On the adoption of canonical quasi-crystalline laminates to achieve pure negative refraction of elastic waves.

A way to achieve negative refraction of elastic anti-plane shear waves is a transmission across an interface between a homogeneous substrate and a periodic transverse laminate. To achieve pure negative refraction, the frequency of the source should be lower than the upper limit of the second transition zone (TZ) of the harmonic spectrum of the laminate. An effective way to control the location of TZ is to consider a canonical configuration for the laminate, a concept that originates from the properties of quasi-crystalline sequences among which the Fibonacci one is a particular case. Based on the universal structure of frequency spectrum, we provide a method based on the reduced torus to study the effect of a change in canonical ratio on the limits of the TZ. A further contribution consists in the analytical estimate of the angle of refraction for a linear relationship between frequency and longitudinal wavenumber. This is achieved by determining the components of the in-plane Poynting vector. The outcome provides a tool for the selection of a suitable laminate-substrate combination to accomplish a particular angle of the refracted wave. Finally, it is shown that for some particular configurations, the transmitted energy displays a peak that can be exploited to maximize the amount of energy travelling across the laminate. This article is part of the theme issue 'Wave generation and transmission in multi-scale complex media and structured metamaterials (part 2)'.

Hepatic vascular anomalies during totally laparoscopic pancreaticoduodenectomy: challenging the challenge.

The presence of hepatic vascular anomalies may add challenges to an already difficult surgery such as pancreatoduodenectomy, particularly when performed laparoscopically. Thus, our aim was to assess the impact of an aberrant right hepatic artery (aRHA) on postoperative outcomes during laparoscopic pancreatoduodenectomy (LPD) . Data of patients who underwent LPD were prospectively gathered and retrospectively analyzed. Patients with types III, IV, VI, VII, VIII, and IX anomalies according to Michels' classification were included in the aRHA group and were compared with the remaining patients (nRHA group). 72 patients underwent LPD; 14 of these had an aRHA (19.4%). Except for BMI (p = 0.021), the two groups did not differ in terms of clinico-pathological characteristics. The two groups had similar postoperative complications (p = 0.123), pancreatic fistula (p = 0.790), biliary leakage (p = 0.209), postpancreatectomy hemorrhage (p = 0.790), reoperations (p = 0.416), and mortality (p = 0.312). The median number of lymph nodes harvested was higher in aRHA group (p = 0.032), while R0 resection rate was similar between groups (p = 0.635). At the multivariate analysis, only moderate/high FRS (OR 3.95, p = 0.039) was an independent predictor of postoperative complications. This study suggests that aRHA has no negative impact on surgical and oncological outcomes in patients undergoing LPD.

Laparoscopic ventral hernia repair in patients with obesity: should we be scared of body mass index?

BACKGROUND: Obesity is a risk factor for ventral hernia development and affects up to 60% of patients undergoing ventral hernia repair. It is also associated with a higher rate of surgical site occurrences and an increased risk of recurrence after ventral hernia repair, but data is lacking on the differences between obesity classes. METHODS: Between 2008 and 2018, 322 patients with obesity underwent laparoscopic ventral hernia repair in our department: class I n = 231 (72%), II n = 55 (17%), III n = 36 (11%). We compared short and long-term outcomes between the three classes. RESULTS: Patients with class III obesity had a longer median length of hospital stay compared to I and II (5 days versus 4 days in the other groups, p = 0.0006), but without differences in postoperative complications or surgical site occurrences. After a median follow up of 49 months, there were no significant differences in the incidence of seroma, recurrence, chronic pain, pseudorecurrence and port-site hernia. At multivariate analysis, risk factors for recurrence were presence of a lateral defect and previous hernia repair; risk factors for seroma were immunosuppression, defect > 15 cm and more than one previous hernia repair; the only risk factor for postoperative complications was chronic obstructive pulmonary disease. CONCLUSION: Class III obesity is associated with longer length of hospital stay after laparoscopic ventral hernia repair, but without differences in postoperative complications and long-term outcomes compared with class I and class II obesity.

Totally Laparoscopic Pancreaticoduodenectomy: Comparison Between Early and Late Phase of an Initial Single-Center Learning Curve.

Despite recent advances in minimally invasive pancreatic surgery, laparoscopic pancreaticoduodenectomy (LPD) has not reach a wide diffusion, mainly due to its technical difficulty. Considering its potential benefits, efforts should be made to improve its adoption. Between January 2017 and March 2020, LPD was offered as the primary approach to all the patients with an indication to pancreaticoduodenectomy. The overall cohort was divided into two groups: the early group (EG), including the first 30 cases, and the late group (LG), with the remaining patients. Perioperative data were gathered from a prospectively collected database and retrospectively analyzed, comparing the short-term outcomes of the two groups. In the study period, 52 patients underwent LPD. Among these, 88.4% patients were preoperatively diagnosed with a malignant disease. No difference was found between EG and LG in terms of baseline characteristics, mean operative time, estimated blood loss, and conversion to laparotomy. The overall complication rate was 57.7%, with severe complications occurring in 14 patients (26.9%). Two patients (3.8%) deceased within 90 days from the operation. No difference was found between EG and LG regarding postoperative outcomes. Among oncological patients, 86.7% received an R0 resection, and 13.3% had an R1 resection. The EG and LG did not differ in terms of oncological radicality and number of lymph nodes retrieved. LPD is a reproducible surgical technique that may provide acceptable results in both early and late phase of experience, when performed by surgical team with broad background in laparoscopic surgery.

Postoperative risk of pancreatic fistula after distal pancreatectomy with or without spleen preservation.

INTRODUCTION: Outcomes after distal pancreatectomy with or without splenectomy are controversial. The present study aims to investigate differences in short-term and long-term outcomes between spleen-preserving distal pancreatectomy (SPDP) and distal pancreatectomy with splenectomy (DPS). METHODS: In this retrospective review of consecutive patients undergoing distal pancreatectomy with or without splenectomy from January 2011 until December 2017 for benign disease, the primary endpoint was to compare postoperative pancreatic fistula (POPF). The secondary endpoint was to compare duration of surgery, intraoperative blood loss, postoperative complications, length of hospital stay, and long-term outcomes. RESULTS: Patients undergoing SPDP had a lower rate of POPF (13.6% vs 46.1%; p = 0.02). Patients undergoing SPDP (n = 22) were discharged earlier than patients undergoing DPS (n = 26) (8 [4-29] vs 12 [6.48] days; p = 0.003). No differences in other intraoperative and postoperative outcomes were found between groups. CONCLUSION: Patients undergoing SPDP developed fewer POPF and were discharged earlier compared to patients undergoing DPS.

Totally laparoscopic versus open pancreaticoduodenectomy: A propensity score matching analysis of short-term outcomes.

INTRODUCTION: Laparoscopic pancreaticoduodenectomy (LPD) is a demanding operation that has not yet gained popularity. Safety, feasibility, and clinical advantages of LPD in comparison with open pancreaticoduodenectomy (OPD) have not been clearly demonstrated. The aim of this study was to compare the short term outcomes of LPD with those of OPD. MATERIAL AND METHODS: Data from a prospectively collected database of patients who underwent pancreaticoduodenectomy at our institution between January 2013 and March 2020 were retrieved and analyzed, comparing the short-term postoperative outcomes of LPD and OPD, using a propensity score matching analysis. RESULTS: In the study period, 177 patients undergoing pancreaticoduodenectomy were selected, 52 of these were LPD. In the LPD group, the conversion rate to OPD was 3.8%. After matching, a total of 50 LPD and 50 OPD were compared. LPD was associated with a shorter length of stay (14 vs 20 days, p = 0.011), decreased blood loss (255 vs 350 ml, p = 0.022), but longer median operative time (590 vs 382.5 min; p < 0.001). No significant difference was found between LPD and OPD in terms of overall complications (56% vs 62%, p = 0.542), severe complications (26% vs 22%, p = 0.640), and postoperative mortality (4% vs 6%, p = 0.646). The groups had similar reoperation rate, pancreatic-specific complications, and readmission rate. CONCLUSIONS: In comparison with the open approach, LPD seems associated to with improved short-term outcomes in terms of hospital stay and blood loss, but with a longer operative time. No difference in morbidity and mortality rate were found in our series.

Permanent end-colostomy parastomal hernia prevention using a novel three-dimensional mesh.

PURPOSE: Prophylactic mesh placement has been proposed to reduce the high occurrence of parastomal hernia (PSH) after stoma formation. METHODS: This is an observational study comparing two cohorts of patients: a mesh prophylaxis group (who received mesh prevention since introduction at our Institution) and a no mesh prophylaxis group (retrospectively selected from our historical series). Same exclusion criteria were applied for both groups. The study was conducted at a tertiary referral center for colorectal surgery. 43 patients were operated with mesh prophylaxis between May 2015 and may 2019. 45 patients underwent end-colostomy formation without prophylaxis between April 2011 and April 2015. The primary outcome measure was PSH development at 12-month follow up. RESULTS: Demographic variables and risk factors for PSH were comparable between the two groups. There was no difference between the two cohorts in terms of operative time and main early postoperative outcomes. 37 patients completed the 12-month follow up in each group. PSH occurrence after 12-months was 11% in the mesh prophylaxis group and 54% in the no mesh prophylaxis group (p < 0.0001). There were no differences in long-term complications. 5% of patients who received mesh prophylaxis underwent emergency surgery for bowel occlusion at 7 and 10 months after surgery, with partial or complete mesh removal. At multivariate analysis, mesh prophylaxis was a protective factor for PSH development at 12 months (p < 0.0001). CONCLUSIONS: Prophylactic intraperitoneal mesh placement appears to be effective in preventing PSH.

Totally Laparoscopic Pancreaticoduodenectomy: Technical Notes.

Introduction: Laparoscopic pancreaticoduodendectomy is still rarely adopted due to its inherent complexity. We hereby present our experience of laparoscopic pancreaticoduodenectomy focused on technical notes. Technical description: A 5 trocars technique is used. Vision is provided by a 30 degree scope with 4K technology for the demolitive phase and 3D for the reconstructive phase. The right colic flexure is mobilized and an extensive Kocher maneuver is carried out exposing the inferior vena cava and left renal vein. The gastric antrum is resected with a mechanical stapler. The common hepatic artery is identified behind the superior pancreatic margin; lymphadenectomy of stations 7, 8, 9, 12 a and b is performed, until the gastroduodenal artery is cleared from the lymphatic tissue; a bull-dog clamp is placed to interrupt the arterial flow through the gastroduodenal artery, in order to exclude aberrant vascularization of the liver from the SMA. The common hepatic duct is transected just above the cystic duct. The pancreas is sectioned with monopolar energy, dividing the main pancreatic duct 2-3 mm distal to the parenchymal transection line with cold scissors, as to leave a stump that will facilitate the duct-to-mucosa anastomosis then the first jejunal loop is sectioned. A complete dissection of the mesopancreas is performed, moving from a caudal to cephalad fashion. Prior to perform the pancreatico-jejunal anastomosis, a fistula risk score based on pancreatic parenchymal texture, tumor type, Wirsung diameter, intraoperative blood loss is assessed. The pancreatico-jejunal anastomosis is carried out using prolene and pds sutures. The end-to-side hepaticojejunostomy is performed about 10 cm distant from the pancreaticojejunostomy. The side to- side gastrojejunostomy is performed using a 60 mm linear stapler. Conclusion: Laparoscopic pancreaticoduodenectomy is a demanding procedure affected by high morbidity rates. The standardization of the technique could lead the way to reduce such rates and favor its adoption.

On the universality of the frequency spectrum and band-gap optimization of quasicrystalline-generated structured rods.

The dynamical properties of periodic two-component phononic rods, whose elementary cells are generated adopting the Fibonacci substitution rules, are studied through the recently introduced method of the toroidal manifold. The method allows all band gaps and pass bands featuring the frequency spectrum to be represented in a compact form with a frequency-dependent flow line on the surface describing their ordered sequence. The flow lines on the torus can be either closed or open: in the former case, (i) the frequency spectrum is periodic and the elementary cell corresponds to a canonical configuration, (ii) the band gap density depends on the lengths of the two phases; in the latter, the flow lines cover ergodically the torus and the band gap density is independent of those lengths. It is then shown how the proposed compact description of the spectrum can be exploited (i) to find the widest band gap for a given configuration and (ii) to optimize the layout of the elementary cell in order to maximize the low-frequency band gap. The scaling property of the frequency spectrum, that is a distinctive feature of quasicrystalline-generated phononic media, is also confirmed by inspecting band-gap/pass-band regions on the torus for the elementary cells of different Fibonacci orders. This article is part of the theme issue 'Modelling of dynamic phenomena and localization in structured media (part 2)'.

Real-world effectiveness and safety of glecaprevir/pibrentasvir in 723 patients with chronic hepatitis C.

BACKGROUND AND AIMS: The efficacy and safety of glecaprevir/pibrentasvir (G/P) for patients infected with hepatitis C virus (HCV) have only been investigated in clinical trials, with no real-world data currently available. The aim of our study was to investigate the effectiveness and safety of G/P in a real-world setting. METHODS: All patients with HCV consecutively starting G/P between October 2017 and January 2018 within the NAVIGATORE-Lombardia Network were analyzed. G/P was administered according to drug label (8, 12 or 16 weeks). Fibrosis was staged either histologically or by liver stiffness measurement. Sustained virological response (SVR) was defined as undetectable HCV-RNA 12 weeks after the end of treatment. RESULTS: A total of 723 patients (50% males) were treated with G/P, 89% for 8 weeks. The median age of our cohort was 58 years, with a median body mass index of 23.9 kg/m2, and median liver stiffness measurement of 6.1 kPa; 84% were F0-2 and 16% were interferon-experienced. Median HCV-RNA was 1,102,600 IU/ml, and 49% of patients had HCV genotype 1 (32% 1b), 28% genotype 2, 10% genotype 3 and 13% genotype 4. The median estimated glomerular filtration rate was 90.2 ml/min, platelet count 209x103/mm3 and albumin 4.3 g/dl. The SVR rates were 94% in intention-to-treat and 99.3% in per protocol analysis (8-week vs. 12 or 16-week: 99.2% vs. 100%). Five patients failed therapy because of post-treatment relapse; a post-treatment NS5A resistance-associated substitution was detected in 1 case. SVR rates were lower in males (p = 0.002) and in HCV genotype-3 (p = 0.046) patients treated for 8 weeks, but independent of treatment duration, fibrosis stage, baseline HCV-RNA, HIV co-infection, chronic kidney disease stage and viral kinetics. Mild adverse events were reported in 8.3% of the patients, and 0.7% of them prematurely withdrew treatment. Three patients died of drug-unrelated causes. CONCLUSIONS: In a large real-world cohort of Italian patients, we confirmed the excellent effectiveness and safety of G/P administered for 8, 12 or 16 weeks. LAY SUMMARY: A large number of patients with hepatitis C virus have been treated with glecaprevir/pibrentasvir (G/P) within the NAVIGATORE-Lombardia Network, in Italy. This is the first real-world study evaluating effectiveness and safety of G/P in patients with hepatitis C virus treated according to international recommendations. This study demonstrated excellent effectiveness (with sustained virological response rates of 99.3%) and safety profiles.

Plasma Exchange for the Treatment of Transient Extreme Hypertriglyceridemia Associated with Diabetic Ketoacidosis and Acute Pancreatitis.

Diabetic ketoacidosis (DKA) can quite frequently present in association with acute pancreatitis (AP) caused by transient severe hypertriglyceridemia (HTG). Here we report the case of a patient presenting with DKA, severe HTG and AP who received urgent plasma exchange for HTG control, and who reached adequate serum triglyceride levels only after appropriate DKA management. The treatment of patients presenting with DKA and coexistent AP associated with severe HTG should focus first on appropriate DKA management. Plasma exchange as a treatment for severe HTG in patients with DKA and AP should be evaluated carefully. LEARNING POINTS: The treatment of patients presenting with diabetic ketoacidosis, acute pancreatitis and severe hypertriglyceridemia should focus first on diabetic ketoacidosis management.Plasma exchange as a treatment for severe hypertriglyceridemia in patients with diabetic ketoacidosis and acute pancreatitis should be evaluated carefully.Triglyceride concentrations should always be measured in case of diabetic ketoacidosis.

NANOG Plays a Hierarchical Role in the Transcription Network Regulating the Pluripotency and Plasticity of Adipose Tissue-Derived Stem Cells.

The stromal vascular cell fraction (SVF) of visceral and subcutaneous adipose tissue (VAT and SAT) has increasingly come into focus in stem cell research, since these compartments represent a rich source of multipotent adipose-derived stem cells (ASCs). ASCs exhibit a self-renewal potential and differentiation capacity. Our aim was to study the different expression of the embryonic stem cell markers NANOG (homeobox protein NANOG), SOX2 (SRY (sex determining region Y)-box 2) and OCT4 (octamer-binding transcription factor 4) and to evaluate if there exists a hierarchal role in this network in ASCs derived from both SAT and VAT. ASCs were isolated from SAT and VAT biopsies of 72 consenting patients (23 men, 47 women; age 45 ± 10; BMI between 25 ± 5 and 30 ± 5 range) undergoing elective open-abdominal surgery. Sphere-forming capability was evaluated by plating cells in low adhesion plastic. Stem cell markers CD90, CD105, CD29, CD31, CD45 and CD146 were analyzed by flow cytometry, and the stem cell transcription factors NANOG, SOX2 and OCT4 were detected by immunoblotting and real-time PCR. NANOG, SOX2 and OCT4 interplay was explored by gene silencing. ASCs from VAT and SAT confirmed their mesenchymal stem cell (MSC) phenotype expressing the specific MSC markers CD90, CD105, NANOG, SOX2 and OCT4. NANOG silencing induced a significant OCT4 (70 ± 0.05%) and SOX2 (75 ± 0.03%) downregulation, whereas SOX2 silencing did not affect NANOG gene expression. Adipose tissue is an important source of MSC, and siRNA experiments endorse a hierarchical role of NANOG in the complex transcription network that regulates pluripotency.

Severe Milk-Alkali Syndrome in a Patient with Hypoparathyroidism Associated with 1,25(OH)2D, Hydrochlorothiazide and Anthranoid Laxative Consumption.

BACKGROUND: Milk-alkali syndrome is a life-threatening condition defined by the triad of hypercalcaemia, metabolic alkalosis and acute renal failure, and is associated with consumption of calcium and absorbable alkali. METHODS: We report the case of a patient admitted to a step-down unit of a large hospital in Italy. RESULTS: The patient was a 59-year-old woman with hypoparathyroidism and mild chronic kidney insufficiency, treated for a preceding episode of hypocalcaemia with high doses of calcitriol and calcium carbonate, who was also taking hydrochlorothiazide and unreported herbal anthranoid laxatives. The patient was admitted to hospital with severe hypercalcaemia, severe metabolic alkalosis and acute renal insufficiency. The patient was successfully treated with urgent dialysis, loop diuretics and calcitonin administration. CONCLUSIONS: This case underlines the need for caution when treating patients with impaired calcium metabolism regulation, and suggests that herbal anthranoid laxatives might act as triggers for milk-alkali syndrome. LEARNING POINTS: Patients with hypoparathyroidism are more prone to develop milk-alkali syndrome.Patients need careful follow-up and review of their need for calcium supplements.Non-prescription and complementary medicines can aggravate hypercalcaemia.

Transanal endoscopic video-assisted (TEVA) resection of early rectal lesions using a SILS port A single center experience.

UNLABELLED: represents a safe and complete technique to remove benign lesions of the rectum not treatable by endoscopy and malignant rectal lesions at early stage. It is a valid alternative to transanal endoscopic microsurgery (TEM), to conventional transanal surgery and to transabdominal resection. METHODS: In our operating Unit we performed a resection of 8 voluminous adenoma in the rectal ampulla with SILSTM-Port. RESULTS: The mean age of the patients was of 51.1 years, the mean BMI was 23. There were not intra or post-operative complications nor conversions to conventional transanal excision or major resective surgery. The postoperative course was normal. The average time of hospitalization was 3 days. CONCLUSIONS: TEVA is easier to perform than TEM and does not require a long training and specific and expensive material as the TEM does. TEVA might go to replace completely TEM. KEY WORDS: Rectal tumours, SILS, TEVA.

Sustained response to combination therapy in patients with chronic hepatitis C who failed to respond to interferon.

BACKGROUND/AIMS: The best treatment for chronic hepatitis C patients who do not respond to interferon is still unknown. Reported rates of response to treatment vary as the result of heterogeneous definitions of non-responders and small study size. METHODS: One hundred nineteen hepatitis C virus (HCV) RNA-positive non-responders to high-dose interferon monotherapy received alpha-interferon, 5 MU tiw plus oral ribavirin, 1000-1200 mg/day for 48 weeks (Group A, n=74) or alpha-interferon, 5 MU daily for 4 weeks, followed by 5 MU tiw plus oral ribavirin, 1000-1200 mg/day for 44 weeks (Group B, n=45) according to the Institution where they were followed. Persistently normal alanine aminotransferase and negative HCV RNA up to 72 weeks from treatment onset defined a sustained response. RESULTS: Eighteen patients discontinued treatment (13 developed anemia, two mucositis, one granulocytopenia; two were dropouts), none for serious adverse events. There were 24 (20%) sustained responders, with similar final response rates in Groups A and B. Sustained response was more frequent in patients aged

Iron reduction and sustained response to interferon-alpha therapy in patients with chronic hepatitis C: results of an Italian multicenter randomized study.

OBJECTIVES: It has been suggested that iron depletion improves the response to interferon in patients with chronic hepatitis C. We aimed to evaluate whether iron reduction by phlebotomy before interferon improves the rate of virological sustained response in previously untreated noncirrhotic patients. METHODS: One hundred fourteen hepatitis C virus (HCV) RNA positive patients with hepatic iron concentrations of > or =700 microg/g dry wt (men) and > or =500 microg/g dry wt (women), stratified according to HCV genotype and gamma-glutamyltransferase values, were randomly allocated to interferon alone (6 MU three times a week) (group A) or to phlebotomy until iron depletion followed by interferon (6 MU three times a week) (group B). After 4 months dosage was reduced to 3 MU three times a week for another 8 months. RESULTS: Virological sustained response was observed in 25 patients (22%), nine (15.8%, 95% CI = 7.5-27.9) of group A and 16 (28.1%, 95% CI = 17.0-41.6) of group B. At univariate analysis the variables associated with the response were HCV genotypes 2-3, normal gamma-glutamyltransferase, higher levels of baseline ALT, normal ALT values, and negativity for HCV-RNA at the 3rd month of therapy. At multivariate analysis, genotype and ALT levels at enrollment maintained their association with the response. A trend toward a better response to interferon was observed in patients who received phlebotomy (odds ratio = 2.32, 95% CI = 0.96-6.24, p = 0.082). Patients with hepatic iron concentration of < or = 1100 microg/g dry wt had a trend toward a higher rate of virological sustained response (p = 0.059) when submitted to treatment B. CONCLUSION: Iron removal by phlebotomy is able to improve the rate of response to interferon, especially in patients with lower hepatic iron deposits; it could be useful as adjuvant therapy to new therapeutic modalities.