occurring in 0.3% to 4.2% of cases. Intraoperative bleeding is an unpleasant complication, and it is often easily manageable, although postoperative bleeding may represent a life-threatening condition for the patient. The purpose of our study was to clarify the role of the Valsalva manoeuvre to reduce postoperative bleeding. Between January 2019 to February 2022, 250 consecutive patients were listed for thyroid surgery at our surgical department. The study cohort consisted of 178 patients, divided into two groups based on the execution of the Valsalva manoeuvre. There was no difference in the duration of surgery between groups. Group B had fewer reinterventions for bleeding. Group A had a significantly greater volume of drainage output than Group B. Cervical haematoma can compromise a patient's life, so bleeding control is crucial. Our results show that using a simple and safe Valsalva manoeuvre can improve the postoperative course with a significant reduction in drainage output, but does not prevent the risk of reoperation for hemorrhage.

Background: Stay-at-home orders in response to the Coronavirus 2 (SARS-CoV-2) pandemic have forced abrupt changes to daily routines. The aim of this study is to describe the behavior of lifestyles of individuals with obesity on the waiting list for bariatric surgery in the Department of Medical and Surgical Sciences of University of Foggia during the COVID-19 pandemic., Materials and Methods: From June 2020 to December 2020 an online survey format was administered to all the patients (n = 52) enrolled for bariatric surgery subjects with obesity, to obtain information about the COVID-19 pandemic's impact on patients with obesity starting 9 March 2020 until 18 May 2020., Results: Our data showed that 58% of patients stated that the pandemic negatively affected their mood, 60% of patients confirmed that they changed their dietary behaviors during the stay-at-home period, as they consumed more unhealthy foods or spent less time cooking home cooked meals. In addition, 71% of patients stated that the closure of the gyms worsened their obesity condition and their mental well-being with an increase of a feeling of anxiety., Conclusions: Results showed that the COVID-19 pandemic has had a significant impact on health behaviors, including quality of life, mental health physical activity, weight maintenance, and consumption of sweets in obese patients.

Background: Indocyanine green (ICG) when injected intravenously into the bloodstream allows us to show stomach vascularity in real time. The aim of our study was to observe the preliminary results of the application of indocyanine green fluorescence (IGF) during laparoscopic sleeve gastrectomy (LSG) in our center and how the perfusion of the staple line of the stomach affects the onset of fistula., Materials and Methods: 82 patients underwent LSG with ICG fluorescence angiography at our center from January 2020 to December 2021. 5 ml of ICG was injected intravenously to identify the blood supply of the stomach, carefully assessing the angle of His., Results: In the ICG-tested LSG, we recorded adequate perfusion in all patients but one: the leakage rate was 1.2%. This data is inferior to the non-tested patients' group., Conclusion: Intraoperative ICG testing may be helpful in determining which patients are at an increased risk for leakage but there are multiple factors contribute to the pathophysiology and the incidence of gastric fistula not only the perfusion. Trial registration Retrospectively registrated., (© 2022. The Author(s).)

Background: Bariatric surgery procedures are the most successful and durable treatment for morbid obesity. Hemorrhage represents a life-threatening complication, occurring in 1.3-1.7% of bariatric surgeries., Materials and Methods: We examined patients undergoing Bariatric Surgery from July 2017 to June 2020 (Group A) and those operated from July 2020 to June 2022 (Group B) in our Department. Starting from July 2020 we have implemented intraoperative measures to prevent postoperative bleeding, increasing mean arterial pressure (MAP) by 30% compared to preoperative and reducing the pneumoperitoneal pressure of CO 2 to 8 mmHg in the last 15 min of the operation., Results: The study gathered 200 patients divided into the two described groups. The mean age of Group A is 44 ± 8.49 and 43.73 ± 9.28. The mean preoperative BMI is 45.6 kg/m 2  ± 6.71 for Group A and 48.9 ± 7.15 kg/m 2 for Group B. Group A recorded a mean MAP of 83.06 ± 18.58 mmHg and group B a value of 111.88 ± 12.46 mmHg (p value < 0.05 and z-score is 4.15226 and the value of U is 13,900). We observed 9 cases of bleeding in group A, most of them being treated with medical therapy and transfusions; only 1 hemodynamically unstable patient underwent re-laparoscopy. We reported only 2 cases of bleeding in group B, one of which required blood transfusions., Conclusion: From our study we can conclude that increasing mean arterial pressure (MAP) by 30% compared to preoperative and reducing the pneumoperitoneum pressure of CO 2 to 8 mmHg in the last 15 min of the operation led to a decrease in bleeding cases in group B and, most importantly, all the bleedings were easily controllable with medical therapy and/or transfusions. These measures allowed us to reduce postoperative bleeding., (© 2022. The Author(s).)

Background and Objectives : Colon diseases can turn in a clinical emergency with the onset of some important complications. Some critical conditions are more common in aged patients because they are frailer. The aim of this study is to examine patients over 80 years of age who are undergoing emergency colorectal surgery, and evaluating the aspects associated with post-operative complications and other problems in the short term. Methods : From November 2020 to February 2022, we included 32 consecutive patients older than 80 undergoing emergency surgery due to colon diseases. We collected and analysed all demographic and operative data, and then applied CR-POSSUM score and correlated this with postoperative hospital stay and the onset of postoperative complications according to the Clavien Dindo classification. Results: Postoperative factors were selectively evaluated based on the clinical scenario and different colic pathologies. There were no statistically significant differences, in terms of postoperative hospital stay, postoperative complications, reoperation rate and 30-day mortality. The number of cases of blood transfusions was significant and was more numerous in cases of intestinal perforation and bleeding cases. The value of the Operative Severity Score in bowel perforations was significantly higher. Conclusions : The use of a score to stratify the risk is a useful tool, especially in elderly patients undergoing emergency surgery. The CR-POSSUM score was important for predicting morbidity in our study. Emergency manifestations of colon diseases in the elderly show higher morbidity and mortality rates. The effect of age on outcome is a concept that needs to be emphasized, so further investigation is needed.

Background: About 1:650-1000 children are born with an extra X or Y chromosome (47,XXX; 47,XXY; 47,XYY), which results in a sex chromosome trisomy (SCT). This international cross-sectional study was designed to investigate gaze towards faces and affect recognition during early life of children with SCT, with the aim to find indicators for support and treatment., Methods: A group of 101 children with SCT (aged 1-7 years old; M age = 3.7 years) was included in this study, as well as a population-based sample of 98 children without SCT (M age = 3.7). Eye gaze patterns to faces were measured using an eye tracking method that quantifies first fixations and fixation durations on eyes of static faces and fixation durations on eyes and faces in a dynamic paradigm (with two conditions: single face and multiple faces). Affect recognition was measured using the subtest Affect Recognition of the NEPSY-II neuropsychological test battery. Recruitment and assessment took place in the Netherlands and the USA., Results: Eye tracking results reveal that children with SCT show lower proportion fixation duration on faces already from the age of 3 years, compared to children without SCT. Also, impairments in the clinical range for affect recognition were found (32.2% of the SCT group scored in the well below average range)., Conclusions: These results highlight the importance to further explore the development of social cognitive skills of children with SCT in a longitudinal design, the monitoring of affect recognition skills, and the implementation of (preventive) interventions aiming to support the development of attention to social important information and affect recognition., (© 2022. The Author(s).)

Background: Fragile X syndrome is characterized by a myriad of physical features, behavioral features, and medical problems. Commonly found behavioral features are hyperactivity, anxiety, socialization difficulties, and ASD. There is also a higher incidence than in the general population of strabismus, otitis media, and mitral valve prolapse. In addition, one of the most common medical problems associated with FXS is an increased risk of seizures. A subset of individuals carrying the full mutation of the FMR1 gene and diagnosed with fragile X syndrome (FXS) are reported to experience seizures, mostly during the first 10 years of their life span., Methods: As part of a larger project to identify genetic variants that modify the risk of seizures, we collected clinical information from 49 carriers with FXS who experienced seizures and 46 without seizures. We compared seizure type and comorbid conditions based on the source of data as well as family history of seizures., Results: We found that the concordance of seizure types observed by parents and medical specialists varied by type of seizure. The most common comorbid condition among those with seizures was autism spectrum disorder (47% per medical records vs. 33% per parent report compared with 19% among those without seizures per parent report); the frequency of other comorbid conditions did not differ among groups. We found a slightly higher frequency of family members who experienced seizures among the seizure group compared with the nonseizure group., Conclusion: This study confirms previously reported features of seizures in FXS, supports additional genetic factors, and highlights the importance of information sources, altogether contributing to a better understanding of seizures in FXS., (© 2022 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

Sex chromosomal trisomies (SCT) are associated with impairments in executive functions in school-aged children, adolescents, and adults. However, knowledge on preschool development of executive functions is limited but greatly needed to guide early intervention. The current study examined emerging executive functions in young children with SCT. Participants were 72 SCT children and 70 population-based controls, aged 3-7 years, who completed a neurocognitive assessment of both global executive function (MEFS) and verbal executive function skills (NEPSY Word Generation). Caregivers completed the Behavior Rating Inventory of Executive Function (BRIEF) questionnaire to capture real-world behavioral manifestations of impairments in executive functions. Results showed that impairments were significantly more prevalent in SCT than in controls and already present from 3 years, specifically verbal executive functions and working memory. Broader more pronounced impairments were found in older children with SCT. Age was significantly related to executive functions, but specific domains showed different relations with age. For example, deficits in planning and organizing remained evident with older age in SCT whereas it declined with age in controls. Impairments in executive functions were present across different levels of intelligence. Already at an early age, impairments across executive functions should be considered part of the neurodevelopmental profile of SCT, which appear more prominent at later age. Future studies should investigate developmental pathways of executive functions in SCT, given its relevance in cognitive, social, and emotional development. Executive functions should be screened and monitored in children with SCT and could be an important target of preventive intervention., (© 2022 The Authors. Genes, Brain and Behavior published by International Behavioural and Neural Genetics Society and John Wiley & Sons Ltd.)

Background: The staple line gastric leak (GL) is estimated to be the most serious complication of the sleeve gastrectomy. The use of indocyanine green (ICG) has been introduced in minimally invasive surgery to show the vascularization of the stomach in real time and its application to the gastroesophageal junction (GE) during Laparoscopic Sleeve Gastrectomy (LSG) seems very promising., Case Presentation: We present the case of a 40-year-old female underwent laparoscopic sleeve gastrectomy. Intraoperative indocyanine green test showed a small dark area in the proximal third of the staple line reinforced with fibrin glue. Two weeks later the patient presented to the emergency room (ED) with abdominal pain, fever, vomiting, intolerance to oral intake and the evidence of a leak on the abdomen Computer Tomography (CT). The UIN for ClinicalTrial.gov Protocol Registration and Results System is: NCT05337644 for the Organization UFoggia., Conclusions: This case report shows that intraoperative ICG test can be helpful in determining which patients are at greater risk of the leak and, more importantly, the cause of the leak but further tests are needed to determine if the ICG predicts leak due to ischemia., (Copyright © 2022. Published by Elsevier Ltd.)

Lung cancer is the most lethal cancer: it has a significant incidence and low survival rates. Lifestyle has an important influence on cancer onset and its progression, indeed environmental factors and smoke are involved in cancer establishment, and in lung cancer. Physical activity is a determinant in inhibiting or slowing lung cancer. Certainly, the inflammation is a major factor responsible for lung cancer establishment. In this scenario, regular physical activity can induce anti-inflammatory effects, reducing ROS production and stimulating immune cell system activity. On lung function, physical activity improves lung muscle strength, FEV1 and forced vital capacity. In lung cancer patients, it reduces dyspnea, fatigue and pain. Data in the literature has shown the effects of physical activity both in in vivo and in vitro studies, reporting that its anti-inflammatory action is determinant in the onset of human diseases such as lung cancer. It has a beneficial effect not only in the prevention of lung cancer, but also on treatment and prognosis. For these reasons, it is retained as an adjuvant in lung cancer treatment both for the administration and prognosis of this type of cancer. The purpose of this review is to analyze the role of physical activity in lung cancer and to recommend regular physical activity and lifestyle changes to prevent or treat this pathology.

Physical activity (PA) and sport play an essential role in promoting body development and maintaining optimal health status both in the short and long term. Despite the benefits, a long-lasting heavy training can promote several detrimental physiological changes, including transitory immune system malfunction, increased inflammation, and oxidative stress, which manifest as exercise-induced muscle damages (EIMDs). Meat and derived products represent a very good source of bioactive molecules such as proteins, lipids, amino acids, vitamins, and minerals. Bioactive molecules represent dietary compounds that can interact with one or more components of live tissue, resulting in a wide range of possible health consequences such as immune-modulating, antihypertensive, antimicrobial, and antioxidative activities. The health benefits of meat have been well established and have been extensively reviewed elsewhere, although a growing number of studies found a significant positive effect of meat molecules on exercise performance and recovery of muscle function. Based on the limited research, meat could be an effective post-exercise food that results in favorable muscle protein synthesis and metabolic performance.

Background: The main adverse effect is gastroesophageal reflux disease (GERD), with concern on the development of Barrett's esophagus and esophageal adenocarcinoma in the long term. However, the relationship between SG and GERD is complex. The aim of this study is to systematically evaluate all published data existing in the literature to evaluate the effect of sleeve gastrectomy on GERD, esophagitis, BE in order to clarify the long-term clinical sequelae of this procedure., Materials and Methods: This systematic review was conducted in accordance with the guidelines for Preferred Reporting Items for Systematic Review. The work has been reported in line with the PRISMA criteria [19]. We evaluated the quality and risk of bias of this Systematic Review using AMSTAR 2 checklist [20]. Published studies that contained outcome data for primary sleeve gastrectomy associated with the primary and secondary outcomes listed below were included. The UIN for ClinicalTrial.gov Protocol Registration and Results System is: NCT05178446 for the Organization UFoggia., Results: 49 articles were eligible for inclusion that met the following criteria: publications dealing with patients undergoing laparoscopic SG, publications describing pre- and postoperative GERD symptoms and/or esophageal function tests, articles in English, human studies and text complete available., Conclusions: We have controversial data on LSG and GERD in the literature as there is a multifactorial relationship between LSG and GERD. The most recent studies have shown satisfactory control of postoperative reflux in most patients and low rates of de novo GERD. These data are leading to wider acceptance of LSG as a bariatric procedure even in obese patients with GERD., Competing Interests: GIOVANNA PAVONE, NICOLA TARTAGLIA, ALESSANDRO PORFIDO, PIERCARMINE PANZERA, MARIO PACILLI, ANTONIO AMBROSI declare no conflict of interests., (© 2022 The Authors.)

Lung cancer is a devastating disease with a high incidence and low survival rates, so recent studies have focused on analyzing the risk factors that might prevent this disease from developing or have protective/therapeutic effects. Nutrition is an important key factor in the prevention and treatment of lung cancer. Various factors appear to be involved in the development of the latter, such as cigarette smoking or certain external environmental factors. The increase in oxidative stress is therefore an integral part of the carcinogenesis process. The biological role of bioactive factors derived from adipose tissue, mainly adipokines, is implicated in various cancers, and an increasing body of evidence has shown that certain adipocytokines contribute to the development, progression and prognosis of lung cancer. Not all adipokines stimulate tumor growth; in fact, adiponectin inhibits carcinogenesis by regulating both cell growth and the levels of inflammatory cytokines. Adiponectin expression is deregulated in several cancer types. Many nutritional factors have been shown to increase adiponectin levels and therefore could be used as a new therapeutic strategy for combating lung cancer. In addition, foods with antioxidant and anti-inflammatory properties play a key role in the prevention of many human diseases, including lung cancer. The purpose of this review is to analyze the role of diet in lung cancer in order to recommend dietary habit and lifestyle changes to prevent or treat this pathology.

Background: Despite weak evidence, antibiotic prophylaxis prior to endoscopic ultrasound-guided through-the-needle biopsy (EUS-TTNB) of pancreatic cystic lesions (PCLs) is routinely used in clinical practice. We aim to compare a group of patients treated with antibiotics before EUS-TTNB of PCLs and a group who did not undergo antimicrobial prophylaxis., Methods: Out of 236 patients with pancreatic cystic lesions referred to two high-volume centers between 2016 and 2021, after propensity score matching, two groups were compared: 98 subjects who underwent EUS-TTNB under antibiotic prophylaxis and 49 subjects without prophylaxis., Results: There was no difference in terms of baseline parameters between groups. Final diagnosis was serous cystadenoma in 36.7% of patients in the group not treated with prophylaxis and in 37.7% of patients in the control group, whereas IPMN and mucinous cystadenoma were diagnosed in 3 (6.1%) and 16 (32.6%) versus 6 (6.1%) and 32 (32.6%) patients in the two groups, respectively ( p = 0.23). Overall, the adverse event rate was 6.1% in the group not treated with antibiotic prophylaxis and 5.1% in the control group ( p = 0.49). Only a single infectious adverse event occurred in each group ( p = 0.48). The diagnostic yields were 89.7% and 90.8% in the two groups ( p = 0.7), and the diagnostic accuracy rate was 81.6% in both groups ( p = 1.0)., Conclusions: Prophylactic antibiotics do not seem to influence the risk of infection, and their routine use should be discouraged.

Introduction: Primary Hyperparathyroidism (PHPT) is a systemic pathology caused by an excessive secretion of parathyroid hormone. Parathyroidectomy is the treatment of choice in PHPT, and the success of surgery is based on precise localization of the abnormal parathyroid gland. Preoperative diagnosis makes use of imaging techniques and functional examinations, however these are insufficient in some cases for the precise location of the pathological gland. Therefore the need arises for an intraoperative localization technique., Materials and Methods: We have retrospectively analyzed 20 consecutive patients with PHPT undergoing parathyroidectomy from April 2019 to September 2021, and divided them in two groups, in base of the use of Indocyanine Green (ICG) fluorescence during the surgery., Results: Of the twenty patients considered in the two groups, all received a preoperative ultrasound evaluation, while second level examinations were reserved for the more difficult cases, with small volume parathyroid adenomas. In the group where the fluorescence method was employed, fluorescence was especially useful in doubtful cases, allowing easier identification of the parathyroid adenoma and consequently a reduction of time and operatory risks. In two procedures using Indocyanine green, a fluorescence signal was weak., Conclusions: ICG represents a convenient and safe way to detect parathyroid adenomas. We found that ICG fluorescence was very useful in all patients with non-localizing preoperative imaging studies. However further investigation is needed, to demonstrate how ICGfluorescence could be a useful localization method during parathyroid surgery., Key Words: Endocrine surgery, Indocyanine green, Parathyroid surgery.

Background: The aim of this study is to evaluate the impact of the actual size and area of the remnant stomach, as measured by Upper gastrointestinal tract radiography, on weight loss after sleeve gastrectomy., Materials and Methods: From May 2017 to December 2019, 56 patients with morbid obesity were admitted to the Department of Medical and Surgical Sciences, University of Foggia and underwent laparoscopic sleeve gastrectomy., Results: 56 patients underwent sleeve gastrectomy with a mean age of 43,5 ± 11 years of which 40 were female. The mean Excess Weight Loss (EWL) at 1 month was 24,09 ± 15,04%, at 6 months was 27,07 ± 19,55% and at 12 months was 69,9 ± 23,7%. The mean Excess Body Mass Index Loss (EBMIL) at 1 month was 23,1 ± 12,5%, at 6 months was 56,6 ± 19,7% and at 12 months was 69,7 ± 23,7%.The EWL % was correlated with the residual stomach area (RSA) at 1 month (r = -0,242 p = 0,072), at 6 months (r = -0,249 p = 0,064) and at 12 months (r = -0,451 p = 0,0005).The EBMIL % was correlated with the RSA at 1 month (r = -0,270; p = 0,043), at 6 months (r = -0,270; p = 0,043) andat 12 months (r = -0,46; p = 0,0004)., Conclusion: A greater postoperative EWL % was correlated with a smaller RSA and this resulted in a statistically significant change at 12 months after surgery., Competing Interests: The authors declare no competing interests., (© 2021 The Authors.)

Introduction Vascular complications of posterior fossa surgery are often deadly although widely preventable through in-depth knowledge of the microsurgical neurovascular anatomy of the infratentorial region and careful surgical planning.   The target of this study is to provide a synoptic overview of the normal anatomy and anatomic variants of the infratentorial neurovascular system, critical to safely operate tumors and neurovascular pathologies of the posterior fossa. Methods Two fresh-frozen and five formalin-fixed cadaveric heads were used. Cervical arteries and internal jugular veins were injected with red and blue latex, respectively. The heads were dissected under a surgical microscope, with magnifications ranging between 3× to 40×, focusing on the infratentorial region. The infratentorial arteries, their collaterals and perforating branches, the brainstem and cerebellar veins, the tentorial venous sinuses, and the relative vascular territories were summarized according to a synoptic approach.    Results The vertebral artery, basilar artery (BA), and posterior cerebral artery (PCA) are the main sources of the arterial supply of the brainstem and cerebellum through the posterior inferior cerebellar artery (PICA), the anterior inferior cerebellar artery (AICA), the superior cerebellar artery (SCA), and the perforating arteries. The perforating arteries of the vertebrobasilar system derive from the PICA, BA, AICA, SCA, and PCA, and provide for a key contribution to the vascularization of the midbrain, pons, medulla oblongata, fourth ventricle, cerebellar and cerebral peduncles, thalamus, hypothalamus, subthalamus, posterior part of the internal capsule, and optic tract. The distal segments and branches of the PCA also add a significant arterial supply to the temporal, occipital, and parietal lobes. The venous outflow of the posterior fossa is a prerogative of the internal jugular veins via the tentorial venous sinuses. Conclusion A perfect mastery of the arterial, venous, and cisternal anatomy of the infratentorial region is vital for the planning and execution of the whole range of posterior fossa approaches.

Introduction A thorough understanding of skull base anatomy is imperative to perform safely and effectively any skull base approach. In this article, we examine the microsurgical anatomy of the skull base by proposing a modular topographic organization in the median, paramedian, and lateral surgical corridors in relation to transcranial and endoscopic approaches. Methods Five dry skulls were studied focusing on the intracranial and exocranial skull base. Two lines were drawn parallel to the lateral border of the cribriform plate of the ethmoid bone and foramen lacerum, respectively. Lines 1 and 2 delimited the median, paramedian and lateral corridors of the skull base. The bony structures that formed each corridor were carefully reviewed in relation to the planning and execution of the skull base transcranial and endoscopic approaches. Results The midline corridor involves the crista galli, cribriform plate, planum and jugum sphenoidale, chiasmatic sulcus, tuberculum sellae, sellar region, dorsum sellae, clivus, and foramen magnum. The paramedian corridor includes the fovea ethmoidalis, the root of the lesser and greater sphenoid wing, anterior clinoid process, foramen lacerum, the upper half of the petro-occipital suture, and jugular tubercle. The lateral corridors include the orbital plates, sphenoid wings, squamosal and petrous parts of the temporal bone, caudal aspect of the petro-occipital suture, internal auditory canal, jugular foramen, the sulcus of the sigmoid sinus. Conclusion In-depth three-dimensional knowledge of skull base anatomy based on the modular concept of the surgical corridors is critical for the planning and execution of the transcranial and endoscopic approaches.

Introduction Treatment of cranial neurovascular pathology requires a detailed understanding of the brain, head, and neck vasculature. This study aims at a comprehensive overview of the microsurgical anatomy of the anterior cerebral circulation. Methods Five formalin-fixed adult cadaveric heads were used. Common carotid arteries, vertebral arteries, and internal jugular veins were injected with colored latex (red for arteries and blue for veins). The heads were dissected under a surgical microscope with magnifications ranging between 3× to 40× focusing on the anterior circulation. A synoptic approach was used to describe in detail the segments, branches, perforating arteries, veins, and vascular territories of the cerebral arteries and veins. Results The anterior arterial circulation of the brain is provided by the internal carotid artery (ICA), anterior cerebral artery (ACA), middle cerebral artery (MCA), anterior communicating artery (ACoA), and perforating arteries. Perforating arteries of the anterior circulation arise from the ICA, ACA, MCA, ACoA, and posterior communicating artery (PCoA). The distal segments and collateral branches of the ICA, ACA, and MCA give the arterial supply to the largest part of the forebrain, whereas perforating arteries of the anterior circulation are related to the striatum, thalamus, and basal ganglia. The ACoA is the core functional anastomosis between the left and right ICA systems. The external carotid artery provides the vascular supply to the region of the face, head, and neck, and most of the meninges. The internal jugular venous system is composed of the internal and external jugular veins, which constitutes the outflow of the cerebral and facial venous system, respectively. Conclusion Thorough knowledge of the topographic, cisternal, and functional anatomy of the anterior circulation of the brain is critical for surgery of the supratentorial lesions.

Microglia are the first line of defense at the level of the central nervous system (CNS). Phenotypic change in microglia can be regulated by various factors, including the orexin system. Neuroinflammation is an inflammatory process mediated by cytokines, by the lack of interaction between neurotransmitters and their specific receptors, caused by systemic tissue damage or, more often, associated with direct damage to the CNS. Chronic activation of microglia could lead to long-term neurodegenerative diseases. This review aims to explore how tocopherol (vitamin E) and the orexin system may play a role in the prevention and treatment of microglia inflammation and, consequently, in neurodegenerative diseases thanks to its antioxidant properties. The results of animal and in vitro studies provide evidence to support the use of tocopherol for a reduction in microglia inflammation as well as a greater activation of the orexinergic system. Although there is much in vivo and in vitro evidence of vitamin E antioxidant and protective abilities, there are still conflicting results for its use as a treatment for neurodegenerative diseases that speculate that vitamin E, under certain conditions or genetic predispositions, can be pro-oxidant and harmful.

Background and study aims  There is limited evidence on the effectiveness of hemostatic powders in the management of lower gastrointestinal bleeding (LGIB). We aimed to provide a pooled estimate of their effectiveness and safety based on the current literature. Patients and methods  Literature review was based on computerized bibliographic search of the main databases through to December 2020. Immediate hemostasis, rebleeding rate, adverse events, and mortality were the outcomes of the analysis. Pooled effects were calculated using a random-effects model. Results  A total of 9 studies with 194 patients were included in the meta-analysis. Immediate hemostasis was achieved in 95 % of patients (95 % confidence interval [CI] 91.6 %-98.5 %), with no difference based on treatment strategy or bleeding etiology. Pooled 7- and 30-day rebleeding rates were 10.9 % (95 %CI 4.2 %-17.6 %) and 14.3 % (95 %CI 7.3 %-21.2 %), respectively. Need for embolization and surgery were 1.7 % (95 %CI 0 %-3.5 %) and 2.4 % (95 %CI 0.3 %-4.6 %), respectively. Overall, two patients (1.9 %, 95 %CI 0 %-3.8 %) experienced mild abdominal pain after powder application, and three bleeding-related deaths (2.3 %, 95 %CI 0.2 %-4.3 %) were registered in the included studies. Conclusion  Novel hemostatic powders represent a user-friendly and effective tool in the management of lower gastrointestinal bleeding., Competing Interests: Competing interests The authors declare that they have no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Background: Obesity is a risk factor for non-alcoholic steatohepatitis (NASH) and increases the risk of several cancer types including cancers of the liver. Bariatric surgery can provide durable weight loss, but little is known about the later development of hepatocellular carcinoma (HCC) after surgery., Aim: To determine whether bariatric surgery reduces the risk of HCC., Methods: We performed a comprehensive literature search of major databases (from inception to November 2020) to identify studies which assess the incidence and risk of HCC following bariatric surgery. Pooled data were assessed using a random-effects model expressed in terms of odds ratio (OR), incidence rate ratio and 95% confidence interval (CI)., Results: Nine studies (two abstracts and seven full texts) were included for meta-analysis which involved 19 514 750 patients (18 423 546 controls and 1 091 204 bariatric patients). Pooled unadjusted odds ratio (OR) was 0.40 (95% CI: 0.28-0.57) which favoured bariatric surgery, though with high heterogeneity (I 2 : 79%). Using an adjusted model derived from matched cohorts (five studies) yielded an OR of 0.63 (95% CI: 0.53-0.75) with moderate heterogeneity (I 2 : 38%). The pooled rate/1000 person-years was 0.05 (95% CI: 0.02-0.07) in bariatric surgery patients and 0.34 (95% CI: 0.20-0.49) in the control group with an incidence rate ratio of 0.28 (95% CI: 0.18-0.42)., Conclusion: Bariatric surgery is associated with a decreased risk of HCC., (© 2021 John Wiley & Sons Ltd.)

There is limited evidence on the efficacy of lenvatinib in advanced hepatocellular carcinoma (HCC) patients. Aim of this meta-analysis was to compare lenvatinib and sorafenib as first-line treatment. Computerized bibliographic search was performed on main databases through November 2020. The primary outcome was overall survival, whereas survival rate (at 1-, and 2-year), progression-free survival (PFS), tumor response, and severe adverse event rate were the secondary outcomes. Results were expressed in terms of odds ratio (OR) or hazard ratio (HR) and 95% confidence interval (CI). Five studies enrolling 1481 patients were included. No difference in terms of overall survival was detected (HR 0.81, 0.58-1.11) and median survival was 13.4 months (9.38-17.48) in lenvatinib and 11.4 months (8.46-14.47) in sorafenib patients. Lenvatinib led to a significant improvement of PFS (HR 0.67, 0.48-0.94) and median PFS was 5.88 months (3.68-8) in lenvatinib and 4.17 months (3.08-5.25) in sorafenib patients. Lenvatinib determined a considerably higher rate of objective response (33.3%, 23.6%-43% versus 6.5%, 3.5%-9.5%; OR 7.70, 2.99-19.82), and of disease control rate (76.9%, 70.4%-83.5% versus 52.7%, 40.7%-64.6%; OR 2.41, 1.55-3.77). No difference between lenvatinib and sorafenib in terms of severe adverse event rate was observed (OR 1.31, 0.82-2.09). Lenvatinib prolongs progression-free survival as compared to sorafenib in HCC patients, although this result does not translate to a significant survival benefit., Competing Interests: None., (AJTR Copyright © 2021.)

Non-alcoholic steatohepatitis (NASH) is a chronic and progressive form of non-alcoholic fatty liver disease (NAFLD). Its global incidence is increasing which makes NASH an epidemic and a public health threat. Due to repeated insults to the liver, patients are at risk for developing hepatocellular carcinoma (HCC). The progression of NASH to HCC was initially defined according to a two-hit model which involved the development of steatosis, followed by lipid peroxidation and inflammation. However, current research defines a "multi-hit" or "multi-parallel hit" model which synthesizes several contributing pathways involved in progressive fibrosis and oncogenesis. This perspective considers the effects of cellular, genetic, immunologic, metabolic, and endocrine pathways leading up to HCC which underscores the complexity of this condition. This article will provide an updated review of the pathogenic mechanisms leading from NASH to HCC as well as an exploration of the role of biomarkers and screening.

Background: Whether or not the laparoscopic technique has substantial advantages over the mini-laparotomy one for ventriculoperitoneal shunt is still controversial. The present study is a literature review and a meta-analysis about this topic, focused on the duration of surgery, length of stay (LOS), infection rate and rate of distal catheter failure., Methods: An extensive online literature search was performed, followed by a meta-analysis implemented with RevMan 5.0 Cochrane software. For laparoscopy and mini-laparotomy group, odds ratio (OR) and 95% confidence interval (CI) was calculated for distal catheter malposition/obstruction and infection rate. Mean difference was considered for duration of surgery and LOS. Fixed-effect model with a significance < 0.05 was employed. A t-test (p< 0.05) between the groups, also including the non-comparative cohort studies, was performed for each primary endpoint., Results: 18 studies, involving 3361 patients, were selected. Average level of evidence was 3.2 ± 0.7. Primary shunts were 93 % in laparoscopy group and 87 % in mini-laparotomy one (p=0.626). A previous abdominal surgery was present in 37.5 % and 33.7% of laparoscopy and laparotomy group, respectively (p=0.449). Laparoscopy had a lower incidence of distal catheter failure (OR 0.52, 95% CI 0.38-0.72; p<0.001). No differences were revealed about the duration of surgery, LOS and infection rate., Conclusion: Laparoscopic technique has a lower risk of distal catheter failure in ventriculoperitoneal shunt for the treatment of hydrocephalus. Duration of surgery, LOS and infection rate are independent by the surgical technique. The overall level of evidence is low, and no absolute conclusions can be drawn., Key Words: Hand-Assisted Laparoscopy, Hydrocephalus, Meta-Analysis, Mini-Laparotomy, Shunt Failure, Shunt Malfunction, Ventriculoperitoneal Shunt.

Introduction: The improvement of surgical procedures and oncological outcomes in the treatment of low-ultralow rectal cancer, made important the evaluation of functional results. The aim of this study is to evaluate the functional results after open and laparoscopic approach., Patients and Methods: From our global experience, over the period 2000/2018, within the patients surgically treated for rectal cancer, we have gathered and studied 37 patients with low-ultralow site of lesion, submitted to sphincterpreserving surgery, subdivided based on the approach: 20 open, 17 laparoscopic, of which 8 robotic . For each type of procedure, as low and ultralow anterior resection, intersphinteric resection, abdominoperineal resection, were investigated functional outcomes, as bowel continence, urinary functions, male and female sexual functions, based on the following tests: Wexner Incontinence Score, International Prostatic Symptom Score, International Index of Erectile Function- 5, Female Sexual Function Index. The controls were performed before surgery and 3-6-12 months postoperatively. Statistical analisis: X2-test, impaired and paired t-test two tailed, Bonferroni post-hoctest., Results: The immediate surgical results and pathological features of the tumor are reported and evaluated. The evaluation of fecal continence in all patients submitted to rectal resection and primary anastomosis showed function compromission without differences statistically significant between the laparo and open approach. In the comparison between specific surgical procedures, the damage of continence function were more severe after intersphinteric resection mached with low-ultralow rectal resection. The rehabilitation therapies continued for several months after surgery showed clear improvement. The urinary continence, in male and female patients, did not show statistically significant alterations in the pre and postoperative comparison in relation to the approach and the type of resective intervention. The sexual function in male patients has had impairment after all type of surgical resection but the damage was more severe after intersphinteric resection. The female sexual function had not significant changes between pre and postoperative evaluation., Conclusion: Bowel continence damage, urinary and sexual dysfunctions after surgical treatment for low-ultralow rectal cancer are frequent and form the low anterior resection syndrome. The severity of the syndrome is connected with the site of anastomosis. The rehabilitation therapies can play an important role in achieving the appreciable improvements of the functional alterations., Key Words: Laparoscopic surgery, Rectal cancer.

Background: The management of cholelithiasis and choledocholithiasis combined is controversial. The more frequent approach is a two-stage procedure, with endoscopic sphincterotomy and stone removal from the bile duct followed by laparoscopic cholecystectomy. This study aims to demonstrate how, on the basis of the personal experience, the Rendez-vous technique, that combines the two techniques in a single-stage operation is better than the sequential treatment., Methods: Between June 2017 to December 2019, 40 consecutive patients with cholelithiasis and choledocholithiasis combined were enrolled for the study: 20 were treated with the sequential treatment and 20 with the Rendez-vous method. The preoperative diagnostic work-up was similar in the two group. The endpoints of the study included incidence of endoscopic and surgical complications, rate of hospitalization and cost analysis., Results: The study showed no difference in demographic parameters between the two groups, but the success rate of clearance of CBD was significantly smaller for sequential arm, with the need of additional procedures. We found a statistical reduction of postoperative acute pancreatitis, hospital stay and charges in Rendez-vous group, at the expense of a prolonged total operating time., Conclusions: The data of the study confirm the superiority of the Rendez-vous technique because it resolves cholelithiasis associated with choledocholithiasis in a single surgical act, with greater acceptance of the patient who avoids a second invasive surgical act, and with a reduction in complications; moreover, it requires shorter hospitalization, resulting in reduced costs. We propose this option in the management of cases where preoperative ERCP-ES has failed., Key Words: Common bile duct stones, Cholecysto-choledocholithiasis, Endoscopic retrograde cholangiopancreatography, Endoscopic sphincterotomy, Laparoscopic cholecystectomy, Laparo-endoscopic Rendez-vous.

Bariatric surgery is recognized as the most effective treatment for morbid obesity, maintaining a stable weight reduction in the long term and reducing comorbidities, with a favorable impact on mortality. The aim of this study is to evaluate the complication rate and treatment techniques adopted in all patients undergoing bariatric surgery procedures in our center. From May 2017 to March 2020, 91 patients with morbid obesity are admitted to the Department of Medical and Surgical Science of the University Hospital of Foggia undergoing bariatric surgery. Seventyone patients underwent sleeve gastrectomy, nineteen gastric bypass and one mini-gastric bypass, five of these were redo operation procedures. Regarding postoperative complications (8,8%), there were 1 gastric leak (1,09%), 4 bleedings (4,39%) - 1 intraluminal bleeding and 3 intra-abdominal bleedings, 2 port-sites infections (2,19%) and 1 haemoperitoneum (1,09%). In our center we have also treated 3 cases of complications after bariatric surgery procedures performed in others centers. There were no deaths. Despite improvement in the performance of bariatric surgical procedures, complications are not uncommon. Flexible endoscopy has become an essential tool in managing bariatric surgery patients and offers the benefit of providing both diagnostic and therapeutic applications. KEY WORDS: Bariatric surgery, Bleeding post-bariatric surgery, Complications bariatric surgery, Gastric bypass, Leak post-sleeve gastrectomy, Mini invasive approach, Sleeve gastrectomy.