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Raffaele Rauso,1 Giovanni Francesco Nicoletti,2 Nicola Zerbinati,3 Giorgio Lo Giudice,4 Romolo Fragola,1 Gianpaolo Tartaro5 1Oral and Maxillofacial Surgery Unit, Multidisciplinary Department of Medical-Surgical and Dental Specialists, University of Campania “Luigi Vanvitelli”, Naples, 80138, Italy; 2Plastic Surgery Unit, Multidisciplinary Department of Medicine, Surgery and Odontological Sciences, “Luigi Vanvitelli” University Hospital, Naples, Italy; 3Dermatology, Department of Medicine and Surgery, “Insubria” University Hospital, Varese, Italy; 4Maxillo-Facial Surgery, Department of Neurosciences, Reproductive and Odontological Sciences, “Federico II” University Hospital, Naples, Italy; 5Maxillo-Facial Surgery Unit, Multidisciplinary Department of Medicine, Surgery and Odontological Sciences, “Luigi Vanvitelli” University Hospital, Naples, ItalyCorrespondence: Raffaele RausoOral and Maxillofacial Surgery Unit, Multidisciplinary Department of Medical-Surgical and Dental Specialities, University of Campania “Luigi Vanvitelli”, Naples 80138, ItalyEmail raffaele.rauso@unicampania.itAbstract: The purpose of the present study is to review published literature regarding complications following self-administration of hyaluronic acid (HA) filler. The following keywords were searched in Pubmed and Cochrane database: filler AND self injection, hyaluronic acid AND self injection; filler AND self administration; hyaluronic acid AND self administration. Two authors performed title and abstract eligibility assessment independently. Gray literature and all articles cited in the included papers were also screened and their reference lists were examined to identify other potentially pertinent studies. Non-English papers were excluded. A total of 4 complications following self injection of HA were identified. Conversely, after performing a general search through the Google Internet search engine, with the item “self-injection of hyaluronic acid filler”, there were 604,000 hits. The number of articles reporting complications after the self administration of HA is few. Despite that internet searches on the same topic shows that self-administration of HA fillers is a widely discussed phenomenon in several on-line forums. The present review suggests that complications after self-injection of HA are an under-reported phenomenon.Keywords: self-administration, DIY, self-injection, complication

In an article by Marfella et al, the author name C. Saron is incorrect and should be listed as C. Sardu. Therefore the correct author list is: R. Marfella, F. Cacciapuoti, M. Siniscalchi, F. C. Sasso, F. Marchese, F. Cinone, E. Musacchio, M. A. Marfella, L. Ruggiero, G. Chiorazzo, D. Liberti, G. Chiorazzo, G. F. Nicoletti, C. Sardu, F. D'Andrea, C. Ammendola, M. Verza and L. Coppola. In an article by Marfella et al, the author name C. Saron is incorrect and should be listed as C. Sardu. Therefore the correct author list is: R. Marfella, F. Cacciapuoti, M. Siniscalchi, F. C. Sasso, F. Marchese, F. Cinone, E. Musacchio, M. A. Marfella, L. Ruggiero, G. Chiorazzo, D. Liberti, G. Chiorazzo, G. F. Nicoletti, C. Sardu, F. D'Andrea, C. Ammendola, M. Verza and L. Coppola.

Squamous Cell Carcinoma (SCC) includes several subtypes and these can be classified according to their clinical behaviours from the least invasive to the most aggressive. Moreover, it is appropriate to analyse their clinicalpathological patterns 1. In light of its wide histopathological variability, we encountered a rare malignant cutaneous lesion: a SCC of a proliferating trichilemmal tumour (PTT) nature.We describe the clinical and pathologic findings of an 82-year-old woman, who developed a SCC with areas of trichilemmal differentiation. It has a surprising thickness of 25 mm, which passes through the dermis, infiltrates the hypodermis and evolves quickly.Considering its exophytic growth and the negative results of the post operative tests (ultrasounds confirmed absence of metastasis), the tumour was eradicated thanks to the surgical approach (a 1 cm border wide excision, including the periosteum in the central part of the lesion, followed by its reconstruction using a full-thickness skin graft) and the prompt intervention, without need for further complimentary treatments. The overall aesthetic results were pleasing.Adnexal tumour, PPT, SCC, Surgery.Il carcinoma sqaumocellulare annovera diversi sottotipi classificabili in base alle loro aggressività. In virtù di questa grande variabilità istopatologica riportiamo il caso clinico di un’ottantaduenne caucasica affetta da una rara forma di carcinoma a cellule squamose, con aree di differenziazione trichilemmale/pilare. Tale paziente giunge alla nosta osservazione con una lesione ulcerata, esofitica, nodulare, di 4 cm x 4 cm, localizzata in regione frontale, già precedentemente sottoposta a biopsia incisionale presso altra struttura e con diagnosi di “adenocarcinoma moderatamente differenziato con immunofenotipo compatibile con istogenesi annessiale cutanea”. Considerate l’età della paziente, le comorbidità nonchè la sua storia clinica, effettuate le dovute indagini preoperatorie, si procede all’intervento chirurgico: ampia escissione en bloc della lesione con un margine radiale di 1 cm e approfondimento fino al periostio, incluso nella porzione centrale della lesione. Chiusura della perdita di sostanza post-chirurgica a mezzo di innesto a tutto spessore prelevato dalla regione anteriore del braccio destro. L’intervento chirurgico è privo di complicanze. Il referto anatomo-patologico diagnostica, con valutazione definitiva, “un carcinoma a cellule squamose, moderatamente differenziato, con aree di differenziazione trichilemmale/ pilare, infiltrante l’ipoderma con uno spessore di 25mm. Margini chirurgici indenni”. Sebbene sia noto un comportamento non invasivo di questo tipo di lesione, la letteratura evidenzia molteplici casi di aggressività locoregionale e presenza di potenziale metastatico, strettamente legati all’infiltrazione dei tessuti adiacenti la neoplasia. Si rendono quindi opportuni follow-up e consulenza oncologica. Alla rivalutazione della paziente, non vi è evidenza di recidiva locale clinicamente nonchè a mezzo di indagine ecografica negativa si per recidia locale che per presenza di metastasi locoregionali. Ecco che nonstante lo spessore, l’invasività della lesione e la rapidità della sua evoluzione, dato anche il suo atteggiamento esofitico, la negatività delle indagini diagnostiche e la prontezza dell’approccio terapeutico, è stato possibile eradicare il tumore grazie al solo approccio chirurgico, scongiurando la necessità di terapie complementari. L’esito estetico è stato soddisfacente.

The role of ubiquitin-proteasome system in the accelerated atherosclerotic progression of diabetic patients is unclear. We evaluated ubiquitin-proteasome activity in carotid plaques of asymptomatic diabetic and nondiabetic patients, as well as the effect of rosiglitazone, a peroxisome proliferator-activated receptor (PPAR)-γ activator, in diabetic plaques. Plaques were obtained from 46 type 2 diabetic and 30 nondiabetic patients undergoing carotid endarterectomy. Diabetic patients received 8 mg rosiglitazone (n = 23) or placebo (n = 23) for 4 months before scheduled endarterectomy. Plaques were analyzed for macrophages (CD68), T-cells (CD3), inflammatory cells (HLA-DR), ubiquitin, proteasome 20S activity, nuclear factor (NF)-κB, inhibitor of κB (IκB)-β, tumor necrosis factor (TNF)-α, nitrotyrosine, matrix metalloproteinase (MMP)-9, and collagen content (immunohistochemistry and enzyme-linked immunosorbent assay). Compared with nondiabetic plaques, diabetic plaques had more macrophages, T-cells, and HLA-DR cells (P < 0.001); more ubiquitin, proteasome 20S activity (TNF-α), and NF-κB (P < 0.001); and more markers of oxidative stress (nitrotyrosine and O 2- production) and MMP-9 (P < 0.01), along with a lesser collagen content and IκB-β levels (P < 0.001). Compared with placebo-treated plaques, rosiglitazone-treated diabetic plaques presented less inflammatory cells (P < 0.01); less ubiquitin, proteasome 20S, TNF-α, and NF-κB (P < 0.01); less nitrotyrosine and superoxide anion production (P < 0.01); and greater collagen content (P < 0.01), indicating a more stable plaque phenotype. Similar findings were obtained in circulating monocytes obtained from the two groups of diabetic patients and cultured in the presence or absence of rosiglitazone (7.0 μmol/l). Ubiquitin-proteasome over-activity is associated with enhanced inflammatory reaction and NF-κB expression in diabetic plaques. The inhibition of ubiquitin-proteasome activity in atherosclerotic lesions of diabetic patients by rosiglitazone is associated with morphological and compositional characteristics of a potential stable plaque phenotype, possibly by downregulating NF-κB-mediated inflammatory pathways. © 2006 by the American Diabetes Association.

Chimeric Antigen Receptor (CAR)-modified T lymphocytes represent one of the most innovative and promising approaches to treating hematologic malignancies. CAR-T cell therapy is currently being used for the treatment of relapsed/refractory (r/r) B-cell malignancies including Acute Lymphoblastic Leukemia, Large B-Cell Lymphoma, Follicular Lymphoma, Multiple Myeloma and Mantle Cell Lymphoma. Despite the unprecedented clinical success, one of the major issues of the approved CAR-T cell therapy – tisagenlecleucel, axicabtagene, lisocabtagene, idecabtagene, ciltacabtagene and brexucabtagene – is the uncertainty about its persistence which in turn could lead to weak or no response to therapy with malignancy recurrence. Here we show that the prognosis of patients who do not respond to CAR-T cell therapy is still an unmet medical need. We performed a systematic review and meta-analysis collecting individual data on Duration of Response from at least 12-month follow-up studies. We found that the pooled prevalence of relapse within the first 12 months after CAR-T infusion was 61% (95% CI, 43%−78%); moreover, one year after the infusion, the analysis highlighted a pooled prevalence of relapse of 24% (95% CI, 11%−42%). Our results suggest that identifying potential predictive biomarkers of response to CAR-T therapy, especially for patients affected by the advanced stage of blood malignancies, could lead to stratification of the eligible population to that therapy, recognizing which patients will benefit and which will not, helping regulators to make decision in that way.

Malignant melanoma (MM) is a highly aggressive neoplasm with a growing worldwide incidence. It is not uncommon that the disease is already metastatic at the time of the first diagnosis. Regional lymph nodes and skin are the first and most common metastatic sites, followed by distant visceral sites (lungs, liver, and central nervous system) and bone. In this clinical setting, fine-needle aspiration (FNA) often represents the first diagnostic approach. FNA is a useful tool to obtain a rapid and accurate diagnosis, in conjunction with ancillary techniques and molecular analysis, as recommended by recent guidelines. The aim of this review was to describe the cytomorphology, immunocytochemical tools, and molecular tools used for the diagnosis of MM metastases on FNA.

Dilated cardiomyopathy (DCM) represents a common genetic cause of mechanical and/or electrical dysfunction leading to heart failure (HF) onset for which truncating variants in titin (TTN) gene result in the most frequent mutations. Moreover, myocyte and endothelial cell apoptosis is a key endophenotype underlying cardiac remodelling. Therefore, a deeper knowledge about molecular networks leading to acute injury and apoptosis may reveal novel circulating biomarkers useful to better discriminate HF phenotypes, patients at risk of heart transplant as well as graft reject in order to improve personalised therapy. Remarkably, increased plasma levels of cell-free DNA (cfDNA) may reflect the extent of cellular damage, whereas circulating mitochondrial DNA (mtDNA) may be a promising biomarker of poor prognosis in patients with HF. Furthermore, some panels of circulating miRNAs may improve the stratification of natural history of disease. For example, a combination of miR-558, miR-122* and miR-520d-5p, as well as miR-125a-5p, miR-550a-5p, miR-638 and miR-190a, may aid to discriminate different phenotypes of HF ranging from preserved to reduced ejection fraction. We give update on the most relevant genetic determinants involved in DCM and discuss the putative role of non-invasive biomarkers to overcome current limitations of the reductionist approach in HF management.

Polycaprolactone nanofibers are used as scaffolds in the field of tissue engineering for tissue regeneration or drug delivery. Polycaprolactone (PCL) is a biodegradable hydrophobic polyester used to obtain implantable nanostructures, which are clinically applicable due to their biological safety. Polydatin (PD), a glycosidic precursor of resveratrol, is known for its antioxidant, antitumor, antiosteoporotic, and bone regeneration activities. We aimed to use the osteogenic capacity of polydatin to create a biomimetic innovative and patented scaffold consisting of PCL-PD for bone tissue engineering. Both osteosarcoma cells (Saos-2) and mesenchymal stem cells (MSCs) were used to test the in vitro cytocompatibility of the PD-PCL scaffold. Reverse-phase (RP) HPLC was used to evaluate the timing release of PD from the PCL-PD nanofibers and the MTT assay, scanning electron microscopy, and alkaline phosphatase (ALP) activity were used to evaluate the proliferation, adhesion, and cellular differentiation in both osteosarcoma and human mesenchymal stem cells (MSCs) seeded on PD-PCL nanofibers. The proliferation of osteosarcoma cells (Saos-2) on the PD-PCL scaffold decreased when compared to cells grown on PLC nanofibers, whereas the proliferation of MSCs was comparable in both PCL and PD-PCL nanofibers. Noteworthy, after 14 days, the ALP activity was higher in both Saos-2 cells and MSCs cultivated on PD-PCL than on empty scaffolds. Moreover, the same cells showed a spindle-shaped morphology after 14 days when grown on PD-PCL as shown by SEM. In conclusion, we provide evidence that nanofibers appropriately coated with PD support the adhesion and promote the osteogenic differentiation of both human osteosarcoma cells and MSCs.

Orthognathic surgery and the Le Fort I osteotomy result in noticeable alterations to the nasal/nasolabial anatomy. The alar base cinch technique is a surgical technique to control lateralization of the base of the nose and is well described in the literature. The aim of this scoping review was to identify every unique alar cinch suture technique reported in orthognathic surgery and to propose a classification for the different techniques described. A search was conducted in the PubMed, Cochrane Library, and Scopus electronic databases covering the period May 1980 to July 2020, which identified 10 articles that were eligible for this review. Among these, there were several proposals for modifications to the technique, and different studies to show the effectiveness of one type among all others. Despite observing multiple techniques and variations of these while performing this review, the lack of a classification for alar cinch suture was noticed. Therefore, we propose a classification of the alar cinch suture that includes four types, which cover all of the cinching techniques described. It is believed that the use of a standardized classification may be useful to avoid duplicate publishing of techniques and to set a standard for further studies.

Introduction Skin tags are benign lesions, that often represent only an aesthetic problem; if subjected to trauma, they can occasionally bleed with possible infection and pain. When they occur in the preauricular region, attention should be paid to the diagnosis and approach; in fact, controversy exists in the differential diagnosis between hair follicle nevi, accessory tragus, and skin tag. Misdiagnosis and failure of treatment can lead to serious consequences, such as chondritis. Materials and Methods In our retrospective study, we evaluated 19 newborns affected by single, unilateral skin tag in the preauricular region. Each patient underwent a careful clinical examination; lesions without a pilosebaceous unit and with a thin, soft pedicle were treated in the nursery with Ligaclip (Johnson & Johnson). Results Skin tag falls between day 7 and 10. We had no cases of edema, cellulitis, clip loss, or bleeding. Scarring results were extremely satisfactory at 3-month follow-up. Conclusion We believe that after a careful clinical examination, cases of skin tags in the preauricular area can be selected and treated with Ligaclip. This procedure can be considered rapid, safe, economical, and simple in the newborn patients.

Background In the multidisciplinary treatment of obesity, the role of a plastic surgeon is to remove the excess of skin after weight loss to obtain cosmetic, functional, and psychological benefits. Obesity modifies body geometry, increases the mass of different segments, and imposes functional limitations in life activities that may predispose the obese to injury. The authors evaluated the postural conditions of obese patients, before and 12 months after surgery. Methods The study included 15 obese patients of both genders affected by class II obesity. Postural function was evaluated preoperatively and 12 months postoperatively. Patients underwent conventional abdominoplasty surgical procedure. In all patients, plantar pressure distribution and balance (stabilometric test) were evaluated before and 3 months after surgery. Results The static pedobarographic revealed a significant reduction in forefoot peak pressure; total plantar force; rearfoot plantar force percentage; midfoot plantar force percentage; and forefoot, midfoot, and rearfoot plantar contact areas percentage 3 months after surgery; the dynamic's one showed a reduction in the first metatarsal peak pressure and plantar contact. The stabilometric values showed a reduction in the range of center of foot pressure (CP) displacement along y axis, the average displacement of the CP speed from the mean (RMS y velocity), and CP mean peak in the condition of vision. Conclusions Our study demonstrates the beneficial effect of dermolipectomies and the consequential weight loss on postural stability of obese men. Such findings may support the hypothesis that dermolipectomy may improve postural stability with and without vision. The data demonstrate that the benefits are related to the magnitude of the resected tissue.

Background Nipple-areolar complex (NAC) reconstruction is the final stage of breast reconstruction. Ideal reconstruction of the NAC requires symmetry in position, size, shape, texture, pigmentation, and permanent projection, and although many technical descriptions of NAC reconstruction exist in the medical literature, there is no gold standard technique. The technique devised by the authors is very versatile, with excellent results, and it enables 1-step reconstruction with optimal results in terms of shape and nipple projection. Methods Our technique consists of a combination of modified local flaps and a full-thickness skin graft. Patients were observed for 18 months to estimate the amount of retraction. This procedure was performed in 40 patients, four of them bilaterally. The duration of the follow- up was 30 months. Complications occurred in 10% of patients, and included infections (5%), ischemia (2.5%), and hematoma (2.5%). Results No cases of total nipple necrosis were reported. The NAC shape remained optimal in all cases, with a very small reduction of the vertical and horizontal diameters of the areola, which maintained its designed round shape well, and negligible retraction in the diameter and projection of the nipple. Conclusions The oval technique represents a major step forward, involving a combination of existing techniques, such as the C-V flap and the cutaneous graft, to achieve excellent results regarding areola shape and nipple projection, significantly reducing the cases of nipple ischemia. These results were substantially obtained through subcutaneous equatorial sutures, skin grafting, and flattening of the apexes of the flap. Background Nipple-areolar complex (NAC) reconstruction is the final stage of breast reconstruction. Ideal reconstruction of the NAC requires symmetry in position, size, shape, texture, pigmentation, and permanent projection, and although many technical descriptions of NAC reconstruction exist in the medical literature, there is no gold standard technique. The technique devised by the authors is very versatile, with excellent results, and it enables 1-step reconstruction with optimal results in terms of shape and nipple projection. Methods Our technique consists of a combination of modified local flaps and a full-thickness skin graft. Patients were observed for 18 months to estimate the amount of retraction. This procedure was performed in 40 patients, four of them bilaterally. The duration of the follow- up was 30 months. Complications occurred in 10% of patients, and included infections (5%), ischemia (2.5%), and hematoma (2.5%). Results No cases of total nipple necrosis were reported. The NAC shape remained optimal in all cases, with a very small reduction of the vertical and horizontal diameters of the areola, which maintained its designed round shape well, and negligible retraction in the diameter and projection of the nipple. Conclusions The oval technique represents a major step forward, involving a combination of existing techniques, such as the C-V flap and the cutaneous graft, to achieve excellent results regarding areola shape and nipple projection, significantly reducing the cases of nipple ischemia. These results were substantially obtained through subcutaneous equatorial sutures, skin grafting, and flattening of the apexes of the flap.

The current management of breast cancer(BC) lacks specific non‑invasive biomarkers able to provide an early diagnosis of the disease. Epigenetic‑sensitive signatures are influenced by environmental exposures and are mediated by direct molecular mechanisms, mainly guided by DNA methylation, which regulate the interplay between genetic and non‑genetic risk factors during cancerogenesis. The inactivation of tumor suppressor genes due to promoter hypermethylation is an early event in carcinogenesis. Of note, targeted tumor suppressor genes are frequently hypermethylated in patient‑derived BC tissues and peripheral blood biospecimens. In addition, epigenetic alterations in triple‑negative BC, as the most aggressive subtype, have been identified. Thus, detecting both targeted and genome‑wide DNA methylation changes through liquid‑based assays appears to be a useful clinical strategy for early detection, more accurate risk stratification and a personalized prediction of therapeutic response in patients with BC. Of note, the DNA methylation profile may be mapped by isolating the circulating tumor DNA from the plasma as a more accessible biospecimen. Furthermore, the sensitivity to treatment with chemotherapy, hormones and immunotherapy may be altered by gene‑specific DNA methylation, suggesting novel potential drug targets. Recently, the use of epigenetic drugs administered alone and/or with anticancer therapies has led to remarkable results, particularly in patients with BC resistant to anticancer treatment. The aim of the present review was to provide an update on DNA methylation changes that are potentially involved in BC development and their putative clinical utility in the fields of diagnosis, prognosis and therapy.

Backgrounds: Obese pre-diabetics over express cytokines that influence myocardial function via microRNAs (miRs) expression. Objectives: To evaluate inflammatory/oxidative stress, miRs’ expression and cardiovascular function in obese pre-diabetics assigned to metformin therapy vs. placebo vs. normo-glycemics at 12 months of follow-up. Materials and methods: Eighty-three obese patients after abdominoplastic surgery were divided in pre-diabetics (n 55), normo-glycemics (n 28), and assigned to hypocaloric diet. Pre-diabetics were assigned to metformin (n 23) or to placebo (n 22) plus hypocaloric diet. Results: Obese pre-diabetics in metformin vs. placebo, and obese pre-diabetics with placebo vs. normoglycemics, had significant differences about IMT, MPI, and LVM (p < 0.05). Obese pre-diabetics in metformin vs. placebo showed significant reduction in serum miR-195 and miR-27 (p < 0.05). Obese pre-diabetics in metformin vs. normoglycemics showed higher expression of serum miR-195 and miR-27 (p < 0.05). Finally, we found inverse relation between IMT and insulin, HOMA-IR, miR-195, miR-27; between LVEF and Insulin, HOMA-IR, miR-195 and miR-27. We found inverse correlation between LVM and sirtuin-1, Insulin, HOMA-IR, miR-195 and miR-27, and direct correlation with interleukin-6. MPI inversely linked to miR-195 and miR-27. Conclusions: In obese pre-diabetics’, metformin significantly reduces inflammation/oxidative stress, and miR-195 and miR-27, with reduction in LVM, IMT.

Summary Giant cell arteritis is a primary granulomatous vasculitis characterised by a strict tissue tropism for large and medium-size vessels, occurring in people older than 50 years. Although considerable progress in understanding some of the pathophysiological mechanisms involved in the pathogenesis of giant cell arteritis has been made in the past 10 years, specific triggers of disease and mechanisms of chronic damage have not yet been identified. The definition of a specific pro-inflammatory hierarchy between the multiple cell types and the different cytokines or chemokines involved in the inflammatory process are still unexplored areas of study. The overall goal of precision medicine is to identify the best possible therapeutic approach for an individual or group of individuals with a given disease. The fundamental prerequisite of this approach is the identification, at baseline, of clinical and imaging findings and of molecular biomarkers that allow a precise stratification of patients and an adequate prediction of the therapeutic response. In this regard, the possibility of obtaining temporal artery biopsies for diagnostic purposes offers incredible exploratory possibilities to define different disease pathotypes potentially susceptible to different therapeutic interventions. In this Series paper, we will describe the most recent evidence relating to the pathogenesis of giant cell arteritis, trying to define, if possible, a new pathogenetic-centred approach to patients with giant cell arteritis.

Introduction: Post-marketing data on the risks associated with direct oral anticoagulants (DOACs) are conflicting and only few studies evaluated a comparison between each different DOAC. Real-world data from pharmacovigilance databases can help to better define the safety profile of each DOAC and warfarin. However, Correspondence Analysis (CA) could represent a useful tool in this context.Objective: In the attempt to assess the usefulness of CA as a signal detection pharmacovigilance tool, we applied this method to the Italian Pharmacovigilance Database (RNF, Rete Nazionale di Farmacovigilanza), by comparing with disproportionality analysis on warfarin and DOACs.Methods: Study based on AEs sent to RNF by Campania Region from 2008 to 2021, in which warfarin, dabigatran, apixaban, edoxaban or rivaroxaban were reported as suspected drug. AEs were clustered into three Standardized MedDRA Queries (SMQs): Central Nervous System Haemorrhages and Conditions (CNSH), GastroIntestinal Perforation, Ulceration, Obstruction or Haemorrhages (GIPUOH) and other Haemorrhages (HH). Non-haemorrhagic AEs were included in a fourth cluster (nHH).Results: We retrieved 1,161 reports: 41.5% are associated to warfarin, 21.0% to dabigatran, 17.8% to rivaroxaban, 13.9% to apixaban and 5.8% to edoxaban. No significant differences in age distribution were observed. Results of CA showed that dabigatran and warfarin have the highest contribution (44.910 and 47.656, respectively) to the inertia of Dimension 1 as well as apixaban and dabigatran to the inertia of Dimension 2 (53.768 and 30.488, respectively). Edoxaban and rivaroxaban showed a negligible total contribution. CA biplot showed positive associations between warfarin and HH, apixaban and CNSH and dabigatran and nHH.Conclusion: Results seem to confirm that DOACs are not interchangeable. Apixaban was surprisingly associated with a higher risk of cerebral haemorrhage. As expected, our data support the better safety profile of DOACs than warfarin in terms of skin and respiratory tract hemorrhagic risks. Finally, we showed how CA could play a complementary role in analyzing data from pharmacovigilance databases.

Highlights • In COVID-19 era, the aim of our effort is to guarantee high-quality and timely oncologic care, minimizing infection risk. • Microvascular flaps, reported to be the gold standard for reconstruction, require an extended resource allocation not affordable in this period. • We are obliged to define a paradigm shift in our approach, based on propeller flap. • This surgical technique could represent a reconstructive landmark in COVID-19 era, besides head and neck reconstructive surgery is most likely heading towards a new reconstructive approach., In COVID-19 pandemic era, one major concern is related to ensure optimal management to oncologic patients, even though a context of radical uncertainty. The aim of our effort is to guarantee high-quality and timely care, minimizing COVID-19 infection risk, according to our head and neck (HN) reconstructive mission, still more challenging because of the criticality of the period. Thus, our reconstructive decision algorithm is changed. Microvascular free flaps, reported to be the gold standard for surgical reconstruction, represent extremely specialized procedures necessitating an extended resource allocation not affordable in the adversities of the period. Therefore, we are obliged to define a paradigm shift in our approach, based on free-style reconstructive surgery principles of propeller flap concept. According to our experience, we believe that this viable and feasible surgical technique could represent a reconstructive landmark in this pandemic era, since any guideline is missing, besides HN reconstructive surgery is most likely heading towards a new reconstructive approach.

Adult adipose tissue-derived mesenchymal stem cells (ASCs) constitute a vital population of multipotent cells capable of differentiating into numerous end-organ phenotypes. However, scientific and translational endeavors to harness the regenerative potential of ASCs are currently limited by an incomplete understanding of the mechanisms that determine cell-lineage commitment and stemness. In the current study, we used reduced representation bisulfite sequencing (RRBS) analysis to identify epigenetic gene targets and cellular processes that are responsive to 5′-azacitidine (5′-AZA). We describe specific changes to DNA methylation of ASCs, uncovering pathways likely associated with the enhancement of their proliferative capacity. We identified 4,797 differentially methylated regions (FDR < 0.05) associated with 3,625 genes, of which 1,584 DMRs annotated to the promoter region. Gene set enrichment of differentially methylated promoters identified “phagocytosis,” “type 2 diabetes,” and “metabolic pathways” as disproportionately hypomethylated, whereas “adipocyte differentiation” was the most-enriched pathway among hyper-methylated gene promoters. Weighted coexpression network analysis of DMRs identified clusters associated with cellular proliferation and other developmental programs. Furthermore, the ELK4 binding site was disproportionately hyper-methylated within the promoters of genes associated with AKT signaling. Overall, this study offers numerous preliminary insights into the epigenetic landscape that influences the regenerative capacity of human ASCs.

Inflammation is strictly associated with cancer and plays a key role in tumor development and progression. Several epidemiological studies have demonstrated that inflammation can predispose to tumors, therefore targeting inflammation and the molecules involved in the inflammatory process could represent a good strategy for cancer prevention and therapy. In the past, several clinical studies have demonstrated that many anti-inflammatory agents, including non-steroidal anti-inflammatory drugs (NSAIDs), are able to interfere with the tumor microenvironment by reducing cell migration and increasing apoptosis and chemo-sensitivity. This review focuses on the link between inflammation and cancer by describing the anti-inflammatory agents used in cancer therapy, and their mechanisms of action, emphasizing the use of novel anti-inflammatory agents with significant anticancer activity.

Syringe plunger: An alternative sterile skin-marker in plastic surgery

Background: Systemic sclerosis (SSc) is an autoimmune disease with multisystem involvement, dominated by a general fibrosis. The early stage of the disease is associated with progressive damage to microcirculation, particularly in the respiratory tract, the gastrointestinal tract and skin. The face assumes a typical appearance characterized by microstomia (reduction of mouth opening) and microcheilia (thinning of the lips). These conditions cause a considerable reduction in performance status of patients. We treated them by fat grafting, rich in adipose stem cells, and we evaluated through time clinical, functional and aesthetic evaluation of oral pathology associated with SSc. Materials and Method: From September 2014 to May 2016, we enrolled and treated seven patients in the plastic, reconstructive and aesthetic surgery clinic. Through time, we evaluated the following parameters: evaluation of mouth opening (maximum opening in superior–inferior and lateral directions) and lip thicknesses, both measured by doctors of the aforementioned operating unit; variation in the quality of life as perceived by patients according to the MHISS scale (Mouth Handicap Systemic Sclerosis); variation in severity of labial fibrosis assessed by microscopic analysis of pre- and post-fat transfer samples in the pathology clinic; safety of the protocol, according to the management of side effects resulting from the procedure; aesthetic evaluation, made by external observers and non-experts in the field, on pre- and post-operative photographs. Results and Conclusions: We reported satisfying results, both functionally and aesthetically, for all parameters except one, for which the sample size might have proven critical. These data should be a starting point for further experimental research and clinical trials. Level of Evidence IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266. Background: Systemic sclerosis (SSc) is an autoimmune disease with multisystem involvement, dominated by a general fibrosis. The early stage of the disease is associated with progressive damage to microcirculation, particularly in the respiratory tract, the gastrointestinal tract and skin. The face assumes a typical appearance characterized by microstomia (reduction of mouth opening) and microcheilia (thinning of the lips). These conditions cause a considerable reduction in performance status of patients. We treated them by fat grafting, rich in adipose stem cells, and we evaluated through time clinical, functional and aesthetic evaluation of oral pathology associated with SSc. Materials and Method: From September 2014 to May 2016, we enrolled and treated seven patients in the plastic, reconstructive and aesthetic surgery clinic. Through time, we evaluated the following parameters: evaluation of mouth opening (maximum opening in superior–inferior and lateral directions) and lip thicknesses, both measured by doctors of the aforementioned operating unit; variation in the quality of life as perceived by patients according to the MHISS scale (Mouth Handicap Systemic Sclerosis); variation in severity of labial fibrosis assessed by microscopic analysis of pre- and post-fat transfer samples in the pathology clinic; safety of the protocol, according to the management of side effects resulting from the procedure; aesthetic evaluation, made by external observers and non-experts in the field, on pre- and post-operative photographs. Results and Conclusions: We reported satisfying results, both functionally and aesthetically, for all parameters except one, for which the sample size might have proven critical. These data should be a starting point for further experimental research and clinical trials. Level of Evidence IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Alar base surgery has been widely studied in modern rhinoplasty. After the equalization of the dorsum-tip relationship and the improvement of the nasolabial, nasocolumellar and nasofrontal angle, also alar base, needs to be harmonized also. Several classifications of alar base deformities have been described, as well as many techniques for correcting them. This work aims to demonstrate that alar base symmetrization suture (abss) is effective in keeping the nasal wings symmetrical immediately after alar wedges resection and also permits maintenance of the symmetrization during time. It is a simple technique to perform with long-lasting esthetic results. Level of evidence: Level V, therapeutic study.

Background: Endoscopic carpal tunnel surgery (ECTR) is a procedure that gained wide popularity resulting in reduced scar length and faster recovery. Different studies focused on how the type of skin closure affected the quality and the appearance of the final scar in carpal surgery release. In this study, we investigated the efficiency of a well-established primary skin closure method using Steri-Strips that, to date, has never been described in ECTR. Methods: We retrospectively reviewed data of 47 consecutive patients who underwent unilateral endoscopic carpal tunnel release at our clinic. All patients underwent the same surgical procedure performed by two different surgeons that differed only in the final skin closure: one used only Steri-Strips (group A), while the other used continuous absorbable subcuticular 4/0 monofilament polyglytone 6211 sutures (group B). Data collected included photographs at 10days and three months after surgery and the visual analogue scale (VAS) for pain evaluation, while the measure for the scar evaluation was the Stony Brook Scar Evaluation Scale. We also performed the Wilcoxon rank test to assess if there was a statistically significant difference between the two groups in terms of pain and scar quality. Results: A total of 47 patients were included in this study. According to skin closure technique performed, the patients were categorised into two groups, A and B. Group A comprised 26 patients in which only Steri-Strips were used for the final skin closure; group B included 21 patients in which the closure was performed through 4/0 polyglytone. Data obtained from the VAS and from the Stony Brook Scar Evaluation Scale showed no significant difference between the two groups (p > 0.05). Data obtained from the evaluation of the visual analogue scale showed no significant differences in the median scores and similar postoperative pain between the two groups for all the 7 days of data recorded (p > 0.05). Conclusions: Skin closure with Steri-Strips is a safe, secure and cheap method that leads to excellent aesthetic results. It is both a first choice and a valid alternative to intradermal suture for wound closure after endoscopic carpal tunnel release. Level of evidence: Level IV, therapeutic study.

The accumulation of adipose tissue in the body occurs because the energy introduced with food and drink exceeds that expense, but to understand why this imbalance is established and why it is maintained over time, it is important to consider the main causes and risk factors of excess weight. In this review, we will refer to the main factors linked to obesity, starting from oxidative stress to hormonal factors including the role of obesity in breast cancer. Among the many hypotheses formulated on the etiopathology of obesity, a key role can be attributed to the relationship between stress oxidative and intestinal microbiota. Multiple evidences tend to show that genetic, epigenetic, and lifestyle factors contribute to determine in the obese an imbalance of the redox balance correlated with the alteration of the intestinal microbial flora. Obesity acts negatively on the wound healing, in fact several studies indicate morbid obesity significantly increased the risk of a post-operative wound complication and infection. Currently, in the treatment of obesity, medical interventions are aimed not only at modifying caloric intake, but also to modulate and improve the composition of diet with the aim of rebalancing the microbiota-redox state axis. The accumulation of adipose tissue in the body occurs because the energy introduced with food and drink exceeds that expense, but to understand why this imbalance is established and why it is maintained over time, it is important to consider the main causes and risk factors of excess weight. In this review, we will refer to the main factors linked to obesity, starting from oxidative stress to hormonal factors including the role of obesity in breast cancer. Among the many hypotheses formulated on the etiopathology of obesity, a key role can be attributed to the relationship between stress oxidative and intestinal microbiota. Multiple evidences tend to show that genetic, epigenetic, and lifestyle factors contribute to determine in the obese an imbalance of the redox balance correlated with the alteration of the intestinal microbial flora. Obesity acts negatively on the wound healing, in fact several studies indicate morbid obesity significantly increased the risk of a post-operative wound complication and infection. Currently, in the treatment of obesity, medical interventions are aimed not only at modifying caloric intake, but also to modulate and improve the composition of diet with the aim of rebalancing the microbiota-redox state axis.

AIMS:Immune endothelial inflammation, underlying coronary heart disease (CHD) related phenotypes, could provide new insight into the pathobiology of the disease. We investigated DNA methylation level of the unique CpG island of HLA-G gene in CHD patients and evaluated the correlation with cardiac computed tomography angiography (CCTA) features. METHODS:Thirty-two patients that underwent CCTA for suspected CHD were enrolled for this study. Obstructive CHD group included fourteen patients, in which there was a stenosis greater than or equal to 50% in one or more of the major coronary arteries detected; whereas subjects with Calcium (Ca) Score = 0, uninjured coronaries and with no obstructive CHD (no critical stenosis, NCS) were considered as control subjects (n = 18). For both groups, DNA methylation profile of the whole 5'UTR-CpG island of HLA-G was measured. The plasma soluble HLA-G (sHLA-G) levels were detected in all subjects by specific ELISA assay. Statistical analysis was performed using R software. RESULTS:For the first time, our study reported that 1) a significant hypomethylation characterized three specific fragments (B, C and F) of the 5'UTR-CpG island (p = 0.05) of HLA-G gene in CHD patients compared to control group; 2) the hypomethylation level of one specific fragment of 161bp (+616/+777) positively correlated with coronary Ca score, a relevant parameter of CCTA (p

INTRODUCTION: Blood transfusion is a lifesaving procedure for patients affected by hematological diseases or hemorrhage risk. AIM: This retrospective study was aimed to evaluate clinical safety of pediatric transfusions by comparing the frequency of adverse events caused by apheretic blood components vs whole blood. METHODS: From 2011 to 2015, 214 patients (blood malignancy patients, n = 144 and thalassemic patients, n = 70) received 12 531 units of blood components. The adverse acute reactions occurred during patient hospitalization were reported to the Hemovigilance system and assessed by fitting a logistic mixed-effect model. RESULTS: A total of 33 (0.3%) adverse acute events occurred. Odds ratio (OR) of adverse events from apheresis vs whole blood transfusion adjusted by patient classification was not statistically significant (OR [95% CI], 0.75 [0.23-2.47]). CONCLUSION: Our findings showed no significant differences in the prevalence of adverse acute events between blood component collected by apheresis vs whole blood in our study center.

Non-dermatophytic moulds (NDMs) have been increasingly recognised as causative agents of onychomycosis. The diagnosis of onychomycosis is most often obtained by microscopic observation of nail specimens where fungal elements can be detected and cultured by standard mycological techniques. Direct microscopic examination does not always result positive in NDM onychomycosis; therefore to perform a correct diagnosis, a proper mycological culture is often required. The purpose of our study was to evaluate the role of direct microscopic examination in the NDM onychomycosis diagnosis. The results show that only 57.2% of the specimens from onychomycosis patients could be properly diagnosed showing positivity to both direct microscopic examination and NDMs culture isolation in two or more subsequent inoculations, while 42.8% of analysed specimens with a negative direct microscopic examination, showed NDMs growth after three or more subsequent inoculations. The large proportion of false negatives (more than 42%) could be related to the duration of the infection and/or to the experience and skills of the personnel dedicated to specimen collection. We point out the need for thoroughly evaluating all specimens showing cultural growth in at least three subsequent medium inoculations, whatever the result of the microscopic examination, in order to reduce false-negative rates. This strategy would allow for more accurate diagnosis of this mycosis.

The use of ultrasound “on the surface” was hypothesized by Scuderi et al. in 19871 and resumed by Zocchi in 1996.2 Ultrasound-assisted liposuction is as a technique that can be associated with suctionassisted lipectomy.3 This new technique is called external ultrasound-assisted lipectomy. Whereas ultrasound- assisted liposuction emulsifies adipose tissue due to adipocyte membrane lysis, external ultrasound- assisted lipectomy, being less “invasive,” induces cell-to-cell contact loss and alters collagenic fibers. This leads to an easier detachment of adipose cells, which remain unaltered and can be mechanically removed. The external ultrasound-assisted lipectomy technique is the transcutaneous application of ultrasound by means of high-frequency ultrasound upon massive infiltrated tissue, followed by traditional liposuction. Results showed that several different effects were detected on both adipocytes and collagen fibers.

The development of a fibrotic capsule around foreign material in the body is a physiologic reaction undertaken by the body to protect itself from a material it does not recognize. The periprosthetic capsule can pathologically contract, pressing on the implant; it can cause pain, firmness, and sometimes implant extrusion. The pathogenesis of capsular contracture is still unclear, but most reports indicate a multifactorial explanation. The aim of this study is to investigate the role of cysteinyl leukotriene receptors (cysLTR) on the inflammatory cells involved in the development of the capsular contracture. We recruited 20 patients affected by severe capsular contracture (Baker III-IV) and a control group composed of normal patients who had undergone implant substitution. In both groups, we performed a semiquantitative analysis of mRNA encoding for cysLTR1, cysLTR2, tumor necrosis factor-alpha (TNF-alpha) and interleukin 10 (IL-10) on myofibroblasts and macrophages of the periprosthetic capsular tissue. The molecular analysis showed an increase in the cysLTR2, TNF-alpha gene expression but no change in the cysLTR1 and IL-10 genes in patients affected by capsular contracture. These preliminary findings suggest a primary role for cysteinyl leukotrienes in the activation and up-regulation of capsular contraction mechanisms.

Erythropoietin is the most important factor in the regulation of erythropoiesis. This study aimed to evaluate the efficacy of rhuESF for patients undergoing plastic surgical procedures during which notable blood loss is expected (reduction mammoplasty in cases of macromastia and abdominoplasty obese patients) to improve the full blood count and reduce the need for transfusion. Erythropoeitin is the most important factor in the regulation of erythropoeisis. This study aimed to evaluate the efficacy of rhuESF for patients undergoing plastic surgical procedures during which notable blood loss is expected (reduction mammoplasty in cases of macromastia and abdominoplasty obese patients) to improve the full blood count and reduce the need for transfusion. The levels of hemoglobin were significantly greater for patients pretreated with erythropoeitin and iron than for the control group.

Obesity is associated with an increased risk of developing atherosclerosis and atherosclerotic lesions are essentially an inflammatory response. The aim of this study was to evaluate the effect of a medically supervised, multidisciplinary weight loss program on endothelial functions and circulating levels of proinflammatory cytokines in obese women. Twenty healthy pre-menopausal obese women and 20 age-matched normal weight women were studied. Endothelial functions were assessed by evaluating the response of blood pressure and platelet aggregation to an intravenous bolus of L-arginine (3 g), the natural precursor of nitric oxide. In obese women, the vascular and rheological responses to L-arginine were significantly lower (p0.05) at baseline, as compared with non-obese women, indicating endothelial dysfunction; on the contrary, basal concentrations of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were significantly higher (p0.01). After one year of a multidisciplinary program of weight reduction consisting of diet, exercise and liposuction surgery, all obese women lost at least 10% of their original weight (10.5 +/- 1.7 kg, range 7.9-13.9 kg). Compared with baseline, sustained weight loss was associated with reduction of cytokine (p0.01) concentrations and with improvement of vascular responses to L-arginine. In conclusion, a multidisciplinary approach aimed at inducing a sustained reduction of body weight in obese women is feasible and is associated with improvement of endothelial functions and reduction of circulating proinflammatory cytokine concentrations.

Although it has been demonstrated that diabetes mellitus may enhance apoptosis in myocardial (4) and endothelial cells (5), still, no evidence exists in humans about the potential role of diabetes in the evolution of diabetic atherosclerotic plaques toward instability by enhancing VSMC apoptosis. We hypothesize that by enhancing the proinflammatory cytokines, diabetes may exert proapoptotic effects on VSMCs of atherosclerotic plaque. To address these issues, cell death by apoptosis and expression and localization of TNF-9 and IL-1b was evaluated in carotid plaques of asymptomatic diabetic and nondiabetic patients. The study group consisted of 26 type 2 diabetic and 30 nondiabetic patients enlisted to undergo carotid endarterectomy for asymptomatic extracranial high-grade (.70%) internal carotid artery stenosis