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Martin and his colleagues in 1989 described for the first time a fasciocutaneous flap based on a posterior branch of the anterior interosseous artery (AIA). Despite its promising characteristics, this flap never achieved popularity and the literature about it is limited. The aim of the present study is to share our experience with the AIA flap both as a local and free flap in reconstructing defects of various body regions.A retrospective review of 26 consecutive patients operated between January2001 and August 2020 was conducted. Seventeen male and nine female patients, mean age 52 years, underwent reconstruction of local and distant soft tissue defects using the AIA flap. Fourteen flaps were raised as free flap and 12 as local flaps for a total of 26 flaps. The locations of the defects included the face, the lower limb, the hand dorsum, and fingers.Twenty-four out of 26 flaps survived completely, and two pedicled flaps presented partial necrosis, with one requiring a new free flap procedure. One free anterior interosseous flap required revision of the venous anastomosis. Two donor site dehiscence were observed, and they both healed by secondary intention healing. Follow-ups were conducted for a mean of 18 months. All patients showed good contour restoration of the affected body part.The AIA flap, either free or pedicled, represents a reliable tool to perform "like-with-like" reconstructions of hand defects. In some occasions, it is well suited for shallow defects in other body parts.

Introduction: Using data from the TackSHS survey, we aim to provide updated estimates on the prevalence and determinants of overweight and obesity in Europe. Methods: A face-to-face survey was conducted in 2017–2018 in 12 European countries (Bulgaria, England, France, Germany, Greece, Ireland, Italy, Latvia, Poland, Portugal, Romania, and Spain). Overall, 10,810 participants, representative in each country of the general adult population, provided information on self-reported height and weight. Results: Almost half of participants (48.1%; 95% confidence interval, CI: 47.2–49.1) reported to be overweight or obese (54.1% in men and 42.5% in women) and 12.6% (95% CI: 12.0–13.2) obese (11.3% in men and 13.8% in women). Obesity prevalence was lowest in Italy (7.5%) and France (8.8%) and highest in Greece (19.7%) and Romania (21.1%). Multilevel logistic random-effects analyses showed that prevalence of obesity was related with higher age and lower level of education and socioeconomic status. As compared to northern European countries, Western and Southern European ones showed a significantly lower obesity prevalence. When compared to a companion study conducted in 2010, Eastern and Northern European countries showed an increased trend in obesity prevalence. Conversely, countries with the lowest obesity prevalence (less than 10%), such as Italy and France, showed a decreased trend. Conclusions: Despite a large heterogeneity across countries, overweight and obesity prevalence estimates in Europe are alarming, with most of the countries reporting obesity prevalence approaching 20% or more, particularly in Eastern and Northern Europe. Since 2010, obesity prevalence increased in most of these countries.

Background The use of intraoperative indocyanine green (ICG) angiography has been well documented for confirmation of arterial perfusion in transferred free flaps. However, no previous report has yet focused on whether ICG angiography can be used to detect congestion in free flaps. The present report investigates the feasibility of ICG angiography for detecting flap congestion intraoperatively through illustrative cases. Methods From September 2019 to September 2020, 65 consecutive female patients who underwent breast reconstructions using a free deep inferior epigastric perforator (DIEP) flap were enrolled in this study. Forty-eight patients with 52 DIEP flaps were eligible for the study after application of the exclusion criteria. ICG angiography was performed after elevation of the flap, after completion of the anastomoses, and after inset of the flap. Results In five cases (9.6%), an inadequate highlight was demonstrated with ICG angiography performed after flap elevation. All such cases were deemed congestive since robust bleeding was observed with the prick test. ICG angiography demonstrated sufficient highlight of the flap after removal of the clamp on the superficial inferior epigastric vein. In two cases (4.2%), kinking of the pedicle vein of the DIEP flap was found with ICG angiography performed after inset of the flap. In both cases, the pedicle and the flap were reinset. All flaps survived completely postoperatively. Conclusion ICG angiography can detect flap congestion, and the proposed 3-step protocol is useful for the prevention of postoperative complications.

Background Defects in the knee area, popliteal fossa region, and upper third of the lower extremity can pose a challenge for reconstructive plastic surgeons. The purpose of this article is to report the authors' experience with the use of the pedicled medial sural artery perforator flap in its simple and chimeric form for reconstruction of defects in three different regions: knee, popliteal fossa, and proximal lower leg. Methods From April of 2018 to April of 2019, 37 patients (29 men and eight women) with a mean age of 51 years (range, 18 to 78 years) underwent reconstruction with 37 pedicled medial sural artery perforator flaps. All flaps were harvested as pedicled perforator flaps in conventional or chimeric fashion and were based on one or two perforators. The defect locations included the knee (18 cases), popliteal fossa (seven cases), and proximal lower leg (12 cases). The cause of reconstruction was trauma in 22 patients (59 percent), tumor in 10 patients (27 percent), and donor-site closure of free medial sural artery perforator in five patients (14 percent). Results The flap sizes varied from 3.5 × 5 cm to 5 × 10 cm. All but one flap, which showed distal tip necrosis, survived completely after surgery. The donor sites were all closed primarily. Minor complications included flap dehiscence (two cases) and minor wound infection delaying the healing process (four cases). All complications were treated conservatively. Follow-up observations were conducted for 3 to 12 months, and all patients had good functional recovery with satisfactory cosmetic results. Conclusion The pedicled medial sural artery perforator flap can be considered an optimal method of reconstruction for covering defects not only in the knee area but also in the popliteal fossa and upper lower leg. Clinical question/level of evidence Therapeutic, IV.

Mutant KRAS (KM), the most common oncogene in lung cancer (LC), regulates fatty acid (FA) metabolism. However, the role of FA in LC tumorigenesis is still not sufficiently characterized. Here, we show that KMLC has a specific lipid profile, with high triacylglycerides and phosphatidylcholines (PC). We demonstrate that FASN, the rate-limiting enzyme in FA synthesis, while being dispensable in EGFR-mutant or wild-type KRAS LC, is required for the viability of KMLC cells. Integrating lipidomic, transcriptomic and functional analyses, we demonstrate that FASN provides saturated and monounsaturated FA to the Lands cycle, the process remodeling oxidized phospholipids, such as PC. Accordingly, blocking either FASN or the Lands cycle in KMLC, promotes ferroptosis, a reactive oxygen species (ROS)- and iron-dependent cell death, characterized by the intracellular accumulation of oxidation-prone PC. Our work indicates that KM dictates a dependency on newly synthesized FA to escape ferroptosis, establishing a targetable vulnerability in KMLC.

Background Over the last few years, the increasing employment of perforators as both donor and recipient vessels for free flap tissue transfer lead the surgeons to perform increasingly smaller anastomosis. Size discrepancy is a common problem that might affect the patency rate. This has many implications in the outcome of the procedure and the "Open-Y" technique might be useful to perform an easier anastomosis by using a bifurcation area. Patients and methods Between April 2018 and April 2020 a total of 98 patients who received a free tissue transfer reconstruction throughout the body were retrospectively recruited. The "Open-Y" technique of anastomosis was used in the recipient artery of 40 perforator-based flaps, while in 58 cases a conventional anastomosis with nonperforator vessel was performed. The size discrepancy rate and the arterial anastomotic site-related complications were evaluated and compared. Results The flap success rate was 100% (40/40) in the "Open-Y" group, slightly better than the conventional group (96.5%; 56/58) despite a higher size discrepancy rate in the "Open-Y" group (27.5%; 11/40) compared to the conventional one (12%; 7/58) (p value, .053). The rate of complications was different, too. Better results were obtained in the "Open-Y" group with 4/40 (10%) complications compared to the 18/58 (31%) of the conventional group (p value, .013). Conclusions The "Open-Y" technique is a simple and interesting procedure to increase the vessels' diameter thus reducing size discrepancy and increasing the reliability of the anastomosis. This is extremely valuable in the perforator-to-perforator free tissue transfer setting where surgeons are often forced to work in a supermicrosurgical field. Every time a suitable bifurcation is encountered this might be a useful procedure to increase the end-surface available for the anastomosis or to reduce vessels size discrepancy.

BACKGROUND Superficial lymphovenous anastomosis (LVA) is a widely accepted procedure for treatment of mild-to-moderate lymphedema throughout the body. Anyway, not always are the superficial lymphatic vessels suitable for the anastomosis nor do they provide a sufficient drainage to significantly improve the condition. The continuous progress of supermicrosurgical technique over the last few years and the recent anatomical researches about the deep lymphatic network opened new perspectives for those lymphedema cases refractory to conventional procedures. Resorting to deep lymphatic vessels offer an additional opportunity to further improve the result obtained by means of superficial LVA. The aim of this report is to describe our experience treating lymphedema with superficial and deep lymphatic vessels LVA. PATIENTS AND METHODS Eight female patients presenting secondary (seven cases) and primary (one case) lymphedema, previously treated by means of multiple superficial LVAs, were considered eligible for deep lymphatics surgery to further improve their results. The affected area was the upper limb in one case and the lower limbs in seven cases. All the patients were evaluated preoperatively and postoperatively resorting to Campisi criteria. Four cases were initially classified as stage III, two stage IV, and two stage II. Five patients received deep LVA in the groin, two patients in the ankle along the posterior tibial artery and one in the wrist along the radial artery. RESULTS In all eight patients both subjective and objective improvements of the condition were reported with decrease of swelling and relief from heaviness sensation. The postoperative course was always uneventful and at the 9 months follow up none of the patients presented recurrence of the disease, even with the complete removal of compressive therapy. CONCLUSIONS Deep lymphatic vessels LVA might represent a valid alternative to the superficial ones to treat lymphedema when previous results are not satisfactory nor when no superficial lymphatic vessels are available for anastomosis.

Introduction Propeller flaps have gained great popularity among reconstructive surgeons; however, the inability to directly close the donor site of large propeller flaps constitutes a well-known limitation of this technique. Skin grafting of the donor area is not always feasible nor desirable. To address large propeller flaps secondary defects, we investigated the use of a second propeller flap harvested from a nearby region of relative skin redundancy to assist the donor site closure generated by the first. Since the donor defect of the second flap is closed by direct suture, the aim of this “sequential” propeller flaps technique is to achieve complete, like-with-like, soft tissue restoration while avoiding skin grafting. Methods From April 2018 to September 2019, eight patients presenting post-traumatic soft tissue defects were planned to be reconstructed by means of the sequential propeller flaps technique, for a total of 16 propeller flaps. The locations of the defects included the distal leg in four cases, the heel in two cases, the proximal lateral thigh in one case and proximal posterior thigh in the remaining one. All the flaps but one were harvested as a perforator-based propeller type and rotated by different degrees around the skeletonized perforator. In one patient, due to an intraoperative complication following the first flap harvest, the harvest of the second flap was abandoned. Results In all but one patient, a complete, tension free primary closure of all wounds was achieved without complications, the functional recovery as well the esthetic outcome were excellent. One patient showed intraoperative signs of vascular insufficiency involving 15% of the first flap. The plan of harvesting the second flap was intraoperatively abandoned and the definitive wound closure with a free muscle gracilis was carried out the following week. Conclusion In some selected cases, the use of multiple propeller flaps performed in sequence allows the surgeon to obtain complete, like-with-like wound closure with vascularized tissue avoiding a free tissue transfer procedure, however, it requires a vast experience with propeller flaps and meticulous preoperative planning.

Item does not contain fulltext Aim: To perform cross-sectional and longitudinal miRNA profiling in plasma from Duchenne muscular dystrophy (DMD) subjects and find non-invasive biomarkers in DMD. Subjects/materials & methods: Plasma was collected from 14 age and sex matched controls and 46 DMD subjects. Free-circulating and extracellular vesicle (EV)-derived miRNA expression was measured by RT-qPCR. Results: Free-circulating and EVs derived miR-29c-3p and miR-133a-3p are dysregulated in DMD subjects. Free-circulating and EV-derived miR-29c-3p are reduced in DMD subjects undergoing daily corticosteroid treatment. Free-circulating miR-1-3p and miR-122-5p are longitudinally upregulated in ambulant DMD subjects. Conclusion: We detected novel free-circulating and EV-derived dysregulated miRNAs in plasma from DMD subjects and characterized the longitudinal profile of free-circulating miRNA on plasma from DMD subjects.

Background Lymphocele is a collection of lymphatic fluid within the body. It is caused by an impairment of lymph drainage and often occurs after a surgical intervention. In this setting conservative treatment is usually ineffective. The aim of this report is to share the outcomes of 11 patients with iatrogenic lymphocele in the thigh area treated by supermicrosurgical lymphovenous anastomosis. Patients and methods Eleven patients presenting iatrogenic lymphocele in the thigh were referred for surgery after an unsuccessful conservative therapy. Patients' mean age was 56 years old, two males and nine females. All of them presented a moderate-to-severe lymphocele in the medial thigh after a surgical intervention that damaged the rich lymphatic pathway present there. Indocyanine green (ICG) lymphography was always performed to visualize the lymphatic vessels and to make the preoperative marking. Results All the 11 patients were successfully treated by means of one or more (range: 1-3; mean: 1.5) lymphaticovenous anastomoses without complications. Three of them also received a pedicled sartorius flap for dead space obliteration. All the patients reached full range of motion (ROM) and no recurrences were observed during follow up (range: 6-12 months; mean: 8). Intra-operative ICG lymphography was performed in all cases to check the patency of the anastomoses. Conclusions Lymphaticovenous anastomosis confirmed to be a minimally-invasive and effective procedure for the treatment of postsurgical lymphoceles in the leg. For large lymphoceles a muscle flap may be indicated for volume restoration and prevention of recurrences.

The primary molecular endpoint for many Duchenne muscular dystrophy (DMD) clinical trials is the induction, or increase in production, of dystrophin protein in striated muscle. For accurate endpoint analysis, it is essential to have reliable, robust and objective quantification methodologies capable of detecting subtle changes in dystrophin expression. In this work, we present further development and optimisation of an automated, digital, high-throughput script for quantitative analysis of multiplexed immunofluorescent (IF) whole slide images (WSI) of dystrophin, dystrophin associated proteins (DAPs) and regenerating myofibres (fetal/developmental myosin-positive) in transverse sections of DMD, Becker muscular dystrophy (BMD) and control skeletal muscle biopsies. The script enables extensive automated assessment of myofibre morphometrics, protein quantification by fluorescence intensity and sarcolemmal circumference coverage, colocalisation data for dystrophin and DAPs and regeneration at the single myofibre and whole section level. Analysis revealed significant variation in dystrophin intensity, percentage coverage and amounts of DAPs between differing DMD and BMD samples. Accurate identification of dystrophin via a novel background subtraction method allowed differential assessment of DAP fluorescence intensity within dystrophin positive compared to dystrophin negative sarcolemma regions. This enabled surrogate quantification of molecular functionality of dystrophin in the assembly of the DAP complex. Overall, the digital script is capable of multiparametric and unbiased analysis of markers of myofibre regeneration and dystrophin in relation to key DAPs and enabled better characterisation of the heterogeneity in dystrophin expression patterns seen in BMD and DMD alongside the surrogate assessment of molecular functionality of dystrophin. Both these aspects will be of significant relevance to ongoing and future DMD and other muscular dystrophies clinical trials to help benchmark therapeutic efficacy.

Objective Helical plates potentially avoid the medial neurovascular structures of the thigh. Recently, two plate designs (90°- and 180°-helix) proved similar biomechanically behavior compared to straight plates. The aims of this study were: (1) feasibility of applying 90°- and 180°-helical plates in MIPO-technique to the femur, (2) Assess the distances to adjacent anatomical structures which are at risk, (3) Compare these distances with medial straight plates, and (4) Correlate measurements performed during anatomical dissection with CT-angiography. Methods MIPO was performed in ten cadaveric femoral pairs using either a 90°-helical 14-hole-LCP (group1) or a 180°-helical 15-hole-LCP-DF (group2). Using CT-angiography, distances between femoral arteries and plates as well as distances between plates and perforators were evaluated. Following, specimens were dissected, and distances determined again. All plates were removed, and all measurements were repeated with straight medial plates (group3). Results Closest overall distances between plates and femoral arteries were 15 mm(11–19 mm) in group1, 22 mm(15–24 mm) in group2 and 6 mm(1–8 mm) in group3 with a significant difference between group1 and group3(p Conclusion MIPO with 90°- and 180°-helical plates is feasible and safe. Attention must be paid to the medial neurovascular structures with 90°-helical implants and to the proximal perforators with 180°-helical implants. Helical implants can avoid medial neurovascular structures compared to straight plates although care must be taken during their distally insertion. Measurements during anatomical dissection correlate with CT-angiography.

Different issues may cause defects in the genital region, including urological, infective, oncological and genetic problems which often lead to significant defects. This is a very delicate region and a successful coverage requires a thin, pliable and reliable solution. In this setting the SCIP flap might be an outstanding procedure. Despite being a well-known solution in the groin region, its employment for genital reconstructions is still poorly described. For this reason, we gather our experience with this procedure showing the efficacy of the SCIP flap in this specific region.In the present case series we included 6 male patients who received a soft tissue defect reconstruction by means of pedicled SCIP flap over the last year. The average age was 53.6 years old (range 34-79 years). Among them, 5 patients received a surgical excision because of severe acne (2 cases), Fournier's gangrene (2 cases), or scrotal squamous cell carcinoma (1 case). In 1 case the cause of the missing volume was testicle agenesis and the reconstruction was performed for cosmetic purposes. Size of the defects ranged from 7 cm × 4 cm to 20 cm × 6 cm. Elliptical shaped flaps were designed either mono- or bilaterally according to the need. All the flaps were supplied by the superficial branch of the SCIA. The range of rotation varied between 150° and 180° in order to reach the affected area.The flaps' dimension ranged from 8 cm × 4 cm to 20 cm × 6 cm. All the patients were successfully treated. In 1 case we encountered a small wound dehiscence, which was managed conservatively. The mean follow-up was 9.5 months (range 6-12 months). Good cosmetic result was achieved in all cases and no urinary or sexual dysfunctions were reported.The pedicle SCIP flap represents a reliable solution for genital and inguinal defects reconstructions. Its versatility can be exploited throughout the region providing very good quality tissues that can be used for the most disparate situations.

Investigating pediatric overweight and physical activity correlates is essential to design effective preventive programs. We used regional data (Lombardy, northern Italy) from the 2019 survey “OKKio alla Salute” (3093 children aged 8–9 years with measured anthropometric data), and from the 2018 wave of the “Health Behaviour in School-aged Children” survey (2916 adolescents aged 11–15 years with self-reported anthropometric data). In both the surveys, a cluster sampling methodology was used. Unconditional multiple logistic regression models were applied to estimate the odds ratios (OR) and corresponding 95% confidence intervals (CI) of overweight, obesity and poor physical activity. The prevalence of overweight (including obesity) was 22.4% for children aged 8–9 years and 14.4% for adolescents aged 11–15 years. A higher prevalence of overweight was observed among males, children with greater birth weight and those with obese parents. Scant physical activity was higher among females and older adolescents. There was a direct relationship between obesity and increased psychological distress (OR = 2.44; 95% CI: 1.12–5.27) or being victims of bullying (OR = 2.25; 95% CI: 1.17–4.34). Increasing physical activity significantly decreased the frequency of mental health outcomes. Prevention campaigns should be promoted to safeguard childhood physical and psychological wellbeing.

Feeding/behavior problems are highly prevalent in autistic children. This study aimed to explore the interplay between autistic features, sensory processing patterns, emotional/behavioral difficulties, and feeding problems in children with a clinical diagnosis of autism spectrum disorder. Ninety-nine children aged 1.5–5 years were assessed using the Children’s Eating Behavior Inventory (CEBI), the Child Behavior Checklist, the Revised Sensory Profile—Second Edition (SP-2), and the Food Frequency Questionnaire. The sample was divided into two subgroups based on the presence of feeding behavior problems as rated by parents on the CEBI. Children with feeding problems showed more severe internalizing symptoms and were more reactive to sensory stimuli than children without feeding problems. We also found a significant relationship between higher levels of autistic features and greater feeding behavior problems. A mediation analysis model indicated that this relationship was mediated by sensory processing, as reflected by SP-2 quadrants scores. Although preliminary, these findings suggest that children with higher levels of autistic features could be at greater risk of developing feeding behavior problems only if they also have a higher sensory sensitivity to environmental stimuli. Lay abstract This study adds to a growing body of research documenting feeding problems in autistic children. Our results indicate that children aged 1.5–5 years with feeding problems may present with elevated internalizing difficulties and alterations in sensory processing when compared to same-age children without feeding problems. Our study also proposes that sensory processing may be an important, mediating factor in the relationship between autism features and feeding problems. The present work suggests, therefore, that implementers should thoroughly consider the sensory profile of autistic children prior to intervening on feeding behaviors. In particular, based on these preliminary findings, feeding interventions could benefit from environments designed to support children who can find them noisy and overwhelming.

Background and Objectives: When a lymphatic-rich area is severely damaged, either after trauma or a surgical procedure, both soft tissue defect reconstruction and lymphatic drainage restoration are necessary. In this setting, we aim to show the potential of the lymphatic flow-through flap (LyFT) concept, which might be an attractive new solution to reduce postoperative lymphatic complications. Materials and Methods: Between 2018 and 2021, 12 patients presenting a soft tissue defect involving damage to the lymphatic drainage pathway received a lymphatic flow-through flap for volume and lymphatic drainage restoration. Different flaps were employed: 3 pedicled superficial circumflex iliac artery perforator (SCIP) flaps, 2 free SCIP flaps, 3 pedicled deep inferior epigastric perforator (DIEP) flaps, 2 pedicled vertical posteromedial thigh (vPMT) flaps, and 2 pedicled anterolateral thigh (ALT) flaps. A range of 1 to 3 lymphovenous anastomosis (LVA) with flap’s veins was performed (mean 1.9). For a better dead space obliteration, an additional vastus lateralis muscle flap was performed in one case. Indocyanine green (ICG) lymphography was used in all cases to identify the lymphatic pathway, make the preoperative markings, and check the patency of the anastomoses. Results: In all cases, the reconstructive results were satisfactory from both the functional and aesthetic points of view. No secondary surgeries were required, and only one minor complication was encountered: an infected seroma that was managed conservatively. The mean follow-up was 9.9 months (range 6–14 months). Conclusions: Lymphatic flow-through flaps seem to effectively reduce the risk of lymphatic complications after the reconstruction of soft tissue defects with a compromised lymph pathway. This is a versatile solution that might be used in different body regions resorting to different flap types.

Obese children are at high risk of developing vitamin D deficiency. Omega-3 polyunsaturated fatty acids and their derivatives might have a beneficial effect on vitamin D status of obese children, due to their anti-inflammatory action, and increasing its absorption. This multicenter, randomized, double-blind controlled study aims to investigate the effect of vitamin D and docosahexaenoic acid (DHA) co-supplementation for six months on vitamin D status, body composition, and metabolic markers of obese children with vitamin D deficiency. A total of 108 children were enrolled and 73 children completed the study: 33 were supplemented with an oral dose of 500 mg of DHA and 1200 IU/day of vitamin D3 and 41 were supplemented with 1200 IU/day of vitamin D3 + wheat germ oil. At the end of the study, more than 50% of the subjects improved their vitamin D status. However, co-supplementation was not more effective than vitamin D plus wheat germ oil. Fat mass percentage was significantly reduced, and body mass index improved in both groups, even if all the subjects were still obese at the end of the study. Children receiving both vitamin D and DHA presented a higher increase of DHA levels that could be relevant to prevent inflammatory-associated complications of obesity, but they had no effect on vitamin D levels.

Lower extremity defects have been and remain one of the greatest challenges in reconstructive surgery. Perforator flaps have been accepted as a valid procedure to cover such a defect. Different techniques have been described and nowadays many options are available. However, there were not studies that comprehensively review the most modern techniques and clinical application of the use of perforator flaps in the lower extremity reconstruction. In the present report, we gathered most of them, presenting an updated and large case series where different pedicled and free perforators flaps were employed in simple and complex scenarios in a large series of cases.Eighty-seven patients presenting soft tissue defects of the lower extremities were treated by means of different perforator-based flaps, in either free or pedicled fashion. The flaps were based on different perforator vessels, namely deep lateral circumflex femoral artery, profunda femoris artery, superficial femoral artery, medial sural artery, peroneal artery, posterior tibial artery, anterior tibial artery, and medial plantar artery. Patients' mean age was 61.9 years old (range 21-87 years old), 58 were males and 29 females. The 12 patients received sequential flaps and 9 received double free flaps, for a total sum of 106 flaps. The causes of the defects were trauma in 41 patients and tumors in 46 patients, located throughout the lower limbs. Size of the defect ranged from 3 cm × 4 cm to 25 cm × 9 cm.The dimensions of the flap skin paddles ranged from 3 cm × 4 cm to 16 cm × 5 cm for the pedicled flaps (42 cases) and from 6 cm × 4 cm to 25 cm × 8 cm for the free ones (45 cases). Mean flap's size was 48 cmThe present case series highlights the reliability and versatility of perforator flaps for lower extremity defect coverage. Following careful consideration of the etiology, dimensions, location, patient comorbidities, and presence of adequate perforators, a pedicled or free perforator flap can be potentially successful in the most disparate circumstances.

Head and neck tissue defects after ablative head and neck surgery often require complex and composite reconstructions. The superficial circumflex iliac artery perforator (SCIP) flap is an extremely versatile perforator-based flap with minimal donor-site morbidity. The authors present their experience with both simple and chimeric SCIP flap reconstructions for complex defects in various head and neck regions.Twenty-two patients undergoing ablative head and neck surgery for oncologic abnormalities were treated by means of a SCIP flap reconstruction. Patients' mean age was 62 years; 21 were men and one was a woman. Seventeen flaps were simple and five were chimeric reconstruction patterns. Indocyanine green perfusion imaging was performed in all cases.Twenty-one of 22 patients (95.5 percent) were successfully treated with good aesthetic and functional results. Two patients (9 percent) showed minor donor-site complications that were managed conservatively. The mean follow-up period was 5.3 months (range, 2 to 8 months).This case series demonstrates the reliability and versatility of the SCIP flap for head and neck reconstruction. The chimeric options combined with bone, double-skin paddle, and muscle offer a broad variety of functional reconstructive solutions for complex head and neck surgery. Intraoperative indocyanine green perfusion examinations are a valuable tool to assess and ascertain proper inset, vitality, and postanastomosis vessel patency in these complex microvascular flap reconstructions. .Therapeutic, IV.

D-dimer assay is used to stratify patients with unprovoked venous thromboembolism (VTE) for the risk of recurrence. However, this approach was never evaluated since direct oral anticoagulants are available. With this multicenter, prospective cohort study, we aimed to assess the value of an algorithm incorporating serial D-dimer testing and administration of reduced-dose apixaban (2.5 mg twice daily) only to patients with a positive test. A total of 732 outpatients aged 18 to 74 years, anticoagulated for ≥12 months after a first unprovoked VTE, were included. Patients underwent D-dimer testing with commercial assays and preestablished cutoffs. If the baseline D-dimer during anticoagulation was negative, anticoagulation was stopped and testing repeated after 15, 30, and 60 days. Patients with serially negative results (286 [39.1%]) were left without anticoagulation. At the first positive result, the remaining 446 patients (60.9%) were given apixaban for 18 months. All patients underwent follow-up planned for 18 months. The study was interrupted after a planned interim analysis for the high rate of primary outcomes (7.3%; 95% confidence interval [CI], 4.5-11.2), including symptomatic proximal deep vein thrombosis (DVT) or pulmonary embolism (PE) recurrence, death for VTE, and major bleeding occurring in patients off anticoagulation vs that in those receiving apixaban (1.1%; 95% CI, 0.4-2.6; adjusted hazard ratio [HR], 8.2; 95% CI, 3.2-25.3). In conclusion, in patients anticoagulated for ≥1 year after a first unprovoked VTE, the decision to further extend anticoagulation should not be based on D-dimer testing. The results confirmed the high efficacy and safety of reduced-dose apixaban against recurrences. This trial was registered at www.clinicaltrials.gov as #NCT03678506.

Aim The aim of this study was to detail the neurodevelopmental profile of subjects affected by ocular albinism (OA) and to collect data on GPR143 gene analysis. Design The design of the study involves a retrospective longitudinal observational case series. Methods We collected data on the neurodevelopmental profile of 13 children affected by OA from clinical annual assessments conducted for a period of 6 years after the first evaluation. We described visual profile, neuromotor development and neurological examination, cognitive profile, communication and language skills and behavioral characteristics. The GPR143 gene analysis was performed as well. Results Children presented a variable combination of ocular and oculomotor disorders unchanged during the follow-up, a deficit in visual acuity and in contrast sensitivity that progressively improved. Abnormalities in pattern visual evoked potential were found. No deficits were detected at neurological examination and neuromotor development except for a mild impairment in hand-eye coordination observed in five cases. A language delay was observed in five cases, two of whom had also a developmental quotient delay at 2 years evolving to a borderline/deficit cognitive level at preschool age, difficulties in adaptive behavior and autistic-like features were found. Mutations in the GPR143 gene were identified in the two patients who presented the most severe clinical phenotype. Conclusion Children with OA may share, in addition to a variable combination of ocular signs and symptoms, a neurodevelopment impairment regarding mostly the cognitive, communicative, and social area, especially those with GPR143 mutation.

BACKGROUND: Pregnant women have been identified as a potentially at-risk group concerning COVID-19 infection, but little is known regarding the susceptibility of the fetus to infection. Co-expression of ACE2 and TMPRSS2 has been identified as a prerequisite for infection, and expression across different tissues is known to vary between children and adults. However, the expression of these proteins in the fetus is unknown. METHODS: We performed a retrospective analysis of a single cell data repository. The data were then validated at both gene and protein level by performing RT-qPCR and two-colour immunohistochemistry on a library of second-trimester human fetal tissues. FINDINGS: TMPRSS2 is present at both gene and protein level in the predominantly epithelial fetal tissues analysed. ACE2 is present at significant levels only in the fetal intestine and kidney, and is not expressed in the fetal lung. The placenta also does not co-express the two proteins across the second trimester or at term. INTERPRETATION: This dataset indicates that the lungs are unlikely to be a viable route of SARS-CoV2 fetal infection. The fetal kidney, despite presenting both the proteins required for the infection, is anatomically protected from the exposure to the virus. However, the gastrointestinal tract is likely to be susceptible to infection due to its high co-expression of both proteins, as well as its exposure to potentially infected amniotic fluid. TWEETABLE ABSTRACT: This work provides detailed mechanistic insight into the relative protection & vulnerabilities of the fetus & placenta to SARS-CoV-2 infection by scRNAseq & protein expression analysis for ACE2 & TMPRSS2. The findings help to explain the low rate of vertical transmission. ispartof: BJOG vol:129 issue:2 pages:256-266 ispartof: location:England status: published

BACKGROUND Sarcoma surgery often requires large tissue resection to be treated safely. When the tumor is localized in the groin and/or medial thigh, lymphocele and lymphedema are common complications because of the rich lymphatic network present there. The aim of this study is to share the outcome of seven patients who received defect reconstruction in this area with combined pedicled superficial circumflex artery perforator (SCIP) flap with lymphatic tissue preservation and lymphovenous anastomosis (LVA) for prevention of lymphatic complications. PATIENTS AND METHODS Seven patients who underwent surgical resection of sarcoma in the groin and/or adductors compartment received defect reconstruction with pedicled SCIP flap combined with LVA. For a better dead space obliteration, four of them also received an additional tissue flap: two pedicled deep inferior epigastric perforator flaps and two free anterolateral thigh flaps. Indocyanine green lymphography was performed in all cases to identify the lymphatic pathway, make the preoperative marking and check the patency of the anastomoses. RESULTS All seven patients were successfully treated reaching a good aesthetic result and a full range of motion. No immediate nor delayed complications such as lymphocele or lymphorrhea and early extremity lymphedema were observed during the follow up (range: 6-9 months; mean: 7.3) and no secondary procedures were required. CONCLUSIONS The combination of the pedicle SCIP lymphatic tissue transfer with LVA seems to be effective in preventing the development of lymphatic sequelae after large resections in the medial thigh.

Objectives To explore the impact of sex and age on relationship between prodromal constipation and disease phenotype in Parkinson’s disease at early stages. Methods A total of 385 Parkinson’s disease patients from the PRIAMO study were classified according to the presence of prodromal constipation and followed for 24 months. Multivariable mixed-effect models were applied. All analyses were performed separately for sex (64.1% men) and median age (different by sex: 67 years-old in men and 68 years-old in women). Results As for sex, prodromal constipation was associated with greater odds of attention/memory complaints and apathy symptoms in women only. As for age, prodromal constipation was associated with lower cognitive and higher apathy scores in older patients only. Conclusions Prodromal constipation anticipates lower cognitive performances and more severe apathy since the earliest stages in women and older patients. Sex- and age-related heterogeneity of prodromal markers of Parkinson’s disease may impact disease phenotype.

BACKGROUND With the rising number of patients in advanced age receiving microsurgical procedures, coronary artery disease (CAD) and its challenging management is of increasing importance. Evidence based data concerning morbidity and mortality are rare. We present our experiences with this highly selected patient population and propose a preoperative assessment algorithm. PATIENTS AND METHODS Between January 2006 and May 2016, a total of 57 patients with CAD received 58 free flaps. Median age of our patients was 64 years (interquartile range 57.5-70.0). Squamous cell carcinoma was the reason for reconstruction in all cases. Defect of the buccal, gum, tongue, lip, trigone, palatal, and hypopharyngeal regions were reconstructed. Patient characteristics and comorbidities were recorded. We especially focused on the preoperative cardiac assessment and treatment of patients who were scheduled for microsurgical free tissue transfer such as medical history, cardiac risk assessment, and further cardiac testing such as Doppler-echocardiography and myocardial perfusion assessment. Intraoperative course as well as postoperative morbidity and mortality was described. RESULTS About 54.4% of the selected cohort received cardiac catheterization due to a clinical preoperative cardiac assessment performed individually by the cardiologist on duty. In total, 52 fasciocutaneous anterolateral thigh flaps, four osteocutaneous fibula flaps, and two radial forearm flaps were performed. The flap survival rate was 96.6%. The overall surgical complication rate was 28.1% (16 patients), mostly due to wound infections (seven cases) and partial flap necrosis (four cases). Three patients died, resulting in a mortality rate of 5.2%. CONCLUSION CAD patients receiving head and neck microsurgical reconstructions are still at high risk for adverse consequences due to surgery. The microsurgical community is requested to share the experience of those cases in order to develop reliable and evidence based statements of the perioperative risks and prognosis for these patients. We additionally introduce a standardized perioperative cardiac assessment and treatment algorithm for head and neck surgery patients with CAD.

Large upper medial thigh defects in prior irradiated tissue require challenging reconstructions. Several techniques have been reported to reconstruct this region and according to the literature, pedicled perforator flaps are the first reconstructive option. The anterolateral thigh flap is considered the gold standard, while surprisingly the pedicle deep inferior epigastric (DIEP) flap in vertical fashion has not been frequently employed, if compared with its muscular counterpart, the pedicle vertical rectus abdomins flap (vRAM). We report a case of a multilayered flaps reconstruction of the left medial thigh after an excision of a sarcoma involving the whole adductors compartment. A 75-year-old male patient underwent a free margins resection of the sarcoma. After the resection, a soft tissue defect of 24 cm × 14 cm × 14 cm spreading from the groin to the medial tuberosity of the tibia, was left. We performed a reconstructive technique based on a pedicled split extended vertical deep inferior epigastric (s-vDIEP) flap and an adipo-dermal thigh local flap in order to fill and cover the thigh defect. The s-vDIEP had 2 islands: a cranial de-epithelialized island to fill the dead space and a caudal for the skin closure. The postoperative follow-up was complicated by seroma formation and it was managed by sclerotherapy and at the 6 months follow-up the patient showed good cosmetic and functional outcomes with no sign of tumor relapse. Our result suggests that the proposed multilayered reconstruction may be employed for the restoration of large and deep upper medial thigh defects.

Duchenne muscular dystrophy (DMD) is an incurable disease caused by out-of-frame DMD gene deletions while in frame deletions lead to the milder Becker muscular dystrophy (BMD). In the last decade several antisense oligonucleotides drugs have been developed to induce a partially functional internally deleted dystrophin, similar to that produced in BMD, and expected to ameliorate the disease course. The pattern of dystrophin expression and functionality in dystrophinopathy patients is variable due to multiple factors, such as molecular functionality of the dystrophin and its distribution. To benchmark the success of therapeutic intervention, a clear understanding of dystrophin expression patterns in dystrophinopathy patients is vital. Recently, several groups have used innovative techniques to quantify dystrophin in muscle biopsies of children but not in patients with milder BMD. This study reports on dystrophin expression using both Western blotting and an automated, high-throughput, image analysis platform in DMD, BMD, and intermediate DMD/BMD skeletal muscle biopsies. Our results found a significant correlation between Western blot and immunofluorescent quantification indicating consistency between the different methodologies. However, we identified significant inter- and intradisease heterogeneity of patterns of dystrophin expression in patients irrespective of the amount detected on blot, due to variability in both fluorescence intensity and dystrophin sarcolemmal circumference coverage. Our data highlight the heterogeneity of the pattern of dystrophin expression in BMD, which will assist the assessment of dystrophin restoration therapies.

Background and Objectives: The definitive treatment of soft tissue sarcomas (STS) requires a radical surgical removal of the tumor, which often leads to large soft tissue defects. When they are located in the limbs, significant damage to the lymphatic pathways is not uncommon. In the present article, we present different techniques aimed at both reconstructing the defect and restoring sufficient lymph drainage, thus preventing short- and long-term lymphatic complications. Materials and Methods: Between 2018 and 2020, 10 patients presenting a soft tissue defect with lymphatic impairment received a locoregional reconstruction by means of either pedicled or free SCIP flap. Seven patients required a second flap to reach a good dead space obliteration. In six cases, we performed an interpositional flap, namely a soft tissue transfer with lymphatic tissue preservation, and in four cases a lymphatic flow-through flap. In all cases, the cause of the defect was STS surgical excision. The average age was 60.5 years old (ranging 39–84), seven patients were females and six were males. Results: All the patients were successfully treated. In two cases, minor post-operative complications were encountered (infected seroma), which were conservatively managed. No secondary procedures were required. The average follow-up was 8.9 months (ranging 7–12 months). No signs of lymphedema were reported during this time. In all cases, complete range of motion (ROM) and a good cosmetic result were achieved. Conclusions: A reconstructive procedure that aims not only to restore the missing volume, but also the lymphatic drainage might successfully reduce the rate of postoperative complications. Both lymphatic interpositional flaps and lymphatic flow-through flaps could be effective, and the right choice must be done according to each patient’s needs.

Summary Introduction Groin defects with exposed complex structures are challenging to treat. Perforator flaps provide a contemporary alternative to established muscle flaps to cover all varieties of groin defects, with minimum donor site morbidity, less postoperative pain, and faster rehabilitation. In this retrospective single-center analysis, we aimed to show that pedicled perforator flaps are a valid option for groin defect reconstruction. We present three different pedicled perforator flaps and discuss the flap selection process and their distinct advantages and disadvantages. Methods A series of 54 consecutive cases of patients with groin defects were allocated into three different treatment groups. Reconstruction was performed utilizing the anterolateral thigh (ALT) flap, the pedicled posteromedial thigh (PMT) perforator flap, and the vertical deep inferior epigastric artery perforator (vDIEP) flap. Results All 54 flaps survived. Early complications included one hematoma (vDIEP) and two infections (ALT and PMT). Delayed complications occurred in three recipient-site seromas (ALT, PMT, and vDIEP), one donor-site seroma (vDIEP), and one flap dehiscence (ALT). All flaps provided stable coverage during 3–12 months of follow-up. Conclusion We propose pedicled perforator flaps to be a safe and reliable option for groin defect reconstruction. The pedicled PMT flap should be the first choice if the profunda femoris artery and its perforators are available. The ALT flap can be applied as a second choice, especially if complex groin defect with exposed vascular prosthesis reconstruction is needed because of its versatile expansion options, for example, as a chimeric flap using a portion of the vastus lateralis muscle. In cases where the profunda femoris artery is not available, the vDIEP flap should be the preferred method.

Management of systemic lupus erythematosus patients is challenging because of disease heterogeneity. Although treatment of renal nephritis is more standardized, treating non-renal lupus activity remains controversial. Our objective was to identify non-renal, non-neurologic persistent active systemic lupus erythematosus patients in our cohort and described therapeutic behaviors in them. All systemic lupus erythematosus patients (American College of Rheumatology and/or Systemic Lupus Erythematosus International Collaborating Clinics criteria) seen at a university hospital between 2000 and 2017 were included and electronic medical records manually reviewed. Persistent lupus activity was defined as a patient with a Systemic Lupus Erythematosus Disease Activity Index score ≥ 6 (without renal and central nervous system manifestations) despite being on a stable treatment regimen for ≥ 30 days. Stable treatment could include prednisone alone (7.5–40 mg/d) or combined with antimalarial drugs and immunosuppressant therapies. A total of 257 lupus patients were included, 230 females (89.5%, 95% confidence interval 85.1–92.7), mean age at diagnosis 29.9 years (SD 16.4). After a median cohort follow-up of 5.7 years (interquartile range 2.4–10.2), 14 patients (5.4%, 95% confidence interval 3.2–9.0) showed persistent non-renal non neurologic lupus activity, with a median disease duration of 11.3 years (interquartile range 3.6–19.4). At that time, 12/14 (85.7 %, 95% confidence interval 52.6–97.0%) had low complement and 11/14 (78.6 %, 95% confidence interval 46.5–93.9%) had positive antiDNA antibodies. The main reasons for being refractory were mucocutaneous disease (50%, 95% confidence interval 23.5–76.5) and arthritis (42.9%, 95% confidence interval 18.5–71.2). Therapeutic choices after being refractory were: only increasing corticosteroid dose in one patient, starting rituximab in four, belimumab in eight, and in one mycophenolate and rituximab; with good response in all of them. In conclusion, 5.4% of systemic lupus erythematosus patients in our cohort were considered to have non-renal non neurologic persistent lupus activity, with mucocutaneous and arthritis the main manifestations. In total, 92.8% of these patients started a biologic treatment at this point (rituximab or belimumab).

A single analysis of hair for determining halogens (chlorine, bromine, fluorine, and iodine) and sulfur by ion chromatography with suppressed conductivity and mass spectrometry detection (IC-MS) was proposed. Inductively coupled plasma optical emission spectrometry (ICP OES) and inductively coupled plasma mass spectrometry (ICP-MS) were also used to compare the results. For this purpose, 300 mg of human hair were digested by microwave-induced combustion (MIC) using 20 bar of oxygen pressure. The analytes were absorbed in 100 mmol L−1 NH4OH. Trueness of the proposed method was evaluated by analysis of a CRM of human hair; by recovery tests, using standard solution at two levels (50% and 100%), and by comparison of results with those obtained by ICP OES (Cl and S) and ICP-MS (Br and I). Suitable recoveries (ranging from 92 to 105%) were obtained, and the results from CRM analysis did not differ significantly from those described in the certificate. Moreover, results obtained by IC-MS did not present significant differences (p > 0.05) from those obtained by ICP OES and by ICP-MS. Precision was evaluated in terms of repeatability and intermediate precision, and the relative standard deviations were always lower than 8%. The proposed method presented good accuracy and it is a reliable strategy for human hair analysis. Final digests obtained using the MIC method were fully compatible with all proposed determination techniques. Compared to others reported in the literature, the proposed method presents several advantages, especially given that it is possible to determine halogens and sulfur in a single analysis.

Medicina : monthly medical journal of Lithuanian Medical Association, Kaunas University of Medicine and Vilnius University 57(9), 884 (2021). doi:10.3390/medicina57090884 special issue: "Special issue "Hip and fragility fracture management" / special issue editor: Matthias Knobe, guest editor", Published by Kaunas Univ. of Medicine, Kaunas

Purpose: The aim of this study was to evaluate the rate of successful peripheral cannulation between short-axis and long-axis ultrasound guided techniques. Methods: A single-center, two-arm randomized controlled, intention-to-treat, open-label study was conducted at the Emergency Department, between August and November 2020. Patients requiring a peripheral intravenous catheter insertion and identified as having a difficult intravascular access, were enrolled and followed for up to 96 h. The primary endpoint was the correct placement of the peripheral intravenous catheter. The secondary endpoints were number of venipunctures, intra-procedural pain, local complications, and positive blood return during the follow up. Results: A total of 283 patients were enrolled: 141 subjects were randomized to the short-axis and 142 to the long-axis group. Success rate was 96.45% (135/141; 95% CI, 91.92%–98.84%) in the short-axis group compared with 92.25% (132/142; 95% CI, 86.56%–96.07%) in the long-axis group ( p = 0.126). No significant differences were found in terms of intraprocedural pain and local complications. Higher rate of positive blood return at 72 h [3/17 long-axis, 14/17 short-axis ( p = 0.005)] and 96 h [1/10 long-axis, 9/10 short-axis 96 h, ( p = 0.022)] was found for the short-axis group. Conclusions: No differences were found between short-axis and long-axis techniques in terms of success rate, intraprocedural pain, and local complications. Despite this, a slightly higher success rate, a lower number of venipunctures, and a higher rate of positive blood return at 72 and 96 h together with an easier ultrasound technique could suggest a short-axis approach.

The present Special Issue of Nutrients aims to host scientific articles contributing to enriching the knowledge in the field of nutritional habits and intervention in childhood [...]

Identification of patent lymphatic vessels without fibrosis and with high flow is difficult but crucial in the preoperative planning of lymphaticovenous anastomosis (LVA). Lymphatic vessels on the operating field cannot always be visualized preoperatively because of the anatomical and physiological characteristics of lymphedema tissue. The purposes of this study were to demonstrate our clinical experience in identifying indocyanine green (ICG)-negative lymphatics intraoperatively and to emphasize the therapeutic potential of performing anastomoses with ICG-negative lymphatics.Indocyanine green-positive lymphatic ducts were marked preoperatively in 5 patients with lower extremity lymphedema; moreover, if ICG-negative lymphatics were identified during surgery, they were used for additional LVA thus implementing multiple anastomoses in one surgical setting.In total, 33 LVAs were performed in 5 patients with lower extremity lymphedema, of which 11 LVAs were implemented with ICG-negative lymphatics. Immediately after the anastomosis, a strong lymphatic drainage could be appreciated in all cases. Six months postoperatively patients reported a subjective decrease in limb circumference and pressure sensation.We believe that ICG-negative lymphatics found intraoperatively should be evaluated for additional LVAs in order to maximize drainage effect and might provide better outcomes.

Introduction: Arterial filter is the part of the cardiopulmonary bypass circuit where blood cells are exposed to high mechanical stress and where cellular aggregates may fasten in large quantities. The aim of this study was to analyse blood cell adhesiveness in the arterial filter through scanning electron microscopy and real-time PCR assay. Methods: Prospective, clinical and observational study performed on 28 patients undergoing cardiac surgery with cardiopulmonary bypass. Arterial filters were analysed by scanning electron microscopy. Real-time PCR assay was performed in extracted material from the arterial filters for analysis of platelet GPIb and CD45 leucocyte gene expression. Blood coagulation was analysed during cardiopulmonary bypass. Patients were followed until hospital discharge or 28 days after surgery. Results: All studied arterial filters used in the subject patients showed a degree of adhesion from blood elements at scanning electron microscopy. All studied filters were positive for platelets GPIb gene expression and 15% had CD45 leucocyte gene expression. The GPIb platelet gene expression in blood lowered at the end of cardiopulmonary bypass ( p = 0.019). There was negative correlation between blood GPIb platelet gene expression and Clot SR (HEPSCREEN2 ReoRox®) (rho = 0.635; p = 0.027). The filter fields count was correlated to the D-dimer dosage (rho = 0.828; p Conclusion: There was adhesion of blood elements, especially nucleated platelets, on all arterial filters studied. Although the arterial filter worked as a safety device, that possibly prevented arterial embolisation, it may also have caused greater hyperfibrinolysis during cardiopulmonary bypass.

During the last decade, multiple clinical trials for Duchenne muscular dystrophy (DMD) have focused on the induction of dystrophin expression using different strategies. Many of these trials have reported a clear increase in dystrophin protein following treatment. However, the low levels of the induced dystrophin protein have raised questions on its functionality. In our present study, using an unbiased, high-throughput digital image analysis platform, we assessed markers of regeneration and levels of dystrophin associated protein via immunofluorescent analysis of whole muscle sections in 25 DMD boys who received 48-weeks treatment with exon 53 skipping morpholino antisense oligonucleotide (PMO) golodirsen. We demonstrate that the de novo dystrophin induced by exon skipping with PMO golodirsen is capable of conferring a histological benefit in treated patients with an increase in dystrophin associated proteins at the dystrophin positive regions of the sarcolemma in post-treatment biopsies. Although 48 weeks treatment with golodirsen did not result in a significant change in the levels of fetal/developmental myosins for the entire cohort, there was a significant negative correlation between the amount of dystrophin and levels of regeneration observed in different biopsy samples. Our results provide, for the first time, evidence of functionality of induced dystrophin following successful therapeutic intervention in the human. Electronic supplementary material The online version of this article (10.1186/s40478-020-01106-1) contains supplementary material, which is available to authorized users.

Objective:Previous studies from European countries noted that food products promoted on TV for children did not comply with international guidelines, including the World Health Organization European Nutrient Profile Model (WHO-ENPM) and the EU Pledge Nutrition Criteria (EU-PNC, an initiative developed by leading food companies). We aim to provide new data from Italy.Design:Evaluation of Italian TV advertisements. Data on nutritional values for food product advertised were compared with nutritional standards issued by the WHO-ENPM and the EU-PNC.Setting:In total, 180 h of TV programmes from six Italian channels, 2016–2017.Participants:Eight hundred and ten consecutive advertisements during children’s programmes.Results:Out of 810 advertisements, 90 (11·1 %) referred to food products. Among these, 84·5 % of the foods promoted did not meet the WHO-ENPM and 55·6 % the EU-PNC guidelines. Advertisements promoting sweet and salty snacks (i.e. ≥ 70 % of all foods) v. other food products showed higher non-compliance with both the WHO-ENPM (OR: 73·8; 95 % CI: 4·09, 1330) and the EU-PNC (OR: 9·21; 95 % CI: 2·82, 30·1).Conclusions:In Italy, most food advertisements during children’s programmes are not compliant with European nutritional standards. Almost all the advertisements for snacks do not meet international guidelines. As the WHO-ENPM guidelines do not propose standards for all the food products, including meals, there is an urgent need to define independent and easy-to-read guidelines for food advertisements targeting children. As a first step towards the complete ban of food advertisements targeting children recommended by other researchers, these guidelines should be enforced by all the TV broadcasts.

The alkaloid berberine presents many biological activities related to its potential to bind DNA structures, such as duplex or G-quadruplex. Recently, it has been proposed that berberine may interact with i-motif structures formed from the folding of cytosine-rich sequences. In the present work, the interaction of this alkaloid with the i-motif formed by the human telomere cytosine-rich sequence, as well as with several positive and negative controls, has been studied. Molecular fluorescence and circular dichroism spectroscopies, as well as nuclear magnetic resonance spectrometry and competitive dialysis, have been used with this purpose. The results shown here reveal that the interaction of berberine with this i-motif is weak, mostly electrostatics in nature and takes place with bases not involved in C·C+ base pairs. Moreover, this ligand is not selective for i-motif structures, as binds equally to both, folded structure, and unfolded strand, without producing any stabilization of the i-motif. As a conclusion, the development of analytical methods based on the interaction of fluorescent ligands, such as berberine, with i-motif structures should consider the thermodynamic aspects related with the interaction, as well as the selectivity of the proposed ligands with different DNA structures, including unfolded strands., Oriol Oliva (University of Barcelona, Spain) is thanked for their help in carrying out some of the experiments. Funding from Spanish Government (PID2019-107158GB-I00 and CTQ2017-84415-R), Italian Government (PIANO DI SOSTEGNO ALLA RICERCA 2018 – Linea 2 azione B (DEFENS)) and recognition from the Autonomous Catalan Government (2017SGR114) are acknowledged.

Glioblastoma (GBM) is highly resistant to chemotherapies, immune-based therapies, and targeted inhibitors. To identify novel drug targets, we screened orthotopically implanted, patient-derived glioblastoma sphere-forming cells using an RNAi library to probe essential tumor cell metabolic programs. This identified high dependence on mitochondrial fatty acid metabolism. We focused on medium-chain acyl-CoA dehydrogenase (MCAD), which oxidizes medium-chain fatty acids (MCFA), due to its consistently high score and high expression among models and upregulation in GBM compared with normal brain. Beyond the expected energetics impairment, MCAD depletion in primary GBM models induced an irreversible cascade of detrimental metabolic effects characterized by accumulation of unmetabolized MCFAs, which induced lipid peroxidation and oxidative stress, irreversible mitochondrial damage, and apoptosis. Our data uncover a novel protective role for MCAD to clear lipid molecules that may cause lethal cell damage, suggesting that therapeutic targeting of MCFA catabolism may exploit a key metabolic feature of GBM. Significance: MCAD exerts a protective role to prevent accumulation of toxic metabolic by-products in glioma cells, actively catabolizing lipid species that would otherwise affect mitochondrial integrity and induce cell death. This work represents a first demonstration of a nonenergetic role for dependence on fatty acid metabolism in cancer. This article is highlighted in the In This Issue feature, p. 2659

To compare the incidence of osteoporotic fractures in patients with rheumatoid arthritis (RA) with matched controls from a university hospital.Consecutive RA patients (n = 100) were matched (age and sex) with controls (1:2). The follow-up period began at the index date, defined as the date of diagnosis for RA patients and the date of the first medical claim at the Health Management Organization (HMO) for non-RA patients. Fracture incidence rates per 1000 persons-years (PY) for distinct types of fractures were calculated. Multivariate cox regression analysis was performed to identify factors associated with fractures.One hundred RA patients were followed for a total of 975.1 patients-years and 200 controls for 1485.7 patients-years. No difference was found in the overall fracture incidence rate per 1000 PY between RA and controls (19.5, 95% CI 12.7-28.6 vs 12.1, 95% CI 7.7-18.7, p = 0.07). In the Cox regression analysis, only age (HR 1.06, 95% CI 1.02-1.11, p = 0.006) and history of a prior fracture (HR 9.85, 95% CI 2.97-32.64, p 0.001) were associated with fractures after the index date. The stratified analysis of the fractures by location showed that only the vertebral fractures were more frequent in RA patients compared with controls (12.9 per 1000 PY, 95% CI 8.9-25.8, vs. 3.4, 95% CI 1.4-8.1, respectively, p = 0.01).Patients with RA didn't show an overall increased risk of osteoporotic fractures compared with matched controls, but vertebral fractures were more frequently observed in patients with RA.

Right now the world is going through an unprecedented pandemic caused by a novel coronavirus. Recent papers pointed out the fatal outcome in most of the severe cases, in which a cytokine storm has been proven to be the cause of a systemic shock, acute respiratory syndrome, multiorgan failure and consequently death. Several explanations have been proposed trying to explain the pathophysiology of the cytokine storm, but viral proteins with a possible superantigen activity as a cause of immune dysregulation have not been addressed. If this hypothesis is proven, a different treatment approach might change the outcome in severe cases.

Background Resorting to perforators as recipient vessels is a valid alternative that might offer a series of advantages in many situations. They allow the use of a shorter pedicle, reduce the time of dissection, and are a good solution when deep vessels are difficult to reach. The aim of this study is to investigate the efficacy of P-to-P tissue transfer for reconstructing defects in different areas of the body. Patients and Methods Between April 2018 and February 2020, 40 patients presenting soft tissue defects were reconstructed by using P-to-P-anastomosed free flap transfer. The cause of the defect was trauma in 16 cases and surgically excised tumor in 24. Five defects were located in the upper extremities, 1 in the neck, 1 in the thorax, and 21 in the lower limb, and 13 cases were breast reconstructions, 2 of which bilateral (43 total flaps). Results Of all 43 flaps, 22 were abdominal flaps, 17 flaps were harvested from the upper thigh, and 4 were harvested from the lower leg. At the 9 month follow-up, 42 flaps were successfully healed, 36 without complications, 3 after wound dehiscence, and 3 after wound infection, and only 1 flap was lost requiring further surgery. Flap failure rate was 2.3%. Conclusions Free flaps anastomosed in perforator-to-perforator fashion can be safely used in different settings throughout the body. Even if they are technically more demanding, they may allow a quicker operation time and lower morbidity. With the developments in microsurgical instruments, we believe that this technique may become the gold standard for tissue-defect reconstruction.

Introduction There is growing evidence of the superior ability of muscular tissue to clear bacterial bone infection. Unfortunately, in the hand, there are almost no small local muscular flaps, and muscular transfers to the hand are mainly microsurgical free transfers. In this report, we present the results of the use of a chimeric posterior interosseous flap including part(s) of the forearm muscles to treat osteomyelitis and soft tissue defect of hand from a series of patients. Patients and methods Four male patients with an average age of 32 years (range 20-46 years), were affected by acute osteomyelitis in hand. Previous fracture fixation with percutaneous K-wires was the cause of bone infection in three case. In one case, the osteomyelitis was a consequence of an open fracture. The bones affected were four metacarpals and one proximal phalanx, all with a minimal cortical defect (from the K-wire) obscuring a larger medullary infection, which required extensive bone and overlying soft tissue debridement, leaving a soft tissue defect to be reconstructed of size ranging from 2 x 4 cm to 5 x 7 cm. The soft tissue defects were due to concomitant superficial infection and consequent debridement. All patients were treated with bone debridement and a chimeric posterior interosseous flap, which included part of the extensor digiti minimi and/or extensor carpi ulnaris to fill the intramedullary canal of the bones. No fixation of bone was necessary. Results The skin paddle of the flaps ranged from 2 x 5 cm to 5 x 6 cm, replicating the defect area, plus a teardrop tail of skin circa 1.5 cm wide and as long as the pedicle of the flap. The muscular components of the flaps used to fill the intramedullary canals ranged from 1 x 1 x 1.5 cm to 1.5 x 1.5 x 4 cm. All flaps survived and osteomyelitis resolved in all cases without major complications. At the final follow-up at 16 months (range 12-26 months), assessment of the hands using TAM, Power Grip and Key Pinch Strength measurements and, where appropriate, Kapandji scores, demonstrated satisfactory hand function. Conclusion The chimeric posterior interosseous flap including part of the muscles of the forearm may be a robust solution for augmenting the flap bulk and may be used in cases of severe osteomyelitis of the hand.

Our objective was to estimate incidence and prevalence rates of granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) using data from a university hospital-based health management organization (HIMCO) in Latin America.Multiple methods for case finding were used to ensure complete ascertainment. GPA was diagnosed if fulfilling ACR 1990 criteria or a clinical diagnosis was made by an experienced rheumatologist. For MPA, a clinical diagnosis made by an experienced rheumatologist in concordance with Chapel Hill 2012 consensus. Renal limited vasculitis (RLV) ANCA-P positive was considered along with MPA. Global, age-specific, and sex-specific incidence and prevalence rates were calculated for members of the HIMCO with continuous affiliation ≥ 1 year from January 2000 to January 2015. Each person was followed up until GPA or MPA were diagnosed, voluntarily withdraw of the HIMCO, death, or study finalization. Prevalence was calculated on January 1, 2015.Nineteen incident cases of GPA and 28 of MPA were identified from January 2000 to January 2015. During this period, a total of 349,775 HIMCO persons contributed a total of 2,073,438 person-years. GPA and MPA overall incidence rate per 1,000,000 person-years were 9 (95% CI 5-13) and 14 (95% CI 9-19), respectively. Age-specific incidence rates in both female and male patients peaked in the seventh decade of life in our population. On January 1, 2015, prevalence rates were 7.4 per 100,000 (95% CI 2.8-12) for GPA and 5.2 per 100,000 (95% CI 1.3-9) for MPA. Prevalence rates were higher in ages over 70 for both genders and both diseases.In this first study from Latin America, incidence and prevalence rates were in ranges of previous reports from other sites of the world. In our population, GPA and MPA were more frequent in women and in older ages, and the incidence of MPA was higher than that of GPA. Key points • In Argentina, MPA incidence was higher than GPA, similar to that reported in other parts of the world. • Prevalence and incidence rates were higher in ages over 70 for both sexes and both diseases.