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The thigh region is often site of soft tissue tumors development. Leiomyosarcoma, in particular, is a malignant tumor that, if not promptly treated, presents a growth rate that often results in large masses. The safest treatment in these cases is margin-free extensive surgical resection. This leads to rather large defects that in a delicate region, such as the medial thigh, implies a series of possible complications from the lymphatic point of view. In this region run major lymphatic vessels, appointed to drain the whole leg. Now that one is aware of this issue, the best solution is trying to obtain an efficient reconstruction and preventing the development of postoperative lymphedema and lymphocele. Here, we present a case of great saphenous vein leiomyosarcoma resection in the right medial thigh reconstructed by means of two superficial circumflex iliac artery perforator (SCIP) flaps with lymphatic tissue preservation, combined with preventive lymphovenous anastomosis (LVA). A 67-years-old woman presented a 22 × 16 cm soft tissue defect after the surgical excision. To fill the defect, we resorted to a larger SCIP flap island, supplied by both the superficial and deep branches of the superficial circumflex iliac artery anastomosed in perforator-to-perforator fashion, and to a smaller SCIP flap island supplied only by the superficial branch. Before surgery, the lymphatic vessels running in the flaps area were identified with indocyanine green lymphography and were carefully preserved during the harvest procedure. They were then transferred with the surrounding tissue and orientated in order to match the lymphatic flow direction, providing further fluid drainage. To boost the lymphatic drainage, an LVA was also performed at the superior-edge-of-the-knee incision point joining a functioning lymphatic vessel to a nearby reflux-free vein. The postoperative course was uneventful and at 7 months follow-up, the patient showed good cosmetic and functional outcomes with no swelling and no signs of tumor relapse. This report provides a series of technical insights and adds further evidence to support the efficacy of this procedure for management of soft tissue defects in the medial thigh region.

The tumors affecting the thigh region are complex to manage, requiring a patient-tailored and multidisciplinary approach. Because of their aggressiveness, soft tissue sarcomas (STS) often grow very quickly and they must be removed before they might cause major impairments. A safe margin excision may lead to large defects that require a surgical reconstruction with either free or pedicled flaps. Another relevant aspect, which is gaining more and more attention in the last few years, regards the lymphatic complications that commonly occur after these procedures. The thigh region anatomically accommodates the major lymphatics responsible for the whole leg drainage, and these vessels are often inevitably compromised during the tumor removal. For this reason, plastic surgeons should take into account not only to the aesthetic and functional result, but they should also try to prevent lymphatic sequelae such as lymphocele and lymphedema. The purpose of this report is to describe the potential of a pedicled SCIP flap, used as a lymphatic interpositional flap, in order to restore the lymphatic drainage of the thigh after a major impairment. A 57-year-old patient presenting a thigh sarcoma received a surgical excision leaving a 35 cm × 25 cm defect affecting the anterior compartment. To fulfill all these concerns, a lymphatic interpositional SCIP flap was performed, in pedicled and chimeric fashion. It allowed to completely bury a large (35 cm × 16 cm) soft tissue island, preserving a smaller (5 cm × 4 cm) skin paddle to monitor the whole flap survival. Moreover, the lymphatic issue was faced by preserving the lymphatic vessels running into the flap and moving them into the affected area in order to enhance the lymphatic neo-angiogenesis and offering an additional pattern for lymph drainage. Post-operative course was uneventful and at 9 months follow up the reconstructive result was successful with no signs of lymphatic sequelae. Therefore, we believe that the SCIP flap might be a promising solution for small-to-moderate size thigh defect reconstructions since it is able to satisfy all the typical requirements of this delicate region.

Worldwide colorectal cancer (CRC) screening rates are suboptimal. This systematic review and meta-analysis examine the role of disgust in CRC screening avoidance.A systematic literature search was conducted. In all, 46 studies were included in the review. Among these, 16 studies were compared with a meta-analytical approach in order to 1) estimate the effect size of state disgust on screening intention and attendance; 2) examine whether methodological characteristics moderate the effect of state disgust on screening behaviour; 3) estimate the effect sizes of trait disgust and type of exam kit on state disgust.In the reviewed studies, state disgust was often associated with CRC screening and especially with CRC screening avoidance. The meta-analysis confirmed low-to-moderate negative effects of state disgust on screening intention and attendance. Population sampling strategy was the only significant moderator of the effect of state disgust on screening attendance, i.e. studies that used convenience (Disgust can boost CRC screening avoidance. Further studies and interventions must be designed to help patients in overcoming this emotional barrier.

Background To compare the incidence of osteoporotic fractures in patients with rheumatoid arthritis (RA) with matched controls from a university hospital. Methods 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. Results 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 p = 0.01). Conclusion 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.

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.

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.

Extensive surgical removal is often required to treat soft tissue sarcomas. When they are localized in the groin-upper medial thigh region, the excision is particularly demanding because of the rich lymphatic network and lymph nodes present in that area. The lymphatic vessels with respective lymph nodes draining the whole leg are most of the time inevitably damaged, causing a series of debilitating sequelae such as lymphocele and lymphedema. To prevent these issues, together with the defect coverage, additional lymphovenous anastomoses (LVA) showed encouraging results. Here we present a case of resected groin sarcoma reconstructed by means of pedicled lower deep inferior epigastric perforator (DIEP) flap combined with multiple LVAs. In particular, the superficial veins of the DIEP flap have been employed as the donor veins for LVAs. A 76-year-old patient presented a leiomyosarcoma in the right trigonum femorale which was surgically excised leaving a defect of about 12 cm × 7 cm with exposed femoral vessels and nerves. The remaining defect was then filled with a pedicled DIEP flap, and three leaking lymphatic vessels in the thigh were anastomosed with three branches of a superficial vein originating from the DIEP flap. The postoperative course was uneventful and at 12 months follow-up no signs of either seroma or lymphocele. This result suggests that the concept of lymphatic flow-through (LyFT) DIEP flap might be a modern and particularly useful solution for those cases that require both dead space obliteration and lymphatic drainage restoration.

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.

Head and neck defect reconstruction is a common challenge for plastic surgeons. Microsurgical free tissue transfer is a frequently used solution but its success strictly depends on the quality of recipient vessels. A particularly demanding situation occurs when there are no nearby available vessels because of previous extensive neck dissection and radiotherapy. In similar cases, it is necessary to resort to other and farther vessels. Common alternatives might be the thoraco-acromial vessels, the transverse cervical vessels, and the internal mammary vessel. Recently, the perforator vessels of the internal mammary artery and vein were shown to be safe alternatives as recipient vessels for autologous breast reconstruction, causing less morbidity and allowing adequate perfusion of rather large flaps. Here we present a floor of the mouth reconstruction after cancer relapse resection. In this case, we employed a chimeric anterolateral thigh (ALT) free flap anastomosed to the internal mammary perforator vessels in end-to-end fashion. A 46-years-old male patient presented a defect in the floor of the mouth and base of the tongue after cancer removal. No nearby vessels were available because of extensive fibrosis and damages due to previous surgeries and radiotherapy. Therefore, on the basis of our experience in autologous breast reconstruction, we chose the internal mammary perforator vessels in the recipient side and we harvested a chimeric ALT-based skin island then split into two parts for mouth reconstruction and monitoring. We performed the anastomosis resorting to internal mammary perforator vessels and we obtained a satisfactory result from both the functional and aesthetic point of view. Postoperative course was uneventful and at 6 months follow up the reconstructive result was good with no functional issue. We believe that this might be a valid and modern evolution of the use of internal mammary vessels as recipient vessels and that it is a worthy addition in the field of perforator-anastomosed flaps, extending its application also to head and neck reconstructions. Moreover, a brief literature review about alternative recipient vessels for depleted neck is also provided.

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.

Breast lymphedema (BLE) is a rather common complication occurring after surgical breast cancer treatment. Microsurgical lymphovenous anastomosis (LVA) is a validated technique for the management of lymphedema in the extremities and it is gaining approval also for the breast one. Here, we report a case of breast lymphedema successfully treated with LVA. A 52 years old woman referred chronic erythema, diffuse swelling and pain after breast surgery, axillary lymphnode dissection and adjuvant radiotherapy. Conservative treatments had been performed for 14 months without improvement of symptoms. The patient was then referred for surgery and multiple LVAs were performed at the right breast. A total of 3 LVAs have been performed, two lymphatic vessels were anastomosed to a single Y-shaped vein and one additional vessel was linked to another nearby vein of similar caliber. All the LVAs were executed using 12-0 microsutures and their patency was confirmed with intraoperative ICG lymphography. Immediately after this intervention the swelling decreased in size and the erythema disappeared and a sensation of relief was reported by the patient. The postoperative course was uneventful and at the 6 and 12 months follow up no signs and symptoms of recurrence were noted. Therefore, we believe that this case adds another significant evidence of the efficacy of LVA for treatment of secondary BLE refractory to conservative treatment. Moreover, we provide a literature review of previous reports of breast lymphedema treated recurring to this procedure.

Soft tissue defects in the buttock area are often related to decubitus ulcers, which are usually small to medium-large size and can be regularly treated with local flaps. However, when the defects have bigger size, such as those involving the whole gluteal region, the coverage can become more challenging, since this specific area needs both a good resistance to pressure and an acceptable functional result. The most common solution for similar cases is the use of multiple local flaps, or, in extreme situations, a free flap. In particular, local flaps based on perforator vessels are, in selected cases, a consolidated alternative to free flap allowing an efficient reconstruction of soft tissue defects using adjacent similar tissues, providing the benefit of "like with like" coverage. Here we present a case of a large mycosis fungoides nidus of the gluteal region measuring 25 cm × 18 cm reconstructed using two large perforator flaps adjacent to the defect combined with a remote one for coverage of the donor site. The cranial flap was designed based on a perforator arising from the superior gluteal artery and transferred into the defect by means of a V-Y advancement, while the two caudal propeller flaps in the posterior thigh were both based on perforators of the profunda femoris artery and rotated 180°, respectively. To obtain a tension-free cover of the donor site defect we applied the concept of "sequential" propeller flaps. Post-operative course was uneventful and the patient was ambulatory with assistive devices after 1 week. At 6 months follow-up, wounds were completely healed without complications and a good functional result was obtained. This report showed the great coverage potential of multiple perforator-based local flaps when properly combined allowing primary closure of the donor site. In particular, we managed to reconstruct a total gluteal defect using just ipsilateral side tissue, reducing morbidity, and obtaining a stable result.

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.

Background and aims Molecular imaging with 18Fluorodeoxyglucose (FDG) and 18F-sodium-fluoride (NaF) captures arterial inflammation and micro-calcification and can reveal potentially unstable atherosclerotic plaques. Methods We performed FDG and NaF PET/CT imaging in two clinically similar cohorts of patients living with HIV (PLWH) with no symptomatic cardiovascular disease. The prevalence and intensity of coronary artery uptake of each tracer, measured as target-to-background ratio (TBR), were assessed in patients at low and high cardiovascular risk. Results Ninety-three PLWH were submitted to PET/CT imaging with FDG (N = 43) and NaF (N = 50); 42% were at low and 58% at high cardiovascular risk. The intensity of uptake and multivessel coronary artery uptake were significantly higher with NaF than FDG both in low and high-risk patients. When each 18F-tracer was tested in low and high-risk patients, an equal proportion of subjects showed no vessel, single and multivessel NaF uptake; the same was true for no and single vessel uptake of FDG (no multivessel FDG uptake was noted). Waist circumference, CRP, D-dimer, HIV duration and treatment with nucleoside reverse transcriptase inhibitors were associated with high NaF uptake in univariable analyses; D-dimer remained significant in multivariable analyses (OR = 1.05; p=0.02). There were no significant associations with FDG uptake. Conclusions The prevalence of coronary artery uptake was higher with NaF compared to FDG both in high and low risk patients, hence microcalcification imaging may be a more sensitive tool to detect coronary atherosclerosis than inflammation imaging. However, the uptake of each 18Fluoride tracer was similar between low and high-risk subjects, and this underscores the discordance between clinical and imaging based risk assessment. Future investigation should address the prognostic significance of NaF coronary artery uptake.

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.

Despite some ongoing criticisms, propeller flaps are still gaining popularity among plastic surgeons. The need of skin grafting of the donor site is one of those limitations that sometime affect the beauty and the efficacy of this reconstructive technique. Similar to a classic bi-lobed skin flap in which the second lobe of the same flap is mobilized to cover the donor site defect of the first lobe, a second, discrete propeller flap can be harvested adjacent to the first, in order to close the first donor site defect, thus avoiding the need for a skin graft. We applied this concept of "sequential" propeller flaps to cover a 4.5 × 4 cm full thickness soft tissue defect at the level of the heel in a 54-year-old patient who underwent melanoma excision and sentinel node biopsy.The first and second propeller flaps of 10 × 4.5 cm respectively were rotated on a distal and on a more proximal perforator of the posterior tibial artery (PTA) respectively, obtaining a tension free closure along the entire wound. The post-operative course was uneventful and the patient returned to full normal activities after 4 weeks. Follow up at 6 months showed a stable reconstruction with no functional deficit. This option, that relies on two separate perforator propeller flaps performed in sequence to obtain complete wound closure, may be kept in mind when dealing with soft tissue defects eligible for propeller flap reconstruction, as long as sizeable perforators in a favorable position are available. Moreover, a brief literature review on propeller flap use in flap donor site closure is also provided.

Isolated penile lymphedema is a rare but severely disabling condition due to reduced lymphatic drainage. In this area treatment opportunities are poor being that conservative management is usually not effective and surgery limited to debulking lymphangiectomy, which is indicated only in very severe cases. Lymphovenous anastomosis (LVA) has a demonstrated efficacy in treatment of upper and lower limbs lymphedema but still has few applications in genital lymphedema and none when the swelling is confined in the penis. Here we present a case of an isolated penile lymphedema treated with super-microsurgical LVA. A 33-year-old patient presented swelling and pain immediately after a traumatic injury at the base of the penis. After 2 years of conservative praxis with manual lymphatic drainage of the penis and upper thigh bandage compression, no improvement of the symptoms was obtained. Indocyanine green lymphography was performed with dye injection in the glans confirming the diagnosis by showing lymphatic drainage stasis (dermal backflow). We consequently decided to undergo a surgical procedure performing lymphovenous anastomosis at the dorsum of the penis. Immediately following this intervention, both objective and subjective symptoms relief were noted with decrease of swelling and pain. The postoperative course was uneventful and at the 6 months follow up the patient reported no recurrence of the swelling even with the complete removal of compression therapy. We consider therefore that LVA may be a valid possibility for management of similar cases to provide a definitive clinical improvement.

Soft tissue sarcomas are a rare group of malignant tumors that often require an extensive surgical resection to be safely treated. When they are localized in the upper medial thigh, this treatment inevitably leads to large defects frequently causing a series of early and late postoperative complications. Among these, lymphocele and lymphedema are rather common and should try to be avoided. Many solutions with a demonstrated efficacy have been described for this purpose after groin dissection procedure, ranging from lymphovenous anastomosis to pedicled or free flaps. Anyway, there is much less information regarding the medial thigh. Here we present a case of resected sarcoma involving the adductors compartment reconstructed using a pedicled deep inferior epigastric (DIEP) flap with lymphatic tissue transfer, combined with preventive lymphovenous anastomosis (LVA) performed at the superior-edge-of-the-knee incision (SEKI) point. A 58-year-old patient presented a 10 cm × 12 cm soft tissue defect after margin free sarcoma removal. To fill this defect, we harvest a 24 × 9 cm pedicled DIEP flap conserving its lymphatic vessels running from the upper margin to the right groin lymphnodes. Then we rotated it maintaining the lymphnodes in their original site and moved it through an inguinal tunnel in the area of the defect. The distal part was de-epithelized and folded down to cover the deeper region. The postoperative course was uneventful and at the 6 months follow up the patient showed a good outcome with no swelling and no signs of tumor relapse. This result therefore may suggest that this kind of combined treatment might be an effective technique to prevent all those complications linked to the impairment of lymphatic system drainage in the proximal medial thigh.

This is a case report of a 64-year-old male with cancer with an unknown primary and bilateral cervical lymph node metastases. Twelve months after chemo-, radio-, immunotherapy, and radical neck dissection, he presented with recurrent cervical metastases. The patient underwent radical revision neck dissection including the deep neck muscles of the cervical plexus and reconstruction with a free anterolateral thigh flap. During tumor resection, parts of the thoracic duct were removed which resulted in a large lymph leak. This was addressed by creating a lymphovenous anastomosis to a branch of the subclavian vein. The flow of lymph was reinstated, and no leak has been observed up to a recent 6-month follow-up.

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).

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

The treatment of soft tissue defects in multimorbid frail patients requires optimized preoperative and perioperative management with a differentiated interdisciplinary approach. Preoperative assessment with established scores, such as the ASA score, is important in order to stratify the operative complication risk. Following the reconstructive ladder is important to avoid unnecessary long operations and consecutively higher operative risks. In cases where a free flap procedure is needed, infections should be treated properly, and vascular status and coagulation should be optimized before performing a free flap procedure. Attention should be paid to maintain independency, functionality and quality of life while choosing the best treatment option.

HRAS, NRAS and KRAS, collectively referred to as oncogenic RAS, are the most frequently mutated driver proto-oncogenes in cancer. Oncogenic RAS aberrantly rewires metabolic pathways promoting the generation of intracellular reactive oxygen species (ROS). In particular, lipids have gained increasing attention serving critical biological roles as building blocks for cellular membranes, moieties for post-translational protein modifications, signaling molecules and substrates for ß-oxidation. However, thus far, the understanding of lipid metabolism in cancer has been hampered by the lack of sensitive analytical platforms able to identify and quantify such complex molecules and to assess their metabolic flux in vitro and, even more so, in primary tumors. Similarly, the role of ROS in RAS-driven cancer cells has remained elusive. On the one hand, ROS are beneficial to the development and progression of precancerous lesions, by upregulating survival and growth factor signaling, on the other, they promote accumulation of oxidative by-products that decrease the threshold of cancer cells to undergo ferroptosis. Here, we overview the recent advances in the study of the relation between RAS and lipid metabolism, in the context of different cancer types. In particular, we will focus our attention on how lipids and oxidative stress can either promote or sensitize to ferroptosis RAS driven cancers. Finally, we will explore whether this fine balance could be modulated for therapeutic gain.

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.

MutantKRAS(KM) is the most common oncogene in lung cancer (LC). KM regulates several metabolic networks, but their role in tumorigenesis is still not sufficiently characterized to be exploited in cancer therapy. To identify metabolic networks specifically deregulated in KMLC, we characterized the lipidome of genetically engineered LC mice, cell lines, patient derived xenografts and primary human samples. We also determined that KMLC, but not EGFR-mutant (EGFR-MUT) LC, is enriched in triacylglycerides (TAG) and phosphatidylcholines (PC). We also found that KM upregulates fatty acid synthase (FASN), a rate-limiting enzyme in fatty acid (FA) synthesis promoting the synthesis of palmitate and PC. We determined that FASN is specifically required for the viability of KMLC, but not of LC harboring EGFR-MUT or wild type KRAS. Functional experiments revealed that FASN inhibition leads to ferroptosis, a reactive oxygen species (ROS)-and iron-dependent cell death. Consistently, lipidomic analysis demonstrated that FASN inhibition in KMLC leads to accumulation of PC with polyunsaturated FA (PUFA) chains, which are the substrate of ferroptosis. Integrating lipidomic, transcriptome and functional analyses, we demonstrated that FASN provides saturated (SFA) and monounsaturated FA (MUFA) that feed the Lands cycle, the main process remodeling oxidized phospholipids (PL), such as PC. Accordingly, either inhibition of FASN or suppression of the Lands cycle enzymes PLA2 and LPCAT3, promotes the intracellular accumulation of lipid peroxides and ferroptosis in KMLC bothin vitroandin vivo. Our work supports a model whereby the high oxidative stress caused by KM dictates a dependency on newly synthesized FA to repair oxidated phospholipids, establishing a targetable vulnerability. These results connect KM oncogenic signaling, FASN induction and ferroptosis, indicating that FASN inhibitors already in clinical trial in KMLC patients (NCT03808558) may be rapidly deployed as therapy for KMLC.

The posteromedial thigh (PMT) flap has been described for breast reconstruction in vertical fashion (vPMT). However, it might not incorporate enough soft tissue for reconstruction of a medium size breast. Here, we present a case utilizing the free inverted-L posteromedial thigh (L-PMT) flap for autologous reconstruction of the breast. A 65-year-old woman with a body max index (BMI) of 24.5 kg/m2 underwent nipple sparring mastectomy and received immediate unilateral breast reconstruction. The flap was raised based on the first medial perforator of the profunda femoris artery (PFA). The internal mammary artery and vein were dissected as recipient vessels. The flap size was 25 cm × 25 cm. The mastectomy specimen and weight of the flap was 260 g and 310 g, respectively. The flap survived completely after surgery. The donor site was primarily closed with minimal morbidities. Follow-up observations were conducted from 1 to 6 months. The patient was satisfied with the reconstruction. The free L-PMT flap may be suitable for breast reconstruction in women with moderate breast size. The inverted-L pattern of the PMT flap allows the surgeon to include a bigger quantity of flap soft tissue enabling a more anatomical shape of the breast and represents an alternative design that may be used for autologous breast reconstruction in selected patients.