Breast surgeons updating on the thresholds of COVID-19 era: results of a multicenter collaborative study evaluating the role of online videos and multimedia sources on breast surgeons education and training.

OBJECTIVE: Current trends show a rise of attention given to breast cancer patients' quality of life and the surgical reconstructive result. Along with this trend, surgical training quality and efficacy are gaining importance and innovative training methods such as online videos shared on social media portals, are becoming main updating tools. In hazardous times like COVID-19 pandemic nowadays, online communication becomes of vital importance and adaptation and innovation are fundamental to keep research and education alive. The authors aimed to investigate the role of video and multimedia sources on the daily activity and surgical training of a representative group of surgeons specifically dedicated to oncologic, oncoplastic and reconstructive breast surgeries. MATERIALS AND METHODS: A survey was produced and administered to 20 major Italian Breast Centers. Collected data were analyzed with Fisher's Exact Test. RESULTS: From October 2019 to March 2020, a total of 320 surveys were collected. Among the responders, there were 188 trainees (intern medical doctors and residents) and 110 faculty, 72% of them belonged to a plastic surgery environment, while 28% to general surgery environment. Almost all respondents have ever watched videos concerning breast surgery. CONCLUSIONS: The results of the study show how breast surgeons rely on videos and web platforms, mostly YouTube, when searching for training info about surgical procedures. Social media offer great opportunities for sharing knowledge and diffusion of new ideas but greater attention to their reliability is mandatory.

Use of anteromedial thigh perforator flap and immunological implications of Gorlin-Goltz syndrome: a case study.

Gorlin-Goltz syndrome is mainly characterised by the development of numerous multicentric and relapsing cutaneous basal cell carcinomas (BCCs). A major problem for patients with Gorlin-Goltz syndrome is the large amount of BCCs that can invade the deep underlying structures, especially the face. Here, we describe the case of a 23-year-old male affected by Gorlin-Goltz syndrome. He had recurrent BCCs on a hairless scalp and dorsum since he was 17 years old and underwent four surgical procedures to excise BCCs, including a reconstruction with anteromedial thigh perforator flap. For each of the surgical procedures, a phenotypic study on peripheral blood mononuclear cells using flow cytometry was performed on the same day of surgery, and on days 7, 14 and 21 after surgery. The role of the tumour-specific cytolytic immune response as a potential future treatment of syndromic BCCs and its trend in relation to surgical ablation of large portions of tumour tissue was examined, and the cosmetic and therapeutic results are shown.

MSCs and inflammation: new insights into the potential association between ALCL and breast implants.

Possible association between anaplastic large cell lymphoma (ALCL) and breast implants has been suggested. In this context, formation of the periprosthetic capsule has been reported as a cause of inflammation, which plays a key role in tumor onset. Tumors take advantage of inflammation to influence and interfere with the host immune response by secreting multiple factors, and their onset and survival is in turn affected by the paracrine effects from mesenchymal stem cells (MSCs). In this study, we tried to clarify how inflammation can modify the immunobiology and the exerted paracrine effect of MSCs. MSCs derived from both inflamed (I-MSCs) and control (C-MSCs) tissues were isolated and co-cultured with an ALCL cell line. Proliferation rate and the expression of selected cytokines were tested. I-MSCs secrete higher levels of cytokine related to chronic inflammation than C-MSCs. After co-cultures with KI-JK cells, C- and I-MSCs show the same variation in the cytokine expression, with an increase of IL2, IL4, IL5, IL10, IL13, TNF-α, TGF-ß, and G-CSF. Proliferation of ALCL cells was not influenced by co-cultures. Our results state that (i) inflamed microenvironment affects the immunobiology of MSCs modifying the profile of the expressed cytokines, and (ii) the paracrine effects exerted by MSCs on ALCL cells are not influenced by inflammation. Moreover, it seems that ALCL cells are able to manipulate MSCs' immunoregulatory properties to evade the host immune control. Nevertheless, this ability is not associated with inflammation and the question about BIA-ALCL is not proved by our experiments.

Does postoperative radiation therapy represent a contraindication to expander-implant based immediate breast reconstruction? An update 2012-2014.

OBJECTIVE: Post-mastectomy radiotherapy (PMRT) is well known in the plastic surgery community for having a negative impact on expander-implant based immediate breast reconstruction (IBBR), although recently some technical improvements allow better results. Very recent papers would suggest that there is no difference in postoperative complications in patients receiving post-mastectomy radiotherapy using modern techniques. However, study results are often biased by small groups of patients and by heterogeneity of radiotherapy timing, different surgical techniques and measured outcomes. MATERIALS AND METHODS: We have conducted a MEDLINE search to summarize the latest data (2012-2014) on the topic. Search was conducted using the following parameters: breast reconstruction AND implant AND expander AND post-mastectomy radiotherapy. RESULTS: The MEDLINE search showed 53 reports, demonstrating a great interest on this topic; among these 37 dealed specifically with post-mastectomy radiotherapy after breast reconstruction. In particular, 15 were amenable to plastic surgeons, 6 to breast surgeons, 9 to radiotherapists and 7 to oncologists. Papers amenable to plastic surgeons highlighted the highest rate of undesired results, although with recent advances such as delayed-immediate reconstruction or protective lipofilling. CONCLUSIONS: PMRT remains an undesired event when pursuing an implant-based breast reconstruction, although it does not represent an absolute contraindication. The higher rate of complications reported by plastic surgeons and not by other specialists can be explained with the greater attention to aesthetic details, such as capsular contractures, that our community has. Technical strategies to prevent complications described in this community now allow better results, should be well known and improved if possible in the future.

Microenvironment and microbiology of skin wounds: the role of bacterial biofilms and related factors.

Wound healing is a systemic response to injury that impacts the entire body and not just the site of tissue damage; it represents one of the most complex biological processes. Our knowledge of wound healing continues to evolve and it is now clear that the wound microenvironment plays a crucial role. The interactions between cells and the surface microenvironment, referred to as the "biofilm," contributes to skin homeostasis and healing. Understanding the functional complexity of the wound microenvironment informs how various factors such as age, ischemia, or bacterial infections can impair or arrest the normal healing processes, and it also allows for the possibility of acting therapeutically on healing defects with microenvironment manipulation. Microbes represent a particularly important factor for influencing the wound microenvironment and therefore wound healing. Moreover, the role of infections, particularly those that are sustained by biofilm-forming bacteria, is mutually related to other microenvironment aspects, such as humidity, pH, metalloproteinases, and reactive oxygen species, on which the modern research of new therapeutic strategies is focused. Today, chronic wounds are a rapidly growing health care burden and it is progressively understood that many non-healing wounds might benefit from therapies that target microorganisms and their biofilm communities. There is no doubt that host factors like perfusion impairments, venous insufficiency, pressure issues, malnutrition, and comorbidities strongly impact the healing processes and therefore must be targeted in the therapeutic management, but this approach might be not enough. In this article, we detail how bacterial biofilms and related factors impair wound healing, the reasons they must be considered a treatment target that is as important as the host's local and systemic pathologic conditions, and the latest therapeutic strategies derived from the comprehension of the wound microenvironment.

Paraplegia in a patient with Von Hippel Lindau syndrome: surgical and reconstructive treatment of Marjolin's ulcer. A case report.

STUDY DESIGN: Marjolin's ulcer is a squamous cell carcinoma that develops in posttraumatic scars and chronic wounds. Suspicion of such lesions should be raised in chronic wounds demonstrating characteristic changes. We have reported the peculiar phenomenon of malignant transformation of chronic pressure sores that occurred in a paraplegic patient. OBJECTIVES: The aim of this study was to cover the extensive defects by a last resort reconstructive option. SETTING: Department of Plastic and Reconstructive Surgery, Università Politecnica delle Marche, Ancona, Italy. METHODS AND RESULTS: A 40-year-old paraplegic man, with multiple hemangioblastomas of the brain and spinal cord due to Von Hippel Lindau syndrome developed pressure ulcers with unstable healing over the sacral, trochanteric, bilateral, and ischiatic areas after 15 years from neurosurgery. The biopsy result showed an invasive squamous carcinoma. Carcinomas in pressure sores are highly aggressive, and they need to be treated more radically. In our case we opted for a demolitive surgical treatment including musculocutaneous rotational flap harvested from total left thigh to cover the extensive defects. The limb was previously disarticulated. CONCLUSION: In Marjolin's ulcer, multiple biopsies are the first-line modality for the early diagnosis as they are a safe method with high rate of accuracy. First-line treatment is surgery consisting of radical excision with lymph node dissection, if they are involved. Adjuvant radiation therapy may be used in selected patients. Management of massive pelvic defects can be a challenging problem. The pedicled lower limb flap offers a technique that can be considered as a last resort procedure for extensive defects where other options are insufficient or not available anymore. In our case the patient is disease-free after 2 years of follow-up.

Characterization and profiling of immunomodulatory genes in resident mesenchymal stem cells reflect the Th1-Th17/Th2 imbalance of psoriasis.

The expression of genes encoding for Th1, Th2 and Th17 cytokines has been extensively evaluated in differentiated skin cells of psoriatic patients. The microenvironment exerts a control on the phenotype of resident mesenchymal stem cells (MSCs) into the skin of psoriasis patients. Aim of the study was to extensively evaluate the relative expression of 43 genes encoding for Th1, Th2 and Th17 cytokines in MSCs isolated from skin of psoriasis patients. MSCs resident into psoriatic skin were isolated, characterized and profiled by PCR array for the relative expression of genes encoding for cytokines involved in Th1, Th2 and Th17 pathways. MSCs isolated from the skin of healthy subjects were used as control. The MSCs isolated from skin of psoriasis patients showed a greater relative expression of the most part of the analyzed genes encoding for Th1 and Th17 cytokines: INF-γ, CCR5, CXCL9, CXCL10, IL6, IL8, TNF-α, IL23A, CCL2, CCL20, CXCL2, CXCL5, IL17C, IL17F, IL17RA, IL21, TLR2 than healthy subjects. On the contrary, the relative expression of genes encoding for Th2 cytokines: CCL1, CCL22, CXCL12, IL2, IL3, IL4, IL13B, IL 22, IL 27, TGF-ß1, was similar between the MSCs isolated from psoriasis and healthy subjects. In conclusion, the MSCs isolated from psoriasis show an imbalance between the Th1-Th17 and Th2 pathways, which reflects the well-known abnormal balance observed in differentiated skin cells. This evidence could strengthen the hypothesis of an early involvement of resident MSCs in the pathogenesis of psoriasis.

Ischemic tolerance modulates TRAIL expression and its receptors and generates a neuroprotected phenotype.

TNF-related apoptosis inducing ligand (TRAIL), a member of the TNF superfamily released by microglia, appears to be involved in the induction of apoptosis following focal brain ischemia. Indeed, brain ischemia is associated with progressive enlargement of damaged areas and prominent inflammation. As ischemic preconditioning reduces inflammatory response to brain ischemia and ameliorates brain damage, the purpose of the present study was to evaluate the role of TRAIL and its receptors in stroke and ischemic preconditioning and to propose, by modulating TRAIL pathway, a new therapeutic strategy in stroke. In order to achieve this aim a rat model of harmful focal ischemia, obtained by subjecting animals to 100 min of transient occlusion of middle cerebral artery followed by 24 h of reperfusion and a rat model of ischemic preconditioning in which the harmful ischemia was preceded by 30 mins of tMCAO, which represents the preconditioning protective stimulus, were used. Results show that the neuroprotection elicited by ischemic preconditioning occurs through both upregulation of TRAIL decoy receptors and downregulation of TRAIL itself and of its death receptors. As a counterproof, immunoneutralization of TRAIL in tMCAO animals resulted in significant restraint of tissue damage and in a marked functional recovery. Our data shed new light on the mechanisms that propagate ongoing neuronal damage after ischemia in the adult mammalian brain and provide new molecular targets for therapeutic intervention. Strategies aimed to repress the death-inducing ligands TRAIL, to antagonize the death receptors, or to activate the decoy receptors open new perspectives for the treatment of stroke.

Outcomes of methicillin-resistant Staphylococcus aureus infection after kidney and/or pancreas transplantation.

BACKGROUND: The true extent of Methicillin-Resistant Staphylococcus aureus (MRSA) colonization and incidence of infection after solid organ transplantation in adults and children is not well-known. The aim of this study was to evaluate the incidence and the outcomes of MRSA infection following kidney and/or pancreas transplantation. MATERIAL AND METHODS: We reviewed the case notes of all patients who developed MRSA colonization and infection within the first year of transplantation between September 2002 and December 2009. The primary endpoint of this study was mortality. The secondary endpoints included morbidity, graft failure, and length of hospital stay. RESULTS: During the study period 1116 transplantations were performed. MRSA colonization was detected in 14 patients (1.25%) and infection occurred in 6 cases (0.53%) post-transplantation. Graft failure was not associated with MRSA colonization/infection in any of the cases. The mortality rate attributed to MRSA was 10% (n = 2). The overall median length of stay was 16 days (range, 6-243 days). CONCLUSIONS: Our study demonstrates that the prevalence of MRSA colonization and infection in our unit is low in spite of immunosuppression. The incidence of MRSA infection was higher among patients who underwent pancreas transplantation. Patients who had MRSA colonization and then developed infection had higher morbidity and mortality rates.

Clinical management of thyroid nodules with indeterminate cytology: our institutional experience using SIAPEC cytological criteria and V600-BRAF test.

BACKGROUND: We evaluated the diagnostic accuracy of thyroid FNAC, integrated with V600E - BRAF mutational study. Herein, we report our experience using the SIAPEC cytological morphological criteria. METHODS: From September 2009 to December 2010, we performed ultrasound-guided fine needle aspiration cytology (FNAC) on 124 patients with clinical evidence of a thyroid nodule, classifying the results in five cytological categories, according to Italian Society of Pathology and Cytology (SIAPEC) consensus conference morphological criteria. In patients with indeterminate (Tir3), suggestive of malignancy (Tir4) or positive for malignancy specimens (Tir5), we obtained a new biopsy in order to study V600E BRAF status. Patients with a diagnosis of Tir2 were assessed every six months with follow-up in the subsequent years. Patients with cytological diagnosis of Tir3, Tir4 and Tir5 underwent thyroid surgical resection with histological assessment of the lesion. Cyto-histological correlation was evaluated. RESULTS: We obtained the following results: Tir2 = 103 (83.1%), Tir3 = 14 (11.3%), Tir4 = 2 (1.6%); Tir5 = 5 (4%). B-RAF mutation was found on 1 Tir3, 1 Tir4 and 2 Tir5. Thyroidectomy was performed on 17 patients classified as Tir3, Tir4 and Tir5. The diagnostic specificity of FNB was of 94.5%, a sensitivity of 100%, a predictive value positive for neoplasia of 77.7 % and a predictive value of malignancy of 61.7%. CONCLUSIONS: Diagnostic accuracy of cytology can be improved through the study of mutational status of BRAF gene. These additional evaluations are well studied, easy to perform and could enter in the current diagnostic procedures to optimize clinical management of thyroid nodular disease.

Non-esterified fatty acid dynamics during oral glucose tolerance test in women with former gestational diabetes.

AIMS: Women with former gestational diabetes are at increased risk of Type 2 diabetes, which likely relates to hyperlipidaemia and ectopic lipid storage, mainly in the liver. Here, we examined the response of non-esterified fatty acid dynamics to oral glucose loading (oral glucose tolerance test). METHODS: We studied women with former gestational diabetes with normal glucose tolerance (n = 60) or impaired glucose metabolism (n = 12) and compared them with healthy women after normal pregnancy (control subjects, n = 15). During a 3-h oral glucose tolerance test, glucose, insulin and non-esterified fatty acid were frequently measured to compute the area under the non-esterified fatty acid curve and parameters of ß-cell function and insulin sensitivity. Through mathematical modelling, we assessed insulin sensitivity of lipolysis inhibition and the fractional non-esterified fatty acid turnover rate. We also measured some serum liver enzymes. RESULTS: Women with former gestational diabetes were slightly older and had greater body mass than control subjects. Subjects with impaired glucose metabolism had lower oral glucose insulin sensitivity, but higher fasting insulin and area under the non-esterified fatty acid curve, which inversely related to oral glucose insulin sensitivity and independently determined mean glycaemia. Model-derived non-esterified fatty acid parameters were lower in subjects with impaired glucose metabolism than in control subjects, particularly sensitivity of non-esterified fatty acid inhibition to insulin (2.50 ± 0.52 vs. 1.06 ± 0.20 · 10(-2) ml/µU). Also, subjects with impaired glucose metabolism had higher liver transaminases. However, all non-esterified fatty acid parameters showed only modest inverse correlation with liver transaminases. CONCLUSIONS: Despite greater insulinaemia, circulating non-esterified fatty acids are higher in women with former gestational diabetes than in control subjects, which likely results from reduced sensitivity of lipolysis inhibition to insulin. This parameter may serve as indicator of an early metabolic derangement in this population at risk for diabetes.

The mesenchymal stem cell profile in psoriasis.

BACKGROUND: The expression of inducible nitric oxide synthase (iNOS) and vascular endothelial growth factor (VEGF) and the level of total oxyradical scavenging capacity have been evaluated extensively in the cutaneous cells of patients with psoriasis. As yet, no indications are available about the undifferentiated cells, the mesenchymal stem cells (MSCs), isolated from skin. OBJECTIVES: To isolate MSCs in patients with psoriasis and to compare them with those obtained from atopic and healthy subjects, in order to analyse whether MSCs show some typical psoriatic profiles and to understand whether pathophysiological events leading to psoriasis start early at the stem cell level. METHODS: MSCs isolated from seven patients with psoriasis, seven patients with acute atopic dermatitis and seven healthy subjects were characterized by fluorescence-activated cell sorting analysis. VEGF and nitric oxide (NO) content was measured in conditioned medium, the expression of VEGF and iNOS was analysed by immunohistochemistry, and the total oxyradical scavenging capacity towards peroxynitrite was tested. RESULTS: VEGF content was highest in the medium conditioned by psoriatic perilesional MSCs, whereas NO concentration was maximally increased in medium conditioned by MSCs isolated from lesional psoriatic skin. The ability to neutralize the oxidizing effects of peroxynitrite was lower for MSCs isolated from lesional psoriatic skin compared with other MSCs, except for MSCs of lesional atopic skin. CONCLUSIONS: The microenvironment in psoriasis differs from those of atopic dermatitis and healthy skin; it could induce resident MSCs to produce angiogenic and proinflammatory mediators which lead to a reduction in the antioxidant capacity of these cells, contributing to the development of skin lesions in psoriasis.

Dynamics of blood electrolytes in repeated hyper- and/or hypoglycaemic events in patients with type 1 diabetes.

AIMS/HYPOTHESIS: Electrolyte disturbances are well-known consequences of the diabetic pathology. However, less is known about the cumulative effects of repeated changes in glycaemia, a characteristic of diabetes, on the electrolyte balance. We therefore investigated the ionic profiles of patients with type 1 diabetes during consecutive hyper- and/or hypoglycaemic events using the glucose clamp. METHODS: In protocol 1, two successive hyperglycaemic excursions to 18 mmol/l were induced; in protocol 2, a hypoglycaemic excursion (2.5 mmol/l) was followed by a hyperglycaemic excursion (12 mmol/l) and another hypoglycaemic episode (3.0 mmol/l). RESULTS: Blood osmolarity increased during hyperglycaemia and was unaffected by hypoglycaemia. Hyperglycaemia induced decreases in plasma Na(+) Cl(-) and Ca(2+) concentrations and increases in K(+) concentrations. These changes were faithfully reproduced during a second hyperglycaemia. Hypoglycaemia provoked rapid and rapidly reversible increases in Na(+), Cl(-) and Ca(2+). In sharp contrast, K(+) levels displayed a rapid and substantial fall from which they did not fully recover even 2 h after the re-establishment of euglycaemia. A second hypoglycaemia caused an additional fall. CONCLUSIONS/INTERPRETATION: Repeated hyperglycaemia events do not lead to any cumulative effects on blood electrolytes. However, repeated hypoglycaemias are cumulative with respect to K(+) levels due to a very slow recovery following hypoglycaemia. These results suggest that recurring hypoglycaemic events may lead to progressively lower K(+) levels despite rapid re-establishment of euglycaemia. This warrants close monitoring of plasma K(+) levels combined with continuous glucose monitoring particularly in patients under intensive insulin therapy who are subject to repeated hypoglycaemic episodes. TRIAL REGISTRATION: Clinicaltrial.gov NCT01060917.

[Influence between sleep and epilepsy: synopsis and prospectus]. / Mutue interazioni tra sonno ed epilessia.

The authors studied the possible theories on the function of the sleep and provided specific information on its representation. They believe useful the hypnogram in monitoring on the pathophysiology of the processes characterized by clinical and subclinical sleep involvement. The continuous and simultaneous registration of the sleep activities by polysomnography have been developed for the evaluation of neurologic diseases with various technique applications: electroencephalography (EEG), electromyography (EMG), and electroculography (EOG). Cyiclic Alternative Pattern (CAP) represents two alternate phases of partial awakening followed from deepened sleeping. Besides CAP rate measures percentage of CAP relative to the quiet sleep or non-Rapid Eyes Movement (non-REM) sleep. There is an intimate relationship between sleep and epilepsy. Sleep is an important activator of interictal epileptiform discharges. The localization of the primary epileptogenic area is more reliable in REM sleep than in wakefulness, and in wakefulness more than in slow-wave sleep. The authors also discuss the role of sleep and sleep deprivation in the EEG evaluation of epilepsy.

Oxidative stress defense in human-skin-derived mesenchymal stem cells versus human keratinocytes: Different mechanisms of protection and cell selection.

Stem cells are undifferentiated cells with the capacity for self-renewal and differentiation. Here we have determined the susceptibility to oxidative stress of isolated mesenchymal stem cells from human skin (S-MSCs) in comparison with keratinocytes, which are differentiated cells of the same lineage. To induce pro-oxidant conditions, S-MSCs and keratinocytes were exposed to 0.5mM H(2)O(2) for 2 h, with oxidative effects analyzed after 4, 12, 24, and 48 h of recovery, in terms of cell growth, vitality, apoptosis, DNA damage, variations in individual antioxidant defense and total oxyradical scavenging capacity toward peroxyl and hydroxyl radicals. The data indicate different abilities across these two cell types to counteract this oxidative stress, which reflects stress that would normally be experienced by these cells under basal conditions. Human keratinocytes seem to have much greater antioxidant defense to counteract the oxidative injury to which they are continuously exposed in the skin. The S-MSCs are surrounded by a complex microenvironment that protects them from external insults, and so they do not have a particularly efficient defense system, and they were generally less responsive to enhanced pro-oxidant challenge. S-MSCs seem particularly prone to apoptotic events, which might thus represent their primary defense mechanism against stress.

Functional characterization of calcium-signaling pathways of human skin-derived mesenchymal stem cells.

BACKGROUND: Mesenchymal stem cells (MSCs) derived from adult human tissues are able to differentiate into various specialized cell types. In research, they can therefore be used like embryonic cells but without the ethical restrictions. Among the various human tissues, skin as a source is characterized by great accessibility and availability using noninvasive procedures and is without the risk of oncogenesis after transplantation. The recent isolation of MSCs has shown the lack of knowledge regarding their specific features, including the calcium-signaling pathways. METHODS: In this study, we isolated MSCs from human skin biopsies (S-MSCs) and characterized them phenotypically and their calcium-signaling pathways by the means of Ca2+ imaging and video microscopic experiments. RESULTS: The cytofluorimetric analysis of the expression of surface markers on S-MSCs revealed that they express the normal pattern present on MSCs. Interestingly, these cells appeared to be successfully cryopreserved at early passages. Calcium imaging on single S-MSCs shows that these cells did not display significant spontaneous activity or a response to a depolarizing agent. However, ATP or acetylcholine-induced intracellular calcium increase via ionotropic or metabotropic receptors, respectively. CONCLUSION: The results presented here reveal that S-MSCs show morphological and functional features that make them useful as an in vitro model to study cell differentiation.

[Nystagmus in ophthalmology]. / Il Nistagmo in Oftalmologia.

Nystagmus is a type of eye movement characterized by alternating smooth pursuit in one direction and saccadic movement in the other direction. Nystagmus may be physiologic when occurring normally and serving its normal function or pathologic when occurring abnormally. The presence of Nystagmus can be benign, or it can indicate an underlying visual or otorhino-neurological problem.Through more and more sophisticated video oculagraphy, video oculoscophy and electronystagmography is possible to study the main characteristics of saccadi such as: amplitude and frequency.In the end it is possible to face the kind of therapy: pharmacological, optical, pleoptic, orthotic, prismatic and surgical.